Haematuria is the presence of red blood cells in the urine, which may be visible (macroscopic) or detectable only on microscopy or dipstick testing (microscopic), indicating potential urological or nephrological pathology.

Haematuria

Risk Factors

These can be organized by the underlying cause of haematuria:

Anatomy and Functional Considerations

To understand haematuria, you need to understand the anatomy of the urinary tract and where bleeding can originate. Think of the urinary system as a continuous tube lined by urothelium (transitional epithelium) from the renal calyces down to the proximal urethra.

Aetiology

The causes of haematuria are best organized anatomically (from kidney to urethra) and by mechanism. We focus on causes relevant to Hong Kong practice.

Frequency	Cause
~60%	UTI
~10%	Urinary stones
~5%	Glomerulonephritis
Variable	Malignancy (most worrying)
Variable	BPH, trauma, iatrogenic (e.g., post-TURP, post-Foley catheter)

Detailed Aetiological Classification

The hallmark is dysmorphic RBCs, RBC casts, and concurrent proteinuria (because GBM damage lets both protein and RBCs through).

Condition	Key Features	Pathophysiology
IgA nephropathy (Berger disease)	Most common GN worldwide; presents with synpharyngitic haematuria (haematuria during or 1–2 days after URTI)	IgA immune complexes deposit in mesangium → mesangial proliferation → GBM damage
Thin basement membrane nephropathy	Benign familial haematuria; persistent microscopic haematuria with normal renal function	Uniformly thin GBM (< 250 nm) → RBCs pass through more easily
Alport syndrome	X-linked; progressive hearing loss + haematuria + renal failure	Mutation in type IV collagen (COL4A3/4/5) → abnormal GBM structure
Post-infectious GN	Haematuria 1–3 weeks AFTER streptococcal pharyngitis/skin infection (latent period, unlike IgA)	Immune complex deposition → complement activation → endocapillary proliferative GN
Lupus nephritis	Part of SLE; haematuria + proteinuria + systemic features	Immune complex deposition in glomeruli → complement activation ^[6]
ANCA-associated vasculitis (GPA, MPA)	Haematuria + rapidly progressive renal failure ± pulmonary haemorrhage	Pauci-immune necrotizing/crescentic GN
Anti-GBM disease (Goodpasture)	Pulmonary-renal syndrome: haemoptysis + haematuria	Autoantibodies against type IV collagen in GBM and alveolar basement membrane
HSP/IgA vasculitis	Purpuric rash (buttocks/legs) + arthralgia + abdominal pain + haematuria	IgA deposition in mesangium (essentially IgA nephropathy with systemic vasculitis)

Condition	Key Features	Pathophysiology
Renal cell carcinoma (RCC)	Classic triad: haematuria + flank pain + palpable mass (only ~10% present with all three); often incidental on imaging	Tumour invades renal collecting system → bleeding; or tumour neovascularization
Polycystic kidney disease (PKD)	Bilateral palpable kidneys, FHx, associated with berry aneurysms	Cyst haemorrhage or rupture into collecting system
Renal infarction	Sudden loin pain + haematuria; AF or endocarditis as embolic source	Ischaemic necrosis of renal parenchyma
Pyelonephritis	Fever + loin pain + haematuria; often with LUTS	Infection → mucosal inflammation and damage
Renal TB	Sterile pyuria (WBCs but negative cultures); chronic disease	Granulomatous inflammation → caseous necrosis of renal parenchyma
Papillary necrosis	Haematuria + passage of tissue; seen in sickle cell disease, analgesic nephropathy, DM, pyelonephritis	Ischaemic necrosis of renal papillae → sloughing into collecting system
Renal vein thrombosis	Flank pain + haematuria; associated with nephrotic syndrome (especially membranous nephropathy)	Venous congestion → haemorrhagic infarction
Vascular malformations (AVM, aneurysm)	Intermittent gross haematuria, sometimes massive	Abnormal vessels rupture into collecting system

Condition	Pathophysiology
Ureteric stones	Mechanical trauma to urothelium as stone passes; mucosal abrasion
Upper tract urothelial carcinoma	Urothelial malignancy — field cancerization concept: multifocal occurrence via intraluminal seeding or intraepithelial migration ^[5]

Condition	Key Features	Pathophysiology
UTI/Cystitis	Most common cause overall; dysuria + frequency + urgency	Bacterial infection → mucosal inflammation → capillary damage → bleeding
Bladder cancer (urothelial carcinoma)	Most common malignancy of the urinary system; painless gross haematuria in elderly ^[1]^[5]	Urothelial neoplasm → tumour neovascularization → friable vessels bleed
Bladder stones	Irritative LUTS + haematuria (often terminal)	Mechanical irritation of bladder mucosa
Radiation cystitis	Delayed (years after pelvic irradiation for cervical/colorectal cancer) ^[4]	Radiation damage → endarteritis obliterans → mucosal telangiectasia → bleeding
Haemorrhagic cystitis	In patients receiving cyclophosphamide/ifosfamide for haematological malignancy ^[4]	Acrolein (metabolite) is directly toxic to urothelium; prevented with MESNA
Schistosomiasis	Relevant in endemic areas (Africa, Middle East); chronic terminal haematuria	S. haematobium eggs deposit in bladder wall → granulomatous inflammation → SCC risk

Condition	Pathophysiology
BPH	Enlarged prostate has increased vascularity (stromal and glandular hyperplasia) → fragile vessels rupture
Prostate cancer	Usually does NOT cause haematuria unless locally advanced with invasion into urethra/bladder
Prostatitis	Infection/inflammation → mucosal bleeding in prostatic urethra

Condition	Pathophysiology
Urethritis (gonococcal/non-gonococcal)	Infection → mucosal inflammation
Urethral stricture	Chronic inflammation → mucosal fragility
Urethral trauma	Direct mucosal disruption (straddle injury for bulbar urethra, pelvic fracture for membranous urethra) ^[2]

Condition	Mechanism
Coagulopathies (haemophilia, VWD, DIC)	Impaired haemostasis → bleeding tendency including into urinary tract. In severe haemophilia, haematuria is common but not associated with decreased renal function ^[7]
Anticoagulant/antiplatelet therapy	Unmasks underlying pathology rather than causing haematuria de novo — these patients STILL need full investigation ^[1]^[2]
Sickle cell disease/trait	Medullary ischaemia → papillary necrosis; also renal medullary carcinoma (rare)
Thrombocytopenia	Reduced platelet plug formation → mucosal bleeding

Classification

Haematuria can be classified in several clinically useful ways:

Type	Definition
Gross (macroscopic)	Visible blood in urine
Microscopic	≥3 RBC/HPF on microscopy (not visible)

Origin	Microscopy Findings	Clots?	Proteinuria?
Glomerular	Dysmorphic RBCs, RBC casts	No (urokinase lyses clots)	Often significant (> 500 mg/day)
Non-glomerular (urological)	Isomorphic RBCs	May be present	Usually absent or minimal

Timing (early/whole/end stream) — though the lecture notes caution this is unreliable in predicting location ^[1]:

Timing	Anatomical Suggestion
Initial stream	Anterior urethra (distal to urogenital diaphragm)
Terminal stream	Bladder neck or posterior urethra/prostate
Throughout	Bladder or upper urinary tract

Type	Suggests
Painful haematuria	UTI, stones, renal infarction, pyelonephritis
Painless haematuria	Malignancy (classically painless gross haematuria in > 35y = malignancy until proven otherwise) ^[1]^[4]; also glomerulonephritis

This is the modern risk-stratification approach that guides the intensity of investigation:

Risk Category	Criteria	Recommended Action
Low/Negligible-Risk	Women < 60, Men < 40; Never smoker or < 10 pack-years; 3–10 RBC/HPF on one UA; No additional risk factors	Repeat UA within 6 months
Intermediate-Risk	Women ≥ 60, Men 40–59; 10–30 pack-years; 11–25 RBC/HPF; One or more additional risk factors; Previously low-risk with no prior evaluation and 3–25 RBC/HPF on repeat UA	Cystoscopy and renal ultrasound. Clinicians may offer urine cytology or validated UBTMs to facilitate decision regarding cystoscopy. Repeat UA within 12 months if cystoscopy is not performed
High-Risk	Men ≥ 60; > 30 pack-years; > 25 RBC/HPF; History of gross haematuria; One or more additional risk factors plus any high-risk feature	Cystoscopy and axial upper tract imaging

Important Note on Risk Stratification

The lecture slide ^[1] explicitly notes that women should not be categorized as high-risk based on age alone. The risk factors for urothelial cancer that drive categorization include smoking history, occupational exposures, prior gross haematuria, and other factors listed above.

Clinical Features

Symptoms

The symptoms of haematuria itself are straightforward (the patient sees blood in urine or it's detected on testing), but the associated symptoms are what guide you toward the underlying cause. Here we systematically link each symptom to its pathophysiological basis.

Signs

Physical examination in a patient with haematuria is directed at finding the underlying cause:

Sign	Significance	Pathophysiological Basis
Pallor	Anaemia from chronic blood loss or underlying malignancy	Reduced haemoglobin → pale conjunctivae, nail beds
Fever	UTI, pyelonephritis, renal abscess, TB	Systemic inflammatory response to infection
Peripheral oedema	Nephrotic/nephritic syndrome from glomerular disease	Proteinuria → hypoalbuminaemia → reduced oncotic pressure (nephrotic); salt/water retention (nephritic)
Hypertension	Glomerulonephritis, polycystic kidney disease, renal artery stenosis	Fluid retention + RAAS activation due to reduced renal perfusion
Purpuric rash	HSP, GPA, SLE	Small vessel vasculitis → extravasation of RBCs into skin
Malar rash	SLE	Immune complex deposition in skin
Cachexia/weight loss	Malignancy	Tumour metabolic demands + cytokine-mediated catabolism
Lymphadenopathy	Metastatic disease	Tumour spread to regional nodes

Sign	Significance	Pathophysiological Basis
Loin/renal angle tenderness	Pyelonephritis, renal infarct, renal stones	Distension/inflammation of renal capsule stretches sensory nerve fibres (T10-T12)
Ballotable kidney	RCC, polycystic kidney disease, hydronephrosis	Enlarged kidney can be felt bimanually (one hand on flank, one anteriorly) → the kidney is felt "bouncing" between hands
Suprapubic mass/tenderness	Distended bladder (clot retention, BOO), bladder tumour	Urine retention → palpable/tender bladder above pubic symphysis
Hepatomegaly	Metastatic disease (RCC, bladder CA)	Common site of metastasis for urological malignancies

Sign	Significance	Pathophysiological Basis
Left-sided varicocele	Renal cell carcinoma (classic sign)	Left renal vein obstruction by RCC tumour thrombus → impaired drainage of left testicular vein (which drains into left renal vein) → varicocele ^[2]
Blood at urethral meatus	Urethral trauma	Disruption of urethral mucosa
Urethral discharge	Urethritis (gonococcal/chlamydial)	Infection of urethral mucosa

Finding	Significance
Smooth, symmetrical enlargement	BPH
Hard, irregular, nodular prostate	Prostate cancer
Tender, boggy prostate	Prostatitis

Key Pathophysiological Concepts Summarised

The entire urothelium (from renal pelvis to urethra) is exposed to the same carcinogens dissolved in urine. This means:

