Post-Streptococcal Glomerulonephritis
Post-streptococcal glomerulonephritis is an immune complex-mediated glomerulonephritis occurring 1–3 weeks after group A β-hemolytic streptococcal infection, characterized by hematuria, proteinuria, edema, and hypertension.
Post-Streptococcal Glomerulonephritis (PSGN)
Post-streptococcal glomerulonephritis (PSGN) is an immune complex–mediated glomerulonephritis that develops as a delayed, non-suppurative complication of infection by nephritogenic strains of Group A β-haemolytic Streptococcus (GAS, Streptococcus pyogenes). It is the prototypical cause of acute nephritic syndrome [1][2][3].
Let's break the name down:
- Post- = after
- Strepto- = twisted chain (morphology of the bacterium under microscopy)
- -coccal = round bacterium
- Glomerulo- = pertaining to the glomerulus (the filtration unit of the kidney)
- Nephritis = inflammation of the kidney ("nephro" = kidney, "-itis" = inflammation)
So the name literally tells you: kidney glomerular inflammation occurring after a streptococcal infection.
"PSGN is the prototypical cause of acute nephritic syndrome" — this is a high-yield framing directly from the GC lecture slides and senior nephrology notes [1][2].
Core Concept
PSGN is NOT a direct infection of the kidney. The streptococci are long gone by the time nephritis appears. It is an immunologically mediated injury — the host's own immune response (complement activation, immune complex deposition) damages the glomeruli.
2. Epidemiology
- Predominantly affects children between the ages of 2 and 10 years [1]
- Estimated ~470,000 cases per year worldwide [3][4]
- 97% of cases occur in developing countries with poor socioeconomic conditions [3][4]
- Incidence in developed countries: approximately 0.3 per 100,000 population [3][4]
- In developed nations, incidence has declined dramatically due to improved hygiene, living standards, and access to antibiotics for streptococcal infections
- In Hong Kong, PSGN is uncommon given the developed healthcare system and ready access to antibiotics
- However, cases still occur sporadically, particularly in children presenting with post-pharyngitis nephritic syndrome
- More common causes of glomerulonephritis in Hong Kong adults include IgA nephropathy (the most common primary GN worldwide and in Asia) and lupus nephritis (more prevalent in Chinese females)
- PSGN remains an important differential diagnosis in any child presenting with acute nephritic syndrome after a recent sore throat or skin infection
| Risk Factor | Explanation |
|---|---|
| Young age (2–12 years) | Immature immune regulation; higher exposure to GAS in school settings |
| Male sex | Unknown mechanism; consistently observed M:F = 2:1 |
| Low socioeconomic status | Overcrowding, poor hygiene → increased GAS transmission |
| Tropical/subtropical climates | Skin infections (impetigo/pyoderma) more common → pyoderma-associated PSGN |
| Preceding GAS pharyngitis or impetigo | Only nephritogenic strains cause PSGN (not all GAS strains) |
| Lack of antibiotic treatment for primary infection | Though evidence that antibiotics prevent PSGN is weak, untreated GAS infections allow prolonged antigenic exposure |
| Indigenous populations (Australia, South America) | Higher rates of skin infections and PSGN in these populations |
3. Anatomy and Function — The Glomerulus
Understanding PSGN requires understanding what the glomerulus does and how immune complexes damage it.
The glomerulus is the filtration unit of the nephron (there are ~1 million nephrons per kidney at birth) [6]. Blood enters via the afferent arteriole, passes through a tuft of capillaries (the glomerular capillary tuft), and exits via the efferent arteriole.
The glomerular filtration barrier consists of three layers (from blood side to urine side):
- Fenestrated endothelium (innermost) — has pores (~70–100 nm) that allow plasma through but block blood cells
- Glomerular basement membrane (GBM) — a thick, negatively charged extracellular matrix (type IV collagen, laminin, heparan sulphate proteoglycans) that acts as both a size barrier and a charge barrier
- Podocytes (visceral epithelial cells) (outermost) — specialized cells with interdigitating foot processes separated by slit diaphragms (~25–60 nm gaps) — the final size-selective barrier
Mesangial cells sit between the capillary loops, providing structural support and regulating glomerular blood flow. They can phagocytose immune complexes and debris. When stimulated by immune complexes, they proliferate — this is mesangial proliferation.
Bowman's capsule is lined by parietal epithelial cells. When these cells proliferate in response to severe injury, they form crescents — a hallmark of rapidly progressive GN (RPGN).
- Produces a cell-free, protein-free ultrafiltrate (~180 L/day)
- Normally, no plasma protein or red cells appear in the urine [6]
- The charge barrier (negative charge of GBM from heparan sulphate) repels negatively charged proteins like albumin
- The size barrier prevents large molecules from crossing
In PSGN, immune complex deposition and complement activation cause:
- Endothelial swelling and inflammation → narrows capillary lumen → ↓GFR → oliguria, fluid retention
- Damage to the filtration barrier → RBCs and protein leak through → haematuria and proteinuria
- Mesangial and endocapillary proliferation → the glomerulus becomes "hypercellular" on biopsy
4. Etiology and Pathophysiology
PSGN is caused by nephritogenic strains of Group A β-haemolytic Streptococcus (GAS) (Streptococcus pyogenes) [1][3][5].
Key points:
- Not all GAS strains cause PSGN — only certain M-protein serotypes are nephritogenic
- Pharyngitis-associated nephritogenic strains: M types 1, 2, 4, 12, 18, 25, 49, 55, 57, 60
- Skin infection–associated nephritogenic strains: M types 2, 42, 49, 56, 57, 60
- The M-protein is a virulence factor that helps bacteria evade host defences [5]
- Two leading candidate streptococcal antigens responsible for PSGN [5]:
- Streptococcal pyogenic exotoxin B (SPE B) — a cysteine protease (also called nephritis strain–associated protein, NSAP)
- Nephritis-associated streptococcal plasmin receptor (NAPlr) — glyceraldehyde-3-phosphate dehydrogenase (GAPDH) that binds plasmin; also called NAPlr or GAPDH
A critical feature that distinguishes PSGN from other post-infectious GNs:
| Preceding Infection | Latency Period | Explanation |
|---|---|---|
| Pharyngitis | 1–3 weeks (typically 7–14 days, GC slide says "10 to 14 days") [1][3][4] | Time needed for the host to mount an antibody response against planted streptococcal antigens |
| Skin infection (impetigo/pyoderma) | 3–6 weeks [3][4][5] | Longer because skin infection has a longer subclinical phase and delayed immune sensitization |
"Streptococcal antigens 'planted' in the glomerulus during early phase of streptococcal infection, followed 10 to 14 days later by a host immune response" — GC 057 slide, high yield [1]
High Yield Exam Point
The latency period is key for differentiating PSGN from IgA nephropathy. In PSGN, haematuria appears 1–3 weeks AFTER pharyngitis. In IgA nephropathy, haematuria is synpharyngitic — it occurs within 1–2 days of URTI (essentially simultaneous). This distinction is a classic exam question.
PSGN is an immune complex (I/C) disease induced by nephritogenic Group A strep infection [3][4].
Here is the sequence of events from first principles:
Detailed mechanism:
-
Antigen Planting Phase (during acute GAS infection):
- During the early streptococcal infection, nephritogenic antigens (SPE B, NAPlr) enter the bloodstream
- These antigens have an affinity for glomerular structures — they "plant" themselves in the glomerulus (particularly the subendothelial space and mesangium)
- This "planting" mechanism is the likely explanation for immune complex formation [1]
-
Immune Response Phase (1–3 weeks later):
- The host generates antibodies (IgG) against these streptococcal antigens
- Immune complex formation occurs by two mechanisms [5]:
- Molecular mimicry: antibodies to streptococcal antigens cross-react with native glomerular components
- In situ immune complex formation: antibodies bind to the already-planted streptococcal antigens within the glomerulus
- Circulating immune complex deposition: preformed antigen–antibody complexes in the blood deposit in the glomerulus
-
Complement Activation Phase:
- Immune complexes in the GBM trigger complement activation [5]
- Both classical pathway (C1q binding to Fc portion of IgG in immune complexes) and alternative pathway (C3 deposition) are activated
- This is why C3 is consumed → serum C3 drops (a hallmark lab finding)
- Complement generates:
- C3a/C5a (anaphylatoxins): recruit and activate neutrophils and macrophages → inflammatory infiltrate
- C5b-9 (membrane attack complex, MAC): directly damages glomerular cells (endothelial cells, podocytes)
-
Inflammatory Injury Phase:
- Immune complex deposition in subendothelial region triggers immune response → activates complement, ↑cellular infiltration → glomerular endothelial injury [3][4]
- Neutrophils and macrophages release reactive oxygen species, proteases, and cytokines
- Endothelial cells and mesangial cells proliferate (endocapillary proliferation)
- This leads to narrowing of capillary lumina and damage to the filtration barrier
-
Clinical Consequence:
- Damaged podocytes allow larger molecules including RBC and proteins to filter through → causing haematuria and proteinuria [5]
- Capillary lumen narrowing → ↓GFR → oliguria → salt and water retention → oedema and hypertension
The renal biopsy findings in PSGN are characteristic (though biopsy is usually NOT done as the disease is self-limiting) [1][2][3]:
| Modality | Findings | Significance |
|---|---|---|
| Light Microscopy (LM) | Hypercellular glomeruli with neutrophils [2]; diffuse glomerular hypercellularity with florid acute inflammatory infiltrate (neutrophils, macrophages) and prominent endocapillary proliferation [3][4]; ± crescent formation (uncommon, only in severe cases) | The "hypercellularity" = increased cellularity from both proliferating intrinsic cells (endothelial, mesangial) AND infiltrating inflammatory cells (neutrophils, macrophages). "Diffuse" means > 50% of glomeruli affected |
| Immunofluorescence (IF) | Granular "starry sky" IgG/C3 deposits [2][3][4] — described as a "starry sky" pattern of granular IgG and C3 deposits along the GBM and mesangium | Granular (not linear) pattern = immune complex deposition. "Starry sky" = scattered bright granular deposits against a dark background. Compare with anti-GBM disease which shows linear IF |
| Electron Microscopy (EM) | Characteristic subepithelial electron-dense hump-like deposits ("subepithelial humps") [2][3][4] — dome-shaped deposits on the epithelial (podocyte) side of the GBM; ± subendothelial deposits | The "humps" are pathognomonic for PSGN. They represent large immune complex deposits that have migrated through or deposited on the outer (subepithelial) aspect of the GBM. They are described as "tall and short humps" [2] |
"Light microscopy: Hypercellular glomeruli with neutrophils. Immunofluorescence: Granular spotty IgG immune deposits. Electron microscopy: Characteristic subepithelial electron dense hump-like deposits → tall and short humps" — directly from lecture/senior notes [2]
Why Subepithelial Humps?
The location of immune deposits matters enormously in nephrology. In PSGN, the initial immune complex formation occurs in the subendothelial space (because that's where planted antigens reside and where circulating antibodies first encounter them). Over time, some complexes migrate through the GBM to the subepithelial space, forming the characteristic "humps." This migration likely relates to the size and solubility of the complexes. The subepithelial location is important because it stimulates podocyte injury and complement activation on the urinary side of the GBM.
5. Classification
PSGN is the most common form of acute post-infectious GN (APGN). However, APGN can be caused by many other organisms [3][4]:
| Category | Examples |
|---|---|
| Streptococcal (PSGN) | Group A β-haemolytic Streptococcus (pharyngitis, impetigo) — the prototype |
| Non-streptococcal bacterial | Staphylococcus aureus (especially in infective endocarditis, shunt nephritis), Streptococcus pneumoniae, Legionella, syphilis |
| Viral | Hepatitis B, Hepatitis C, EBV, mumps, varicella, echovirus |
| Parasitic | Malaria, schistosomiasis, toxoplasmosis, trichinosis |
PSGN sits alongside other non-suppurative (immune-mediated) complications of GAS infection [8]:
| Complication | Latency | Mechanism |
|---|---|---|
| Acute Rheumatic Fever (ARF) | 2–3 weeks after pharyngitis | Molecular mimicry (anti-strep antibodies cross-react with cardiac, joint, CNS tissue) |
| PSGN | 1–3 weeks (pharyngitis), 3–6 weeks (skin) | Immune complex deposition in glomeruli |
| Scarlet fever | During or shortly after pharyngitis | Erythrogenic exotoxin |
| PANDAS | Variable | Autoimmune neuropsychiatric disorder |
ARF vs PSGN – Important Distinctions
- ARF occurs only after pharyngitis (NOT skin infection). PSGN occurs after both pharyngitis and skin infection.
- ARF requires secondary prophylaxis with long-term penicillin to prevent recurrence. PSGN does NOT require prophylactic antibiotics [7] — this is because re-infection with the same nephritogenic strain is rare (the host develops type-specific immunity) and antibiotics have not been shown to prevent PSGN.
- They can co-exist but this is rare (different M-protein serotypes are rheumatogenic vs nephritogenic).
PSGN presents along a spectrum [3][4]:
| Severity | Description |
|---|---|
| Subclinical / Asymptomatic | Microscopic haematuria ± mild proteinuria only (most common presentation — many cases are never diagnosed) |
| Classic acute nephritic syndrome | Gross haematuria, oliguria, oedema, hypertension, variable proteinuria |
| Severe / RPGN | Rapidly progressive renal failure with crescent formation on biopsy (rare but serious) |
By age group, the most likely causes of nephrotic vs nephritic syndrome differ [7]:
| Age Group | Nephrotic | Nephritic |
|---|---|---|
| < 15 years | MCD, FSGS | PSGN, IgA nephropathy / HSP |
| 15–40 years | MCD, FSGS, membranous | IgA nephropathy, PSGN, lupus nephritis, RPGN |
| > 40 years | MCD, membranous, diabetic, amyloid | PSGN, IgA nephropathy, RPGN |
6. Clinical Features
"PSGN is an acute, reversible disease characterized by spontaneous recovery in the vast majority of patients" [2][3][4]
| Symptom | Frequency | Pathophysiological Basis |
|---|---|---|
| Gross (macroscopic) haematuria | 30–50% [3][4] | Immune complex–mediated damage to the glomerular filtration barrier → RBCs leak through into urine. Urine is typically described as "smoky, tea or cola-coloured" [3][4] — not bright red (because blood is modified as it passes through the tubule, where haemoglobin is oxidized to methaemoglobin, giving it a brown hue). The absence of blood clots distinguishes glomerular bleeding from urological causes (urokinase in glomerular filtrate lyses clots) [9] |
| Microscopic haematuria | Very common (almost universal in symptomatic cases) | Same mechanism as above but less severe; detected on dipstick or microscopy |
| Oliguria | Common | ↓GFR due to endocapillary proliferation and inflammatory infiltrate narrowing the capillary lumen → reduced filtration surface area → less urine produced |
| Generalised oedema | ~2/3 of cases [3][4] | Oliguria → salt and water retention → expansion of intravascular and extravascular fluid compartments → oedema (periorbital swelling, often noticed in the morning; peripheral oedema). May cause respiratory distress in severe cases [3][4] due to pulmonary oedema from fluid overload |
| Non-specific symptoms | Variable | Anorexia, fatigue, lethargy [5] — due to uraemia (accumulated toxins from reduced GFR) and systemic inflammatory response |
| Abdominal or flank pain | Variable | Acute renal swelling stretching the renal capsule [3][4] — the kidney parenchyma is oedematous and inflamed, distending Gerota's fascia and the fibrous renal capsule, which is richly innervated with pain fibres |
| Headache | Variable | Secondary to hypertension (see Signs below) |
| Nausea/vomiting | Variable | Uraemia; also may be secondary to hypertension |
| Reduced urine output / dark urine | Common | Patient may notice "smoky" or "tea-coloured" urine, and reduced frequency/volume of urination |
Exam Pearl – Colour of Urine
The "smoky, tea or cola-coloured" urine of glomerular haematuria is distinct from the bright red urine of urological haematuria (e.g. bladder cancer, renal stones). Glomerular blood undergoes haemoglobin degradation as it traverses the nephron. Also, glomerular haematuria produces dysmorphic RBCs and RBC casts on urine microscopy.
