Overview
Haematuria as a presenting problem, worked through five clinical cases, with the imaging chosen at each step linked back to anatomy and pathology. The cases cover renal trauma, renal cell carcinoma, urinary tract calculi, polycystic kidney disease and prostate disease, and the lecture closes with the primary care algorithm for investigating visible and non-visible haematuria. The stated objectives are to provide a differential diagnosis for haematuria and to link knowledge of anatomy and pathology to radiological imaging.
Differential diagnosis of haematuria
The lecture builds the differential through its cases rather than as a single list. Causes presented are:
- Trauma to kidney (and associated liver or spleen injury).
- Malignancy: bladder malignancy, kidney malignancy, prostate carcinoma.
- Calculi: renal and ureteric stones.
- Polycystic kidney disease.
- Lower urinary tract disease in the elderly male: presenting with poor flow, hesitancy, dysuria and haematuria, with prostate cancer, benign prostatic hypertrophy and chronic prostatitis as the pathologies shown.
Painless macroscopic haematuria in an older smoker is treated as malignancy until proven otherwise; haematuria accompanied by colicky loin to groin pain points to calculi.
Case 1: renal trauma
Presentation: 18 year old farm worker, quad bike accident, helicopter transfer to ED. On assessment tachycardic 120/min, hypotensive 80/60, acute abdomen with maximum tenderness in the right upper quadrant and flank around into the renal angle, and passed a small amount of bloody urine.
Differential: trauma to liver, spleen and/or kidney.
Imaging:
- FAST scan in ED (ultrasound). A normal sagittal ultrasound of the right kidney shows the kidney (here 10.50 cm) with liver lying superficial to it, oriented head to feet.
- Contrast-enhanced CT is the modality of choice. It demonstrates parenchymal lacerations, vascular injuries, perinephric haematomas, extravasation of contrast-enhanced urine, and associated injuries.
CT findings shown: right renal laceration as an irregular hypodense defect through the parenchyma surrounded by haematoma, with hepatic and splenic lacerations on higher axial slices.
Management is conservative or operative. Surgical repair of a lacerated kidney will leave an area of infarct.
AAST renal injury grading
The American Association for the Surgery of Trauma grading scale (illustration via Radiopaedia, “S Hapu”, CC BY-SA):
- Grade I: subcapsular haematoma and/or contusion, no laceration.
- Grade II: laceration less than 1 cm deep; perirenal haematoma confined to the perinephric fascia.
- Grade III: laceration more than 1 cm deep; vascular injury or active haemorrhage confined to the perinephric fascia.
- Grade IV: laceration with pelvic involvement and/or ureteropelvic disruption; or segmental vein or artery injury causing segmental or complete infarct from vessel thrombosis without active bleeding.
- Grade V: active bleed extending beyond the perinephric fascia; or main artery or vein laceration or hilar avulsion producing a devascularised, shattered kidney with active bleeding.
Coronal CT of a grade IV injury shows a laceration splitting the left kidney into perfused upper and lower fragments, and renal pelvis disruption with low density leaked urine at the pelvis.
Post-traumatic hypertension
Progress: managed conservatively, then two months later persistent hypertension at 160/100. The mechanism is an ischaemic kidney driving the RAAS and producing hypertension. Treatment depends on kidney function, which is assessed with a renogram.
Nuclear medicine studies
Four nuclear studies are covered, each defined by its tracer and what the tracer does.
Technetium99 MAG3 renogram: Tc99 bound to MAG3 (mercaptoacetyltriglycine), excreted by the kidneys. Tc99 emits gamma rays and is imaged with a gamma camera. Output is a posterior gamma camera image of both kidneys plus a time-activity curve for each. In the case shown the two kidneys are asymmetric: the better-functioning kidney gives a curve that rises sharply then washes out, while the impaired or ischaemic kidney gives a flat, low and sustained curve.
Technetium99 bone scan: Tc99 bound to MDP (methyldiphosphonate), which binds to sites of osteoblastic activity, imaged with a gamma camera. Whole body anterior and posterior views show generalised skeletal uptake with focal hot spots at metastases (right femur in the case shown).
SPECT-CT for bony prostate metastases: single photon emission computed tomography, combining scintigraphy for localisation with 3D information from CT, using Tc99-MDP. Fused images show focal intense tracer uptake within bone (left iliac bone in the example) against the CT bony background.
PSMA PET-CT: prostate specific membrane antigen is over-expressed in prostate cancer cells; 68-Ga is linked to PSMA, giving both metabolic and anatomical information. Fused axial pelvic images show intense uptake in the prostate cancer alongside physiological tracer excretion in the bladder, and can pick up uptake in a small pelvic lymph node that is only a small rounded node on plain CT.