Multifocal tumours can arise simultaneously at different sites ^[5]
A patient with bladder UCC has a 2–4% risk of concurrent or subsequent upper tract UCC ^[5]
This is why upper tract imaging is essential in patients diagnosed with bladder cancer, and vice versa
Spreads through urothelium via intraluminal seeding or intraepithelial migration ^[5]

High Yield Summary

Definition: Gross haematuria = visible blood in urine. Microscopic haematuria = ≥3 RBC/HPF on microscopy. Always confirm with microscopy — dipstick alone cannot distinguish true haematuria from pigmenturia.
Most common cause: UTI (~60%). Most worrying cause: Malignancy — until proven otherwise in anyone > 35–40 years old.
Glomerular vs Urological: Dysmorphic RBCs/RBC casts/no clots/proteinuria = glomerular. Isomorphic RBCs ± clots/minimal proteinuria = urological.
Painless gross haematuria in the elderly = malignancy until proven otherwise.
Key risk factors for urothelial CA: Smoking (pack-years), occupational chemical exposure, aristolochic acid (TCM — HK relevant), cyclophosphamide, chronic UTI/indwelling catheter.
Timing in stream: Initial = anterior urethra; Terminal = bladder neck/prostate; Throughout = bladder or above. (But unreliable in predicting location.)
Blood clots = urological origin (urokinase in glomerular filtrate prevents clot formation in glomerular haematuria).
Left-sided varicocele that doesn't decompress supine → suspect RCC obstructing left renal vein.
IgA nephropathy = synpharyngitic haematuria (during URTI). Post-infectious GN = haematuria 1–3 weeks after streptococcal infection (latent period).
AUA risk stratification guides investigation intensity: low-risk → repeat UA; intermediate → cystoscopy + US; high-risk → cystoscopy + axial upper tract imaging.
Anticoagulants/antiplatelets do NOT explain away haematuria — always investigate for underlying pathology.
Field cancerization: Urothelial CA can be multifocal throughout the urinary tract → always image the whole tract.

Active Recall - Haematuria: Definition, Epidemiology, Aetiology, and Clinical Features

Differential Diagnosis of Haematuria

The differential diagnosis of haematuria is one of the most commonly tested clinical scenarios. The key to approaching it logically is to remember that blood can enter the urine at any point along the urinary tract — from the glomerulus all the way to the urethral meatus. Your job is to figure out where and why.

The first and most critical branch point is: Is the bleeding glomerular or non-glomerular (urological)? This single determination narrows your differential by half and dictates the entire subsequent workup.

Before you even think about specific diagnoses, urine microscopy tells you which "world" you are in:

Feature	Glomerular	Non-Glomerular (Urological)
RBC morphology	Dysmorphic (irregular membrane, acanthocytes) — because RBCs are deformed as they squeeze through damaged GBM under filtration pressure	Isomorphic (normal, round) — because RBCs enter urine directly without traversing GBM
RBC casts	Present (RBCs trapped in Tamm-Horsfall protein secreted by tubular cells)	Absent
Blood clots	Absent — urokinase and tPA in glomerular filtrate prevent clot formation ^[8]^[2]	May be present — blood clots indicate heavy focal bleeding with whole blood shed into urine in amounts sufficient to support clot formation ^[8]
Proteinuria	Usually significant (> 500 mg/day; often nephrotic-range) — GBM damage lets both protein and RBCs through	Usually absent or minimal (< 500 mg/day)
Urine colour	Smoky brown / cola-coloured — haemoglobin degrades during transit through nephron ^[4]^[9]	Bright red or pink — fresh blood mixes directly with urine

Gross haematuria with passage of clot ALWAYS indicates NON-glomerular bleeding ^[8]. This is a high-yield exam point — if there are clots, you can essentially exclude a glomerular source.

Why No Clots in Glomerular Bleeding?

Glomerular bleeding is a diffuse capillary process where minute amounts of blood are added to a relatively large volume of glomerular filtrate. Additionally, urokinase and tissue-type plasminogen activator (tPA) produced in the glomeruli and tubules actively lyse any fibrin that forms. The combination of dilution and active fibrinolysis makes clot formation essentially impossible in glomerular haematuria ^[8]^[2].

Step 2: The Complete Differential — Organized Anatomically

The most systematic way to build your differential is to walk down the urinary tract from kidney to urethra, then consider systemic causes. This ensures you never miss a diagnosis ^[4]^[8]^[9].

These present with dysmorphic RBCs, RBC casts, proteinuria, cola-coloured urine, and no clots.

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
IgA nephropathy	Synpharyngitic haematuria (during/within 1–2 days of URTI); adult onset; may have flank pain + low-grade fever during episodes; slowly progressive over decades ^[10]	Abnormally glycosylated IgA1 → mesangial deposition → complement activation → mesangial proliferative GN
Post-infectious GN	Haematuria 1–3 weeks AFTER streptococcal pharyngitis/impetigo (latent period); nephritic features (HTN, oedema, oliguria); typically children	Immune complex (IgG + streptococcal antigen) deposition → subepithelial humps → complement activation → endocapillary proliferative GN
Thin basement membrane disease	Persistent microscopic haematuria; benign course; FHx of haematuria (AD inheritance); normal renal function and BP ^[11]	Uniformly thin GBM (< 250 nm vs normal ~300–400 nm) → RBCs cross more easily; 30–50% have FHx
Alport syndrome	X-linked dominant (80%); progressive sensorineural hearing loss + ocular abnormalities (anterior lenticonus, dot-and-fleck retinopathy); FHx of renal failure/deafness in male relatives; childhood onset ^[11]	Mutation in type IV collagen (COL4A3/4/5) → structurally abnormal GBM → progressive nephritis
Lupus nephritis	Part of SLE — malar rash, oral ulcers, arthralgia, serositis, cytopenias; isolated proteinuria/haematuria or nephrotic/nephritic syndrome ^[6]^[12]	Immune complex deposition → complement activation → variable patterns of glomerular inflammation (Class I–VI)
ANCA-associated vasculitis (GPA, MPA, EGPA)	Haemoptysis (pulmonary-renal syndrome); epistaxis/rhinorrhoea (GPA); purpuric rash; rapidly progressive renal failure ^[2]	Pauci-immune necrotizing/crescentic GN; ANCA activates neutrophils → endothelial damage
Anti-GBM disease (Goodpasture)	Pulmonary-renal syndrome: haemoptysis + rapidly progressive GN; young males (smoking predisposes lung involvement)	Autoantibodies against α3 chain of type IV collagen in GBM + alveolar BM → linear IgG deposition
IgA vasculitis (HSP)	Purpuric rash (buttocks/legs) + abdominal pain + arthralgia + haematuria; typically children	IgA deposition in mesangium (histologically identical to IgA nephropathy) + systemic small vessel vasculitis
MPGN	Episodic gross haematuria in children/young adults; may have low C3	Subendothelial/intramembranous immune complex deposition → mesangial proliferation + GBM thickening

IgA Nephropathy vs Post-Infectious GN: Timing is Everything

Both present with haematuria after pharyngitis, but the timing is completely different. IgA nephropathy = synpharyngitic (haematuria during the URTI, because a mucosal infection triggers a surge in already-elevated IgA). Post-infectious GN = haematuria 1–3 weeks after infection (the latent period reflects the time needed to generate IgG antibodies against streptococcal antigens and form immune complexes). This is the most commonly tested distinction in exams ^[10]^[11].

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
Renal cell carcinoma (RCC)	Traditional triad: painless haematuria + flank pain + palpable flank mass (only ~10% have all three); constitutional symptoms; paraneoplastic features (HTN, hypercalcaemia, polycythaemia); left varicocele ^[4]^[9]	Tumour invades collecting system; neovascularization with fragile vessels
Polycystic kidney disease (PKD)	Bilateral palpable kidneys; insidious HTN; FHx (AD); associated berry aneurysms ^[4]^[9]	Cyst haemorrhage or rupture into collecting system
Pyelonephritis	High fever, vomiting, loin pain; often with LUTS ^[9]	Ascending infection → parenchymal inflammation → mucosal damage
Renal infarction	Sudden-onset loin pain + haematuria; source of embolism (AF, endocarditis, aortic athero) ^[9]	Ischaemic necrosis of renal parenchyma → haemorrhage into collecting system
Renal TB	Sterile pyuria; chronic constitutional symptoms; TB contact history ^[4]	Granulomatous inflammation → caseous necrosis → erosion into collecting system
Papillary necrosis	Flank pain + haematuria + passage of tissue; seen in sickle cell, analgesic nephropathy, DM, pyelonephritis ^[10]	Ischaemic necrosis of renal papillae (which have tenuous blood supply) → sloughing into collecting system
Renal vein thrombosis	Flank pain + haematuria; associated with nephrotic syndrome (esp. membranous nephropathy)	Venous congestion → haemorrhagic infarction of kidney
Renal AVM / angiomyolipoma	Intermittent gross haematuria, sometimes massive; angiomyolipoma associated with tuberous sclerosis ^[8]	Abnormal/fragile vessels rupture into collecting system
Simple renal cyst	Usually asymptomatic; rarely spontaneous rupture → haematuria + flank pain ^[10]	Cyst rupture or haemorrhage into collecting system

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
Ureteric stones	Unilateral colicky loin-to-groin pain; may have passage of stones; Hx of previous stones ^[9]	Mechanical abrasion of urothelium by calculus at points of ureteric narrowing (PUJ, pelvic brim, VUJ)
Upper tract urothelial carcinoma	Painless haematuria; smoking/chemical exposure Hx; may have clot colic (vermiform clots from ureter) ^[8]	Field cancerization — same urothelium exposed to same carcinogens as bladder → neoplastic transformation

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
UTI / Cystitis	Most common cause of haematuria (~60%) ^[2]; dysuria, frequency, urgency, suprapubic pain	Bacterial infection → acute mucosal inflammation → capillary damage → bleeding
Bladder cancer (urothelial carcinoma)	Painless gross haematuria in elderly = malignancy until proven otherwise ^[1]^[4]; irritative LUTS; risk factors: smoking, occupation, chemicals ^[1]	Neoplastic transformation of urothelium → tumour neovascularization → friable vessels bleed into bladder lumen
Bladder stones	Irritative LUTS + terminal haematuria (stone irritates trigone/bladder neck); may have intermittent stream (stone "ball-valves" at bladder outlet) ^[9]	Mechanical irritation of bladder mucosa
Radiation cystitis	Delayed presentation (years after pelvic irradiation for cervical/colorectal cancer) ^[4]^[9]	Radiation → endarteritis obliterans → mucosal ischaemia → telangiectasia → bleeding
Haemorrhagic cystitis	Patient on cyclophosphamide/ifosfamide for haematological malignancy; or viral cystitis (BK virus, adenovirus) ^[4]^[9]	Acrolein (cyclophosphamide metabolite) directly toxic to urothelium; prevented with MESNA (2-mercaptoethane sulfonate, which binds acrolein in urine)
Schistosomiasis	Endemic travel history (Africa, Middle East); chronic terminal haematuria; long-term → SCC of bladder	S. haematobium eggs deposit in bladder wall → granulomatous inflammation → fibrosis