| Sign | Frequency | Pathophysiological Basis |
|---|---|---|
| Hypertension | 50–90% [3][4] | Salt and fluid retention is the primary mechanism — oliguria leads to ↑intravascular volume → ↑blood pressure. This is a volume-dependent hypertension (not RAAS-driven like renovascular hypertension). Severity varies from mild to severe; can rarely cause hypertensive encephalopathy in children |
| Generalised oedema | ~2/3 | Same as above; periorbital oedema (often the first sign noticed, especially in the morning as fluid redistributes with gravity while lying down), lower limb oedema, sacral oedema |
| Elevated JVP | Variable | Fluid overload → ↑central venous pressure |
| Pulmonary crackles/gallop rhythm | In severe cases | Fluid overload → pulmonary oedema → bilateral basal crackles; volume overload on the heart → S3 gallop |
| Pallor | Variable | May have mild dilutional anaemia from fluid overload; rarely from microangiopathic haemolysis |
| Sterile pyuria | Common | White blood cells (neutrophils) from the glomerular inflammatory process appear in the urine in the absence of urinary tract infection — hence "sterile" pyuria [3][4] |
| Finding | Pathophysiological Basis |
|---|---|
| Dysmorphic RBCs | RBCs squeezed through damaged GBM become distorted (acanthocytes, "Mickey Mouse" cells) |
| RBC casts | RBCs trapped in Tamm-Horsfall protein matrix within tubules → pathognomonic of glomerular haematuria |
| Variable proteinuria | Usually sub-nephrotic (< 3.5 g/day) but can occasionally reach nephrotic range. Due to disruption of the GBM charge and size barrier |
| Sterile pyuria | Neutrophils from glomerular inflammation, not infection |
| Granular casts | Degenerated cellular material within tubular casts |
Why Is Proteinuria Usually Sub-Nephrotic in PSGN?
In nephritic syndrome (like PSGN), the predominant pathology is endocapillary proliferation and inflammation — the GBM is damaged but not as severely as in nephrotic syndrome (where podocyte foot process effacement is the primary lesion). The inflammatory process reduces GFR (fewer molecules get through), which paradoxically limits the degree of proteinuria. In nephrotic conditions (e.g. MCD), the GFR is relatively preserved but the podocyte slit diaphragms are widely effaced, allowing massive protein leak.
Understanding the natural history is essential for monitoring and for recognizing when things are not following the expected course (which should prompt re-evaluation of diagnosis):
| Parameter | Expected Resolution |
|---|---|
| Diuresis | 1–2 weeks [2][3][4] |
| RFT normalisation | ~4 weeks [2][3][4] |
| C3 normalisation | 6–8 weeks (persistently low C3 > 8 weeks → consider lupus nephritis or MPGN) [2][3][4] |
| Microscopic haematuria | May persist for up to 1–2 years |
| Mild proteinuria | May persist for several months |
| Hypertension | Usually resolves within 1–2 weeks with diuresis |
"Persistently low C3 > 8 weeks raises the possibility of lupus nephritis or membranoproliferative glomerulonephritis (complement-mediated MPGN)" [2][3][4]
Red Flags in Suspected PSGN
If any of the following are present, question the diagnosis and consider renal biopsy:
- C3 persistently low > 8 weeks
- No improvement in renal function by 4 weeks
- Nephrotic-range proteinuria that persists
- RPGN presentation (rapidly rising creatinine)
- Recurrent episodes of haematuria (think IgA nephropathy instead)
- Positive ANA/anti-dsDNA (think lupus nephritis)
This is a commonly tested concept. PSGN shows:
| Complement Component | Level | Explanation |
|---|---|---|
| C3 | ↓↓↓ | Consumed by both classical and alternative pathway activation by immune complexes |
| CH50 (total haemolytic complement activity) | ↓↓↓ | Reflects overall complement system activity; low because complement is being consumed |
| C4 | Normal or mildly ↓ [5] | C4 is consumed only in the classical pathway; since the alternative pathway is also heavily involved in PSGN (and is a C4-independent pathway), C4 depletion is relatively less prominent |
"↓C3 and CH50 level with ↔ C4 level" [5] — this pattern (low C3 with relatively normal C4) is characteristic of PSGN and suggests predominant alternative pathway activation.
Differential Diagnosis by Complement Pattern (High Yield)
| Condition | C3 | C4 | Pathway |
|---|---|---|---|
| PSGN | ↓ | Normal/mildly ↓ | Alternative > Classical |
| Lupus nephritis | ↓ | ↓ | Classical (C1q, C4, C2 involved) |
| MPGN (complement-mediated) | ↓↓ | ↓ or Normal | Alternative (C3 nephritic factor stabilizes C3 convertase) |
| IgA nephropathy | Normal | Normal | Complement NOT typically consumed |
| Anti-GBM disease | Normal | Normal | No immune complex → no complement consumption |
| ANCA-associated vasculitis | Normal | Normal | Pauci-immune (minimal immune complex deposition) |
8. Key Differentiating Features from Close Mimics
| Feature | PSGN | IgA Nephropathy |
|---|---|---|
| Timing of haematuria | 1–3 weeks AFTER pharyngitis | Synpharyngitic (within 1–2 days of URTI) [7] |
| Recurrence | Usually single episode | Recurrent episodic haematuria triggered by URTI |
| Complement | ↓C3 | Normal C3 |
| Serum IgA | Normal | Elevated in ~50% |
| Age | Children 2–12 years | Young adults (20–30 years) |
| Biopsy IF | "Starry sky" granular IgG/C3 | Mesangial IgA deposits |
| EM | Subepithelial humps | Mesangial electron-dense deposits |
| Prognosis | Self-limiting, excellent | Chronic, 20–40% progress to CKD over 20 years |
| Feature | PSGN | Lupus Nephritis |
|---|---|---|
| Demographics | Children, M > F | Young women, F >> M |
| Systemic features | None (renal-limited) | Multisystem: rash, arthritis, serositis, cytopenias |
| Complement | ↓C3, normal C4 | ↓C3 AND ↓C4 |
| Duration of low C3 | Normalizes by 8 weeks | Persistently low |
| Serologies | ANA negative | ANA, anti-dsDNA positive |
High Yield Summary
Post-Streptococcal Glomerulonephritis (PSGN) — Key Points:
- Definition: Immune complex–mediated GN occurring as a non-suppurative complication of nephritogenic GAS infection
- Epidemiology: Most common cause of acute nephritis in children (ages 2–12); M:F = 2:1; rare in developed countries
- Latency: 1–3 weeks after pharyngitis, 3–6 weeks after skin infection (GC slide: "10 to 14 days after streptococcal infection")
- Pathogenesis: Streptococcal antigens planted in glomerulus → host antibody response → in situ immune complex formation → complement activation → inflammatory injury
- Pathology: LM: diffuse endocapillary proliferation with neutrophil infiltrate; IF: "starry sky" granular IgG/C3; EM: subepithelial humps (pathognomonic)
- Clinical features: Nephritic syndrome — gross haematuria (smoky/cola-coloured), oliguria, oedema, hypertension, sub-nephrotic proteinuria
- Complement: ↓C3 and ↓CH50 (normalizes by 8 weeks); normal C4
- Prognosis: Self-limiting; diuresis in 1–2 weeks, RFT normalizes by 4 weeks
- Persistently low C3 > 8 weeks → think lupus nephritis or MPGN
- Key DDx: IgA nephropathy (synpharyngitic, normal C3, recurrent), lupus nephritis (↓C3 AND ↓C4, multisystem), MPGN (persistent low C3)
- No prophylactic antibiotics needed (unlike ARF)
Active Recall - PSGN (Definition, Epidemiology, Pathophysiology, Clinical Features)
[1] Lecture slides: GC 057. Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p34 — Poststreptococcal glomerulonephritis) [2] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p18–19 — Acute nephritic syndrome, PSGN) [3] Senior notes: Ryan Ho Urogenital.pdf (p65–66 — Post-streptococcal Glomerulonephritis) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (p327–328 — Post-streptococcal Glomerulonephritis) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p128, p420 — PSGN overview, pathogenesis, clinical features) [6] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf (p3 — Normal kidney anatomy and histology) [7] Senior notes: Maksim Medicine Notes.pdf (p231, p233 — GN with nephritic features, Post-strep GN, RPGN classification) [8] Senior notes: Ryan Ho Respiratory.pdf (p52 — Complications of GAS pharyngitis) [9] Senior notes: Maksim Surgery Notes.pdf (p308 — Haematuria, glomerular vs urological causes)
Differential Diagnosis of Post-Streptococcal Glomerulonephritis (PSGN)
PSGN is usually diagnosed clinically — a child presents with acute nephritic syndrome (haematuria, oedema, hypertension, oliguria) 1–3 weeks after a sore throat, with low C3 and positive streptococcal serology. Renal biopsy is usually NOT done [2][3][4]. But the critical question on a ward round is: "What if it's NOT PSGN?" — because some mimics require urgent immunosuppression (e.g. RPGN, lupus nephritis) while PSGN is self-limiting. Missing a mimic can cost the patient their kidneys.
"Consider renal biopsy if suspect alternative diagnosis" — this framing from the senior notes captures the entire rationale for differential diagnosis in PSGN [4].
The differential diagnosis centres on two clinical questions:
- Is this really a nephritic syndrome? (vs. other causes of haematuria or oedema)
- If it IS nephritic syndrome, is it truly PSGN or another GN mimicking PSGN?
The DDx can be systematically organized by starting broad (all causes of the presenting features — haematuria, oedema, hypertension) and then narrowing to the most relevant GN mimics.
Before anchoring on a glomerular cause, always consider that haematuria may be non-glomerular. The GC 057 slide on differential diagnosis of haematuria lists [1]:
Differential diagnosis:
- Urologic conditions: Stones, Tumour
- Renal conditions: Glomerulonephritis, Acute interstitial nephritis, Polycystic kidney disease
- Infection: Cystitis, TB, Schistosomiasis
| Category | Examples | How to Distinguish from PSGN |
|---|---|---|
| Urological: Stones [1] | Renal/ureteric calculi | Colicky loin-to-groin pain; isomorphic RBCs (not dysmorphic); no RBC casts; no proteinuria; imaging shows calculus |
| Urological: Tumour [1] | Wilms tumour (children), RCC (adults), bladder TCC | Painless gross haematuria (often bright red, not smoky); may have clots (urokinase in glomerular filtrate prevents clot formation in glomerular haematuria); mass on imaging |
| Infection: Cystitis / UTI [1] | Bacterial cystitis, pyelonephritis | Dysuria, frequency, suprapubic pain; positive urine culture (NOT sterile pyuria); isomorphic RBCs; no ↓C3 |
| Infection: TB [1] | Renal tuberculosis | Chronic sterile pyuria; urine AFB culture; history of TB exposure; calcified kidney on imaging |
| Infection: Schistosomiasis [1] | Schistosoma haematobium | Terminal haematuria; eggs on urine microscopy; travel to endemic area (Africa, Middle East) |
| Acute interstitial nephritis (AIN) [1] | Drug-induced (NSAIDs, antibiotics), idiopathic | Eosinophiluria; skin rash + fever + eosinophilia triad; drug history (NSAIDs particularly relevant — "NSAID-induced nephrotic syndrome with AKI, eosinophilia" [11]); WBC casts (not RBC casts); renal impairment out of proportion to urinalysis findings |
| Polycystic kidney disease [1] | ADPKD, ARPKD | Family history; bilateral enlarged kidneys with multiple cysts on ultrasound; flank pain; hypertension may be present but usually in adults |
| Exercise-induced haematuria | Vigorous exercise | Transient, resolves within 48–72 hours of rest; no proteinuria, no hypertension |
| Coagulopathy / Anticoagulants | Bleeding disorder, warfarin overdose | Antiplatelet/anticoagulant use is NOT a satisfactory explanation for haematuria, except in warfarin overdose [9] — always investigate further |
Key Bedside Distinction: Glomerular vs Urological Haematuria
| Feature | Glomerular (e.g. PSGN) | Urological (e.g. stone, tumour) |
|---|---|---|
| Urine colour | Smoky, tea/cola-coloured | Bright red |
| Blood clots | Absent (urokinase in filtrate lyses clots) | May be present |
| RBC morphology | Dysmorphic (acanthocytes) | Isomorphic |
| RBC casts | Present (pathognomonic for GN) | Absent |
| Proteinuria | Present (usually sub-nephrotic) | Usually absent or trace |
This distinction should be made on urine microscopy — every positive dipstick should be followed by formal microscopy [9].
B. Glomerular Causes — The Core Differential of PSGN
Once you've established that this is a nephritic syndrome (haematuria + proteinuria + hypertension + oedema + renal impairment with dysmorphic RBCs / RBC casts), the differential narrows to causes of acute GN. The table below compiles the major differentials from the lecture slides and senior notes [2][3][4][5][7][10][12].
"APGN due to other infections, e.g. Staphylococcus, pneumococcus, Legionella, syphilis, mumps, varicella, HBV, HCV, echovirus, EBV, toxoplasmosis, malaria, schistosomiasis, trichinosis" [4]
PSGN is the prototype of acute post-infectious GN, but the same pattern of immune complex–mediated nephritis can occur with many other infections. The key differentiator is the documentation of recent GAS infection (positive ASOT, throat culture, or streptozyme test). If streptococcal serology is negative, consider these alternative causes:
| Organism | Clinical Clue |
|---|---|
| Staphylococcus aureus | Infection-associated GN (especially in setting of infective endocarditis, shunt nephritis, deep-seated abscess); may have low C3; IgA-dominant on biopsy ("IgA-dominant infection-related GN"); older/immunocompromised patients |
| Pneumococcus | Following pneumococcal pneumonia or meningitis |
| HBV | HBV most often induces membranous nephropathy [5], but can also cause MPGN; check HBsAg/HBeAg |
| HCV | HCV most often induces membranoproliferative GN [5]; check anti-HCV antibodies; associated with cryoglobulinaemia |
| HIV | HIV is associated with a collapsing form of FSGS [5]; check HIV serology |
| Syphilis | Congenital and secondary syphilis associated with membranous nephropathy [5]; check VDRL |
| Malaria | Travel history; thick/thin blood film; P. malariae classically causes nephrotic syndrome |
| Infective endocarditis | Fever + new/changing murmur + splinter haemorrhages + positive blood cultures; GN often caused by circulating immune complexes from chronic bacteraemia |
GN Workup — What to Test For
The standard workup for glomerulonephritis as per the GC/Nephrology Introduction to Renal Investigation slides [13][14]:
"Autoimmune markers: ANA, Anti-dsDNA, C3/4, ANCA, Anti-GBM, CRP, cryoglobulins" "Exclude infective causes (e.g. HBV/HCV/HIV/VDRL/malaria)" "Malignancy screen (e.g. tumour markers, SIEP) especially in elderly" "Renal biopsy: LM/IF/EM findings → Diagnosis, guide treatment decisions and prognosis"
This systematic workup ensures you don't miss a treatable secondary cause.