Case 2: renal cell carcinoma
Presentation: 70 year old male, heavy smoker, presented to the GP with an episode of painless macroscopic haematuria and normal renal function. Differential: bladder malignancy, kidney malignancy.
Imaging and staging findings:
- Axial contrast CT abdomen showing a large heterogeneous mass replacing the left kidney, much larger than the normal right kidney.
- CT chest (lung window) showing multiple small nodules through both lungs, that is pulmonary metastases.
- Tc99-MDP bone scan showing metastases in the right femur.
Pathology shown:
- Renal clear cell tumour: bisected kidney with a large, pale yellow-tan, well circumscribed tumour in the upper pole.
- Renal papillary cell carcinoma: a friable, nodular, tan-pink tumour within a fibrous capsule, and a bivalved kidney with pale friable tumour replacing the renal pelvis and medulla region.
Case 3: urinary tract calculi
Presentation: 45 year old male with sudden onset severe right sided flank pain radiating from flank to groin, severe 9/10 with waves of colic, and an episode of macroscopic haematuria associated with the pain.
Imaging findings:
- Plain abdominal X-ray (KUB): radio-opaque calcification over the right kidney and proximal ureter.
- Coronal CT: calculi at the right renal pelvis and proximal ureter, and a second further down the right ureter near the pelvic brim.
- Axial CT: a small hyperdense calculus within the right ureter at the pelvic level, adjacent to the iliac vessels.
- Secondary signs of obstruction: right perinephric fat stranding with a dilated right renal pelvis and collecting system, with a normal left kidney.
Stone composition: a scanning electron micrograph of a calcium oxalate calculus shows sharp pyramidal and prismatic crystals characteristic of that composition.
Warning
One slide is a urinary tract diagram (kidneys, ureters, bladder, urethra, with an inset kidney stone and a stone specimen photograph) that carries no title text; its role as an illustration of urinary stone anatomy and location was inferred from the surrounding calculi case rather than stated on the slide.
Case 4: polycystic kidney disease
Presentation: 25 year old male with sudden onset severe right sided flank pain following a rugby game. The pain does not radiate, is severe at 7/10 but not really colicky, with an episode of macroscopic haematuria associated with the pain. The question posed is trauma or something else, and the answer is polycystic kidney disease presenting after minor trauma.
Imaging and pathology:
- Axial and coronal contrast CT: both kidneys grossly and massively enlarged, replaced by multiple round well-defined cysts of varying size, with a large hepatic cyst also present (polycystic kidneys and liver).
- Ultrasound: multiple anechoic round cysts of varying size in the parenchyma of both kidneys, with an enlarged kidney length of 13.83 cm measured on the right.
- Gross pathology: a pair of bivalved kidneys, both grossly enlarged and studded throughout with numerous cysts of varying size and colour (tan and dark red haemorrhagic), consistent with autosomal dominant polycystic kidney disease.
Case 5: prostate disease
Presentation: elderly man with poor urinary flow and hesitancy who has an episode of dysuria and haematuria. The question posed is aetiology.
MRI prostate: axial and sagittal images demonstrate the prostate with the bladder above and behind it. On the dedicated sequences a prostate cancer lesion appears as a focal area of low signal in the peripheral zone on T2-weighted imaging, with a corresponding focus of restricted diffusion (bright signal) at the same site on diffusion-weighted imaging.
Staging for bony metastases uses SPECT-CT Tc99-MDP and PSMA PET-CT as above.
Pathology of the prostate:
- Normal versus cancer: the cancer gland shows irregular nodular growth on the gland surface.
- Benign hypertrophy: the gland is uniformly enlarged compared with normal size, sitting between bladder and rectum. Grossly it is nodular, with multiple bulging nodules within the gland.
- Prostatic cancer is multifocal: serial sections through the gland show multiple pale tumour nodules distributed at different levels.
- Chronic prostatitis: glandular tissue with a dense infiltrate of inflammatory cells (lymphocytes) within and around the glands, plus scattered red cells and haemorrhage, contrasted with normal prostate showing glandular epithelium with papillary infolding surrounded by fibromuscular stroma and no significant inflammatory infiltrate.
Investigating haematuria: the clinical algorithm
The algorithm splits at the entry point into non-visible and visible haematuria.
Non-visible and asymptomatic, under 40 years: consider nephrological causes. Measure blood pressure, test creatinine (eGFR) and ACR/PCR, and request urine microscopy for dysmorphic red cells and urinary casts. Then ultrasound the urinary tract, then monitor for a nephrologic cause.
Symptomatic non-visible haematuria, asymptomatic non-visible haematuria over 40 years, or any visible haematuria: urinary tract imaging where direct access permits, for example intravenous urogram (IVU), ultrasound or CTU.