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
BPH	Advanced age; obstructive LUTS (hesitancy, weak stream, straining, dribbling, incomplete emptying); diagnosis by exclusion after malignancy ruled out ^[4]^[9]	Stromal/glandular hyperplasia → increased vascularity with fragile vessels → rupture → haematuria
Prostate cancer	Usually obstructive LUTS; haematuria uncommon unless locally advanced ^[9]	Local invasion into prostatic urethra or bladder neck
Prostatitis	Perineal pain; dysuria; fever (if acute); tender/boggy prostate on DRE	Infection/inflammation → mucosal bleeding in prostatic urethra

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
Urethritis	Urethral discharge; dysuria; STI risk factors	Gonococcal/chlamydial infection → mucosal inflammation
Urethral stricture	History of previous infection, trauma, or instrumentation; poor stream	Chronic fibrosis → mucosal fragility → bleeding
Urethral trauma	History of straddle injury (bulbar urethra) or pelvic fracture (membranous urethra); blood at meatus; high-riding prostate ^[2]	Direct mucosal disruption

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
Haemophilia	Known bleeding disorder; haemarthrosis, soft tissue haematoma; haematuria common in severe haemophilia but NOT associated with ↓ renal function ^[7]	Deficiency of factor VIII (A) or IX (B) → impaired coagulation → mucosal bleeding tendency
Anticoagulant/antiplatelet use	Drug history; does NOT cause haematuria de novo but unmasks underlying pathology ^[1]^[2]	Reduced haemostatic capacity → easier bleeding from pre-existing lesions
Sickle cell disease/trait	African descent; episodes of pain crisis; papillary necrosis; rare: renal medullary carcinoma	Sickling in vasa recta → medullary ischaemia → papillary necrosis
DIC	Acutely ill patient; petechiae, mucosal bleeding, oozing from IV sites	Consumption of clotting factors + fibrinolysis → widespread haemorrhagic tendency
Thrombocytopenia	Petechiae, purpura, mucosal bleeding	Insufficient platelet plug formation

Bleeding tendencies seldom cause haematuria on their own — 81% are associated with an underlying urinary cause ^[4]^[9]. Always investigate further.

Diagnosis	Distinguishing Clinical Features	Key Pathophysiology
Exercise-induced haematuria	Transiently after strenuous exercise; resolves after rest; diagnosis by exclusion ^[4]^[9]	Possibly friction abrasion of collapsed bladder walls during dehydration in runners
Benign idiopathic haematuria	May be associated with exercise, febrile illness, or vaccination; may be familial; diagnosis by exclusion ^[9]	Unknown; likely multifactorial including subclinical injury
Endometriosis of urinary tract	Cyclical haematuria coinciding with menstruation (rare) ^[8]	Ectopic endometrial tissue in bladder/ureter responds to hormonal cycle
Nutcracker syndrome	Left flank pain + haematuria; young/thin patients	Left renal vein compression between aorta and SMA → venous hypertension
Loin pain haematuria syndrome	Recurrent unilateral loin pain + haematuria; no identifiable cause; typically young women	Unknown; diagnosis of exclusion

These are the clinical features that should immediately raise your index of suspicion for specific diagnoses:

Red Flag	Think...	Why?
Painless gross haematuria, age > 35 ^[1]^[4]	Malignancy	Tumours bleed without pain (no acute obstruction/inflammation)
Blood clots in urine ^[1]^[8]	Non-glomerular cause (likely urological)	Urokinase prevents clots in glomerular bleeding
Cola-coloured urine + proteinuria + RBC casts	Glomerulonephritis	GBM damage allows RBCs + protein; Hb degrades during transit
Haematuria during URTI	IgA nephropathy	IgA surge during mucosal infection → mesangial deposition
Haematuria 1–3 weeks after pharyngitis	Post-infectious GN	Latent period for adaptive immune response
Haemoptysis + haematuria ^[2]	Pulmonary-renal syndrome (anti-GBM, ANCA vasculitis)	Shared antigen in alveolar + glomerular basement membranes
Colicky loin-to-groin pain	Ureteric stone	Peristalsis against obstruction
Smoking history, rubber/dye/chemical worker ^[1]	Urothelial carcinoma	Aromatic amines concentrated in urine → direct urothelial carcinogenesis
Bilateral flank masses + FHx	Polycystic kidney disease	Autosomal dominant; bilateral cyst expansion
New left varicocele (non-decompressing supine)	RCC	Tumour thrombus in left renal vein → obstructed left testicular vein drainage
Sterile pyuria + haematuria	Renal TB	Granulomatous infection; standard cultures negative for TB
Cyclical haematuria with menses	Bladder/ureteral endometriosis	Ectopic endometrial tissue responds to hormonal cycle

Special Considerations in Differential Diagnosis

Always review the drug chart:

Cyclophosphamide / ifosfamide → haemorrhagic cystitis (acrolein metabolite)
Anticoagulants / antiplatelets → unmask underlying lesion (not a cause per se)
NSAIDs → can cause AIN, papillary necrosis
Radiation → radiation cystitis (delayed by years)

High Yield Summary

First branch point: Urine microscopy — dysmorphic RBCs/casts = glomerular; isomorphic RBCs ± clots = non-glomerular. Clots ALWAYS indicate non-glomerular bleeding.
Most common cause: UTI (~60%). Most worrying: Malignancy. Others: Stones (~10%), GN (~5%), BPH, trauma, iatrogenic.
Painless gross haematuria in > 35y = malignancy until proven otherwise.
IgA nephropathy = synpharyngitic (during URTI). Post-infectious GN = 1–3 weeks after strep infection. Timing distinguishes them.
Isolated glomerular haematuria in young patient = IgA nephropathy vs Alport syndrome vs thin basement membrane disease.
Pulmonary-renal syndrome (haemoptysis + haematuria) = anti-GBM disease, ANCA vasculitis, SLE.
Bleeding tendencies (haemophilia, anticoagulants) seldom cause haematuria alone — 81% have underlying urinary pathology → always investigate.
Risk-stratify microscopic haematuria using AUA criteria (age, sex, smoking pack-years, RBC/HPF count, additional risk factors) to guide investigation intensity.
Anatomical walk-through (kidney → ureter → bladder → prostate → urethra → systemic) ensures no diagnosis is missed.
Don't forget pseudohaematuria: haemoglobinuria, myoglobinuria, food/drug pigments — confirmed by microscopy showing no RBCs.

Active Recall - Differential Diagnosis of Haematuria

References

^[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p6, p13) ^[2] Senior notes: maxim.md (Section 2.1 Common urological complaints - Haematuria) ^[4] Senior notes: Ryan Ho Urogenital.pdf (p130, p132, p136) ^[6] Senior notes: Ryan Ho Rheumatology.pdf (p69–70 - SLE) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p124 - Haemophilia) ^[8] Senior notes: felixlai.md (Haematuria section) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p340, p342) ^[10] Senior notes: Ryan Ho Urogenital.pdf (p59 - IgA Nephropathy; p94 - Analgesic Nephropathy) ^[11] Senior notes: Ryan Ho Fundamentals.pdf (p358 - Isolated Glomerular Haematuria) ^[12] Senior notes: Ryan Ho Rheumatology.pdf (p32 - Extra-articular features)

Diagnostic Criteria, Diagnostic Algorithm, and Investigations for Haematuria

Diagnostic Criteria: Confirming True Haematuria

There is no single "diagnostic criteria" for haematuria the way there is for, say, SLE. Instead, the diagnosis of haematuria itself is straightforward — it is a laboratory finding. The challenge is confirming it is real (not pseudohaematuria) and then systematically determining its cause. Let's build this from first principles.

Urine dipstick is the initial screening test. It detects the peroxidase activity of the haem moiety — which is present in intact RBCs (haematuria), free haemoglobin (haemoglobinuria), AND myoglobin (myoglobinuria). Therefore:

All Hb-positive dipstick results should be accompanied by urine microscopy to differentiate true haematuria from pigmenturia ^[2].

Dipstick Result	Microscopy Finding	Interpretation
Hb positive	RBCs present	True haematuria
Hb positive	No RBCs	Pigmenturia — haemoglobinuria (haemolysis) or myoglobinuria (rhabdomyolysis) ^[3]
Hb negative	No RBCs	Not haematuria — consider food/drug pigments if urine is discoloured

Definitions for confirmed haematuria ^[2]^[8]:

Gross haematuria: Red or brown urine visible to the naked eye; confirmed by centrifugation → red sediment with clear supernatant = haematuria; red supernatant → test with dipstick (positive = haemoglobinuria/myoglobinuria; negative = drug/food pigment) ^[8]
Microscopic haematuria: ≥3 RBC per HPF in 2 out of 3 properly collected midstream urine specimens processed by centrifugation ^[2]

False Positives on Dipstick

Dipstick can give false-positive results for blood in the presence of: menstrual contamination, post-ejaculation, myoglobinuria, haemoglobinuria, high-dose vitamin C (rarely causes false negatives via interference with peroxidase reaction), and concentrated/alkaline urine. Always confirm with microscopy ^[8]^[4].

Once true haematuria is confirmed, the single most important diagnostic step is urine microscopy to determine the origin of bleeding:

Finding	Glomerular	Non-Glomerular
RBC morphology	Dysmorphic RBCs — irregular cell membrane, budding. Acanthocytes (ring-shaped RBCs with vesicle-shaped protrusions) are diagnostic of GN ^[8]^[13]	Isomorphic RBCs — normal round biconcave discs
RBC casts	Present — RBCs conform to the tubular shape when trapped in Tamm-Horsfall protein secreted by tubular cells → diagnostic of GN ^[8]^[13]	Absent
Blood clots	Absent — urokinase + tPA in glomerular filtrate prevent clot formation ^[8]^[2]	May be present — whole blood shed in sufficient volume to support coagulation
Proteinuria	Usually significant (> 500 mg/day), often with concurrent nephrotic-range features	Minimal or absent
Urine colour	Smoky brown / cola-coloured (Hb degradation during transit) ^[4]^[9]	Bright red or pink (fresh blood)

High Yield: Acanthocytes (> 5% of urinary RBCs) are considered the most specific dysmorphic RBC type for glomerular bleeding ^[8]. RBC casts are diagnostic of glomerulonephritis ^[8]^[13].

Detailed Investigation Modalities

Now let's go through each investigation systematically — what it is, why we do it, what we find, and how to interpret the results.

1. Urinalysis (Bedside — The Most Important First Test)

This is always the starting point. It encompasses dipstick, biochemistry, microscopy, microbiology, and cytology.