The most common primary GN worldwide [7]. This is the single most important differential for PSGN in an exam setting.
| Feature | PSGN | IgA Nephropathy |
|---|---|---|
| Timing of haematuria | 1–3 weeks AFTER pharyngitis (latent period for antibody response) | Synpharyngitic: gross haematuria within 1–2 days of URTI [4][7] — there is no latency because pre-formed IgA immune complexes are already deposited; mucosal infection simply triggers a burst of IgA production and further mesangial deposition |
| Recurrence | Usually a single episode (host develops type-specific immunity to that nephritogenic strain) | Recurrent episodic haematuria triggered by URTI [4] — each URTI provokes a new flare |
| Prior history | Usually none (first and only episode) | May be associated with prior history of haematuria [4] |
| Complement (C3) | ↓C3 | NOT usually associated with ↓complement [4][7] — normal C3 |
| Serum IgA | Normal | Elevated IgA in ~50% [7] |
| Age | Children 2–12 y | Young adults (peak 20–30 y), though can occur at any age |
| IF pattern | Granular IgG/C3 ("starry sky") | Mesangial IgA deposits (dominant) |
| Course | Self-limiting (excellent prognosis in children) | Chronic; 20–40% progress to CKD over 20 years |
Why is IgA nephropathy synpharyngitic while PSGN has a latent period? In IgA nephropathy, aberrantly glycosylated IgA1 is already circulating and deposited in the mesangium at baseline. When a mucosal infection (URTI, GI infection) occurs, there is an immediate surge in IgA production → more immune complex formation → immediate flare of haematuria. In PSGN, the host has NOT yet developed antibodies against the streptococcal antigen — it takes 10–14 days to mount an adaptive immune response, explaining the latent period.
"2° GN, e.g. lupus nephritis" [4]
| Feature | PSGN | Lupus Nephritis |
|---|---|---|
| Demographics | Children, M > F | Young women (F >> M), typically 15–45 y; more prevalent in Chinese populations (relevant to HK) |
| Systemic features | Isolated renal disease | Multi-system: malar rash, photosensitivity, oral ulcers, hair loss, arthralgia/arthritis, serositis, cytopenias [10] |
| Complement | ↓C3, normal/mildly ↓ C4 | ↓C3 AND ↓C4 (classical pathway activation — both early components consumed) |
| Duration of hypocomplementaemia | Normalizes by 6–8 weeks | Persistently low (active disease keeps consuming complement) |
| Serology | ANA negative; ASO elevated | ANA positive, anti-dsDNA positive [5][10] |
| Course | Self-limiting | Chronic, relapsing-remitting; requires immunosuppression |
"Persistently low C3 > 8 weeks raises the possibility of lupus nephritis or membranoproliferative glomerulonephritis" [2][3][4] — this is the most important red flag for misdiagnosed PSGN.
The Nephrology Interactive Tutorial (Case 1) specifically presents a young Chinese lady with nephritic syndrome, small joint pain, and lower limb swelling — prompting the following workup clues [10]:
"Ask for constitutional symptoms → Autoimmune: Hair loss, oral ulcers, rashes → photosensitivity → Lupus nephritis" "Investigate more into small hand joints + specific involvement"
This illustrates how lupus nephritis enters the DDx when systemic features are present.
"MPGN: acute presentation may be indistinguishable from PSGN, but usually persists beyond 4–6 weeks with further ↑serum Cr" [4]
| Feature | PSGN | MPGN |
|---|---|---|
| Acute presentation | Typical nephritic syndrome | May be indistinguishable [4] — can present with nephritic or nephrotic syndrome or both |
| Course | Resolves in 4 weeks | Persists beyond 4–6 weeks, progressive renal impairment [4] |
| Complement | ↓C3 (normalizes by 8 weeks) | Persistently low C3 (due to C3 nephritic factor — an autoantibody that stabilizes C3 convertase, causing ongoing alternative pathway activation) |
| Biopsy | Subepithelial humps, endocapillary proliferation | Mesangial proliferation + GBM thickening ("tram-track" appearance on silver stain) |
| Cause | Post-GAS infection | Idiopathic, HCV/cryoglobulinaemia, complement dysregulation (C3 glomerulopathy), autoimmune |
Key clinical discriminator: If a patient with presumed PSGN does not improve by 4–6 weeks or has persistently low C3 beyond 8 weeks, MPGN must be considered and renal biopsy performed [2][3][4].
"RPGN is a clinical syndrome but NOT a specific etiology of GN" [7][12]
RPGN presents with haematuria, proteinuria, and rapidly declining renal function leading to ESRD within days to weeks [7][12]. PSGN itself can rarely progress to RPGN (Type II crescentic GN, immune complex–mediated) [3][4][12], but more importantly, other causes of RPGN must be excluded because they require urgent immunosuppression.
RPGN is classified by IF staining pattern [7][12]:
| Type | IF Pattern | Cause | Key Features |
|---|---|---|---|
| Type I | Linear | Anti-GBM disease (Goodpasture syndrome if lung involved) [7] | Anti-GBM antibody positive; ± pulmonary haemorrhage (haemoptysis, SOB, CXR infiltrates); normal complement; treatment: plasmapheresis + steroids + cyclophosphamide/rituximab |
| Type II | Granular | Immune complex–mediated | Can complicate most GN associated with nephritic syndrome (e.g. SLE, IgAN, PSGN) [12]; low complement if IC-mediated |
| Type III | Negative (pauci-immune) | Pauci-immune, usually ANCA-positive [7] | Associated with ANCA-associated vasculitis (GPA, MPA, EGPA); normal complement; may have extra-renal features (rhinosinusitis, pulmonary nodules/haemorrhage, purpura, neuropathy) |
"Histology: > 50% glomeruli with crescent" [7]
When to suspect RPGN instead of PSGN:
- Creatinine rising rapidly (doubling within days) rather than stabilizing
- No spontaneous improvement within 1–2 weeks
- Presence of extra-renal features (haemoptysis → Goodpasture/ANCA vasculitis; rash + arthritis → SLE)
- Patient is an adult (RPGN is more common in adults; PSGN causing RPGN is rare)
RPGN is a Medical Emergency
HSP is essentially systemic IgA vasculitis — histologically identical to IgA nephropathy but with extra-renal manifestations.
| Feature | PSGN | HSP |
|---|---|---|
| Demographics | Children 2–12 y | Children 3–10 y (overlap with PSGN age group) |
| Skin | None | Palpable purpura (must be present!) — especially over buttocks and lower extremities [7] |
| GI | None | Colicky abdominal pain (mesenteric vasculitis); risk of intussusception |
| Joints | None | Arthralgia / arthritis (large joints, periarticular oedema) |
| Renal | Nephritic syndrome | GN (identical to IgA nephropathy histologically — mesangial IgA deposits) |
| Complement | ↓C3 | Normal |
| Mnemonic | — | "FA GASP": Fever, Arthralgia, GN, Abdominal pain, Skin rash, Periarticular oedema [7] |
The key differentiator is the palpable purpuric rash — if a child has nephritic syndrome PLUS purpura on the legs/buttocks, think HSP, not PSGN.
| Condition | Key Distinguishing Features |
|---|---|
| NSAID-induced nephropathy | Drug history of NSAID use (relevant if patient was taking NSAIDs for sore throat or arthralgia); minimal change GN + acute tubulo-interstitial nephritis; eosinophilia (40%); higher risk in elderly [11]; bland sediment (no RBC casts typically) |
| Infective endocarditis–associated GN | Prolonged fever; new/changing murmur; splinter haemorrhages, Osler nodes, Janeway lesions; positive blood cultures; immune complex GN from chronic bacteraemia; low C3 possible |
| Thrombotic microangiopathy (HUS/TTP) | Microangiopathic haemolytic anaemia (schistocytes on blood film) + thrombocytopaenia + renal impairment; no RBC casts (this is a vascular, not glomerular, process); in children, typical HUS follows E. coli O157:H7 bloody diarrhoea |
| Alport syndrome | Family history of renal failure + sensorineural deafness + ocular abnormalities; persistent microscopic haematuria in a male child; X-linked dominant inheritance (most common form) |
This is the single highest-yield table for exams. The complement pattern (C3/C4) is the first branching point after confirming nephritic syndrome:
| Low C3 | Normal C3 | |
|---|---|---|
| Low C4 | Lupus nephritis (classical pathway); Cryoglobulinaemia / Mixed essential cryoglobulinaemia | Rare; consider hereditary C4 deficiency |
| Normal C4 | PSGN (alternative pathway predominant); MPGN / C3 glomerulopathy; Infection-associated GN (non-strep) | IgA nephropathy; HSP nephritis; Anti-GBM disease; ANCA-associated vasculitis; FSGS; Alport syndrome |
"Hypocomplementaemia in lupus nephritis, post-infectious glomerulonephritis, membranoproliferative glomerulonephritis and mixed cryoglobulinaemia" [5]
Based on the compiled lecture and senior note material, you should question the diagnosis of PSGN and consider renal biopsy if any of the following are present:
| Red Flag | What It Suggests |
|---|---|
| Persistently low C3 > 8 weeks [2][3][4] | Lupus nephritis or MPGN |
| No improvement in renal function by 4 weeks | MPGN or RPGN |
| Rapidly rising creatinine (doubling in days) | RPGN — medical emergency |
| Nephrotic-range proteinuria that persists | Membranous, FSGS, or MPGN |
| Recurrent episodes of haematuria with URTIs | IgA nephropathy |
| Synpharyngitic haematuria (within 1–2 days) | IgA nephropathy (not PSGN) |
| Systemic symptoms (rash, arthritis, serositis) | SLE / ANCA vasculitis / HSP |
| Haemoptysis + nephritic syndrome | Goodpasture syndrome or ANCA vasculitis (pulmonary-renal syndrome) |
| Positive ANA / anti-dsDNA | Lupus nephritis |
| Positive ANCA | ANCA-associated vasculitis (GPA, MPA) |
| Positive anti-GBM antibody | Anti-GBM disease |
| Negative streptococcal serology | Non-streptococcal post-infectious GN, or not post-infectious at all |
| Age > 60 with nephritic syndrome | Consider RPGN, ANCA vasculitis, malignancy-associated GN; malignancy screen especially in elderly [13][14] |
| Palpable purpura | HSP / ANCA vasculitis |
When you encounter a patient with acute nephritic syndrome and want to differentiate PSGN from its mimics, the systematic approach follows the GN workup from the GC/Nephrology lecture slides [13][14]:
Step 1: Confirm glomerular origin of haematuria
- Urine microscopy: dysmorphic RBCs, RBC casts (pathognomonic for GN)
- Urine protein quantification
Step 2: Serological workup
| Test | What It Screens For |
|---|---|
| C3 and C4 [13][14] | Complement-consuming GN (PSGN, lupus, MPGN, cryoglobulinaemia) |
| ASO titre / Streptozyme | Recent GAS infection (supports PSGN) |
| ANA, Anti-dsDNA [13][14] | Lupus nephritis |
| ANCA [13][14] | ANCA-associated vasculitis (GPA, MPA, EGPA) |
| Anti-GBM antibody [13][14] | Anti-GBM disease / Goodpasture syndrome |
| CRP [13][14] | Inflammatory activity; elevated in vasculitis, infection |
| Cryoglobulins [13][14] | Mixed cryoglobulinaemia (often HCV-related) |
| HBV/HCV/HIV/VDRL serology [13][14] | Infection-associated GN |
| Serum IgA | IgA nephropathy (elevated in 50%) |
| Malignancy screen (tumour markers, SIEP) [13][14] | Malignancy-associated GN (especially in elderly) |
Step 3: Throat swab / skin swab
Step 4: Renal biopsy — if diagnosis is uncertain or atypical features present
- Renal biopsy: LM/IF/EM findings → Diagnosis, guide treatment decisions and prognosis [13][14]
- Usually NOT needed for typical PSGN in children
High Yield Summary — Differential Diagnosis of PSGN
- Always confirm glomerular haematuria first (dysmorphic RBCs, RBC casts) — exclude urological causes (stones, tumour), UTI, AIN, PKD
- The #1 DDx is IgA nephropathy — distinguish by timing (synpharyngitic vs latent), complement (normal vs low C3), and recurrence pattern
- Low C3 DDx: PSGN (resolves by 8 weeks), lupus nephritis (↓C3 AND ↓C4, systemic features, persistent), MPGN (persistent ↓C3, progressive), cryoglobulinaemia
- Normal C3 DDx: IgA nephropathy, HSP, anti-GBM disease, ANCA vasculitis
- Red flags for alternative diagnosis: persistently low C3 > 8 weeks, RPGN course, systemic features, positive ANA/ANCA/anti-GBM, synpharyngitic timing, recurrent haematuria
- RPGN is the most dangerous mimic — requires urgent immunosuppression; classified by IF pattern (Type I linear = anti-GBM, Type II granular = immune complex, Type III negative = pauci-immune/ANCA)
- Systematic GN workup: C3/C4, ASO, ANA, anti-dsDNA, ANCA, anti-GBM, cryoglobulins, HBV/HCV/HIV/VDRL, malignancy screen in elderly, renal biopsy if atypical
Active Recall - Differential Diagnosis of PSGN
References
[1] Lecture slides: GC 057. Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p16 — Differential diagnosis of haematuria) [2] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p18–19 — PSGN investigations, persistent low C3) [3] Senior notes: Ryan Ho Urogenital.pdf (p65–66 — PSGN laboratory features, diagnosis) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (p328 — PSGN D/dx: MPGN, IgAN, APGN due to other infections, 2° GN) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p415 — Biochemical tests for GN workup; p420 — PSGN overview) [7] Senior notes: Maksim Medicine Notes.pdf (p231, p233 — GN by age, IgA nephropathy, HSP, RPGN classification) [9] Senior notes: Maksim Surgery Notes.pdf (p308 — Haematuria DDx, anticoagulant caveat) [10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (p1, p3 — Acute nephritis DDx, lupus clues, RPGN) [11] Senior notes: Block A - Drugs and the Kidney.pdf (p14 — NSAID-induced nephrotic syndrome + AKI) [12] Senior notes: Ryan Ho Fundamentals.pdf (p361 — RPGN classification, IF pattern, management) [13] Lecture slides: Introduction-kidney-Ix.pdf (p23 — GN workup: autoimmune markers, infective causes, malignancy screen, renal biopsy) [14] Lecture slides: Nephrology - ntroduction to Renal Investigation.pdf (p23 — GN workup) [15] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p995, p999, p1008 — GN classification, PSGN description, biochemical tests)
Diagnostic Criteria, Diagnostic Algorithm, and Investigations for PSGN
1. Diagnostic Criteria — A Clinical Diagnosis
PSGN does not have formal, universally codified diagnostic criteria like the Jones criteria for ARF or the SLICC criteria for SLE. Instead, it is diagnosed on the basis of a constellation of clinical and laboratory findings. This is because the gold-standard test (renal biopsy) is usually NOT done — the disease is self-limiting and biopsy is reserved for atypical cases [2][3][4].
