Lucan · Conditions

Approach to haematuria

Australian guidance: Kidney Health Australia CKD Management Handbook (5th ed, 2024) + USANZ Haematuria Guidance

1. Definition and epidemiology

Haematuria is the presence of red blood cells in the urine beyond the normal physiological range; it is a sign that always demands an explanation and is never a diagnosis in itself. Visible (macroscopic) haematuria is blood seen by the naked eye, and Kidney Health Australia is explicit that visible haematuria must always be investigated, even if it has already settled by the time the patient is reviewed. Non-visible (microscopic) haematuria is detected only by dipstick or microscopy and is confirmed when at least 3 red blood cells per high power field are seen on a freshly voided, clean-catch, midstream specimen. The most common causes of haematuria overall are non-glomerular: menstrual contamination and urological conditions such as urinary tract infection, kidney calculi, prostatic disease, or urinary tract tumours.

Age fundamentally changes the pre-test probability of malignancy and is the reason the same symptom is worked up so differently in a 25-year-old and a 55-year-old. Under the age of 40, isolated haematuria (haematuria without albuminuria, reduced eGFR, or evidence of urinary tract malignancy) is usually due to an underlying glomerulonephritis with a low propensity for progression, and annual follow-up is generally sufficient. From age 40 onward, the incidence of bladder and upper tract urothelial carcinoma rises sharply, especially in smokers, and painless visible haematuria is its commonest presenting feature. Kidney Health Australia lists age over 40 as an explicit risk factor demanding investigation for urological malignancy, and Australian urological practice (USANZ) treats visible haematuria in a patient over 40 as urothelial cancer until proven otherwise, warranting prompt referral for cystoscopy and upper tract imaging rather than watchful waiting.

2. Pathophysiology

The central organising concept in haematuria is the distinction between a glomerular and a non-glomerular source, because the mechanism of bleeding differs and this determines which specialty leads the work-up. In glomerular bleeding, red cells cross a damaged or inflamed glomerular capillary wall and basement membrane, then transit the full length of the tubular system, where they are exposed to changing pH and osmolality that mechanically deform and fragment the cell membrane, producing dysmorphic red cells (classically acanthocytes, with irregular blebs and vesicles). A subset of these cells become trapped within a Tamm-Horsfall protein matrix in the distal tubule and collecting duct, forming red cell casts, a finding that is essentially diagnostic of a glomerular source (Robbins Ch 20). Because glomerular blood is delivered in small volumes mixed with a large flow of tubular fluid, and because urokinase-rich tubular and collecting system fluid has fibrinolytic activity, glomerular bleeding essentially never forms clots. In non-glomerular bleeding, red cells enter the urinary space directly from the urothelium, renal parenchyma, or vasculature without transiting the nephron, so they remain isomorphic (uniform, biconcave) in shape; when bleeding is brisk, as with a bleeding tumour, stone, or traumatic injury, the blood is not diluted or exposed to fibrinolytic tubular fluid in the same way and can form clots. Loin pain in non-glomerular disease typically reflects capsular stretch from obstruction (a stone or clot) or direct parenchymal or urothelial irritation from infection or tumour.

The urine dipstick detects blood using the pseudoperoxidase activity of haem, which catalyses oxidation of a chromogen on the strip to produce a colour change. This reaction is triggered equally by haem packaged inside intact red blood cells, by free haemoglobin released during intravascular haemolysis (haemoglobinuria, as in a haemolytic transfusion reaction, severe malaria, or a G6PD deficiency crisis), and by myoglobin released from damaged skeletal muscle (myoglobinuria, as in rhabdomyolysis from crush injury, prolonged seizure, or extreme exertion). All three give a dipstick positive for blood, but only true haematuria shows intact red blood cells on microscopy; haemoglobinuria and myoglobinuria are microscopy-negative because the pigment is free in solution rather than cell-bound, and this is precisely why microscopy, not dipstick, is the confirmatory test for true haematuria. Conversely, some causes of visibly red or orange urine do not involve haem at all and therefore leave the dipstick negative for blood: beeturia, the passage of red urine after eating beetroot due to incomplete metabolism of the pigment betalain (more common in people with iron deficiency, which increases absorption of the pigment), and rifampicin, which imparts an orange-red colour to urine, tears, and sweat through its own pigment rather than any haem breakdown product. Menstrual contamination behaves differently again: actual red blood cells from menstrual flow genuinely contaminate a voided specimen, so both the dipstick and the microscopy are truly positive; the clue here is not a special confirmatory test but the clinical history, and the correct step is to defer testing until menstruation has finished or to collect a clean-catch or catheter specimen.