- Positive imaging leads to cystoscopy and urology referral, after which either a cause is found or no cause is found.
- Negative imaging leads to the question “age over 40 years, or positive urine cytology?”. If yes, cystoscopy and urology referral. If no, monitor for a urologic cause. Consider cystoscopy below age 40 if risk factors for urothelial cancer are present.
- “No cause found” after cystoscopy also feeds into the monitor for urologic cause pathway. Both monitoring pathways are carried out in primary care.
Monitoring for a nephrologic cause: annually with urine dipstick, BP, eGFR and ACR/PCR while the haematuria persists. Refer to nephrology if any of:
- eGFR less than 30 mL/min/1.73m²
- eGFR less than 45 mL/min/1.73m² in a person with diabetes
- eGFR declining by more than 10 mL/min at any stage in the last five years, or more than 5 mL/min in the last year
- Proteinuria ACR at or above 30 mg/mmol, or PCR at or above 50 mg/mmol
- Uncontrolled blood pressure (140/90 mmHg)
Monitoring for a urologic cause: annually for two years with urine dipstick, eGFR, ACR/PCR and cytology. Refer back to urology if any of: haematuria persists; urine cytology is positive; urinary tract symptoms develop or increase.
Important
Risk factors that should raise clinical suspicion of significant urological disease in a person with haematuria: history of recurrent visible haematuria; age over 40 years; current smoker or recent history of smoking; history of recurrent urinary tract infection or other urological disorders; occupational exposure to chemicals or dyes; previous pelvic irradiation; history of excessive analgesic use; treatment with cyclophosphamide.
Self-test
- List the causes of haematuria covered in this lecture, with the case presentation that introduced each.
- Explain why contrast-enhanced CT rather than ultrasound is the modality of choice in suspected renal trauma, listing what it demonstrates.
- Describe the five AAST grades of renal injury.
- Distinguish a grade IV renal injury with perfused fragments from one with renal pelvis disruption on coronal CT.
- Explain why a conservatively managed renal trauma patient developed a BP of 160/100 two months later, and how kidney function is then assessed.
- Describe how a Tc99 MAG3 renogram works, and predict the shape of the time-activity curve for an ischaemic kidney compared with a normally functioning one.
- Distinguish Tc99-MAG3 from Tc99-MDP in terms of what the tracer does in the body.
- Explain what SPECT-CT adds to a plain Tc99-MDP bone scan.
- Describe the principle of PSMA PET-CT and one pitfall in interpreting uptake on a pelvic image.
- A 70 year old heavy smoker has one episode of painless macroscopic haematuria with normal renal function. State the differential and describe the imaging findings that established the diagnosis and its spread in this case.
- Distinguish the gross appearances of renal clear cell tumour and renal papillary cell carcinoma.
- Describe the direct and indirect CT findings of an obstructing right ureteric calculus.
- Distinguish the pain of case 3 from the pain of case 4, and give the diagnosis in each.
- Describe the imaging and gross pathology findings of autosomal dominant polycystic kidney disease.
- Describe the appearance of a prostate cancer lesion on T2-weighted and on diffusion-weighted MRI.
- Distinguish benign prostatic hypertrophy from prostatic carcinoma on gross pathology.
- Describe the initial investigations for asymptomatic non-visible haematuria in a person under 40 years.
- List the eGFR-based criteria for referring a person with haematuria to nephrology.
- List the risk factors that should raise suspicion of significant urological disease in a person with haematuria.
- A 45 year old smoker has visible haematuria and negative urinary tract imaging. Predict the next step in the algorithm and explain why.
Answers
Reveal answers
- Trauma to the kidney with liver or spleen injury (18 year old quad bike accident); kidney and bladder malignancy (70 year old smoker with painless macroscopic haematuria); urinary calculi (45 year old with colicky loin to groin pain); polycystic kidney disease (25 year old after a rugby game); prostate disease, that is prostate carcinoma, benign prostatic hypertrophy and chronic prostatitis (elderly man with poor flow, hesitancy and dysuria).
- Contrast-enhanced CT is the modality of choice because it demonstrates parenchymal lacerations, vascular injuries, perinephric haematomas, extravasation of contrast-enhanced urine and associated injuries. Ultrasound is used as the FAST scan in ED.
- Grade I: subcapsular haematoma and/or contusion, no laceration. Grade II: laceration under 1 cm deep with perirenal haematoma confined to the perinephric fascia. Grade III: laceration over 1 cm deep, or vascular injury or active haemorrhage confined to the perinephric fascia. Grade IV: laceration with pelvic involvement and/or ureteropelvic disruption, or segmental vein or artery injury causing segmental or complete infarct from vessel thrombosis without active bleed. Grade V: active bleed extending beyond the perinephric fascia, or main artery or vein laceration or hilar avulsion with a devascularised, shattered kidney and active bleeding.