"Renal biopsy seldom done, usually based on: (1) Clinical findings of acute nephritis: haematuria, variable proteinuria, renal impairment; (2) Documentation of recent GAS infection by culture or serology" [3][4]
The diagnostic framework rests on two pillars [4][5][15]:
"Abrupt onset of macroscopic haematuria, oliguria, acute renal failure, fluid retention → oedema and hypertension, urinary protein < 3 g/day" [2]
The clinical features that constitute acute nephritis:
| Feature | Detail | Why It Occurs |
|---|---|---|
| Haematuria | Macroscopic (smoky/cola-coloured) or microscopic ± RBC casts | Immune complex–mediated breach of glomerular filtration barrier → RBCs leak into urine |
| Proteinuria | Variable, usually sub-nephrotic ( < 3.5 g/day) | Disruption of the GBM charge and size barriers |
| Oliguria | Reduced urine output | Endocapillary proliferation + inflammation → ↓GFR |
| Oedema | Generalised (periorbital, peripheral) | Salt and water retention from oliguria → intravascular volume expansion |
| Hypertension | New-onset; may range from mild to severe | Volume-dependent HTN from fluid retention |
| Renal impairment | ↑ Serum creatinine, ↑ urea | ↓GFR from glomerular inflammation |
| Sterile pyuria | WBCs in urine without bacteriuria | Neutrophils from glomerular inflammatory infiltrate |
This is what makes it "post-streptococcal" — you need evidence linking the nephritis to a preceding GAS infection. Evidence comes from three sources (in descending sensitivity) [5]:
| Evidence Type | Test | Sensitivity / Notes |
|---|---|---|
| Serological (most sensitive) | Streptozyme test — measures antibodies to multiple streptococcal antigens | Positive in > 95% of patients with pharyngitis-associated PSGN and ~80% of skin infection–associated PSGN [5]. More sensitive than any single antibody test |
| Single antibody titres | Anti-streptolysin O (ASO) | Commonly elevated post-pharyngitis but RARELY increases after skin infections [2][5]. If only ASO is used, it may be false-negative in skin infections or blunted by prior antibiotic therapy [5] |
| Anti-deoxyribonuclease B (Anti-DNase B) | Best single antibody titre to document cutaneous streptococcal infection [5]. Elevated after both pharyngitis and skin infection | |
| Anti-hyaluronidase (AHase) | Elevated after both pharyngitis and skin infection [5] | |
| Culture | Throat swab or skin swab for GAS | Only positive in ~25% [3][4] — low sensitivity because the infection has often resolved by the time nephritis presents |
| Clinical history | History of sore throat or skin infection in appropriate latency window | History of specific infection may be ABSENT since symptoms may have been mild [5] |
High Yield — ASO vs Anti-DNase B
| ASO | Anti-DNase B | |
|---|---|---|
| Post-pharyngitis | ✅ Usually elevated | ✅ Usually elevated |
| Post-skin infection | ❌ Rarely increases [5] | ✅ Best test for cutaneous streptococcal infection [5] |
| After antibiotics | May be blunted | Less affected |
If you only order ASO and the patient had a skin infection, you may miss the diagnosis. Always order Anti-DNase B (or the streptozyme panel) alongside ASO when skin infection is the suspected source [5].
"↓ C3 and CH50 level with ↔ C4 level" [5]
| Finding | Expected in PSGN | Explanation |
|---|---|---|
| C3 | ↓↓ (significantly reduced in > 90% of patients in first 2 weeks) [5] | Consumed by both classical and alternative complement pathways activated by immune complexes |
| CH50 (total haemolytic complement activity) | ↓↓ [3][4][5] | Reflects global complement activity; low because complement is being consumed |
| C4 | NORMAL [5] | C4 is predominantly consumed via the classical pathway; alternative pathway (C4-independent) is prominently involved in PSGN |
| Timeline | Returns to normal within 6–8 weeks [5] | Complement production catches up as immune complexes are cleared |
"Hypocomplementaemia is consistent with diagnosis of PSGN but can also be detected in other forms of GN including MPGN" [5] — so low C3 alone is not diagnostic; it must be interpreted in context.
"Persistently low C3 > 8 weeks raises the possibility of lupus nephritis or membranoproliferative glomerulonephritis (complement-mediated MPGN)" [2][3][4]
While not a formal criterion set, the diagnosis of PSGN requires all three of the following to be present:
| # | Criterion | How Established |
|---|---|---|
| 1 | Acute nephritic syndrome | Clinical features (haematuria ± RBC casts, proteinuria, oedema, hypertension, oliguria, renal impairment) |
| 2 | Evidence of recent GAS infection | Positive streptococcal serology (ASO, Anti-DNase B, Streptozyme) OR positive throat/skin culture. Note: history alone is insufficient as it may be absent [5] |
| 3 | Hypocomplementaemia (↓C3 with normal C4) | Serum complement levels. Supports the diagnosis but not absolutely required (C3 may already be normalizing if presentation is delayed) |
When is PSGN NOT the Diagnosis?
If any of the following is true, reconsider and pursue renal biopsy [4]:
- No serological evidence of recent GAS infection
- C4 also low (→ lupus nephritis)
- C3 persistently low > 8 weeks (→ lupus nephritis or MPGN)
- Rapidly progressive course (creatinine doubling in days) (→ RPGN)
- Systemic features (rash, arthritis, haemoptysis) (→ SLE, ANCA vasculitis, Goodpasture)
- Synpharyngitic haematuria / recurrent episodes (→ IgA nephropathy)
- Age < 2 or adult without clear streptococcal history (→ broaden DDx)
The following algorithm represents the clinical approach to a patient presenting with features suggestive of PSGN, integrating the GC lecture material and senior notes.
3. Investigations — Detailed Modalities, Findings, and Interpretation
3A. Urine Investigations
| Parameter | Expected Finding | Interpretation |
|---|---|---|
| Blood | Positive (1+ to 3+) | Detects haemoglobin — but does NOT distinguish glomerular from urological haematuria or even pigmenturia (myoglobin, haemoglobin from haemolysis). Must be followed by urine microscopy [10][16] |
| Protein | Positive (trace to 3+) | Detects albumin primarily; suggests glomerular pathology |
| Nitrite | Negative | If positive → suggests UTI (enterobacteriaceae convert nitrate to nitrite [16]); PSGN causes sterile pyuria |
| Leukocyte esterase | May be positive | Released by lysed neutrophils [16]; in PSGN this reflects glomerular inflammatory infiltrate, NOT infection |
"Confirmation by light field microscopy / Visualise casts" — the Nephrology Interactive Tutorial emphasises that dipstick alone is insufficient; you must look under the microscope [10].
False Positives on Dipstick
A positive blood dipstick does NOT always mean haematuria. The dipstick detects free haemoglobin, so it can also be positive in [10]:
- Haemoglobinuria (e.g. paroxysmal nocturnal haemoglobinuria, transfusion reactions)
- Myoglobinuria (e.g. rhabdomyolysis)
- Dehydrated/concentrated urine (false positive at low thresholds)
Always follow up with formal urine microscopy.
This is the most important bedside investigation for distinguishing glomerular from non-glomerular haematuria.
| Finding | Significance | Pathophysiology |
|---|---|---|
| Dysmorphic RBCs | Glomerular origin of haematuria | RBCs are physically distorted as they squeeze through the damaged GBM — they become crenated, fragmented, or develop membrane blebs ("acanthocytes" or "Mickey Mouse" cells). Isomorphic (normal-looking) RBCs suggest a urological source where RBCs enter the urine without being mechanically deformed |
| RBC casts | Diagnostic of glomerulonephritis [16] — pathognomonic | RBCs become enmeshed in Tamm-Horsfall protein (uromodulin, secreted by cells of the thick ascending limb of the Loop of Henle) within the renal tubules, forming cylindrical "casts" that take the shape of the tubular lumen. Their presence proves that haematuria originates from the glomerulus/tubule (not the lower urinary tract) |
| WBCs | Sterile pyuria | Neutrophils from glomerular inflammatory infiltrate; no bacteria on Gram stain / culture |
| Granular casts | Non-specific glomerular/tubular injury | Degenerated cellular material |
| Blood clots | Signs of NON-glomerular bleeding [16] | In glomerular haematuria, minute amounts of blood mix with large volumes of filtrate and urokinase in the filtrate lyses any clots. Clots indicate heavy focal bleeding from a urological source (e.g. tumour, stone) |
"Smoky brown and 'Coca-cola' urine = signs of glomerular bleeding. Combination of prolonged transit time through nephron and acidic urine result in formation of methaemoglobin" [16] — this explains why glomerular haematuria is brown rather than red.
| Method | Normal | PSGN Expected | Significance |
|---|---|---|---|
| 24-hour urine protein | < 150 mg/day | Variable — usually sub-nephrotic ( < 3.5 g/day) | Quantifies total proteinuria; nephrotic range ( > 3.5 g/day) is uncommon in PSGN and should prompt alternative diagnoses |
| Spot urine albumin-to-creatinine ratio (ACR) | < 30 mg/g | Elevated | Convenient alternative to 24-hour collection; correlates well |
| Urine protein-to-creatinine ratio (PCR) | < 0.15 g/g | Elevated | Quick bedside estimation |
3B. Blood Investigations
| Test | Expected Finding | Interpretation |
|---|---|---|
| Serum creatinine | Variable ↑ (may range from mildly elevated to significantly elevated) | Reflects ↓GFR from glomerular inflammation. Acute RF requiring dialysis is uncommon [3][4] |
| Blood urea nitrogen (BUN) / Serum urea | ↑ | Retained due to ↓GFR; also ↑ in pre-renal states (dehydration) |
| eGFR | ↓ | Calculated from creatinine; reflects the functional impairment |
| Electrolytes (Na, K, Cl) | Usually normal; ± mild ↑K | Hyperkalaemia can occur with significant ↓GFR due to impaired K+ excretion |
| Timeline | RFT normalises by ~4 weeks [2][3][4] | If creatinine continues to rise beyond 4 weeks, reconsider diagnosis (MPGN, RPGN) |
"When creatinine rises, GFR has already been reduced by at least 50%" [10] — serum creatinine is an insensitive marker; by the time it is elevated, substantial nephron function has been lost.
| Finding | Explanation |
|---|---|
| Normochromic normocytic anaemia [5] | Due to haemodilution (expanded intravascular volume from fluid retention) and low-grade haemolysis [5]. NOT iron deficiency — the anaemia is dilutional |
| ↓ Haematocrit | Same mechanism — fluid retention dilutes the haematocrit |
| ± ↑ WBC | May be mildly elevated if recent active infection |
| Normal platelets | Thrombocytopaenia should prompt consideration of HUS/TTP or SLE |
This is the single most important serological investigation for supporting PSGN diagnosis and narrowing the DDx.
| Test | Expected in PSGN | Notes |
|---|---|---|
| C3 | ↓↓ (significantly reduced in > 90% of patients in first 2 weeks of disease) [5] | The hallmark finding. If C3 is normal, diagnosis of PSGN is unlikely (though it may have already normalized if presentation is delayed > 2 weeks from onset) |
| CH50 | ↓↓ [3][4][5] | Total haemolytic complement activity reflects functional capacity of the entire complement cascade; consumed in PSGN |
| C4 | NORMAL [5] | This is a critical discriminator — C4 is consumed primarily in the classical pathway. In PSGN, the alternative pathway is prominently involved (C4-independent), so C4 remains normal. If C4 is ALSO low → think lupus nephritis (classical pathway activation) |
| Timeline | Returns to normal within 6–8 weeks after presentation [5] | Monitor C3 serially. Persistently low C3 > 8 weeks → consider lupus nephritis or MPGN [2][3][4] |
"Total haemolytic complement activity and C3 concentration → reduced. Antibodies to streptolysin O → may be raised. But not all strains of strep will produce streptolysin O" [2]
| Test | What It Measures | Expected | Key Points |
|---|---|---|---|
| Streptozyme test | Measures multiple antibodies to different streptococcal antigens [5] | Positive | Positive in > 95% post-pharyngitis, ~80% post-skin infection [5]. Most sensitive single test because it casts a wide net (measures ~5 antibodies simultaneously) |
| Anti-streptolysin O (ASO / ASOT) | Antibody against streptolysin O (a haemolysin produced by GAS) | May be raised [2] — elevated in ~70–80% post-pharyngitis cases | Commonly elevated post-pharyngitis but rarely increases after skin infections [2][5]. If only ASO is used, may be false-negative in skin infections or blunted by prior antibiotic therapy [5] |
| Anti-DNase B (ADB) | Antibody against DNase B (a streptococcal enzyme) | Elevated in ~70% | Best single antibody titre to document cutaneous streptococcal infection [5]. Also elevated after pharyngitis. The most useful single test if skin infection is suspected |
| Anti-hyaluronidase (AHase) | Antibody against streptococcal hyaluronidase | Elevated in ~40% | Elevated after both pharyngitis and skin infection [5] |
| Anti-NAD | Antibody against nicotinamide-adenine dinucleotidase | May be elevated | Part of the streptozyme panel; elevated after pharyngitis [5] |
"Serological evidence for streptococcal infection is more sensitive than history of recent infection and more sensitive than positive bacterial culture obtained at the time of onset of acute nephritis" [5]
Interpreting Streptococcal Serology — Practical Tips
- A single titre is less useful than demonstrating a rising titre — ideally, compare acute and convalescent samples 2–4 weeks apart. A ≥ 2-fold rise is significant.
- Normal values vary by age and geography — in endemic areas, baseline titres may be higher.
- ASO alone may miss up to 50% of skin-associated PSGN — always add Anti-DNase B.
- "ASLO may be negative in some strains, esp in skin infection" [3][4] — this is a commonly tested pitfall.