Parameter Tested	Clinical Relevance
Blood (Hb)	Detects haem → must confirm with microscopy (true haematuria vs pigmenturia)
Protein	Concomitant proteinuria suggests glomerular origin
Nitrites	Produced by Gram-negative bacteria (e.g., E. coli) reducing urinary nitrates → suggests UTI
Leukocyte esterase	Enzyme released by WBCs → suggests pyuria/infection
Glucose	Glycosuria → DM (relevant because DM nephropathy causes proteinuria ± haematuria)
pH	Alkaline pH (> 7.0) → UTI with urease-producing organisms (Proteus) → struvite stones

This is where the magic happens. The centrifuged urine sediment tells you almost everything:

Finding	Significance	Mechanism
Dysmorphic RBCs	Glomerular origin	Mechanical + osmotic trauma as RBCs pass through damaged GBM and through tubules with varying osmolality
Acanthocytes	Diagnostic of glomerulonephritis ^[8]	Ring-shaped RBCs with vesicle-shaped protrusions — most specific type of dysmorphic RBC
RBC casts	Diagnostic of glomerulonephritis ^[8]^[13]	RBCs trapped in Tamm-Horsfall protein (uromodulin) secreted by thick ascending limb → conform to tubular shape
Isomorphic RBCs	Non-glomerular (urological) origin	Normal RBCs entering urine directly without traversing GBM
WBCs (pyuria > 5 WBC/HPF)	UTI, interstitial nephritis, renal TB	Inflammatory response → WBCs migrate into urine
WBC casts	Pyelonephritis, interstitial nephritis	WBCs trapped in Tamm-Horsfall protein in tubules
Granular casts ("muddy brown")	Acute tubular necrosis (ATN) ^[13]	Degenerating tubular cells + protein matrix
Epithelial casts	ATN	Sloughed tubular epithelial cells in Tamm-Horsfall matrix
Bacteria	UTI	Direct visualisation of organisms
Crystals	Urolithiasis (depending on type)	Supersaturation → crystal formation in urine

Test	Indication	Key Findings
Culture and sensitivity (C/ST)	All patients with haematuria — to exclude UTI	Significant bacteriuria (> 10⁵ CFU/mL in midstream specimen) + sensitivity pattern guides antibiotic choice
Early morning urine (EMU) × AFB ^[4]^[9]	Suspect renal TB — sterile pyuria, constitutional symptoms, TB contact	M. tuberculosis on AFB culture (Sens 10–90%, Spec ~100%) or TB-PCR (Sens 87–100%, Spec 93–98%) ^[14]

Sterile Pyuria: Always Think TB

If you see WBCs in the urine but standard cultures are negative ("sterile pyuria"), the differential includes: renal TB (send EMU × 3 for AFB culture + TB-PCR), partially treated UTI, interstitial nephritis, and appendicitis/diverticulitis adjacent to the ureter. In Hong Kong, always consider TB ^[4]^[14].

Test	Purpose	Key Findings and Interpretation
CBC	Anaemia from chronic blood loss or malignancy; leukocytosis in UTI/infection ^[4]^[9]	Normocytic normochromic anaemia (chronic disease, haemolysis); microcytic hypochromic (iron deficiency from chronic blood loss); ↑WCC (infection)
RFT (Cr, urea, eGFR)	Assess renal function; renal impairment suggests intrinsic renal disease ^[4]^[9]^[13]	↑Cr + ↓eGFR → renal cause. Urea >> creatinine disproportionately → pre-renal state
Clotting profile (PT, APTT)	Screen for coagulopathy; assess if on anticoagulants ^[8]	Prolonged PT/APTT → coagulopathy → but still investigate for underlying urological cause
ESR / CRP	Non-specific inflammatory markers	↑ in infection, autoimmune disease, malignancy
Serum albumin	Nephrotic syndrome if low	↓albumin → nephrotic-range proteinuria → glomerular cause
Blood glucose / HbA1c	DM (risk factor for UTI, diabetic nephropathy, papillary necrosis)
Serum calcium	Hypercalcaemia → hyperparathyroidism → stones; paraneoplastic (RCC)

Immunological/Serological Panel (When Glomerular Origin Suspected) [4][9][15]

This panel helps narrow the glomerular differential. The logic is based on the pathogenesis of each GN:

Test	What It Detects	Interpretation
Serum complement C3/C4 ^[15]	Complement consumption by immune complexes	↓C3/C4 → immune complex (IC)-mediated GN: PSGN, lupus nephritis, MPGN, cryoglobulinaemia, infective endocarditis. Normal C3/C4 → non-IC-mediated GN: IgA nephropathy, anti-GBM disease, ANCA-associated vasculitis, HSP, Alport, TBMD ^[15]
ANCA (c-ANCA, p-ANCA)	Anti-neutrophil cytoplasmic antibodies	c-ANCA (anti-PR3) → GPA; p-ANCA (anti-MPO) → MPA, EGPA
ANA, anti-dsDNA	Antinuclear antibodies	ANA + anti-dsDNA → SLE/lupus nephritis
Anti-GBM antibodies	Antibodies against type IV collagen α3 chain	Positive → anti-GBM disease (Goodpasture)
ASLO titre	Evidence of recent streptococcal infection	↑ASLO → PSGN (confirms recent strep, NOT diagnostic alone)
HBsAg, anti-HCV	Hepatitis B/C infection	HBV/HCV-associated MPGN or PAN
Cryoglobulins (cryocrit)	Cryoglobulinaemia	A/w HCV infection → IC-mediated GN
Blood cultures	Infective endocarditis	Persistent bacteraemia → IC deposition → GN
Serum IgA	IgA nephropathy	↑IgA in ~50% (non-specific but supportive)
SPE (serum protein electrophoresis)	Multiple myeloma	Monoclonal spike → light chain deposition, amyloid

The Complement Shortcut

The serum complement level is one of the most useful "shortcut" tests in glomerular haematuria. If C3/C4 is low, you know the GN is immune-complex mediated (complement being consumed). If C3/C4 is normal, the GN is pauci-immune (ANCA-vasculitis, anti-GBM) or IgA-related (IgA nephropathy activates complement via the alternative pathway, but levels are usually normal clinically) ^[15]. This single test cuts your differential in half.

Test	Method	Purpose
Spot urine albumin-to-creatinine ratio (UACR)	Single voided sample; albumin corrected for creatinine concentration	Quick screening for significant proteinuria; > 30 mg/mmol suggests glomerular pathology
24-hour urine protein	Collect all urine over 24 hours; measure total protein	Gold standard for quantifying proteinuria; > 150 mg/day abnormal; > 3.5 g/day = nephrotic range

Why this matters: Significant proteinuria (> 500 mg/day) alongside haematuria strongly suggests glomerular origin and is an indication for renal biopsy ^[4]^[15].

4. Imaging — Anatomical Assessment of the Urinary Tract

What it is: Bedside, non-invasive, no radiation, no contrast
Why we do it: First-line screening for renal masses, hydronephrosis, cortical thinning, large bladder lesions, prostate size
Advantages:
- Can readily detect renal masses, hydronephrosis, cortical thinning (chronic obstruction), some bladder lesions (if large), prostate size measurement ^[4]
- Safe in pregnancy, children, renal impairment
Disadvantages:
- Difficulty in defining ureteric lesions (only proximal and distal ends of ureter visualised due to bowel gas obscuring mid-ureter) ^[4]
- Operator-dependent; small tumours can be missed
Key findings:

Finding	Suggests
Hydronephrosis	Ureteric obstruction (stone, tumour, stricture)
Renal mass (solid, enhancing)	RCC
Multiple bilateral cysts	Polycystic kidney disease
Cortical thinning	Chronic obstruction, reflux nephropathy, CKD
Thickened bladder wall / mass	Bladder tumour
Increased post-void residual	Bladder outflow obstruction (BPH)
Small echogenic kidneys bilaterally	CKD (chronic irreversible damage)

What it is: CT without IV contrast; the standard investigation for suspected ureteric stones/renal colic
Why we do it: Stones are best visualised on NCCT (most urinary stones are radio-opaque on CT, including uric acid stones which are radiolucent on plain XR)
Advantages: Allows assessment of level, size, density, and degree of obstruction of calculi ^[4]
Disadvantages: Radiation exposure; does not assess soft tissue detail as well as contrast-enhanced CT; cannot detect small urothelial tumours
Key findings:

Finding	Suggests
High-density focus in ureter	Ureteric stone
Perinephric stranding	Acute obstruction
Hydronephrosis/hydroureter	Proximal obstruction

What it is: Multi-phase CT with IV contrast — this is the preferred initial and standard imaging modality in unexplained haematuria ^[8]. It has largely replaced IVU ^[4].
Phases:
- Non-contrast phase: Detect stones (which can be masked by contrast)
- Nephrographic phase (~90–100s): Detect renal parenchymal lesions (masses enhanced by contrast become conspicuous)
- Excretory/delayed phase (~10–15 min): Contrast excreted into collecting system → opacifies renal pelvis, ureters, bladder → detect urothelial lesions (filling defects)
Why it's the gold standard: Higher sensitivity and specificity than other imaging modalities for detection of renal mass, urinary tract calculi, pelvicalyceal and ureteric transitional cell carcinoma ^[8]
Disadvantages: Radiation (↑↑), contrast allergy risk, contrast nephropathy risk (especially in pre-existing renal impairment or diabetes) ^[4]
Key findings:

Finding	Suggests
Enhancing renal mass	RCC
Filling defect in renal pelvis/ureter	Upper tract urothelial carcinoma
Filling defect in bladder	Bladder tumour
Ureteric stricture with proximal dilatation	Stone, tumour, or TB
Thickened/enhancing bladder wall	Bladder CA or cystitis
Calcified renal papillae	Papillary necrosis

What it is: IV injection of non-ionic contrast → excreted by kidneys → opacifies urinary system on serial radiographs. "IVU" = "intra" (within) + "venous" (vein) + "urogram" (image of urinary tract)
Status: Gradually replaced by CT urogram (which provides more information in the same sitting) ^[4]
Common indications: Haematuria, loin pain ^[16]
Procedure sequence ^[16]:
- Preliminary KUB → may already show stones
- 0 min → nephrogram (kidneys highlighted)
- 5 min → calyces and renal pelvis opacified
- 10 min → ureters and bladder opacified
- Post-micturition film → assess for urinary retention
Key findings ^[4]:

Finding	Suggests
Distortion of renal outline/calyces ± calcification	RCC
No contrast uptake	Obstruction or non-functioning kidney
Filling defect with proximal dilatation	Stone or tumour
Filling defect in bladder	Bladder tumour
↑Residual bladder volume post-micturition	BPH or BOO
Horseshoe kidney configuration	Anatomical variant (risk factor for stones)

Contraindications ^[16]: Pregnancy (radiation), previous serious contrast reaction, diabetes with renal insufficiency (risk of contrast nephropathy)
Advantages: Economical; good for upper tract lesions
Disadvantages: Not sensitive for renal lesions < 3 cm; cannot provide coronal/sagittal imaging; cannot detect small bladder lesions ^[4]

What it is: Plain abdominal X-ray from superior aspect of kidneys to pubic symphysis
Status: Previously relied upon; now mainly an initial screening tool
Key findings ^[4]^[9]:

Finding	Suggests
Radio-opaque density along ureteric course	Urinary stone (~90% of urinary stones are radio-opaque on plain XR — calcium-containing and struvite; uric acid and cystine stones are radiolucent)
Loss of psoas shadow	Haematoma, trauma, retroperitoneal infection
Renal calcification	Nephrocalcinosis, renal TB (dystrophic calcification)

Trace the ureter: Kidney → tip of transverse process → sacroiliac joint → curve around ischial spine → bladder posteriorly ^[4]

What it is: "Cysto" = bladder, "scopy" = to look. A scope (flexible or rigid) inserted via the urethra to directly visualise the urethra, prostate, and entire bladder mucosa.
Types:
- Flexible cystoscopy (16 Fr): Performed under local anaesthetic in clinic; standard for diagnostic purposes ^[4]
- Rigid cystoscopy: Performed under general/spinal anaesthesia; allows washout of clots, TURBT, and more complex procedures ^[2]
Indications: Should be done in ALL patients with gross non-glomerular haematuria (even if a stone is found on KUB — because a concurrent malignancy could coexist) ^[4]^[9]
Possible findings ^[4]:

Finding	Significance
Papillary tumour with narrow stalk	Low-grade non-invasive bladder CA
Large, broad-based, irregular/ulcerated, sessile or nodular mass	High-grade invasive bladder CA
Patchy flat velvety lesions	Carcinoma in situ (CIS)
Ureteric jet indicating upper tract bleeding	Bleeding source is in kidney/ureter (localises side)
Normal bladder despite positive urine cytology	Suspect upper tract urothelial CA → proceed to upper tract imaging (CTU) or ureteroscopy ^[4]
Bladder stones, inflamed mucosa	Calculi, cystitis

Allows biopsy for histopathological diagnosis ^[4]^[8]

Why Cystoscopy Cannot Be Replaced

Even with excellent imaging and urine biomarkers, cystoscopy remains irreplaceable ^[4]. CT can miss flat CIS lesions that are only a few millimetres thick. Cystoscopy can directly visualise papillary lesions as small as 1 mm — too small for any imaging modality to detect ^[4]^[9]. It also allows simultaneous biopsy/resection. For bladder cancer diagnosis and surveillance, cystoscopy is the gold standard — full stop.