- Perfused fragments: the laceration splits the kidney into upper and lower fragments that both still enhance with contrast. Renal pelvis disruption: there is a region of low density, unenhanced leaked urine at the renal pelvis.
- The kidney is ischaemic, which drives the RAAS and produces hypertension. Treatment depends on kidney function, which is assessed with a Tc99 MAG3 renogram.
- Tc99 is bound to MAG3 (mercaptoacetyltriglycine), which is excreted by the kidneys; Tc99 emits gamma rays that are imaged with a gamma camera, giving an image of both kidneys plus a time-activity curve. The normally functioning kidney gives a curve that rises sharply then washes out; the ischaemic or impaired kidney gives a flat, low and sustained curve with reduced uptake.
- MAG3 is excreted by the kidneys, so it reports renal function and drainage. MDP (methyldiphosphonate) binds to sites of osteoblastic activity, so it reports bone turnover and detects skeletal metastases.
- SPECT-CT combines scintigraphy, which provides localisation, with 3D anatomical information from CT, so tracer uptake can be placed precisely within a named bone rather than just a region of the skeleton.
- 68-Ga is linked to PSMA (prostate specific membrane antigen), which is over-expressed in prostate cancer cells, so the study gives both metabolic and anatomical information. The pitfall is that the tracer is excreted into the bladder, producing intense physiological bladder uptake next to the prostate that must not be mistaken for tumour.
- Differential: bladder malignancy and kidney malignancy. CT abdomen showed a large heterogeneous mass replacing the left kidney; CT chest showed multiple small nodules in both lungs, that is lung metastases; a Tc99-MDP bone scan showed metastases in the right femur.
- Clear cell: a large, pale yellow-tan, well circumscribed tumour, here occupying the upper pole of a bisected kidney. Papillary: a friable, nodular, tan-pink tumour within a fibrous capsule, with pale friable tumour replacing the renal pelvis and medulla region.
- Direct: a hyperdense calculus within the ureter, seen at the renal pelvis and proximal ureter and again lower near the pelvic brim on coronal CT, and as a small hyperdense focus in the ureter on axial CT. Indirect: perinephric fat stranding on the affected side with a dilated renal pelvis and collecting system, with the other kidney normal.
- Case 3: severe 9/10 pain radiating from flank to groin with waves of colic, plus macroscopic haematuria, that is a ureteric calculus. Case 4: severe 7/10 flank pain after a rugby game that does not radiate and is not really colicky, plus macroscopic haematuria, that is polycystic kidney disease rather than simple trauma.
- CT: both kidneys grossly and massively enlarged and replaced by multiple round, well-defined cysts of varying size, often with hepatic cysts as well. Ultrasound: multiple anechoic round cysts of varying size in the parenchyma, with enlarged kidney length (13.83 cm in the case shown). Gross pathology: bivalved kidneys grossly enlarged and studded throughout with numerous cysts of varying size and colour, tan and dark red haemorrhagic.
- T2-weighted: a focal area of low signal within the peripheral zone. Diffusion-weighted: a corresponding focal area of restricted diffusion, that is bright signal, in the same region.
- Benign prostatic hypertrophy is nodular, with multiple bulging nodules within a diffusely enlarged gland. Prostatic cancer is multifocal, with multiple pale tumour nodules distributed through the gland at different levels on serial sections, and on diagrams shows irregular nodular growth at the gland surface.
- Consider nephrological causes: measure blood pressure, test creatinine (eGFR) and ACR/PCR, and request urine microscopy to detect dysmorphic red cells and urinary casts, then ultrasound the urinary tract, then enter annual monitoring for a nephrologic cause.
- eGFR under 30 mL/min/1.73m²; eGFR under 45 mL/min/1.73m² if the person has diabetes; eGFR declining by more than 10 mL/min at any stage in the last five years, or more than 5 mL/min in the last year. (The other referral triggers are ACR at or above 30 mg/mmol or PCR at or above 50 mg/mmol, and uncontrolled blood pressure at 140/90 mmHg.)
- History of recurrent visible haematuria; age over 40 years; current smoker or recent history of smoking; history of recurrent urinary tract infection or other urological disorders; occupational exposure to chemicals or dyes; previous pelvic irradiation; history of excessive analgesic use; treatment with cyclophosphamide.
- Visible haematuria goes down the urinary tract imaging arm; with negative imaging the algorithm asks whether the person is over 40 years or has positive urine cytology. This patient is over 40, so the next step is cystoscopy and urology referral. Smoking is also a risk factor for urothelial cancer, which would justify cystoscopy even below 40.