- 10–25% of the population carries GAS in the pharynx [8] — a positive throat swab alone does not prove causation; serology showing an immune response is more reliable.
| Test | Expected | Sensitivity | Interpretation |
|---|---|---|---|
| Throat swab for GAS culture | May isolate GAS | Only positive in ~25% [3][4] | Low sensitivity because the infection has usually resolved by the time nephritis appears (1–3 week latency). A positive culture supports but a negative culture does NOT exclude PSGN |
| Skin swab (if active skin lesion) | May isolate GAS | Variable | More useful if there is still an active impetigo lesion at time of nephritis presentation |
The GN workup recommended by the GC Introduction to Renal Investigation slides [13][14]:
"Autoimmune markers: ANA, Anti-dsDNA, C3/4, ANCA, Anti-GBM, CRP, cryoglobulins" "Exclude infective causes (e.g. HBV/HCV/HIV/VDRL/malaria)" "Malignancy screen (e.g. tumour markers, SIEP) especially in elderly"
| Test | Target Condition | Expected in PSGN |
|---|---|---|
| ANA, Anti-dsDNA [5][13][14] | Lupus nephritis | Negative |
| ANCA (c-ANCA / p-ANCA) [5][13][14] | ANCA-associated vasculitis (GPA, MPA, EGPA) | Negative |
| Anti-GBM antibody [5][13][14] | Anti-GBM disease / Goodpasture syndrome | Negative |
| Cryoglobulins [5][13][14] | Cryoglobulinaemic GN (often HCV-related) | Negative |
| HBV serology (HBsAg, HBeAg) [5][13][14] | HBV-associated GN (membranous or MPGN) | Negative (unless co-existing) |
| HCV serology (anti-HCV) [5][13][14] | HCV-associated MPGN | Negative |
| HIV serology [5][13][14] | HIV-associated collapsing FSGS | Negative |
| VDRL [5][13][14] | Syphilis-associated membranous nephropathy | Negative |
| Serum IgA | IgA nephropathy | Normal (elevated in ~50% of IgAN) |
| CRP / ESR | Infection / inflammation | ESR usually increased [3]; CRP may be elevated if residual streptococcal infection |
| SIEP, serum free light chains [5][13][14] | Myeloma / amyloidosis (especially in elderly) | Normal |
The rationale: you order these not because you expect them to be positive in PSGN, but to exclude the dangerous mimics that require urgent treatment (lupus, ANCA vasculitis, anti-GBM disease). Think of it as a "rule-out" panel.
3C. Imaging
| Finding | Interpretation |
|---|---|
| Normal-sized or mildly enlarged kidneys | In acute GN, kidneys may be oedematous and slightly enlarged. Normal size excludes chronic kidney disease (where kidneys are shrunken) |
| Normal cortical echogenicity or mildly increased | Acute inflammation causes increased echogenicity; however, significant cortical thinning or loss of corticomedullary differentiation suggests chronicity |
| No hydronephrosis | Rules out post-renal obstruction as a cause of AKI |
| No masses or cysts | Excludes PKD, renal tumour |
USG is performed mainly to exclude obstructive causes of AKI and to assess kidney size (small kidneys = chronic disease, not appropriate for biopsy). In typical PSGN in a child, USG often shows normal findings or mildly enlarged kidneys.
| Purpose | Finding |
|---|---|
| Assess for pulmonary oedema | If fluid overload is significant → bilateral pulmonary infiltrates, Kerley B lines, pleural effusions |
| Exclude pulmonary-renal syndrome | Bilateral infiltrates + haemoptysis → Goodpasture or ANCA vasculitis; this is NOT expected in PSGN |
3D. Renal Biopsy — When and What You See
"Renal biopsy: usually NOT done (resolution begins within 1 week of presentation)" [3][4]
Renal biopsy is not routine in PSGN because the diagnosis is clinical and the disease is self-limiting. However, it is indicated when the clinical picture is atypical and an alternative diagnosis is suspected [4][5][6]:
Indications for renal biopsy in suspected PSGN:
- Persistently low C3 > 8 weeks [2][3][4]
- No improvement in renal function by 4 weeks (expected RFT normalisation timeline)
- Rapidly progressive course (RPGN — creatinine doubling in days)
- Nephrotic-range proteinuria ( > 3.5 g/day) that persists
- Negative streptococcal serology with no alternative explanation
- Systemic features suggesting lupus, vasculitis, or other secondary GN
- Recurrent episodes suggesting IgA nephropathy
- Normal complement levels at presentation (expected to be low in PSGN)
- Anuria or need for dialysis (unusual in PSGN)
"Renal biopsy: still essential for definitive diagnoses of a number of renal diseases — glomerulonephritis (e.g. minimal change disease, FSGS, IgAN, membranous GN, MPGN), tubulointerstitial diseases, vascular diseases" [6]
"Renal biopsy: LM/IF/EM findings → Diagnosis, guide treatment decisions and prognosis" [13][14]
Contraindications to renal biopsy [17]:
- Contracted/small kidneys (hard to target, likely only fibrotic tissue)
- Large renal cysts (risk of bleeding that cannot be controlled)
- Solitary kidney (risk of losing only functioning kidney)
- Uncontrolled coagulopathy / anticoagulation
- Uncontrolled hypertension
- Active renal or perirenal infection
| Modality | Findings | Description / Significance |
|---|---|---|
| Light Microscopy (LM) | Hypercellular glomeruli with neutrophils [2] — diffuse mesangial cell proliferation with an increase in mesangial matrix; infiltration of neutrophils; ± formation of crescents (uncommon, seen in severe cases, associated with poor prognosis) [15] | "Diffuse" means > 50% of glomeruli affected. "Endocapillary proliferation" means increased cellularity WITHIN the capillary lumen — from proliferating endothelial/mesangial cells AND infiltrating neutrophils/macrophages. This is why the capillary lumina are narrowed → ↓GFR. Crescents and interstitial inflammation are seen in severe cases and are uncommon and associated with a poor prognosis [15] |
| Immunofluorescence (IF) | Granular "starry sky" IgG/C3 deposits — "Deposits of IgG and C3 in a diffuse granular pattern on glomerular basement membrane and in mesangium. Other immune reactants including IgM, C4, C5–9 may also be present" [15] | The granular pattern = immune complex deposition (compare with linear pattern in anti-GBM disease). The "starry sky" appearance = scattered bright fluorescent dots against a dark background. The presence of IgG + C3 confirms immune complex + complement-mediated pathology |
| Electron Microscopy (EM) | Characteristic subepithelial electron-dense hump-like deposits ("subepithelial humps") → tall and short humps [2][15]; ± subendothelial deposits | "Most characteristic feature are the dome-shaped subepithelial electron-dense deposits that are referred to as humps" [15]. These humps are pathognomonic for PSGN. They represent large aggregates of immune complexes (antigen–antibody–complement) on the outer (epithelial) side of the GBM |
The IF pattern is most helpful for diagnosis in nephritic syndrome [3] — it classifies the type of GN (granular = immune complex; linear = anti-GBM; pauci-immune = ANCA vasculitis).
| Category | Investigation | Expected Finding in PSGN | Purpose |
|---|---|---|---|
| Urine | Dipstick | Blood 3+, protein 1–3+, nitrite −ve | Screening |
| Microscopy | Dysmorphic RBCs, RBC casts, sterile pyuria | Confirm glomerular origin | |
| Protein quantification | Sub-nephrotic ( < 3.5 g/day) | Quantify; nephrotic range → reconsider Dx | |
| Blood — Baseline | CBC | NcNc anaemia (haemodilution + mild haemolysis) | Baseline; exclude thrombocytopaenia |
| RFT | ↑ Creatinine, ↑ urea, ↓ eGFR | Quantify renal impairment | |
| ESR | Usually ↑ | Non-specific inflammation | |
| Blood — Complement | C3 | ↓↓ (> 90% in first 2 weeks) | Hallmark; supports diagnosis |
| CH50 | ↓↓ | Functional complement assessment | |
| C4 | Normal | Distinguishes from lupus (↓C4) | |
| Blood — Strep serology | ASO | ↑ (post-pharyngitis; may be negative post-skin) | Evidence of recent GAS |
| Anti-DNase B | ↑ (best for skin infection) | Evidence of recent GAS | |
| Streptozyme | Positive ( > 95% pharyngitis, ~80% skin) | Most sensitive single test | |
| Blood — Exclusion panel | ANA, Anti-dsDNA | Negative | Rule out lupus |
| ANCA | Negative | Rule out ANCA vasculitis | |
| Anti-GBM | Negative | Rule out Goodpasture | |
| Cryoglobulins | Negative | Rule out cryoglobulinaemia | |
| HBV/HCV/HIV/VDRL | Negative | Rule out infection-associated GN | |
| SIEP, FLC (elderly) | Negative | Rule out myeloma/amyloid | |
| Culture | Throat/skin swab | GAS (only +ve in ~25%) | Low sensitivity; supports if positive |
| Imaging | USG kidneys | Normal or mildly enlarged; no obstruction | Exclude CKD, obstruction, PKD |
| CXR | ± Pulmonary oedema | Assess fluid overload; exclude pulmonary-renal syndrome | |
| Biopsy | Renal biopsy | LM: diffuse endocapillary proliferation + neutrophils. IF: starry sky granular IgG/C3. EM: subepithelial humps | Only if atypical; definitive diagnosis |
Once PSGN is diagnosed, the following should be monitored to confirm the expected self-limiting course:
| Parameter | Monitoring Schedule | Expected Timeline | Action if Abnormal |
|---|---|---|---|
| Urine dipstick | Daily during admission, then weekly | Gross haematuria resolves within 2 weeks; microscopic may persist 1–2 years | Persistent gross haematuria > 4 weeks → biopsy |
| Serum creatinine | Every 1–2 days acutely, then weekly | Normalises by ~4 weeks [2] | Rising creatinine → RPGN; arrange urgent biopsy |
| Blood pressure | Daily initially | Resolves with diuresis (1–2 weeks) | Persistent HTN → volume overload or alternative Dx |
| Body weight | Daily | Falling weight indicates diuresis | No diuresis by 2 weeks → reassess |
| Serum C3 | At presentation + repeat at 6–8 weeks | Returns to normal within 6–8 weeks [5] | Persistent low C3 > 8 weeks → lupus or MPGN [2][3][4] |
| Urine protein | At presentation, then periodically | Resolves over weeks to months | Persistent nephrotic-range → biopsy |
High Yield Summary — Diagnosis and Investigations of PSGN
- PSGN is a clinical diagnosis — renal biopsy is usually NOT needed. Diagnosis requires: acute nephritic syndrome + evidence of recent GAS infection + hypocomplementaemia (↓C3, normal C4)
- Streptozyme test is the most sensitive serological test ( > 95% pharyngitis, ~80% skin). ASO may be false-negative in skin infections — always add Anti-DNase B
- C3 is ↓↓ in > 90% of patients in the first 2 weeks; CH50 also ↓; C4 is NORMAL — normalises by 6–8 weeks
- Persistently low C3 > 8 weeks → lupus nephritis or MPGN — this is the most important monitoring red flag
- Urine microscopy is critical: dysmorphic RBCs + RBC casts = glomerular haematuria; blood clots = non-glomerular
- Renal biopsy findings (if done) — LM: diffuse endocapillary proliferation with neutrophils; IF: starry sky granular IgG/C3; EM: subepithelial humps (pathognomonic)
- GN workup to exclude mimics: ANA, anti-dsDNA, ANCA, anti-GBM, C3/C4, cryoglobulins, HBV/HCV/HIV/VDRL, malignancy screen in elderly, renal biopsy if atypical
Active Recall - PSGN Diagnostic Criteria, Algorithm, and Investigations
References
[2] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p18–19 — PSGN investigations, persistent low C3, histopathology) [3] Senior notes: Ryan Ho Urogenital.pdf (p55, p63, p65–66 — PSGN laboratory features, diagnostic approach, nephritic syndrome evaluation) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (p325, p327–328 — PSGN diagnosis, DDx, complement, serology, evaluation of nephritic syndrome) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p128, p406, p423 — PSGN diagnostic approach, streptozyme, ASO, Anti-DNase B, C3/C4/CH50) [6] Senior notes: Block A - Nephrotology Teaching Clinic RTD.pdf (p3–4 — Renal biopsy role, definitive diagnosis of GN) [7] Senior notes: Maksim Medicine Notes.pdf (p233 — Post-strep GN lab findings, RPGN classification) [8] Senior notes: Ryan Ho Respiratory.pdf (p52 — GAS pharyngitis carrier rate, complications) [10] Senior notes: Block A - Nephrology Interactive Tutorial.pdf (p1, p3 — Dipstick false positives, confirmation by microscopy, AKI criteria) [13] Lecture slides: Introduction-kidney-Ix.pdf (p23 — GN workup: autoimmune markers, infective causes, malignancy screen, renal biopsy) [14] Lecture slides: Nephrology - ntroduction to Renal Investigation.pdf (p23 — GN workup) [15] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p999, p1008 — PSGN morphology, biochemical tests for GN diagnosis) [16] Senior notes: MBBS Final MB (Surgery) (Felix PY Lai).pdf (p769 — Urinalysis interpretation, dysmorphic RBCs, RBC casts, blood clots) [17] Senior notes: Block A - Introduction to Renal Investigations (RFT, urine tests and US kidneys).pdf (p1, p5 — Renal biopsy contraindications, AKI criteria)
Management of Post-Streptococcal Glomerulonephritis (PSGN)
"Depends on etiology → but remember this is a self-limiting condition, no definitive treatment exists. For acute poststreptococcal GN, penicillin may be indicated. Otherwise, supportive therapy ± temporary dialysis may be needed." — GC 057 Lecture Slide [1]
This single slide encapsulates everything about PSGN management. Unlike lupus nephritis or ANCA vasculitis where you must aggressively immunosuppress, PSGN is a disease where the host's immune response has already done the damage and is winding down by the time you see the patient. The streptococcal infection is over. The immune complexes are being cleared. Your job is to support the patient through the self-resolving inflammation and treat the consequences of ↓GFR (fluid overload, hypertension, electrolyte derangements) until the kidneys recover on their own.
"Treatment is mainly SUPPORTIVE. Directed at treating the acute effects of hypertension, volume overload and renal insufficiency. NO role for immunosuppressive therapy even in the setting of crescents." [5]
High Yield Exam Point
No role of immunosuppressants [5][15] — this is a commonly tested distinction. Unlike other immune complex–mediated GNs (e.g. lupus nephritis, anti-GBM disease) where you must suppress the ongoing immune process, in PSGN the immune injury is a one-off, self-limiting event. By the time the patient presents, complement activation is already subsiding. Adding steroids or cyclophosphamide would expose the patient to immunosuppressive side effects with no proven benefit.
Step 1: Monitoring and General Measures (All Patients)
These are the bread-and-butter ward management steps for any patient with acute nephritic syndrome from PSGN. Every single measure targets a specific pathophysiological consequence of ↓GFR and fluid retention.
"Renal chart. Strict I/O chart. BP/P Q1–4H. Bed rest if hypertensive or significant oedema." [5]
| Monitoring Parameter | Rationale | Frequency |
|---|---|---|
| Strict Intake/Output (I/O) chart [5] | Oliguria → fluid retention → oedema + HTN. Tracking I/O guides fluid restriction and diuretic dosing. If output increases (diuresis), the disease is resolving | Continuous (hourly) |
| Blood pressure and pulse [5] | HTN is a major source of morbidity (risk of hypertensive encephalopathy, seizures in children). Pulse monitors volume status | Q1–4H [5] |
| Daily body weight (BW) [5][15] | Weight change is the most reliable indicator of net fluid balance. ↓BW = diuresis = resolving disease. Aim for ~1 kg/day loss if fluid-overloaded | Daily |
| Urine dipstick [5] | Track haematuria and proteinuria resolution. Gross haematuria should resolve within 2 weeks | Daily initially, then weekly |
| Serum creatinine | Track renal function recovery. Should normalise by ~4 weeks [2] | Every 1–2 days acutely |
| Serum C3 | Confirm complement recovery. Should normalise by 6–8 weeks [3][4][5] | At presentation, then repeat at 6–8 weeks |
| Serum electrolytes (K+) | Hyperkalaemia risk with ↓GFR; guide need for dietary K restriction or urgent treatment | Daily initially |
"Bed rest if hypertensive or significant oedema" [5]
- Why bed rest? In the acute phase, physical activity can exacerbate hypertension and increase renal metabolic demand. Bed rest promotes venous return → ↑renal perfusion → promotes diuresis. Once BP is controlled and oedema is resolving, activity can be gradually resumed.