What it is: Percutaneous needle biopsy of renal cortex under ultrasound guidance
Why we do it: Definitive diagnosis of glomerular disease (light microscopy, immunofluorescence, electron microscopy)
Indications ^[8]^[4]:
- Glomerular haematuria with significant proteinuria (> 1 g/day)
- Rising serum creatinine not otherwise explained
- Active urinary sediment (dysmorphic RBCs, RBC casts) with progressive renal impairment
- Nephritic syndrome (most cases require biopsy ^[15])
- Suspected lupus nephritis with proteinuria > 500 mg/day ^[4]
- NOT usually done for isolated microscopic haematuria with normal renal function and minimal proteinuria (usually benign course)
Key immunofluorescence patterns — this is the most helpful diagnostic feature ^[15]:

Pattern	Diagnosis
Mesangial IgA deposition	IgA nephropathy / HSP
Granular IgG + C3 ("lumpy bumpy")	Immune complex GN (PSGN, lupus, MPGN)
Linear IgG along GBM	Anti-GBM disease (Goodpasture)
Pauci-immune (scant/absent Ig)	ANCA-associated vasculitis
Thin GBM (electron microscopy)	Thin basement membrane disease
Splitting/lamellation of GBM ("basket-weave")	Alport syndrome

Contraindications to percutaneous renal biopsy ^[8]:
- Bleeding diathesis (coagulopathy, anticoagulation)
- Severe hypertension (uncontrolled)
- Solitary functioning kidney
- Small kidneys indicative of chronic irreversible disease (biopsy won't change management)
- Hydronephrosis
- Renal or perirenal infection

Investigation	What It Is	When Used
Retrograde pyelogram	Contrast injected via catheterisation of lower ureter during cystoscopy → opacifies upper tract	Undiagnosed upper tract lesion when CT urogram equivocal or contraindicated
Ureteroscopy (URS)	Scope passed up the ureter to directly visualise upper tract urothelium	Suspect upper tract TCC with positive cytology but negative imaging; allows brush cytology (90% sensitivity) and biopsy — but invasive with risk of bleeding/perforation ^[4]
Photodynamic diagnosis (PDD)	Fluorescence cystoscopy using intravesical 5-ALA or hexaminolevulinate → tumour cells fluoresce pink/red under blue light	Enhanced detection of papillary tumours and flat CIS lesions missed by standard white-light cystoscopy ^[4]

Test	Indication	Interpretation
Pure tone audiometry	Suspected Alport syndrome	Bilateral sensorineural hearing loss (typically high-frequency)
Molecular genetic testing for COL4A3-5	Alport syndrome or TBMD ^[11]^[4]	Confirms mutations in type IV collagen genes
PSA	Males > 50 with LUTS + haematuria	Elevated in prostate CA (but also BPH, UTI, prostatitis — organ-specific but NOT tumour-specific) ^[2]
Urine-based biomarkers (e.g., FISH for chromosomal aneuploidy)	Adjunct for urothelial CA surveillance	↑Sensitivity for early recurrence, but rarely done in HK ^[4]

This is the modern, evidence-based approach specifically for microscopic haematuria detected on urinalysis. It replaces the old "investigate everyone the same way" approach with a nuanced risk-stratification system:

Risk Category	Criteria	Recommended Investigation
Low/Negligible-Risk	Women < 60, Men < 40; Never smoker or < 10 pack-years; 3–10 RBC/HPF on one UA; No additional risk factors for urothelial cancer	Repeat UA within 6 months
Intermediate-Risk	Women ≥ 60, Men 40–59; 10–30 pack-years; 11–25 RBC/HPF on one UA; One or more additional risk factors; Previously low-risk with no prior evaluation and 3–25 RBC/HPF on repeat UA	Cystoscopy and renal ultrasound. Clinicians may offer urine cytology or validated urine biomarkers (UBTMs) to facilitate decision regarding cystoscopy. Repeat UA within 12 months if cystoscopy is not performed
High-Risk	Men ≥ 60; > 30 pack-years; > 25 RBC/HPF on one UA; History of gross haematuria; One or more additional risk factors for urothelial cancer plus any high-risk feature	Cystoscopy and axial upper tract imaging

Important: Women and High-Risk Category

The AUA guideline explicitly states that women should not be categorized as high-risk based on age alone ^[1]. This is because the prevalence of bladder cancer in women is lower than in men of the same age. Women need additional risk factors (e.g., heavy smoking, chemical exposure, history of gross haematuria) to be classified as high-risk.

What counts as "additional risk factors for urothelial cancer"? ^[1]

Smoking history (quantified in pack-years)
Occupational exposure (rubber, dye, chemical, petroleum industries)
History of gross haematuria
Prior urological disease, pelvic radiation, chronic UTI, chronic indwelling catheter
Exposure to known bladder carcinogens (e.g., cyclophosphamide, aristolochic acid)

After urological investigation is complete, refer to nephrologist if:

Urological cause excluded but haematuria persists
Evidence of ↓GFR or chronic renal failure (eGFR < 30 mL/min)
Significant proteinuria
Young patient (< 40 years) with hypertension and isolated haematuria
Visible haematuria with intercurrent URTI (suspect IgA nephropathy)
If urological cancer is ruled out, treat as CKD — monitor RFT and urinalysis yearly ^[2]

High Yield Summary

Always confirm true haematuria: Dipstick → microscopy. No RBCs = pigmenturia (haemoglobinuria or myoglobinuria), not haematuria.
Glomerular vs non-glomerular is determined by urine microscopy: dysmorphic RBCs/acanthocytes/RBC casts = glomerular. Isomorphic RBCs ± clots = non-glomerular.
Key investigation for non-glomerular/urological haematuria: Cystoscopy (gold standard for lower tract — cannot be replaced by imaging) + upper tract imaging (CT urogram preferred).
Key investigation for glomerular haematuria: Complement C3/C4 (to branch IC-mediated vs non-IC GN) → targeted serology → renal biopsy when indicated.
CT urogram is the preferred standard imaging for unexplained haematuria (higher Sens/Spec than IVU/USG for renal masses, stones, and urothelial CA). IVU is largely replaced.
Cystoscopy must be done in ALL gross non-glomerular haematuria — even if a stone is found on imaging (concurrent malignancy may coexist).
Urine cytology: Low sensitivity (~50%) but very high specificity (> 98%); best for high-grade TCC and CIS. Send fresh, 2nd void, on 3 consecutive days.
AUA risk stratification for microscopic haematuria: Low-risk → repeat UA; Intermediate → cystoscopy + USG; High-risk → cystoscopy + axial upper tract imaging.
Renal biopsy indications: Glomerular haematuria with significant proteinuria (> 1 g/day), rising creatinine, or nephritic syndrome. Immunofluorescence pattern is the most diagnostic feature.
Complement C3/C4: Low = IC-mediated GN (PSGN, lupus, MPGN). Normal = non-IC (IgAN, ANCA vasculitis, anti-GBM, HSP).

Active Recall - Diagnosis and Investigations of Haematuria

References

^[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p6, p13) ^[2] Senior notes: maxim.md (Section 2.1 Common urological complaints - Haematuria) ^[3] Senior notes: Ryan Ho Neurology.pdf (p196 - Rhabdomyolysis) ^[4] Senior notes: Ryan Ho Urogenital.pdf (p133–135, p153) ^[8] Senior notes: felixlai.md (Haematuria section - Diagnosis, p767) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p343–345) ^[11] Senior notes: Ryan Ho Fundamentals.pdf (p358 - Isolated Glomerular Haematuria) ^[13] Senior notes: Ryan Ho Critical Care.pdf (p27 - AKI workup, urinalysis) ^[14] Senior notes: Ryan Ho Respiratory.pdf (p78 - Genitourinary TB) ^[15] Senior notes: Ryan Ho Urogenital.pdf (p55, p57, p63 - Glomerular haematuria evaluation) ^[16] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p17 - IVU)

Management of Haematuria

Part 1: Acute Management of Severe / Life-Threatening Haematuria

Before any aetiological treatment, if the patient presents with massive haematuria (profuse bleeding, haemodynamic instability, or clot retention causing acute urinary retention), the priority is resuscitation and stabilisation.

When haematuria produces clots that obstruct the bladder outlet, the patient develops acute retention of urine (AROU) — they are in pain, unable to void, and the bladder is distended with clot.

Management ^[8]^[17]:

3-way Foley catheter insertion (large bore, typically 22–24 Fr):
- 3-way catheter has three lumina: one for balloon inflation, one for drainage, and one for irrigation
- Indicated in patients with haematuria with clot formation which can lead to AROU or in patients requiring pharmacological therapy ^[8]
- The large bore is needed because clots can block smaller catheters
Manual bladder washout (first step):
- Using a 50 mL bladder syringe, flush normal saline through the catheter to manually evacuate clots
- Repeat until irrigant runs clear
Continuous bladder irrigation (CBI):
- Saline is infused through the irrigation port and drained through the catheter ^[8]
- Purpose: Dilute blood in the bladder to prevent further clot formation, maintain catheter patency
- Adjust irrigation rate to keep effluent light pink/clear
If catheterisation fails or clots cannot be cleared:
- Cystoscopy under GA → clot evacuation using Ellik evacuator + direct visualisation to identify and cauterise bleeding source (e.g., diathermy of a bleeding bladder tumour)

Catheterisation contraindications and alternatives ^[8]^[4]:

Route	Contraindications	Alternative
Urethral catheterisation	Urethral injury (blood at meatus, high-riding prostate, pelvic fracture); recent radical prostatectomy; urethral reconstruction; artificial sphincter ^[8]	Suprapubic catheterisation
Suprapubic catheterisation	Non-distended bladder; uncorrected bleeding tendency; known/suspected urothelial cancer ^[8]^[4]	Urgent cystoscopy for clot evacuation

Scenario	Key Action
Clot retention	3-way catheter, manual washout, CBI, ± cystoscopy for clot evacuation
Haematuria + haemodynamic instability	Aggressive resuscitation, urgent imaging (CT angiogram), consider embolisation or surgical exploration
Haematuria post-trauma (renal/urethral)	If urethral injury suspected (blood at meatus) → do NOT catheterise → suprapubic catheter; CT with contrast for renal trauma grading
Massive haematuria from known RCC	Selective renal artery embolisation (interventional radiology) as temporising measure before definitive surgery

Part 2: Management by Underlying Cause — Urological Pathway

The haematuria resolves when the infection is treated. Detailed UTI management is covered elsewhere, but in summary:

Type	Treatment	Rationale
Uncomplicated cystitis (female)	Empirical oral antibiotics: nitrofurantoin 100 mg BD × 5 days (1st line), or fosfomycin 3 g single dose, or trimethoprim 200 mg BD × 3 days	Short courses sufficient because infection is superficial and mucosal
Uncomplicated cystitis (male)	Generally need longer (7 days) treatment for male cystitis ^[4] — e.g., ciprofloxacin 500 mg BD × 7 days or trimethoprim × 7 days	Males have longer urethra → infection more likely involves prostate → needs longer penetration
Pyelonephritis	Oral ciprofloxacin × 7–14 days or IV ceftriaxone if septic, then step-down orally	Need systemic drug levels to penetrate renal parenchyma
Acute bacterial prostatitis	Quinolone (excellent prostatic penetration) for 2–6 weeks ^[4]	Prostate has blood-prostate barrier → few antibiotics penetrate well; fluoroquinolones achieve high prostatic concentrations

Repeat urinalysis after treatment to confirm haematuria has resolved
If haematuria persists after UTI treatment, investigate for underlying malignancy (the UTI may have been incidental)

B. Urolithiasis — Stones (~10%)

Management depends on stone size, location, and complications. The principle is: small stones pass spontaneously, larger stones need intervention.

