Hematuria differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Adnan Ezici, M.D[2], Steven C. Campbell, M.D., Ph.D., Amandeep Singh M.D.[3], Omer Kamal, M.D.[4], Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [5] Aditya Ganti M.B.B.S. [6]

Overview

Gross hematuria(GH) must be distinguished from pigmenturia, which may be due to endogenous sources (e.g., bilirubin, myoglobin,and porphyrins), foods ingested (e.g., beets and rhubarb), drugs (e.g., phenazopyridine), and simple dehydration. This distinction can be made easily by urinalysis with microscopy. Notably, myoglobinuria and other factors can cause false-positive chemical tests for hemoglobin, so urine microscopy is required to confirm the diagnosis of hematuria. GH also must be distinguished from vaginal bleeding in women, which usually can be achieved by obtaining a careful menstrual history, collecting the specimen when the patient is not having menstrual or gynecologic bleeding, or, if necessary, obtaining a catheterized specimen. GH may also be detected by the presence of blood spotting on the undergarments of incontinent patients. After ruling out vaginal bleeding and mimics of hematuria, a urologic source must be suspected.

Differential Diagnosis

Hematuria should be differentiated from other conditions which might mimic hematuria such as hemoglobinuria, myoglobinuria, porphyria, bile pigments, and alkaptonuria.

• Hematuria is usually characterized by red/rusty urine color, positive heme test, red blood cells and casts on microscopy, and normal plasma. These characteristic findings might be helpful for differentiaton of hematuria from abovementioned conditions.
• Hemoglobinuria is usually characterized by pink/red urine color, positive heme test, no cells on microscopy, and pink plasma.
• Myoglobinuria is usually characterized by rusty urine color, positive heme test, no cells on microscopy (casts might be seen), and normal plasma.
• Porphyria is usually characterized by urine color turns black/brown/red when the urine exposed to sunlight, negative heme test, normal microscopic findings, and normal plasma.
• Bile pigments is usually characterized by brown urine color, negative heme test, normal microscopic findings, and dark to bright yellow (icteric) plasma.
• Alkaptonuria is usually characterized by urine color turns black when the urine exposed to sunlight, negative heme test, normal microscopic findings, and normal plasma.

Hematuria differential diagnosis

Differentiating the diseases that can cause hematuria:

Diseases		Clinical manifestations									Para-clinical findings		Gold standard
		Symptoms						Physical examina
											Lab Findings	Diagnosi
		Low back pain	Fever	Nausea/ Vomiting	Urinary symptoms			Hypertension	Pitting edema	Other
					Dysuria	Frequency	Oliguria
Glomerular diseases	IgA nephropathy (Berger nephropathy)		+	-	-	-	+	+	+	-	-	Biopsy: IgA deposited in a diffuse granular pattern in the mesangium	Biopsy
	Hereditary nephritis (Alport syndrome)	-	-	-	-	-	-	+	-	Cataract Hearing loss	Pyuria Red cell casts Cylindrical casts	Biopsy: Monoclonal antibodies directed against alpha-3 (IV), alpha-4 (IV), and alpha-5 (IV) chains of typ-e IV collagen	Genetic analysis
	Post-streptococcal glomerulonephritis	+/-	+	-	-	+	+	+	+	Edema Anemia Increased Blood Pressure	Urine samples for protein and blood	Biopsy Irregularly thin and attenuated GBM Splitting of GBM Scarring Immunoglobulin G and C3 in a diffuse granular pattern Starry sky pattern	Biopsy
	Focal segmental glomerular sclerosis	-	-	-	-	-	-	+	+	Nephrotic syndrome ESRD Pleural effusion Ascites Abdominal pain	Urinalysis reveals large amounts of protein, along with hyaline and broad waxy casts Hepatitis B or C infection Anti-neutrophil cytoplasmic antibody titers, serum protein electrophoresis	Biopsy Segmental solidification in the perihilar region and peripheral areas, especially the tubular pole Coarsely granular deposits -of IgM and C3	Biopsy
	Rapidly progressive glomerulonephritis	+	+	+	-	-	-	+	-	Abdominal pain Painful cutaneous nodules Migratory poly arthropathy Sinusitis Cough Hemoptysis.	Low iron Eosinophilia Increased serum creatinine level Eleated LDH and CPK Proteinuria	Biopsy: Diffuse, proliferative, necrotizing glomerulonephritis with crescent formation	Biopsy
	Lupus nephritis	-	+	-	-	-	-	+	+	Foamy dark urine Weight gain	Hematuria Pyuria Proteinuria Cellular casts Low iron	Biopsy, Different pathologies, CLICK HERE for more information.	Biopsy
	Fabry disease	-	-	-	-	-	-	+	+	-	Hematuria Proteinuria	Biopsy	Biopsy
Disease		Low back pain	Fever	Nausea/ Vomiting	Dysuria	Frequency	Oliguria	Hypertension	Pitting edema	Other	Lab Findings	Diagnosis method	Gold standard
Tubulointerstitial diseases		+	+	+	–	–	–	–	–	Rash	Eosinophilia Eosinophiluria Isosthenuria	Biopsy: Edema and infiltration by mononuclear cells, (principally lymphocytes) Eosinophils are present, often in large numbers.	Renal biopsy
Nephrolithiasis		+	±	+	±	±	±	–	–	Radiating pain to groin	Hypercalciuria Hyperoxaluria Hypocitraturia Hyperuricemia Hyperuricosuria	Ultrasound: Hydronephrosis +/- Abdominal CT scan without contrast	Abdominal CT scan without contrast
Reflux nephropathy (hydronephrosis)		+	+	-	-	-	-	-	+	Abdomen pain Chest pain Shortness of breath	Elevated WBC count Elevated BUN Hyperkalemia	Ultrasound: Hydronephrosis +/- Biopsy: Kidney scar	–
Malignancy	Renal cell carcinoma (RCC)	-	-	-	-	-	-	±	±	Flank mass	Anemia Hematuria	Both CT and MRI may be used to detect neoplastic masses that may define renal cell carcinoma or metastasis of the primary cancer. CT scan and use of intravenous (IV) contrast is generally used for work-up and follow-up of patients with renal cell carcinoma. The histological pattern of renal cell carcinoma depends whether it is papillary, chromophobe or collecting duct renal cell carcinoma.	–
	Nephroblastoma (Wilms tumor)	-	-	-	-	-	-	-	-	Abdominal pain	Anemia Hematuria	Ultrasound is the best initial diagnostic study used in cases suspected with Wilms tumor. Doppler ultrasonography can help to detect invasion of renal vein and IVC by the tumor. Findings on CT scan: Heterogeneous soft-tissue density masses Abdominal lymph nodes and contralateral involvement Biopsy: Primitive tubules and glomeruli are often seen comprised of neoplastic cells. Spindled cell stroma surrounding abortive tubules and glomeruli is characteristic. The stroma may include: Striated muscle cartilage bone Fat tissue Fibrous tissue.	Biopsy
	Bladder cancer	-	-	-	-	±	±	-	-	Suprapubic pain	Anemia Hematuria	Ultrasound, CT scan, Biopsy	Biopsy