- This is a short-term measure (days to 1–2 weeks); prolonged bed rest is not needed and may increase VTE risk.
"Na+ and fluid restriction. Low salt diet. Requires only insensible water loss 400 mL/m²/day + previous day urine output." [5]
| Modification | Detail | Rationale |
|---|---|---|
| Na+ restriction | 2–3 mEq/kg/day (Max = 2 g/day) [5][15] | Sodium drives water retention via the renin-angiotensin-aldosterone system (RAAS) and directly expands extracellular fluid volume. Restricting sodium ↓ the osmotic drive for water retention → ↓ oedema and ↓ BP |
| Fluid restriction | Insensible losses (~400 mL/m²/day) + previous day's urine output [5] | In oliguric patients, unrestricted fluid intake exceeds output → progressive fluid accumulation → pulmonary oedema. By matching input to output + insensible losses, you prevent worsening overload |
| Fluid restriction "can be considered but generally not needed" [15] | Reserve aggressive restriction for severely oliguric patients | In milder cases where urine output is reasonable, strict restriction may not be necessary |
| K+ restriction | Avoid high-potassium foods if hyperkalaemic | ↓GFR → impaired K+ excretion → hyperkalaemia |
| Protein | Normal protein intake — protein restriction is NOT recommended [12] | Unlike CKD where protein restriction may slow progression, in acute GN with significant proteinuria, you do not want to worsen the negative nitrogen balance |
"For acute poststreptococcal GN, penicillin may be indicated" [1]
"PO Penicillin 50 mg/kg/day QID for 10 days" [5]
| Drug | Dose | Duration | Indication |
|---|---|---|---|
| PO Penicillin V (phenoxymethylpenicillin) | 50 mg/kg/day divided QID [5] | 10 days [5] | If streptococcal infection still present at diagnosis [3][4] or for eradication of carriage |
| PO Amoxicillin | 50 mg/kg/day divided TDS | 10 days | Alternative (better palatability for children who can't swallow pills [8]) |
| Erythromycin / Azithromycin | Standard dosing | 5–10 days | If penicillin-allergic |
Key principles:
-
"10 days of systemic antibiotic with penicillin is recommended to limit the spread of nephritogenic organisms but it does NOT alter the natural history of PSGN" [5] — the antibiotic does NOT treat the glomerulonephritis (the immune damage has already occurred). It eradicates any remaining GAS to prevent transmission to close contacts and prevent re-infection.
-
"Antibiotic treatment for streptococcal infection should be given to all patients AND their cohabitants" [5] — household contacts may harbour the same nephritogenic strain. Treating them prevents spread and protects others who may be susceptible.
-
"No need for prophylactic antibiotics (c.f. rheumatic fever)" [7] — this is a critical distinction:
ARF vs PSGN — Prophylaxis
| ARF | PSGN | |
|---|---|---|
| Long-term prophylaxis needed? | YES — monthly IM benzathine penicillin for years | NO |
| Why? | Recurrent GAS pharyngitis causes cumulative valve damage. Prophylaxis prevents new GAS infections | PSGN recurrence is extremely rare — the host develops type-specific immunity to the nephritogenic M-protein serotype. There is no evidence that prophylaxis prevents recurrence [4][7] |
Many students confuse these. PSGN does NOT require secondary prophylaxis [4][7].
Step 3: Managing Specific Complications
"IV Furosemide (Lasix) 1–4 mg/kg/day Q6H. Promotes diuresis with reduction of BP and oedema." [5]
| Drug | Dose | Route | Mechanism | Notes |
|---|---|---|---|---|
| Furosemide (frusemide) | 1–4 mg/kg/day, divided Q6H [5] | IV (preferred in acute setting — more reliable bioavailability than oral in oedematous patients whose gut may be congested) | Inhibits the Na-K-2Cl co-transporter (NKCC2) in the thick ascending limb of the Loop of Henle → blocks sodium and water reabsorption → promotes natriuresis and diuresis | The most important single drug in PSGN management. By promoting fluid loss, it simultaneously treats oedema, reduces intravascular volume → lowers BP, and can prevent/treat pulmonary oedema |
| ± Spironolactone | 1–3 mg/kg/day | PO | Aldosterone antagonist — blocks sodium reabsorption in the collecting duct via ENaC | "Can be added to decrease the risk of hypokalaemia" [15] from loop diuretics. However, use with caution in PSGN because patients may already be hyperkalaemic from ↓GFR |
Why IV route? In patients with significant oedema, gut wall oedema can impair oral drug absorption. IV furosemide bypasses this, acting within minutes. Once diuresis is established and the patient is improving, you can switch to oral.
"Furosemide ± Spironolactone: ONLY indicated in severe symptomatic oedema with normal intravascular status. May precipitate hypovolemic shock, AKI and increased thrombosis risk in a child with marked hypoalbuminaemia with intravascular volume depletion." [15]
Caution with Diuretics in Nephrotic Overlap
In PSGN, the oedema is primarily volume-overload driven (salt and water retention from ↓GFR). This is different from nephrotic syndrome where oedema may be "underfill" (low oncotic pressure from hypoalbuminaemia → fluid shifts to interstitium → intravascular depletion). In pure PSGN, the patient is genuinely fluid-overloaded, so diuretics are safe. But if there is significant hypoalbuminaemia (overlap with nephrotic features), aggressive diuresis can precipitate intravascular volume depletion → shock → AKI [15]. Always assess volume status before diuresing.
Hypertension in PSGN is volume-dependent — it is caused by salt and water retention, not by RAAS activation. Therefore, the primary treatment is fluid removal (salt restriction + furosemide). If BP remains elevated despite adequate diuresis, add specific antihypertensives.
| Severity | Treatment | Rationale |
|---|---|---|
| Mild–Moderate | Salt restriction + Furosemide [3][4] → diuresis reduces intravascular volume → ↓BP | Often sufficient — as the patient diureses, BP normalises |
| Severe / Refractory | PO Nifedipine (Adalat) 0.25 mg/kg/dose [5] | Dihydropyridine calcium channel blocker (CCB) → directly relaxes vascular smooth muscle → ↓peripheral vascular resistance → ↓BP. Safe in renal impairment, does not worsen hyperkalaemia |
| Parenteral (hypertensive urgency/emergency) | IV Nicardipine [5] | IV dihydropyridine CCB; allows titrated BP control in ICU setting |
| ACEI / ARB | "Should be used with caution due to risk of hyperkalaemia" [5] | ACEI/ARB reduce aldosterone → ↓K+ excretion. In PSGN, GFR is already ↓ → K+ excretion is already impaired → adding ACEI/ARB can cause dangerous hyperkalaemia. Also, ACEI/ARB lower GFR further (by dilating the efferent arteriole) which is undesirable in the acute phase. Reserve for the recovery phase or for patients with persistent proteinuria |
Why nifedipine and NOT ACEI/ARB as first-line in acute PSGN? In most hypertension guidelines, ACEI/ARB are first-line for CKD and proteinuric renal disease because they reduce intraglomerular pressure and slow progression [18]. However, in acute PSGN:
- The patient has acute renal impairment (not chronic) — reducing GFR further with ACEI/ARB is counterproductive
- Hyperkalaemia risk is already high from ↓GFR
- The hypertension is transient and will resolve with diuresis
- ACEI/ARB are better suited for chronic proteinuric states where long-term renoprotection is needed [12]
"Temporary dialysis if acute renal impairment or life-threatening complications" [3][4]
Dialysis is rarely needed in PSGN — most patients recover spontaneously [4]. However, indications for emergency dialysis follow the standard AKI indications (mnemonic: AEIOU) [19]:
| Indication | Detail | Mechanism |
|---|---|---|
| A — Refractory metabolic Acidosis | pH < 7.1 refractory to bicarbonate infusion [19] | ↓GFR → inability to excrete H+ → HAGMA. Severe acidosis can cause myocardial depression and vasodilatation |
| E — Refractory Electrolyte imbalance | HyperK > 6.5 or rapidly rising K refractory to medical Rx [19] | ↓GFR → impaired K+ excretion → cardiac arrhythmia risk. Medical management: IV calcium gluconate (cardioprotection) + insulin/dextrose + nebulised salbutamol + sodium polystyrene sulphonate |
| I — Intoxication | Drug removal in overdose (less relevant to PSGN) | — |
| O — Refractory fluid Overload | Pulmonary oedema refractory to IV furosemide [19] | Fluid overload → pulmonary oedema → respiratory failure. If high-dose IV furosemide fails, dialysis/ultrafiltration removes fluid directly |
| U — Uraemia | Features of uraemia: pericarditis, neuropathy, ↓ mental status [19] | Accumulated uraemic toxins cause end-organ damage |
"Haemodialysis: last-resort treatment for renal support. Usually pumped venovenous haemofiltration via central venous catheter. Consider admission to ICU." [19]
In PSGN, if dialysis is needed, it is almost always temporary — renal function recovers and dialysis can be discontinued. If the patient requires prolonged dialysis or does not recover, the diagnosis should be questioned (consider RPGN, MPGN) [4].
| Treatment | Mechanism | Onset | Duration |
|---|---|---|---|
| IV Calcium gluconate 10% | Stabilises myocardial membrane (does NOT lower K+) — protects against arrhythmia | 1–3 min | 30–60 min |
| Insulin 10 units + 50 mL 50% dextrose | Insulin drives K+ into cells via Na-K-ATPase; dextrose prevents hypoglycaemia | 15–30 min | 4–6 hours |
| Nebulised salbutamol | β2-agonist → activates Na-K-ATPase → shifts K+ intracellularly | 15–30 min | 2–4 hours |
| IV Sodium bicarbonate | Corrects acidosis → shifts K+ intracellularly (H+/K+ exchange) | 15–30 min | 2 hours |
| PO/PR Sodium polystyrene sulphonate (Resonium) | Cation exchange resin — binds K+ in the gut in exchange for Na+; promotes faecal K+ excretion | Hours | Until discontinued |
| Dialysis | Removes K+ directly from blood | Minutes | As long as treatment continues |
This is just as important as knowing what to give.
| Treatment | Status in PSGN | Why NOT |
|---|---|---|
| Immunosuppressants (steroids, cyclophosphamide, rituximab) | NO role — even in the setting of crescents [5][15] | PSGN is a self-limiting, one-off immune injury. The antigens have been cleared, the immune process is winding down. Immunosuppression would not shorten the course but would expose the patient to infection risk, metabolic side effects, and growth suppression (in children). This is in stark contrast to lupus nephritis or ANCA vasculitis where ongoing immune activation requires suppression |
| NSAIDs | Avoid | NSAIDs inhibit prostaglandin synthesis → constrict the afferent arteriole → further ↓GFR → worsen AKI. They also cause sodium retention (worsening oedema/HTN) and can cause AIN |
| ACEI/ARB in acute phase | Use with caution [5] | Worsen AKI (↓GFR by efferent arteriolar dilatation) and risk hyperkalaemia (↓aldosterone-mediated K+ excretion). May be appropriate later in recovery phase if persistent proteinuria |
| Nephrotoxic drugs (aminoglycosides, contrast agents) | Avoid | Superimposed nephrotoxic injury on already inflamed kidneys can tip the patient into dialysis-requiring AKI |
"Antibiotics for streptococcal infection. NO role of immunosuppressants." [15]
"Consider renal biopsy to rule out other causes if: severe renal impairment requiring dialysis (rarely occurs in genuine PSGN); persistent ↓C3 > 6 weeks or normal C3 (incompatible with classical PSGN); recurrent haematuria (suggestive of IgAN)" [3][4]
| Red Flag | Action |
|---|---|
| Persistent ↓C3 > 6–8 weeks [3][4] | Renal biopsy → rule out lupus nephritis, MPGN |
| No diuresis by 2 weeks / creatinine not improving by 4 weeks | Renal biopsy → rule out MPGN, RPGN |
| Rapidly rising creatinine (RPGN course) | Urgent renal biopsy + consider empirical pulse methylprednisolone (treat as RPGN until proven otherwise) |
| Recurrent haematuria | Renal biopsy → rule out IgA nephropathy |
| Normal C3 at presentation | Unusual for PSGN → consider IgAN, anti-GBM disease, ANCA vasculitis |
| Dialysis required | Uncommon in genuine PSGN → biopsy to confirm diagnosis |
Understanding prognosis helps you counsel the patient and family, and set expectations for follow-up.
"Good prognosis in general with permanent renal failure being uncommon. Recovery occurs in children with elderly patients having poorer outcomes." [15]
| Population | Prognosis | Detail |
|---|---|---|
| Children | Excellent | Complete recovery occurs in > 95% of children [5]. Permanent renal failure < 1%. Recurrences are extremely rare despite repeated streptococcal infections [5]. Early death is rare [5] |
| Elderly | Poorer | High incidence of azotaemia (up to 60%), nephrotic-range proteinuria and ESRD. Early death can occur [5] |
| Long-term sequelae (rare) | Variable | Some patients develop glomerulosclerosis → HTN, recurrent proteinuria (with bland urine sediment) and renal insufficiency 10–40 years after initial illness [3][4]. This may be due to irreversible damage to some nephrons, leading to compensatory hyperfiltration in remaining nephrons → raised intraglomerular pressure → non-immunologic glomerular injury → progressive glomerulosclerosis [3][4] |
Why Does Hyperfiltration Cause Late Glomerulosclerosis?
Even if the acute immune injury resolves completely, a small fraction of nephrons may be permanently damaged. The remaining nephrons must handle the full filtration load, so each individual nephron increases its single-nephron GFR — this is compensatory hyperfiltration. While beneficial short-term, chronic hyperfiltration increases intraglomerular pressure → mechanical stress on the remaining glomeruli → endothelial injury → sclerosis → further nephron loss → a vicious cycle. This is the same mechanism by which any cause of nephron loss (e.g. surgical nephrectomy, reflux nephropathy) can lead to CKD decades later. It also explains why ACEI/ARB may be beneficial in the long-term for patients with residual proteinuria after PSGN — they reduce intraglomerular pressure and slow this process [12].
| Parameter | Schedule | Purpose |
|---|---|---|
| Urinalysis (dipstick) | Every 3–6 months for 1–2 years | Confirm resolution of haematuria (microscopic haematuria may persist up to 1–2 years) and proteinuria |
| Blood pressure | At follow-up visits | Ensure resolution; persistent HTN may indicate residual renal damage |
| Serum creatinine / eGFR | At follow-up visits | Confirm normalised renal function; rising creatinine years later suggests late glomerulosclerosis |
| Urine protein quantification | If proteinuria persists | Persistent proteinuria may warrant ACEI/ARB therapy for renoprotection and further evaluation |
| Component | Detail |
|---|---|
| Core principle | Self-limiting disease → Supportive care. No immunosuppressants. |
| Monitoring | I/O chart, BP/P Q1–4H, daily BW, urine dipstick, serial RFT, C3 at 6–8 weeks |
| Diet | Na restriction ( < 2 g/day), fluid restriction (insensible + UO), normal protein |
| Antibiotic | PO Penicillin V 50 mg/kg/day QID × 10 days — eradicates GAS, limits spread; does NOT change natural history; treat cohabitants; NO prophylactic antibiotics (unlike ARF) |
| Oedema | IV Furosemide 1–4 mg/kg/day Q6H ± spironolactone (caution: hyperK) |
| Hypertension | Salt restriction + Furosemide first; if refractory → PO Nifedipine 0.25 mg/kg/dose or IV Nicardipine; ACEI with caution (hyperK risk) |
| Severe AKI | Temporary dialysis (AEIOU indications); rarely needed |
| Avoid | Immunosuppressants, NSAIDs, ACEI/ARB in acute phase, nephrotoxins |
| Biopsy triggers | Persistent ↓C3 > 8w, no improvement by 4w, RPGN, dialysis needed, recurrent haematuria |
| Prognosis | > 95% complete recovery in children; worse in elderly; rare late glomerulosclerosis |
High Yield Summary — Management of PSGN
- PSGN is self-limiting — treatment is SUPPORTIVE. There is NO role for immunosuppressants, even with crescents.