Stone Size/Location	Treatment Modality	Rationale
≤ 4 mm ureteric	Conservative + medical expulsion therapy (MET) — tamsulosin 0.4 mg QD × 4 weeks (α1-blocker relaxes distal ureter; 1.45× more likely to pass) ^[4]	95% pass spontaneously
5–10 mm ureteric	MET first trial ± definitive intervention	Progressive ↓ chance of spontaneous passage
≥ 10 mm ureteric	Definitive stone removal indicated ^[4]	Unlikely to pass spontaneously
Renal < 10 mm	ESWL or RIRS > PCNL	Minimally invasive approaches preferred for small stones
Renal 10–20 mm	ESWL or RIRS or PCNL	Choice depends on stone composition and anatomy
Renal > 20 mm	PCNL > RIRS or ESWL ^[4]	Large stone burden needs direct access for removal

Modality	How It Works	Indications	Contraindications	Key Complications
ESWL (Extracorporeal Shock Wave Lithotripsy)	High-energy shock waves produced by electrical discharge directed at stone under US/XR guidance → stone fragments pass naturally ^[5]	Renal and upper ureteric stones visible on imaging; stone < 20 mm; HU < 1000 on CT	Pregnancy, active UTI/urosepsis, uncontrolled bleeding diathesis, distal obstruction (stricture) ^[5]^[4]	Incomplete fragmentation, Steinstrasse ("stone street" — column of fragments obstructing ureter), perinephric/subcapsular haematoma, urosepsis ^[5]
URSL (Ureteroscopic Lithotripsy / RIRS)	Rigid or flexible ureteroscope passed through urethra → laser lithotripsy (Holmium laser) fragments stone	Ureteric stones (esp. mid and distal); renal stones up to 20 mm via flexible scope (RIRS)	Active UTI (relative); anatomical factors preventing scope passage	Ureteric perforation, stricture, bleeding, infection
PCNL (Percutaneous Nephrolithotomy)	Puncture through skin into renal collecting system → nephroscope inserted → direct stone visualisation and fragmentation/extraction ^[16]	Large renal stones (> 20 mm), staghorn calculi, stones in calyceal diverticulum, failed ESWL	Bleeding tendency, distorted surface anatomy, obesity (relative) ^[4]	Haemorrhage, sepsis, pneumothorax, urinoma, injury to adjacent organs

ESWL Limitations

ESWL is minimally invasive and doesn't need anaesthesia, but it has important limitations ^[5]^[4]: 1) Skin-to-stone distance matters → poorer efficacy in obese patients. 2) NOT ideal for hard stones (cystine, calcium oxalate monohydrate, brushite — predicted by > 1000 HU on CT). 3) NOT ideal for lower pole stones (gravity retains fragments in dependent calyx). 4) NOT ideal for stones in calyceal diverticulum (narrow infundibulum traps fragments). If a patient has had multiple failed ESWL sessions, consider a calyceal diverticulum.

Definitive treatment should be initiated ONLY when an acute episode of urosepsis (if present) has resolved ^[5] — operating on an infected obstructing system risks overwhelming sepsis.

C. Urological Malignancy — The Most Worrying Cause

This is the most critical branch. Management depends on the specific tumour and its stage:

Stage	Management	Rationale
Non-muscle invasive (Ta, T1, Tis)	TURBT (Transurethral Resection of Bladder Tumour) ± intravesical BCG ^[4]^[9]	TURBT provides diagnosis, staging, AND treatment for superficial tumours. BCG (Bacillus Calmette-Guérin — attenuated M. bovis) provokes local immune response against residual tumour cells, reducing recurrence
Muscle invasive (≥ T2)	Radical cystectomy (removal of entire bladder + lymph node dissection) ± neoadjuvant cisplatin-based chemotherapy ^[4]^[9]	Tumour has invaded detrusor muscle → local resection insufficient → need radical surgery
Metastatic	Systemic chemotherapy (cisplatin-based regimens, e.g., GC or MVAC) ± immunotherapy (checkpoint inhibitors: atezolizumab, pembrolizumab)	Palliation and life extension

Surveillance: Extremely important due to field cancerization and high recurrence rate (50–70% for superficial bladder CA). Protocol: cystoscopy + cytology at 3 months, then at increasing intervals (3-monthly for 2 years → 6-monthly for 3 years → annually).
Despite advancing imaging/urine biomarkers, non-invasive tests alone CAN NEVER replace cystoscopy/TURBT for diagnosis of CA bladder ^[4]

Stage	Management
Localised (T1a ≤ 4 cm)	Nephron-sparing (partial) nephrectomy — preferred to preserve renal function
Localised (T1b–T2)	Radical nephrectomy (removal of kidney + Gerota's fascia ± adrenal ± lymph nodes)
Locally advanced (T3–T4)	Radical nephrectomy ± IVC thrombectomy (if tumour thrombus extends into renal vein/IVC)
Metastatic	Systemic therapy: targeted therapy (sunitinib, pazopanib — TKIs) or immunotherapy (nivolumab + ipilimumab — checkpoint inhibitors); cytoreductive nephrectomy in selected cases

RCC is chemo-resistant and radio-resistant — this is why targeted therapy and immunotherapy are mainstays for metastatic disease.

Management
Nephroureterectomy (removal of kidney + entire ureter + bladder cuff) — standard for high-grade/invasive UTUC due to field cancerization risk ^[4]^[9]
Kidney-sparing approaches (ureteroscopic ablation) only for low-grade, small, unifocal tumours or solitary kidney

Management is guided by risk stratification (Gleason score, PSA, clinical stage):

Risk Group	Options
Low risk	Active surveillance (most important — avoids overtreatment)
Intermediate risk	Radical prostatectomy OR radiotherapy (external beam ± brachytherapy)
High risk / locally advanced	Radical prostatectomy + extended lymph node dissection, OR radiotherapy + androgen deprivation therapy (ADT)
Metastatic	ADT (LHRH agonists/antagonists, anti-androgens) ± chemotherapy (docetaxel) ± novel hormonal agents (abiraterone, enzalutamide)

BPH rarely causes significant haematuria, but when it does (due to increased prostatic vascularity → fragile vessels), the haematuria usually resolves with treatment of the BPH itself:

Approach	Treatment	Mechanism
Watchful waiting	Lifestyle measures (avoid caffeine/alcohol, timed voiding, fluid management)	Mild symptoms, not bothersome
Medical therapy	Alpha-blockers (tamsulosin, alfuzosin): relax prostatic smooth muscle → improve flow. 5α-reductase inhibitors (finasteride, dutasteride): shrink prostate over months by blocking testosterone → DHT conversion → also reduces prostatic vascularity and risk of haematuria	Target both dynamic (smooth muscle tone) and static (gland volume) components of obstruction
Surgical therapy	TURP (gold standard): transurethral resection of prostate tissue ^[4]. Alternatives: laser enucleation (HoLEP), photoselective vaporisation (PVP — especially useful in patients with bleeding tendency ^[4])	Indications: refractory AROU, bladder stones, recurrent UTI, obstructive uropathy, bothersome symptoms despite medical treatment ^[4]

Finasteride and Haematuria from BPH

5α-reductase inhibitors (finasteride) can specifically reduce haematuria from BPH by shrinking the gland and reducing its vascularity. This is a recognized off-label use when recurrent haematuria is the presenting problem in BPH. The effect takes weeks to months.

Cause	Management
Radiation cystitis	Conservative (hydration, bladder irrigation); hyperbaric oxygen therapy (promotes neoangiogenesis in ischaemic tissue); intravesical agents (alum, formalin as last resort); embolisation if refractory
Haemorrhagic cystitis (cyclophosphamide-related)	Prevention: MESNA (2-mercaptoethane sulfonate sodium — binds acrolein, the toxic metabolite, in urine) + vigorous hydration during chemotherapy. Treatment: bladder irrigation, hyperbaric oxygen, intravesical agents
Trauma	Depends on grade: renal contusion → conservative; Grade III–V lacerations → surgical exploration ± repair; urethral injury → suprapubic catheter, delayed repair
Exercise-induced haematuria	Reassurance; resolves with rest; confirm by exclusion of other causes ^[4]^[9]

Part 3: Management by Underlying Cause — Nephrology Pathway

Regardless of the specific GN subtype, the following supportive measures apply:

Measure	Details	Mechanism/Rationale
ACEI/ARB (anti-proteinuric therapy)	Indicated in ALL glomerulonephropathy ^[9]. Goal: proteinuria < 1 g/day or UPCR < 0.5–1 g/g	↓Intraglomerular pressure → ↓proteinuria, which is associated with ↓rate of GFR decline. Efferent arteriole dilation reduces filtration pressure across damaged GBM → less protein leak ^[9]
Salt restriction	Dietary sodium ~2 g/day	Reduces fluid retention and oedema; synergistic with diuretics
Diuretics	Loop diuretics (furosemide) preferred; add thiazide/K+-sparing if inadequate	Treat oedema; monitor for hypovolaemia and hypokalaemia ^[9]
Statins	If hyperlipidaemia persists after treatment of underlying disease and ACEI/ARB	Nephrotic syndrome → hyperlipidaemia (liver upregulates lipoprotein synthesis due to hypoalbuminaemia) ^[9]
Anti-thrombotic therapy	Usually only if thromboembolic events occur; prophylactic use NOT routine unless high risk (e.g., membranous nephropathy with very low albumin) ^[9]	Nephrotic syndrome → loss of antithrombin III, protein C/S in urine → hypercoagulable state
Pneumococcal vaccination	Indicated for ALL patients with nephrotic syndrome ^[9]	Loss of immunoglobulins in urine → ↑ susceptibility to encapsulated organisms (especially pneumococcus)

Note: Protein restriction is NOT recommended despite heavy urinary protein loss — patients should have normal protein intake because ↑albumin excretion is associated with poorer outcomes ^[9].