	Prostate cancer	±	-	-	-	±	±	-	-	-	Anemia Hematuria	Ultrasound, CT scan, Biopsy	Biopsy
Disease		Low back pain	Fever	Nausea/ Vomiting	Dysuria	Frequency	Oliguria	Hypertension	Pitting edema	Other	Lab Findings	Diagnosis method	Gold standard
Familial diseases	Polycystic kidney disease	+	-	-	-	-	-	+	+	Palpable mass in the flank Palpable abdominal mass in the lumbar quadrant Palpable nodular hepatomegaly	Hypocitraturia in 65% on patients Hyperuricemia in 20% of patients Hyperoxaluria in 20% of patients Low urine pH Hematuria (microscopic or macroscopic) Proteinuria usually less than 1 g/day	Ultrasound: Unilateral or bilateral cysts CT: Hyperdense appearance, Septations Calcifications Genetic testing demonstrates: Frame insertions/deletions Non-canonical splice site alterations Combined missense changes Biopsy: Interstitial fibrosis Tubular atrophy Thickening and lamellation of tubular basement membranes	Ultrasound
Vascular diseases	Renal vein thrombosis	+	+	+	-	-	-	-	-	Asymptomatic Abdominal pain Acute in onset	Elevation in serum lactate dehydrogenase Cholesterol levels for hyper-cholesterolemia Albumin levels for hypoalbuminemia Serum complement levels	Ultrasound Venography	Renal venography: Gold standard
	Wegner's granulomatosis polyangiitis	-	-	-	-	-	+/-	+	+	URTI CNS involvement Ophthalmic involvement	Proteinuria Microscopic hematuria RBC casts	CT chest: Multiple lung nodules Consolidation Ground-glass opacities. Biopsy: Subendothelial edema Microthrombosis, and Degranulation of neutrophils.	Biopsy
	Henoch-Schönlein purpura	-	-	-	-	-	+/-	+/-	+	Abdominal pain Rash Hematuria	Proteinuria Microscopic hematuria RBC casts	Biopsy: IgA deposited in a diffuse granular pattern in the mesangium	Renal biopsy, and clinical syndrome
Disease		Low back pain	Fever	Nausea/ Vomiting	Dysuria	Frequency	Oliguria	Hypertension	Pitting edema	Other	Lab Findings	Diagnosis method	Gold standard
Lower urinary tract diseases	Benign prostatic hyperplasia	+/-	-	-	+	+	-	-	-	Nocturia Other voiding symptoms Slow urinary stream Splitting or spraying of the urinary stream Intermittent urinary stream Hesitancy Straining to void Terminal dribbling	Urinalysis to rule out UTI Elevated BUN/Cr High PSA values	Urine cytology to screen for bladder cancer Biopsy to rule out cancer	Biopsy
	Urolithiasis	+	+/-	+	+	+	+	-	-	Flank Groin pain	Urine analysis High Cr	Abdominppelvic CT scan without contrast	Abdominppelvic CT scan without contrast
Disease		Low back pain	Fever	Nausea/ Vomiting	Dysuria	Frequency	Oliguria	Hypertension	Pitting edema	Other	Lab Findings	Diagnosis method	Gold standard
Infectious diseases	Pyelonephritis	+	+	+	+	+	+	-	-	Delirium Headache	Positive leukocyte esterase test and nitrite test. Blood/urine cultures	CT and ultrasound: Enlarged kidneys Round swollen kidneys Hypodense appearance Abscesses may not be present	-
	Cystitis	-	-	-	+	+	+	-	-	Dyspareunia Supra pubic tenderness	Pyuria: > 5-10 WBC/hpf or 27 WBC/microliter Positive leukocyte esterase test and nitrite test. Positive urine/blood cultures	Ultrasound: Presence of gas in the bladder wall. Also, help to detect the presence of a tumor or a stone.	Urine culture
	Prostatitis	-	+	-	+	+	+	-	-	Body aches	Increased leukocytes (>10 per high power field) on CBC Bacteria seen on urine culture Elevated C-reactive protein Transiently elevated PSA (prostate specific antigen) levels	Ultrasound: Focal hypoechoic region located in the peripheral part of the prostate CT scan: Edema of the prostate gland with diffuse enlargement,.	-
	Urethritis	-/-	+	-	+	+	+	-	-	Urethral discharge	Mucoid, mucopurulent, or purulent discharge Gram stain of urethral secretions demonstrating ≥2 WBC per field Positive leukocyte esterase test.	CT scan: Diffuse, circumferential urothelial wall thickening and contrast-enhancement Periureteric or perinephric fat stranding.	Urine culture
Urogenital trauma	Inserted bladder or ureteral catheters	-	-	-	+	+	+	-	-	History of trauma	Hematuria	Retrograde urethrogram (RUG)	Retrograde urethrogram (RUG)