- GC 057 slide: "For acute poststreptococcal GN, penicillin may be indicated. Otherwise, supportive therapy ± temporary dialysis may be needed."
- Antibiotic: PO Penicillin V × 10 days — eradicates GAS and limits spread but does NOT alter natural history of PSGN. Treat cohabitants. No long-term prophylaxis needed (unlike ARF).
- Oedema: IV Furosemide 1–4 mg/kg/day Q6H. Assess volume status before diuresing.
- Hypertension: Salt restriction + furosemide first → Nifedipine if refractory. ACEI/ARB with caution (hyperK risk).
- Dialysis: Temporary, only for life-threatening complications (AEIOU: Acidosis, Electrolytes, Intoxication, Overload, Uraemia).
- Prognosis: > 95% complete recovery in children. Elderly have poorer outcomes. Rare late glomerulosclerosis from hyperfiltration injury.
- Follow-up: Monitor C3 at 6–8 weeks (must normalise), RFT, urinalysis. Persistent ↓C3 > 8 weeks or no improvement by 4 weeks → renal biopsy.
Active Recall - Management of PSGN
References
[1] Lecture slides: GC 057. Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p37 — Treatment of PSGN) [2] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p18–19 — Treatment, monitoring) [3] Senior notes: Ryan Ho Urogenital.pdf (p66 — Management, prognosis, biopsy indications) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (p328 — Management, prognosis, biopsy indications, glomerulosclerosis mechanism) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p425 — Treatment of PSGN: penicillin dose, furosemide, nifedipine, ACEI caution, prognosis) [7] Senior notes: Maksim Medicine Notes.pdf (p233 — Post-strep GN management, no prophylactic Abx) [8] Senior notes: Ryan Ho Respiratory.pdf (p52 — GAS pharyngitis treatment, amoxicillin alternative) [12] Senior notes: Ryan Ho Fundamentals.pdf (p368 — General GN management, anti-proteinuric therapy, ACEI/ARB) [15] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p999 — PSGN treatment, no immunosuppressants; p1022 — General GN management, diuretics, diet, renal biopsy contraindications) [18] Senior notes: Block A - High blood pressure_ hypertension.pdf (p42 — ACEI/ARB as renoprotective in CKD) [19] Senior notes: Ryan Ho Critical Care.pdf (p25–26 — AKI management, dialysis indications AEIOU, immediate approach)
Complications of Post-Streptococcal Glomerulonephritis (PSGN)
Although PSGN is typically a self-limiting disease — "Good prognosis in general with permanent renal failure being uncommon. Recovery occurs in children with elderly patients having poorer outcomes" [5][15] — complications can arise during the acute phase or, rarely, manifest years later. Understanding these complications requires you to trace them back to the core pathophysiology: ↓GFR → fluid overload → hypertension + oedema, and immune-mediated glomerular injury → haematuria + proteinuria.
We can organise complications into three temporal categories:
- Acute complications (during the first 1–4 weeks)
- Subacute complications (the disease does not follow the expected self-resolving course)
- Long-term complications (months to decades later)
1. Acute Complications (During the Active Disease Phase)
These complications arise directly from the pathophysiology of acute nephritic syndrome: glomerular inflammation → ↓GFR → salt and water retention → intravascular volume expansion.
| Aspect | Detail |
|---|---|
| Mechanism | Oliguria from endocapillary proliferation → sodium and water retention → expanded intravascular volume → ↑ preload on the heart → volume-overload cardiac failure. This is NOT failure from myocardial disease — the heart itself is usually structurally normal. The heart simply cannot cope with the acutely expanded circulating volume. The raised hydrostatic pressure in pulmonary capillaries causes fluid transudation into alveoli → pulmonary oedema → respiratory distress [3][4] |
| Clinical features | Dyspnoea, orthopnoea, tachypnoea, bilateral basal pulmonary crackles, S3 gallop rhythm, elevated JVP, ↑BP. CXR shows bilateral pulmonary infiltrates, Kerley B lines, upper lobe diversion, pleural effusions |
| Risk factors | Severe oliguria, excessive fluid/salt intake, delayed presentation, elderly patients (poorer cardiac reserve) |
| Management | Salt and fluid restriction; IV Furosemide to promote diuresis; oxygen therapy; sit the patient upright; in refractory cases → temporary dialysis/ultrafiltration [3][4][19] |
| Prognosis | Resolves with diuresis (usually within 1–2 weeks). Unlike chronic heart failure, this is entirely reversible once fluid is removed |
"Generalised oedema: common, may be associated with respiratory distress in severe cases" [3][4] — this specifically refers to pulmonary oedema from fluid overload.
Why Pulmonary Oedema in a Young Child with Normal Heart?
This is volume-overload, NOT pump failure. Imagine pouring too much water into a container — the container (heart) is perfectly fine, but there's simply too much fluid. The ventricles are acutely dilated from excessive preload. Reducing the volume (with furosemide or dialysis) immediately fixes the problem. There is no need for inotropes or long-term cardiac medications. This distinction is important because treatment is fluid removal, not cardiac support.
| Aspect | Detail |
|---|---|
| Mechanism | Severe volume-dependent hypertension from ↓GFR + sodium retention → if untreated, systemic BP rises to dangerously high levels → exceeds the cerebral autoregulatory range → cerebral hyperperfusion → vasogenic oedema → hypertensive encephalopathy. Children are particularly susceptible because they have a narrower autoregulatory range than adults |
| Clinical features | Severe headache, visual disturbances (blurred vision, papilloedema), confusion, drowsiness, vomiting, seizures (hypertensive convulsions). BP typically > 180/120 in adults or significantly above the 99th percentile + 5 mmHg for age/height in children |
| Risk factors | Severe oliguria, delayed diagnosis, non-compliance with salt/fluid restriction, pre-existing renal impairment |
| Management | Hypertensive urgency/emergency protocol: IV antihypertensives for controlled BP reduction (do NOT lower too rapidly — risk of cerebral ischaemia). IV Nicardipine (titratable) [5]; PO Nifedipine for less severe cases [5]. Furosemide to reduce volume. In refractory cases → temporary dialysis [3][4]. Aim: reduce BP by no more than 25% in the first hour, then gradually normalise over 24–48 hours |
| Prognosis | Resolves with BP control and diuresis. Seizures typically stop once BP is controlled. No long-term neurological sequelae if treated promptly |
"Hypertension (50–90%) due to salt and fluid retention" [3][4] — while most have mild-moderate HTN, some may have "dangerous hypertension" [4] requiring urgent treatment.
| Aspect | Detail |
|---|---|
| Mechanism | Severe endocapillary proliferation and inflammatory infiltrate → markedly ↓GFR → oliguria/anuria → accumulation of uraemic toxins, metabolic acidosis, hyperkalaemia. In rare severe cases, extensive crescent formation (RPGN) can cause near-complete loss of filtration |
| Clinical features | Progressive oliguria/anuria, rapidly rising serum creatinine, nausea/vomiting (uraemia), drowsiness, acidotic breathing (Kussmaul's), arrhythmia (hyperkalaemia) |
| Frequency | Variable ↓GFR, but acute renal failure requiring dialysis is uncommon [3][4]. Most patients have only mild-moderate creatinine elevation |
| Management | Supportive: salt/fluid restriction, loop diuretics. Treat hyperkalaemia (IV calcium gluconate, insulin/dextrose, nebulised salbutamol, Resonium). Correct acidosis (IV bicarbonate). Temporary dialysis if life-threatening complications (AEIOU indications) [4][19] |
| Prognosis | RFT normalises by ~4 weeks [2] in the vast majority. Even patients who require temporary dialysis usually recover completely. Dialysis is a bridge, not a destination |
| Aspect | Detail |
|---|---|
| Mechanism | ↓GFR → impaired potassium excretion by the distal tubule and collecting duct → K+ accumulates in the blood. Metabolic acidosis (from retained H+) worsens hyperkalaemia through transcellular K+/H+ exchange (H+ moves into cells, K+ moves out to maintain electroneutrality) |
| Clinical features | Often asymptomatic until K+ > 6.0–6.5 → then: muscle weakness, paraesthesia, cardiac arrhythmia (peaked T waves → widened QRS → sine wave → VF/asystole). ECG changes are the best bedside monitor |
| Management | Dietary K+ restriction. Medical management per standard protocol (see Management section — IV calcium, insulin/dextrose, salbutamol, bicarbonate, Resonium). Dialysis if refractory (K+ > 6.5 not responding to medical therapy) [19] |
| Aspect | Detail |
|---|---|
| Mechanism | ↓GFR → impaired excretion of non-volatile acids (sulphate, phosphate, organic acids) → high anion gap metabolic acidosis (HAGMA). Additionally, ↓GFR may impair ammoniagenesis (NH3 production by proximal tubular cells), reducing the kidney's ability to buffer and excrete H+ as NH4+ |
| Clinical features | Kussmaul's breathing (deep, rapid respirations as respiratory compensation for metabolic acidosis), nausea, fatigue. ABG shows ↓pH, ↓HCO3, ↑AG |
| Management | IV sodium bicarbonate if pH < 7.1 or symptomatic. Dialysis if refractory [19] |
| Aspect | Detail |
|---|---|
| Mechanism | Usually secondary to hypertensive encephalopathy (see B above) — cerebral vasogenic oedema from uncontrolled HTN. Less commonly, severe uraemia or electrolyte derangements (hypocalcaemia from hyperphosphataemia, hyponatraemia from dilution) can also lower the seizure threshold |
| Clinical features | Generalised tonic-clonic seizures. Always check BP urgently in any child with PSGN who has a seizure |
| Management | Control BP (the seizure will stop once BP is controlled). Benzodiazepines (IV lorazepam or diazepam) for immediate seizure termination. Correct underlying metabolic derangement |
| Aspect | Detail |
|---|---|
| Mechanism | A complication of severe hypertension (can also occur with immunosuppressive drugs, eclampsia, renal disease). Acute hypertension exceeds cerebral autoregulatory capacity → breakdown of the blood–brain barrier → vasogenic oedema, predominantly affecting the posterior cerebral circulation (occipital and parietal lobes). Why posterior? The posterior circulation has less sympathetic innervation than the anterior circulation, so it has a lower threshold for autoregulatory failure |
| Clinical features | Headache, visual disturbances (cortical blindness, visual field defects — occipital lobes), confusion, seizures. MRI brain shows bilateral symmetrical white matter oedema in parieto-occipital regions (T2/FLAIR hyperintensity) |
| Management | Controlled BP reduction. Usually fully reversible ("reversible" is in the name) if treated promptly. Irreversible infarction can occur if diagnosis or treatment is delayed |
2. Subacute Complications (Disease Not Resolving as Expected)
These represent situations where the clinical course deviates from the expected self-limiting pattern. They are less "complications" and more diagnostic red flags suggesting an alternative or superimposed pathology.
| Aspect | Detail |
|---|---|
| Mechanism | In rare severe cases of PSGN, the glomerular injury is severe enough to trigger crescent formation — parietal epithelial cells of Bowman's capsule proliferate in response to massive plasma protein leak into Bowman's space. Crescents and interstitial inflammation are seen in severe cases — uncommon and associated with a poor prognosis [15]. Initially cellular crescents (potentially reversible) → fibroblast proliferation → fibrous crescents (irreversible) [12]. RPGN from PSGN is classified as Type II RPGN (granular IF — immune complex–mediated) [7][12] |
| Clinical features | Creatinine continues to rise rapidly (doubling within days) rather than stabilising. Rapidly declining renal function leading to ESRD in days to weeks [12] |
| Frequency | Uncommon in PSGN [4][15]. When crescents are seen, they usually affect only a minority of glomeruli. Extensive crescentic PSGN ( > 50% crescents) is rare |
| Management | Controversial. In PSGN-associated RPGN, some centres use pulse IV methylprednisolone ± cyclophosphamide, though the senior notes state "NO role for immunosuppressive therapy even in the setting of crescents" [5] for PSGN specifically. In practice, if RPGN is identified on biopsy and the diagnosis is genuinely PSGN (not lupus or ANCA vasculitis masquerading as PSGN), the approach is often expectant with close monitoring, because even PSGN with crescents often recovers — "majority have excellent outcome especially in children, even if have RPGN or acute renal failure" [4] |
RPGN in PSGN vs Other Causes
The key distinction: RPGN from PSGN (Type II, immune complex) has a much better prognosis than RPGN from anti-GBM disease (Type I) or ANCA vasculitis (Type III). In those conditions, RPGN mandates aggressive immunosuppression + plasmapheresis. In PSGN-associated RPGN, the immune process is self-limiting and crescents often resolve spontaneously. Always confirm the aetiology by renal biopsy before deciding on immunosuppression — if the biopsy shows linear IF (anti-GBM) or pauci-immune (ANCA), the management changes completely [7][12].
| Aspect | Detail |
|---|---|
| Mechanism | If the clinical picture does not improve within the expected timeframe (diuresis by 1–2 weeks, RFT normalisation by 4 weeks, C3 normalisation by 6–8 weeks), the diagnosis of PSGN should be questioned |
| What it suggests | Persistently low C3 > 8 weeks raises the possibility of lupus nephritis or membranoproliferative glomerulonephritis (complement-mediated MPGN) [2]. MPGN: acute presentation may be indistinguishable from PSGN but usually persists beyond 4–6 weeks with further ↑serum Cr [4] |
| Action | Consider renal biopsy to rule out other causes [3][4] |
3. Long-Term Complications (Months to Decades Later)
This is the most clinically significant long-term complication, though it is rare in children.