Diagnosis	Treatment	Key Points
IgA nephropathy	Supportive Mx (ACEI/ARB) for most; immunosuppression (corticosteroids) only if high risk of progression (proteinuria > 1 g/day despite 3–6 months of optimal ACEI/ARB, declining GFR); SGLT2 inhibitors (dapagliflozin) for CKD protection	Most patients have indolent course; ~30% reach ESRD over 30 years
Lupus nephritis (Class III/IV)	Non-immunosuppressive therapy in ALL + immunosuppressive therapy in active disease ^[4]: Induction: IV pulse methylprednisolone → oral prednisolone + mycophenolate mofetil (MMF) or IV cyclophosphamide. Maintenance: MMF or azathioprine + low-dose prednisolone	Treatment guided by histologic subtype on biopsy — clinical presentation may not reflect severity ^[4]
ANCA-associated vasculitis	Induction: IV pulse methylprednisolone + rituximab (preferred) or cyclophosphamide. Maintenance: rituximab or azathioprine. Plasma exchange (PLEX) for severe renal/pulmonary involvement	Rapidly progressive → early aggressive treatment essential
Anti-GBM disease (Goodpasture)	Plasma exchange (to remove circulating anti-GBM antibodies) + cyclophosphamide + corticosteroids	Medical emergency; prognosis depends on degree of renal damage at presentation
Post-streptococcal GN	Supportive only (usually self-limiting in children); antibiotics for residual streptococcal infection; manage HTN, fluid overload	Most recover completely; immunosuppression NOT indicated
Membranous nephropathy	Supportive for 6 months (spontaneous remission in 30%); immunosuppression (rituximab or cyclophosphamide + corticosteroids) if nephrotic + poor prognostic factors ^[4]	Anti-PLA2R antibodies guide monitoring of disease activity
Alport syndrome	ACEI/ARB to delay progression; no specific immunosuppression (genetic, not inflammatory); ultimately may need renal transplant	Genetic counselling important
Thin basement membrane disease	Reassurance; no treatment needed; monitor annually	Benign prognosis

Finding	Refer To	Why
Gross non-glomerular haematuria	Urology	Cystoscopy + upper tract imaging to exclude malignancy
Microscopic haematuria, intermediate/high-risk	Urology	Risk-stratified workup per AUA guidelines
Dysmorphic RBCs / RBC casts / significant proteinuria	Nephrology	Glomerular origin → needs serological workup ± biopsy
Persistent haematuria after urological workup is negative	Nephrology	May have occult glomerular disease
Haematuria + declining GFR	Nephrology (urgent)	Rapidly progressive GN needs prompt diagnosis and treatment
Haematuria + haemoptysis	Nephrology + Respiratory + ICU	Pulmonary-renal syndrome — medical emergency

High Yield Summary

Haematuria is managed by treating the underlying cause — medical (nephrology) vs urological (urology) pathway.
Acute massive haematuria: ABC → 3-way catheter with CBI → manual clot washout → cystoscopy under GA if refractory. Reverse anticoagulation if applicable.
UTI (most common cause): Antibiotics tailored to organism and site; repeat urinalysis after treatment to confirm resolution.
Stones: Acute → NSAIDs (1st line) + alpha-blockers; ≤ 4 mm passes spontaneously (95%); definitive Mx by ESWL (small/moderate), URSL (ureteric), PCNL (large renal). Never operate during active urosepsis — decompress first.
Bladder cancer: TURBT ± intravesical BCG for non-muscle invasive; radical cystectomy for muscle invasive. Surveillance cystoscopy mandatory due to high recurrence.
RCC: Partial or radical nephrectomy; chemo/radio-resistant → targeted therapy or immunotherapy for metastatic disease.
Upper tract UCC: Nephroureterectomy (standard) due to field cancerization.
Glomerulonephritis: ACEI/ARB for ALL (anti-proteinuric); immunosuppression guided by biopsy result; complement and serology to narrow differential.
Haemophilia haematuria: Forced diuresis; AVOID antifibrinolytics (risk of obstructive clots in urinary tract); AVOID NSAIDs.
No cause found: Surveillance with repeat UA, cytology, and cystoscopy at intervals guided by risk stratification.
Refer nephrology if: Urological cause excluded, ↓GFR, significant proteinuria, young + HTN + haematuria, visible haematuria with URTI.

Active Recall - Management of Haematuria

References

^[1] Lecture slides: GC 183. Common urological malignancies and their presentations - Nov 7.pdf (p6, p13) ^[2] Senior notes: maxim.md (Section 2.1 Common urological complaints - Haematuria) ^[4] Senior notes: Ryan Ho Urogenital.pdf (p88, p128, p135, p140–141, p167, p176, p182) ^[5] Senior notes: felixlai.md (Urinary stones - ESWL section; Urological diseases section) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p124, p127 - Haemophilia treatment) ^[8] Senior notes: felixlai.md (Haematuria section; Catheterisation section) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p345, p352, p368) ^[13] Senior notes: Ryan Ho Critical Care.pdf (p26 - AKI management) ^[16] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p17, p83 - PCN) ^[17] Senior notes: Ryan Ho Haemtology.pdf (p19 - IDA and transfusion) ^[18] Senior notes: Ryan Ho Neurology.pdf (p84 - Anticoagulation reversal)

Complications of Haematuria

Haematuria itself is a symptom, but it can lead to its own set of complications — both directly (from the bleeding) and indirectly (from the underlying cause and its treatment). This section covers complications arising from:

The haematuria itself (direct consequences of blood in the urinary tract)
The underlying cause (complications of the disease producing the haematuria)
Investigations and treatments (iatrogenic complications)

Think of it this way: the blood entering the urinary tract can cause problems mechanically (clots → obstruction), haematologically (blood loss → anaemia), and psychologically (anxiety). Meanwhile, the underlying disease can cause its own devastating complications (malignancy → metastasis, stones → urosepsis, GN → renal failure).

1. Direct Complications of Haematuria

These result from the presence of blood in the urinary tract itself, regardless of cause.

2. Complications of the Underlying Cause

The haematuria is a signal of an underlying disease, and each disease carries its own complications. Here are the major ones organised by cause:

Complication	Mechanism	Key Features
Urosepsis	Infected urine proximal to an obstructing stone → bacterial stasis → bacteraemia → sepsis	Fever, rigors, tachycardia, hypotension. This is a life-threatening emergency — obstructed infected kidney must be decompressed urgently (PCN or JJ stent) before definitive stone treatment ^[5]
Pyelonephritis and pyonephrosis	Urinary stasis → ascending infection → pyelonephritis; if pus accumulates in an obstructed collecting system = pyonephrosis	High fever, loin pain, sepsis. Pyonephrosis = pus under pressure = surgical emergency
Hydroureter and hydronephrosis	Ureteric obstruction → proximal dilatation of ureter and renal pelvis	May be asymptomatic or cause constant dull loin ache; detected on USG/CT
Obstructive nephropathy	Prolonged obstruction → tubular damage → interstitial fibrosis → irreversible parenchymal loss	Progressive renal impairment; more severe in bilateral obstruction or solitary kidney
Acute kidney injury (AKI)	Complete bilateral obstruction (or unilateral in single kidney) → zero urine output → uraemia	Oliguria/anuria, rising creatinine, hyperkalaemia, metabolic acidosis ^[5]^[13]
Steinstrasse ("stone street")	Post-ESWL complication — column of stone fragments obstructs the ureter ^[5]	Loin pain + obstruction after lithotripsy; may need JJ stent or ureteroscopy

Complication	Mechanism
Hydronephrosis and hydroureter	Invasive bladder tumours can cause distal ureteral obstruction and secondary hydronephrosis ^[5] — tumour at the ureteric orifice compresses or invades the intramural ureter
Fistula formation	Local extension to adjacent organs ^[4]: Vesicocolic fistula → pneumaturia (air in urine from bowel gas passing into bladder); Vesicovaginal fistula → continuous urinary incontinence
Metastasis	Common sites: liver, lung, bone ^[5] — spread via lymphatic and haematogenous routes. Bone metastases cause pain; liver metastases cause deranged LFT; brain metastases cause neurological deficits
Recurrence	Careful follow-up is required for all patients with bladder cancer ^[5] — recurrence rate is 50–70% for superficial disease due to field cancerization. Secondary primary tumours can develop in urothelium anywhere along the urinary tract including the renal pelvis, ureter, urethra and bladder ^[5]
Bladder outlet obstruction	Large tumour at bladder neck or trigone → obstructive LUTS, retention

Complication	Mechanism
Local invasion	RCC classically extends into the renal vein → IVC → even into the right atrium as a tumour thrombus. This can cause: left-sided varicocele (renal vein obstruction), Budd-Chiari syndrome (hepatic vein obstruction), lower limb oedema (IVC obstruction)
Metastasis	Lung (most common), bone, liver, brain, contralateral kidney. "Cannonball" pulmonary metastases on CXR are classic
Paraneoplastic syndromes	Polycythaemia (erythropoietin production), hypercalcaemia (PTHrP), hypertension (renin secretion), Stauffer syndrome (non-metastatic hepatic dysfunction), amyloidosis

Complication	Mechanism
Progressive chronic kidney disease (CKD)	Chronic GN is an important cause of CKD ^[9] — ongoing glomerular inflammation → sclerosis → nephron loss → progressive renal insufficiency. Features: proteinuria, haematuria allowed to progress untreated; often associated with long-standing secondary hypertension ^[9]
Nephrotic syndrome	Severe GBM damage → massive proteinuria (> 3.5 g/day) → hypoalbuminaemia → oedema, hyperlipidaemia, hypercoagulability, susceptibility to infection
Rapidly progressive GN (RPGN) / Crescentic GN	Aggressive glomerular inflammation → crescent formation (proliferation of Bowman's capsule epithelium compressing glomerular tuft) → rapid loss of renal function over days-weeks. Medical emergency — without treatment → ESRD
Pulmonary-renal syndrome	Anti-GBM disease or ANCA vasculitis → concurrent haemoptysis + haematuria → life-threatening pulmonary haemorrhage + renal failure
Hypertension	Sodium and water retention (volume expansion) + RAAS activation from ↓renal perfusion → secondary hypertension → further renal damage (vicious cycle)
End-stage renal disease (ESRD)	Terminal consequence of progressive GN; requires renal replacement therapy (dialysis or transplantation). For IgA nephropathy, ~30% reach ESRD within 30 years ^[4]

Complication	Mechanism
Pyelonephritis	Ascending infection from lower tract → renal parenchymal involvement → fever, loin pain, sepsis
Urosepsis	Bacteraemia from urinary tract → systemic inflammatory response → septic shock
Renal/perinephric abscess	Untreated or inadequately treated pyelonephritis → localised collection of pus
Emphysematous pyelonephritis	Gas-forming organisms (in DM patients) → necrotising infection of renal parenchyma → high mortality

Complication	Mechanism
Acute urinary retention (AROU)	Enlarged prostate obstructs urethra; may be precipitated by haematuria-related clot retention ^[9]
Chronic retention + overflow incontinence	Incomplete emptying → progressive bladder distension → overflow
Recurrent UTI	Residual urine provides a medium for bacterial growth
Bladder stones	Urinary stasis → stone crystallisation
Obstructive nephropathy	Chronic BOO → bilateral hydroureter → renal damage