3. Clinical presentation and diagnostic criteria

Bedside localisation begins with the pattern of findings. A glomerular pattern is suggested by dysmorphic red cells and red cell casts on microscopy, subnephrotic or heavier proteinuria, hypertension, and oedema, often with a reduced eGFR; a non-glomerular pattern is suggested by clots, frank uniform red blood, loin pain, and the absence of significant proteinuria. The timing of blood within the urinary stream is a useful bedside clue in men: initial haematuria, seen only at the start of the stream, localises to the urethra; terminal haematuria, seen only at the end of the stream, localises to the bladder neck or prostate, as the bladder contracts on the already-emptying bladder neck; and total haematuria, present throughout the stream, localises to the upper urinary tract (kidney or ureter) or to diffuse bladder pathology, because blood has been mixed throughout the stored urine before voiding begins.

Among the glomerular causes, IgA nephropathy is the most common primary glomerulonephritis worldwide and classically produces synpharyngitic haematuria, visible haematuria appearing within 1 to 2 days of an upper respiratory tract or gastrointestinal infection, reflecting a rapid mucosal IgA immune response; between episodes it often causes persistent asymptomatic non-visible haematuria, and complement levels are normal. Post-streptococcal glomerulonephritis, by contrast, follows a streptococcal pharyngitis by 1 to 3 weeks or a streptococcal skin infection (impetigo) by 3 to 6 weeks, reflecting the time needed to generate a circulating immune complex response; it produces a nephritic syndrome with oedema and hypertension, and a low C3 that is expected to normalise within 6 to 8 weeks, and is most common in children with a generally self-limiting course. Thin basement membrane disease is an autosomal dominant condition, usually from a heterozygous COL4A3 or COL4A4 mutation, causing persistent isolated microscopic haematuria with a family history of haematuria but, importantly, a benign long-term prognosis without progression to renal failure. Alport syndrome, most commonly X-linked from a COL4A5 mutation, produces the more sinister triad of progressive haematuric nephritis advancing toward chronic kidney disease and end-stage kidney failure, sensorineural hearing loss, and ocular abnormalities such as anterior lenticonus; family history often shows more severely affected males, consistent with X-linked inheritance. Two glomerular presentations are true nephrological emergencies: anti-GBM disease, in which autoantibodies against the alpha-3 chain of type IV collagen produce a linear immunofluorescence pattern and rapidly progressive glomerulonephritis often with concurrent pulmonary haemorrhage, and ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), which produces a pauci-immune crescentic glomerulonephritis with little or no immunoglobulin deposition; both require same-day nephrology review (Robbins Ch 20).

Autosomal dominant polycystic kidney disease (ADPKD) deserves separate emphasis because haematuria and hypertension together are its classic early presentation, often preceding any decline in renal function. ADPKD is caused by loss-of-function mutations in PKD1 (chromosome 16, around 85 percent of cases) or PKD2 (chromosome 4, around 15 percent), producing progressive bilateral cyst formation; haematuria results from cyst haemorrhage or rupture into the collecting system, and hypertension results from intrarenal renin-angiotensin-aldosterone activation driven by cyst-related ischaemia, a mechanism active well before eGFR begins to fall. Diagnosis is by renal ultrasound using age-stratified cyst count criteria, supported by a family history in around 90 percent of cases. Extrarenal manifestations are common and include hepatic cysts, the most frequent extrarenal finding, mitral valve prolapse, and colonic diverticula. The complication most important not to miss is an intracranial berry (saccular) aneurysm, present in around 5 to 10 percent of patients, screened for with magnetic resonance angiography in those with a family history of aneurysm or subarachnoid haemorrhage, given the catastrophic consequence of a missed rupture (full detail in the ADPKD topic).