"However, some patients develop glomerulosclerosis → HTN, recurrent proteinuria (with bland urine sediment) and renal insufficiency 10–40 years after initial illness" [3][4]
| Aspect | Detail |
|---|---|
| Mechanism | "This may be due to irreversible damage to some nephrons, leading to compensatory hyperfiltration in remaining nephrons. This raises intraglomerular pressure, leading to non-immunologic glomerular injury and progressive glomerulosclerosis." [3][4] — This is the "Brenner hypothesis." Even if the acute immune injury resolves completely, if enough nephrons are destroyed, the surviving nephrons must increase their individual filtration rate (single-nephron hyperfiltration). This chronic mechanical stress causes: podocyte injury → proteinuria → mesangial expansion → segmental sclerosis → further nephron loss → a self-perpetuating vicious cycle, independent of the original immune insult |
| Clinical features | Appears 10–40 years after the initial episode [3][4]. Presents with: hypertension (secondary to progressive CKD), recurrent proteinuria (with bland urine sediment — meaning no active haematuria or RBC casts, unlike the original nephritic episode), and slowly progressive renal insufficiency |
| Risk factors | Severity of initial episode (extensive crescent formation, prolonged AKI, elderly age). Elderly patients are at particular risk: "prognosis in elderly patients is worse with high incidence of azotaemia up to 60%, nephrotic-range proteinuria and ESRD. Early death can occur in the elderly" [5] |
| Detection | Long-term follow-up with periodic urinalysis and BP monitoring. Rising creatinine or new proteinuria years after apparent recovery should raise concern |
| Management | If proteinuria develops → ACEI/ARB (reduce intraglomerular pressure → slow progression of hyperfiltration-mediated sclerosis) [12]. Standard CKD management principles: BP control, manage metabolic complications (anaemia, mineral bone disease, acidosis, hyperK), and prepare for renal replacement therapy if approaching stage 5 CKD (eGFR < 15) [20] |
CKD complications that may develop if glomerulosclerosis progresses [20]:
- Fluid retention
- Metabolic acidosis
- Hypertension
- Normochromic normocytic anaemia (↓ erythropoietin production)
- Secondary hyperparathyroidism (↓ 1,25-dihydroxyvitamin D synthesis + hyperphosphataemia → ↓ Ca → PTH ↑)
- Renal osteodystrophy / Mineral bone disease
| Aspect | Detail |
|---|---|
| Mechanism | Even after clinical resolution, subclinical glomerular injury may persist. Microscopic haematuria can persist for up to 1–2 years, and mild proteinuria for several months, without necessarily implying a poor prognosis |
| Clinical significance | Usually benign and self-resolving. However, if haematuria or proteinuria persist beyond 2 years, the diagnosis should be reconsidered (possible underlying IgA nephropathy or other chronic GN) |
| Complication | Timing | Mechanism | Frequency | Key Management |
|---|---|---|---|---|
| Pulmonary oedema / CHF | Acute (days) | Fluid overload from oliguria → ↑ preload → volume-overload failure | Common in severe cases | Furosemide, salt/fluid restriction, O2, dialysis if refractory |
| Hypertensive encephalopathy | Acute (days) | Severe volume-dependent HTN → exceeds cerebral autoregulation → vasogenic oedema | Uncommon but serious | IV antihypertensives (nicardipine), furosemide, dialysis |
| Seizures | Acute | Usually secondary to hypertensive encephalopathy | Uncommon | Control BP; IV benzodiazepines |
| PRES | Acute | Severe HTN → posterior cerebral vasogenic oedema | Uncommon | Controlled BP reduction; reversible |
| Severe AKI | Acute (1–4 weeks) | Severe endocapillary proliferation ↓↓GFR | Requiring dialysis: uncommon [3][4] | Supportive; temporary dialysis if AEIOU |
| Hyperkalaemia | Acute | ↓GFR → impaired K+ excretion; acidosis drives K+ out of cells | Common (mild); severe is uncommon | Dietary restriction; medical Rx; dialysis if refractory |
| Metabolic acidosis | Acute | ↓GFR → impaired acid excretion | Common (mild) | Bicarbonate; dialysis if pH < 7.1 |
| RPGN / Crescentic GN | Acute–subacute | Severe injury → crescent formation | Uncommon, associated with poor prognosis [15] | Controversial; often expectant in PSGN; biopsy essential |
| Failure to resolve | Subacute (4–8 weeks) | May indicate alternative diagnosis (lupus, MPGN) | — | Renal biopsy |
| Late glomerulosclerosis → CKD | 10–40 years later [3][4] | Compensatory hyperfiltration of surviving nephrons → non-immunologic sclerosis | Rare in children; more common in elderly | ACEI/ARB for proteinuria; CKD management |
| Persistent microscopic haematuria | Weeks to 1–2 years | Subclinical ongoing glomerular injury | Common | Observation; reconsider Dx if > 2 years |
| Feature | Children | Elderly |
|---|---|---|
| Overall prognosis | Complete recovery > 95% [5] | Poorer: high incidence of azotaemia (up to 60%), nephrotic-range proteinuria, ESRD [5] |
| Acute complications | Usually mild-moderate | More severe (less renal and cardiac reserve) |
| Need for dialysis | Rare | More common |
| Mortality | Early death is rare in children [5] | Early death can occur in the elderly [5] |
| Recurrence | Extremely rare despite repeated streptococcal infections [5] | Rare |
| Late glomerulosclerosis | Permanent renal failure uncommon, occurring in < 1% of children when the acute phase is severe [5] | Higher risk of progression to CKD |
PSGN itself is a complication of GAS infection, and it's worth remembering the other non-suppurative complications that may co-exist or be confused with PSGN sequelae [8][21]:
| Complication | Occurs After | Key Feature |
|---|---|---|
| Acute Rheumatic Fever (ARF) | Pharyngitis ONLY (2–4 weeks) | Pancarditis, migratory polyarthritis, Sydenham's chorea, erythema marginatum, subcutaneous nodules. ARF and PSGN can co-exist but this is rare because different M-protein serotypes are rheumatogenic vs nephritogenic |
| PSGN | Pharyngitis (1–3 weeks) or skin infection (3–6 weeks) | Nephritic syndrome |
| Scarlet fever | During pharyngitis | Diffuse erythematous eruption, strawberry tongue, Pastia's lines |
| Streptococcal toxic shock syndrome | During active infection | Hypotension + multi-organ failure |
| PANDAS | Variable | OCD or tics exacerbated by GAS infection |
"Streptococcal pharyngitis is the ONLY streptococcal infection clearly associated with ARF. Streptococcal impetigo or pyoderma have NOT been proven to lead to ARF but impetigo IS associated with PSGN." [21]
High Yield Summary — Complications of PSGN
Acute complications (all driven by ↓GFR → fluid overload → HTN):
- Pulmonary oedema — volume-overload CHF, NOT pump failure; treat with furosemide + fluid restriction
- Hypertensive encephalopathy / PRES — severe HTN exceeds cerebral autoregulation → seizures, visual disturbance; treat with IV antihypertensives
- Severe AKI — dialysis rarely needed; temporary if required (AEIOU indications)
- Hyperkalaemia and metabolic acidosis — consequences of ↓GFR; standard medical management
Subacute red flags (disease not resolving): 5. RPGN — crescent formation; uncommon in PSGN; usually still has good prognosis in children 6. Persistent ↓C3 > 8 weeks → reconsider diagnosis (lupus, MPGN) → renal biopsy
Long-term (rare, most important): 7. Late glomerulosclerosis → HTN, proteinuria, CKD 10–40 years later — from compensatory hyperfiltration of surviving nephrons 8. Children: > 95% complete recovery; < 1% permanent renal failure 9. Elderly: poorer outcomes — up to 60% azotaemia, higher ESRD and mortality
Active Recall - Complications of PSGN
References
[2] Senior notes: Block A - Glomerular and Tubulo-interstitial Diseases and Acute Kidney Injury.pdf (p18–19 — Clinical course, persistent low C3) [3] Senior notes: Ryan Ho Urogenital.pdf (p65–66 — Management, prognosis, glomerulosclerosis mechanism) [4] Senior notes: Adrian Lui Pediatrics Notes.pdf (p327–328 — Management, prognosis, glomerulosclerosis, biopsy indications) [5] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p406, p420, p425 — Treatment, prognosis in children vs elderly, crescents) [7] Senior notes: Maksim Medicine Notes.pdf (p232–233 — RPGN classification, complications of nephrotic syndrome) [8] Senior notes: Ryan Ho Respiratory.pdf (p52 — Non-suppurative complications of GAS pharyngitis) [12] Senior notes: Ryan Ho Fundamentals.pdf (p359, p361, p368 — RPGN pathogenesis, crescent formation, anti-proteinuric therapy) [15] Senior notes: MBBS Final MB (Medicine) (Felix PY Lai).pdf (p999 — Prognosis, crescents, no immunosuppressants) [19] Senior notes: Ryan Ho Critical Care.pdf (p25–26 — AKI management, dialysis indications AEIOU) [20] Senior notes: Block A - Chronic Kidney Disease and its Complications.pdf (p8, p23 — Causes of CKD, systemic complications of CKD) [21] Senior notes: MBBS Final MB (Pediatrics) (Felix PY Lai).pdf (p303 — ARF vs PSGN, GAS complications); MBBS Final MB (Medicine) (Felix PY Lai).pdf (p444 — ARF pathogenesis, pharyngitis only for ARF)
High Yield Summary
Post-Streptococcal Glomerulonephritis (PSGN) — Key Points:
- Definition: Immune complex–mediated GN occurring as a non-suppurative complication of nephritogenic GAS infection
- Epidemiology: Most common cause of acute nephritis in children (ages 2–12); M:F = 2:1; rare in developed countries
- Latency: 1–3 weeks after pharyngitis, 3–6 weeks after skin infection (GC slide: "10 to 14 days after streptococcal infection")
- Pathogenesis: Streptococcal antigens planted in glomerulus → host antibody response → in situ immune complex formation → complement activation → inflammatory injury
- Pathology: LM: diffuse endocapillary proliferation with neutrophil infiltrate; IF: "starry sky" granular IgG/C3; EM: subepithelial humps (pathognomonic)
- Clinical features: Nephritic syndrome — gross haematuria (smoky/cola-coloured), oliguria, oedema, hypertension, sub-nephrotic proteinuria
- Complement: ↓C3 and ↓CH50 (normalizes by 8 weeks); normal C4
- Prognosis: Self-limiting; diuresis in 1–2 weeks, RFT normalizes by 4 weeks
- Persistently low C3 > 8 weeks → think lupus nephritis or MPGN
- Key DDx: IgA nephropathy (synpharyngitic, normal C3, recurrent), lupus nephritis (↓C3 AND ↓C4, multisystem), MPGN (persistent low C3)
- No prophylactic antibiotics needed (unlike ARF)
High Yield Summary — Differential Diagnosis of PSGN
- Always confirm glomerular haematuria first (dysmorphic RBCs, RBC casts) — exclude urological causes (stones, tumour), UTI, AIN, PKD
- The #1 DDx is IgA nephropathy — distinguish by timing (synpharyngitic vs latent), complement (normal vs low C3), and recurrence pattern
- Low C3 DDx: PSGN (resolves by 8 weeks), lupus nephritis (↓C3 AND ↓C4, systemic features, persistent), MPGN (persistent ↓C3, progressive), cryoglobulinaemia
- Normal C3 DDx: IgA nephropathy, HSP, anti-GBM disease, ANCA vasculitis
- Red flags for alternative diagnosis: persistently low C3 > 8 weeks, RPGN course, systemic features, positive ANA/ANCA/anti-GBM, synpharyngitic timing, recurrent haematuria
- RPGN is the most dangerous mimic — requires urgent immunosuppression; classified by IF pattern (Type I linear = anti-GBM, Type II granular = immune complex, Type III negative = pauci-immune/ANCA)
- Systematic GN workup: C3/C4, ASO, ANA, anti-dsDNA, ANCA, anti-GBM, cryoglobulins, HBV/HCV/HIV/VDRL, malignancy screen in elderly, renal biopsy if atypical
High Yield Summary — Diagnosis and Investigations of PSGN
- PSGN is a clinical diagnosis — renal biopsy is usually NOT needed. Diagnosis requires: acute nephritic syndrome + evidence of recent GAS infection + hypocomplementaemia (↓C3, normal C4)
- Streptozyme test is the most sensitive serological test ( > 95% pharyngitis, ~80% skin). ASO may be false-negative in skin infections — always add Anti-DNase B
- C3 is ↓↓ in > 90% of patients in the first 2 weeks; CH50 also ↓; C4 is NORMAL — normalises by 6–8 weeks
- Persistently low C3 > 8 weeks → lupus nephritis or MPGN — this is the most important monitoring red flag
- Urine microscopy is critical: dysmorphic RBCs + RBC casts = glomerular haematuria; blood clots = non-glomerular
- Renal biopsy findings (if done) — LM: diffuse endocapillary proliferation with neutrophils; IF: starry sky granular IgG/C3; EM: subepithelial humps (pathognomonic)
- GN workup to exclude mimics: ANA, anti-dsDNA, ANCA, anti-GBM, C3/C4, cryoglobulins, HBV/HCV/HIV/VDRL, malignancy screen in elderly, renal biopsy if atypical
High Yield Summary — Management of PSGN
- PSGN is self-limiting — treatment is SUPPORTIVE. There is NO role for immunosuppressants, even with crescents.
- GC 057 slide: "For acute poststreptococcal GN, penicillin may be indicated. Otherwise, supportive therapy ± temporary dialysis may be needed."
- Antibiotic: PO Penicillin V × 10 days — eradicates GAS and limits spread but does NOT alter natural history of PSGN. Treat cohabitants. No long-term prophylaxis needed (unlike ARF).
- Oedema: IV Furosemide 1–4 mg/kg/day Q6H. Assess volume status before diuresing.
- Hypertension: Salt restriction + furosemide first → Nifedipine if refractory. ACEI/ARB with caution (hyperK risk).
- Dialysis: Temporary, only for life-threatening complications (AEIOU: Acidosis, Electrolytes, Intoxication, Overload, Uraemia).
- Prognosis: > 95% complete recovery in children. Elderly have poorer outcomes. Rare late glomerulosclerosis from hyperfiltration injury.
- Follow-up: Monitor C3 at 6–8 weeks (must normalise), RFT, urinalysis. Persistent ↓C3 > 8 weeks or no improvement by 4 weeks → renal biopsy.
High Yield Summary — Complications of PSGN
Acute complications (all driven by ↓GFR → fluid overload → HTN):
- Pulmonary oedema — volume-overload CHF, NOT pump failure; treat with furosemide + fluid restriction
- Hypertensive encephalopathy / PRES — severe HTN exceeds cerebral autoregulation → seizures, visual disturbance; treat with IV antihypertensives
- Severe AKI — dialysis rarely needed; temporary if required (AEIOU indications)
- Hyperkalaemia and metabolic acidosis — consequences of ↓GFR; standard medical management
Subacute red flags (disease not resolving): 5. RPGN — crescent formation; uncommon in PSGN; usually still has good prognosis in children 6. Persistent ↓C3 > 8 weeks → reconsider diagnosis (lupus, MPGN) → renal biopsy
Long-term (rare, most important): 7. Late glomerulosclerosis → HTN, proteinuria, CKD 10–40 years later — from compensatory hyperfiltration of surviving nephrons 8. Children: > 95% complete recovery; < 1% permanent renal failure 9. Elderly: poorer outcomes — up to 60% azotaemia, higher ESRD and mortality
Thin Basement Membrane Disease
Thin basement membrane disease is a benign hereditary condition characterized by diffuse thinning of the glomerular basement membrane, typically presenting with persistent microscopic hematuria and a favorable prognosis.
ANCA-Associated Glomerulonephritis
ANCA-associated glomerulonephritis is a pauci-immune necrotizing and crescentic glomerulonephritis caused by antineutrophil cytoplasmic antibodies directed against myeloperoxidase or proteinase 3, leading to rapidly progressive renal failure.