3. Iatrogenic Complications (From Investigations and Treatment)

Complication	Mechanism	Prevention/Management
Haematuria (from the catheterisation itself)	Trauma to urethral or bladder mucosa during insertion	Adequate lubrication (lignocaine gel); gentle technique
Urinary tract infections	Foreign body in urethra → biofilm formation → ascending infection	Aseptic insertion technique; remove catheter as soon as possible; avoid unnecessary catheterisation
Urethral stricture	Chronic urethral inflammation from indwelling catheter → fibrosis	Minimise duration of catheterisation; use appropriate catheter size
Bladder spasm	Catheter balloon irritating trigone	Anticholinergics; check catheter position
Post-obstructive diuresis	After decompression of chronically obstructed bladder → tubular damage → ↓concentrating ability → rapid fluid and solute loss ^[9] — represents physiological response to excrete excess retained fluid	Monitor urine output Q2h; replace 50% of hourly output with oral fluids or IV normal saline; monitor electrolytes (risk of hypoNa, hypoK, hypovolaemia) ^[9]
Haemorrhage ex-vacuo (transient haematuria)	Bladder mucosal disruption with sudden emptying of greatly distended bladder ^[9]	Usually self-limiting and rarely significant ^[9]. Gradual decompression (clamping catheter intermittently) is traditionally taught but evidence is limited
Transient hypotension	Vagovagal response or relief of pelvic venous congestion upon bladder decompression ^[9]	Monitor vitals; keep patient supine; IV fluids if symptomatic

Post-Obstructive Diuresis: Don't Ignore It

Post-obstructive diuresis occurs after decompression of a chronically obstructed bladder (e.g., BPH with chronic retention). The damaged tubules cannot concentrate urine → the patient produces litres of dilute urine per hour. If unmonitored, this can lead to severe dehydration, hyponatraemia, hypokalaemia, and haemodynamic collapse. Chart urine output every 2 hours and replace 50% of output with oral fluids (preferred) or IV normal saline ^[9].

Complication	Mechanism
Haematuria	Mucosal trauma from scope insertion
UTI	Introduction of bacteria during instrumentation
Urethral injury / false passage	Forceful passage through a stricture or enlarged prostate
Bladder perforation	Rare; more common during TURBT than diagnostic cystoscopy; can be extraperitoneal (managed conservatively with catheter drainage) or intraperitoneal (requires surgical repair)

Procedure	Complications
ESWL	Incomplete fragmentation; urosepsis; perinephric or subcapsular haematoma; Steinstrasse ("stone street" — column of fragments obstructing ureter) ^[5]
URSL	Ureteric perforation, ureteric stricture, bleeding, infection, false passage
PCNL	Haemorrhage (may need embolisation), sepsis, pneumothorax (if upper pole access), urinoma, injury to adjacent organs (colon, pleura) ^[16]

Complication	Mechanism
TUR syndrome	Absorption of hypotonic irrigant (glycine) during monopolar TURP → dilutional hyponatraemia → confusion, seizures, visual disturbances, haemodynamic instability. Avoided by using bipolar TURP (uses normal saline) ^[4]
Retrograde ejaculation (70–80%)	Resection of bladder neck → semen enters bladder during ejaculation instead of exiting via urethra ^[4]
Bladder perforation	Resection too deep, especially at thin bladder dome
Bleeding	Resection bed; may require re-intervention
Urethral stricture	From urethral instrumentation
Incontinence	Urge (early, common) / stress (late, rare — 1%) ^[4]

Complication	Mechanism
Perinephric haematoma	Needle puncture through renal parenchyma → bleeding from intarenal vessels
Gross haematuria	Needle tract communicates with collecting system → blood in urine
AV fistula	Needle punctures adjacent artery and vein simultaneously → abnormal communication
Infection	Introduction of organisms via needle tract
Loss of kidney (extremely rare)	Massive uncontrollable haemorrhage → nephrectomy

Patients with chronic haematuria (e.g., from irradiation cystitis, inoperable bladder cancer) may require prolonged catheterisation, which carries its own set of complications ^[9]:

Complication	Mechanism
Catheter-associated UTI (CAUTI)	Biofilm formation on catheter surface → bacterial colonisation → ascending infection. Risk increases ~3–10% per day of catheterisation
Catheter encrustation and blockage	Calcium and phosphate deposits on catheter (especially with Proteus UTI → urease → alkaline urine → struvite crystal formation)
Urethral erosion	Chronic pressure from catheter on urethral mucosa → tissue necrosis
Squamous cell carcinoma of bladder	Chronic irritation from indwelling foreign body → metaplasia → dysplasia → SCC. This is a long-term risk with > 10 years of catheterisation
Bladder stones	Foreign body nidus + urinary stasis → stone formation around catheter

Category	Key Complications
Direct from haematuria	Clot retention → AROU; anaemia (iron deficiency); haemodynamic instability; obstructive uropathy (ureteric clots); anxiety
From stones	Urosepsis, pyelonephritis, pyonephrosis, hydronephrosis, obstructive nephropathy, AKI
From bladder cancer	Hydronephrosis (ureteral obstruction by tumour), fistulae (vesicocolic → pneumaturia; vesicovaginal → incontinence), metastasis, recurrence
From GN	Progressive CKD, nephrotic syndrome, RPGN, pulmonary-renal syndrome, hypertension, ESRD
From catheterisation	UTI, urethral stricture, haematuria, post-obstructive diuresis, haemorrhage ex-vacuo, hypotension
From procedures	ESWL: steinstrasse, haematoma; TURP: TUR syndrome, retrograde ejaculation; PCNL: haemorrhage, pneumothorax; Biopsy: haematoma, AV fistula

High Yield Summary

Clot retention is the most important direct complication of haematuria — blood clots obstruct the bladder outlet causing AROU. Managed with large-bore 3-way catheter, manual washout, and CBI.
Anaemia — chronic haematuria causes iron-deficiency anaemia. Always check CBC and iron studies.
Obstructive uropathy — clots or the underlying cause (stone, tumour) can obstruct ureters → hydronephrosis → AKI. Bilateral obstruction or single kidney obstruction = medical emergency.
Urosepsis — the most feared complication of an obstructing infected stone. Obstructed infected kidney = urgent decompression (PCN or JJ stent).
Bladder cancer complications: Hydronephrosis from ureteral obstruction by invasive tumour; fistulae (vesicocolic → pneumaturia; vesicovaginal → incontinence); metastasis (liver, lung, bone); high recurrence rate requiring lifelong surveillance.
GN complications: Progressive CKD → ESRD; RPGN is a medical emergency; pulmonary-renal syndrome (haemoptysis + haematuria).
Post-obstructive diuresis — after decompression of chronically obstructed bladder, tubular damage causes massive diuresis. Monitor UO Q2h, replace 50% of output, watch for hyponatraemia and hypokalaemia.
Haemorrhage ex-vacuo — transient haematuria after sudden emptying of an overdistended bladder; usually self-limiting.
TUR syndrome — absorption of hypotonic irrigant during monopolar TURP → dilutional hyponatraemia. Avoided by bipolar TURP (uses normal saline).
Long-term catheterisation risks: CAUTI, encrustation, urethral erosion, bladder stones, and SCC of bladder (chronic irritation).

Active Recall - Complications of Haematuria

References

^[4] Senior notes: Ryan Ho Urogenital.pdf (p132, p136, p153, p176) ^[5] Senior notes: felixlai.md (Complications of urinary stones section; Complications of urothelial cancer section; ESWL complications) ^[7] Senior notes: Ryan Ho Haemtology.pdf (p124 - Haemophilia complications) ^[8] Senior notes: felixlai.md (Haematuria section; Catheterisation section; Renal biopsy contraindications) ^[9] Senior notes: Ryan Ho Fundamentals.pdf (p340, p342, p350–353, p362) ^[13] Senior notes: Ryan Ho Critical Care.pdf (p26–27 - AKI management and complications) ^[16] Senior notes: Ryan Ho Diagnostic Radiology.pdf (p83 - PCN complications)

Haematuria

Definition

Epidemiology

Risk Factors

Risk Factors for Urological Malignancy (Most Important to Identify)

Risk Factors for Urinary Stones

Risk Factors for Glomerular Disease

Drug-Related Risk Factors

Anatomy and Functional Considerations

The Urinary Tract — From Top to Bottom

The Glomerular Filtration Barrier

Aetiology

Overview of Common Causes [2]

Detailed Aetiological Classification

A. Glomerular Causes (Medical/Nephrological)

B. Non-Glomerular Renal (Parenchymal) Causes

C. Ureteral Causes

D. Bladder Causes

E. Prostatic Causes (Males)

F. Urethral Causes

G. Systemic/Haematological Causes

H. Other/Miscellaneous

Classification

1. By Visibility

2. By Origin (Most Important Clinically)

3. By Timing in Urinary Stream [1][4]

4. By Presence of Pain

5. AUA Risk Stratification for Microscopic Haematuria (AUA 2020) [1]

Clinical Features

Symptoms

A. Characteristics of the Haematuria Itself

B. Associated Urological Symptoms

C. Associated Pain

D. Systemic and Autoimmune Symptoms [2]

E. Respiratory Symptoms [2]

F. Drug and Exposure History

Signs

A. General Examination

B. Abdominal Examination [2]

C. Genital/Perineal Examination [2]

D. Digital Rectal Examination (DRE) [2]

E. Fundoscopy

Key Pathophysiological Concepts Summarised

Why Does Glomerular Haematuria Not Form Clots?

Why Does IgA Nephropathy Present During URTI (Synpharyngitic)?

Why Does Painless Haematuria Suggest Malignancy?

Field Cancerization in Urothelial Carcinoma

Active Recall - Haematuria: Definition, Epidemiology, Aetiology, and Clinical Features

References

Step 1: Glomerular vs Non-Glomerular (Urological) Haematuria

Step 2: The Complete Differential — Organized Anatomically

A. Renal — Glomerular Causes

B. Renal — Non-Glomerular (Tubular/Interstitial/Vascular) Causes

C. Ureteral Causes

D. Bladder Causes

E. Prostatic Causes (Males)

F. Urethral Causes

G. Systemic / Haematological Causes

H. Miscellaneous / Benign Causes

Step 3: Clinical Reasoning Algorithm — Narrowing the Differential

Step 4: Key Discriminating Features — The "Red Flags"

The "Big Three" Differentials You Must Always Consider

Special Considerations in Differential Diagnosis

Isolated Glomerular Haematuria [11]

Haematuria with Concurrent Haemoptysis (Pulmonary-Renal Syndrome) [2]

Drug-Related Haematuria [8][4]

Active Recall - Differential Diagnosis of Haematuria

Diagnostic Criteria: Confirming True Haematuria

Step 1: Confirm True Haematuria

Step 2: Determine Glomerular vs Non-Glomerular Origin

The Diagnostic Algorithm

Detailed Investigation Modalities

1. Urinalysis (Bedside — The Most Important First Test)

a) Urine Dipstick [4][9]

b) Urine Microscopy [2][4][8][13]

c) Urine Microbiology [4][9]

d) Urine Cytology [4][9]

2. Blood Tests

3. Urine Protein Quantification

4. Imaging — Anatomical Assessment of the Urinary Tract