Among the non-glomerular causes, urothelial carcinoma is the presentation to never miss, classically causing painless visible haematuria in an older adult; smoking is the single strongest risk factor, accounting for around half of attributable risk, and occupational exposure to aromatic amines (historically in the rubber, dye, leather, and printing industries) is a recognised occupational risk, alongside pelvic irradiation and cyclophosphamide exposure. Renal cell carcinoma classically presents with the triad of flank pain, haematuria, and a palpable abdominal mass, but the full triad is now uncommon, seen in only around 10 to 15 percent of cases, because most renal cell carcinomas are detected incidentally on imaging performed for another reason. Renal calculi cause colicky loin pain radiating to the groin with haematuria in up to 90 percent of cases. Urinary tract infection and pyelonephritis cause haematuria alongside dysuria, frequency, and, if upper tract, fever and loin pain. Benign prostatic hyperplasia can cause haematuria from friable, vascular prostatic or bladder neck tissue in older men, but it is a diagnosis of exclusion once malignancy has been ruled out. Trauma, whether blunt or penetrating, should be evident from the history. Schistosoma haematobium infection, relevant in patients who have lived in or travelled to endemic areas of Africa or the Middle East, causes chronic bladder wall inflammation and calcification and is a major risk factor for squamous cell carcinoma of the bladder, a diagnosis that should not be missed in migrant and refugee populations. Exercise-induced haematuria is a benign, transient, visible or non-visible haematuria following strenuous exercise such as long-distance running, thought to reflect repetitive bladder wall trauma against the posterior wall, transient renal vasoconstriction, or mild rhabdomyolysis; it resolves within 24 to 72 hours of rest, but persistent haematuria after this window still requires standard investigation.

4. Investigations and AU-specific cutoffs

Kidney Health Australia's algorithm for persistent microscopic haematuria formalises the approach. The first step for any dipstick-positive result is to rule out infection with urine microscopy and culture; if infection is present, it is treated and the urine retested. If infection is absent, the branching question is whether there is associated albuminuria and/or a reduced eGFR. If yes, glomerular causes are considered: an underlying glomerulonephritis is investigated, a renal tract ultrasound is arranged, the patient is managed according to the standard CKD clinical action plan, and referral to a nephrologist is made. If no albuminuria or eGFR reduction is present, urological malignancy is considered when risk factors are present: age over 40, a history of macroscopic haematuria, smoking, pelvic irradiation, or occupational exposure to chemicals, dyes, or cyclophosphamide; the work-up here is urine cytology on three samples, renal tract ultrasound, and referral to a urologist for consideration of cystoscopy.

This algorithm is reinforced by the standard CKD diagnostic evaluation tests. Always indicated: repeat serum urea, electrolytes, creatinine and eGFR within a week; urine microscopy for dysmorphic red cells and red cell casts; full blood count, fasting lipids, glucose, HbA1c, urate, liver function tests, hsCRP and ESR; and renal tract ultrasound at least once. Sometimes indicated, and prompting likely referral: anti-GBM antibody, ANCA, ANA and extractable nuclear antigens, complement (C3/C4), and ESR, when there are signs of systemic disease (rash, arthritis, connective tissue disease features, pulmonary symptoms, deteriorating kidney function) or the presence of glomerular haematuria itself; hepatitis B, hepatitis C, and HIV serology when risk factors for these are present, given their association with glomerular disease. CT urography is the imaging modality of choice for the upper tracts when malignancy is being excluded, identifying renal masses, stones, hydronephrosis, and upper tract urothelial tumours, and cystoscopy remains the only reliable way to directly visualise and exclude bladder urothelial carcinoma; a low-dose non-contrast CT is the equivalent first-line study when loin pain suggests a stone rather than a tumour. uACR staging follows the standard Australian convention: less than 3.0 mg/mmol is normal, 3.0 to 30 mg/mmol is microalbuminuria, and greater than 30 mg/mmol is macroalbuminuria, with macroalbuminuria supporting a glomerular source.

5. Management

Management follows directly from where the algorithm lands. If infection explains the haematuria, it is treated and urinalysis repeated to confirm resolution. If glomerular causes are identified, the patient is managed by nephrology according to the standard CKD clinical action plan; the two glomerular emergencies, anti-GBM disease and ANCA-associated vasculitis, both require same-day nephrology referral for urgent high-dose corticosteroids combined with cyclophosphamide or rituximab, with plasma exchange added for anti-GBM disease and for severe ANCA-associated disease (further detail in the glomerulonephritis approach topic). IgA nephropathy and post-streptococcal glomerulonephritis are usually managed supportively: blood pressure control and RAAS blockade for proteinuria in IgA nephropathy, and supportive management of oedema and hypertension in post-streptococcal glomerulonephritis, which is generally self-limiting in children. If urological malignancy risk factors are present, referral to a urologist for cystoscopy is made without delay, regardless of whether the visible bleeding has already settled. Persistent haematuria in the absence of albuminuria, once malignancy and infection are excluded, is followed up annually with repeat testing for haematuria, albuminuria, eGFR, and blood pressure for as long as the haematuria persists, and family members should also be screened for haematuria, particularly relevant for the inherited causes such as thin basement membrane disease and Alport syndrome. ADPKD is managed jointly with nephrology, with blood pressure control as the cornerstone of non-specific management and tolvaptan available for rapidly progressive disease (full detail in the ADPKD topic). Suspected urothelial or renal malignancy should never be managed with a trial of antibiotics in the absence of infective features on culture; this delays a time-critical diagnosis and is a recognised contributor to late-stage urothelial cancer diagnosis.

6. Pharmacology and AU PBS notes

ACE inhibitors (for example ramipril or perindopril) or angiotensin receptor blockers (for example irbesartan or candesartan) are first-line for proteinuric glomerular disease of any cause, including IgA nephropathy and ADPKD, because RAAS blockade reduces intraglomerular pressure and proteinuria in addition to lowering systemic blood pressure; both classes are PBS-listed for hypertension, and dual RAAS blockade (combining an ACE inhibitor with an ARB) is avoided because it increases adverse events without added benefit. The immunosuppressive regimens used for the two RPGN emergencies, high-dose corticosteroids with cyclophosphamide or rituximab, and plasma exchange for anti-GBM disease, are detailed in the glomerulonephritis approach topic and are always initiated by nephrology given the toxicity of these agents and the need for concurrent infection and bone protection monitoring. Tolvaptan, a selective vasopressin V2 receptor antagonist, is the disease-modifying option for rapidly progressive ADPKD; it requires nephrologist initiation under a PBS streamlined listing and monthly liver function monitoring for the first 18 months given its hepatotoxic potential (full dosing in the ADPKD topic). Analgesia for stone-related haematuria follows standard renal colic management, with NSAIDs first-line where renal function permits. Nephrotoxic agents, particularly NSAIDs taken regularly, should be avoided or used cautiously in any patient under active investigation for haematuria with a reduced eGFR, and empirical antibiotic choice for a confirmed urinary tract infection should follow local eTG guidance rather than being used as a default, unproven explanation for haematuria.

7. Complications and monitoring

Delay in the haematuria work-up carries specific, avoidable harms: unrecognised glomerulonephritis can progress silently to chronic and then end-stage kidney disease, unrecognised urothelial or renal cell carcinoma can progress from an organ-confined, curable stage to metastatic disease, an unrecognised ADPKD-associated intracranial aneurysm carries a risk of subarachnoid haemorrhage, and an unrecognised obstructing stone with infection can progress to pyonephrosis and urosepsis. Once a benign or reversible cause is identified, a repeat urinalysis confirming resolution closes the episode. Once a glomerular disease is confirmed, monitoring follows the standard Australian CKD schedule: eGFR and uACR every 3 months in active or progressive disease and every 6 to 12 months once stable, blood pressure at every review with a target below 130/80 mmHg, and complement or ANCA titres where relevant to the underlying diagnosis. Persistent haematuria without albuminuria, once malignancy is excluded, still requires annual review of haematuria, albuminuria, eGFR, and blood pressure for as long as it persists, and screening of first-degree relatives is appropriate for the inherited causes. Patients diagnosed with urothelial carcinoma enter a structured cystoscopic surveillance program under urology, with frequency determined by tumour grade and stage. Patients with ADPKD and a known or high-risk family history of intracranial aneurysm undergo periodic MRA surveillance of the circle of Willis as advised by nephrology or neurosurgery.

Written for Australian practice and grounded in the guidance named above. Study material only — not medical advice. Always check against current guidelines.