Hematuria differential diagnosis

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Steven C. Campbell, M.D., Ph.D. Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [1] Omer Kamal, M.D.[2

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 disease which mimic hematuria especially hemoglobinuria and myoglobinuria which are dipstick positive but negative for microscopy.

Hematuria differential diagnosis

Differentiating the diseases that can cause hematuria:

Diseases			Clinical manifestations									Para-clinical findings						Gold standard	Additional findings
			Symptoms						Physical examination
												Lab Findings	Imaging			Histopathology
			Low back pain	Fever	Nausea/ Vomiting	Urinary symptoms			Hypertension	Pitting edema	Other		Ultrasonography	CT scan	Other
						Dysuria	Frequency	Oliguria								Light microscopy	Immunoflourescence pattern
Hematuria	Glomerular diseases	IgA nephropathy (Berger nephropathy)		+	-	-	-	+	+	+	-	-	-	-	Electron microscopy shows mesangial hypercellularity and increased mesangial matrix	Focal or diffuse mesangial proliferation Extracellular matrix expansion	IgA deposited in a diffuse granular pattern in the mesangium	Biopsy	-
		Hereditary nephritis (Alport syndrome)	-	-	-	-	-	-	+	-	Cataract Hearing loss	Pyuria Red cell casts Cylindrical casts	Shrunken kidneys	-	High-frequency sensorineural hearing loss	-	Monoclonal antibodies directed against alpha-3 (IV), alpha-4 (IV), and alpha-5 (IV) chains of type IV collagen	Genetic Analysis	-
		Poststreptococcal glomerulonephritis	+/-	+	-	-	+	+	+	+	Edema Anemia Increased Blood Pressure	Urine samples for protein and blood	Renal Biopsy Irregularly thin and attenuated GBM Splitting of GBM Scarring	-	-	Hypercellularity of the glomeruli Endothelial and mesangial cells and migrant inflammatory cells Hyaline droplets	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 Antineutrophil cytoplasmic antibody titers, serum protein electrophoresis	Shrunken kidneys	-	-	Segmental solidification in the perihilar region and peripheral areas, specially the tubular pole	Coarsely granular deposits of IgM and C3	Biopsy	-
		Rapidly progressive glomerulonephritis	+	+	+	-	-	-	+	-	Abdominal pain Painful cutaneous nodules Migratory polyarthropathy Sinusitis Cough Hemoptysis.	Low iron Eosinophilia Increased serum creatinine level Eleated LDH and CPK Proteinuria	-	-	-	Diffuse, proliferative, necrotizing glomerulonephritis with crescent formation	-	Biospy	80% of patients have ANCA-positive microscopic polyangiitis
		Lupus nephritis	-	+	-	-	-	-	+	+	Foamy dark urine Weight gain	Hematuria Pyuria Proteinuria Cellular casts Low iron	-	-	-	-	-	Biopsy	-
		Thin basement membrane disease
		Fabry disease	-	-	-	-	-	-	+	+	-	Hematuria Proteinuria	-	-	-	Non-specific+/- nephrotic picture	-	-	-
	Tubulointerstitial diseases	Renal papillary necrosis	Flank pain	+	–	+	+	±	Hypotension	±		Bacteriuria Pyuria Microscopic hematuria		Blunted renal calyces Contrast material–filled clefts in the renal medulla Non-enhanced lesions surrounded by rings of excreted contrast material Hyperattenuated medullarycalcifications
		Acute interstitial nephritis	+	+	+
		Analgesic
		Nephrolithiasis	+
		Reflux nephropathy (hydronephrosis)	+
	Malignancy	Renal cell carcinoma (RCC)	–
		Nephroblastoma
		Transitional cell carcinoma (TCC)
		Prostate cancer
	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	Unilateral or bilateral cysts	Hyperdense appearance, Septations Calcifications	Genetic testing demonstrates: Frame insertions/deletions Non-canonical splice site alterations Combined missense changes	Interstitial fibrosis Tubular atrophy Thickening and lamellation of tubular basement membranes Microcysts	Negative immunofluorescence for complement and immunoglobulin	Ultrasound
	Vascular diseases	Renal vein thrombosis	+	+	+	-	-	-	-	-	Asymptomatic Abdominal pain Acute in onset	Elevation in serum lactate dehydrogenase Cholesterol levels for hypercholesterolemia Albumin levels for hypoalbuminemia Serum complement levels	Diagnostic screening		Renal venography: Gold standard
		Polyarteritis nodosa	-	-/+	-	-	-	+	+	-	Fatigue Abdominal pain Unintentional weight loss Muscle aches	CBC may show: Leukocytosis Normochromic anemia thrombocytosis Hypergammaglobulinemia ESR and C-reactive protein Hepatitis B surface antigen and hepatitic C serologies
		Wegner's granulomatosis polyangiitis
		Henoch-Schönlein purpura
	Lower urinary tract diseases	Benign prostatic hyperplasia
		Urolithiasis
		Interstitial cystitis
		Radiogenic cystitis
	Systemic diseases	Coagulopathy (hemophilia)
		Sickle cell anemia
		Abdominal aortic aneurysm
		Lymphomas
		Multiple myeloma
	Infectious diseases	Pyelonephritis	+	+	+	+	+	+	-	-	Delirium Headache	Positive leukocyte esterase test and nitrite test. Blood/urine cultures	Enlarged kidneys	Round swollen kidneys Hypodense appearance Abscesses may not be present	Contrast nephrograms Focal areas of striated or wedge-shaped hypoperfusion	Neutrophils Interstitial fibrosis Renal casts	-
		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	Presence of a gas in the bladder wall. Also help to detect the presence of a tumor or a stone.		MRI Fibrosed bladder with a thick wall Hydronephrosis Calcification
		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	Focal hypoechoic region located in the peripheral part of the prostate	Edema of the prostate gland with diffuse enlargement,.	Hyperintense lesions on MRI	Neutrophils Between the epithelial cells or inside the stroma.
		Urethritis	-/-	+	-	+	+	+	-	-	Urethral discharge	Mucoid, mucopurulent, or purulent discharge Gram stain of urethral secretions demonstrating ≥2 WBC per field Positive leukocyte esterase test.	-	Diffuse, circumferential urothelial wall thickening and contrast-enhancement Periureteric or perinephric fat stranding.	-
		Epididymitis	-/+	+	+	-	-	-
		Cytomegalovirus
		Infectious mononucleosis
		Condylomata acuminata
	Urogenital trauma	Inserted bladder or ureteral catheters
	Drugs	Anticoagulants
Dark urine	Hemoglobinuria	Autoimmune hemolytic anemia
		Microangiopathic hemolytic anemia
		Thrombotic thrombocytopenic purpura
		Paroxysmal nocturnal hemoglobinuria
		Paroxysmal cold hemoglobinuria
		Falciparum malaria
	Myoglobinuria	Crush injury
		Vigorous muscle exercise
		Hyperthermia (Heat stroke)
		Electric shock
		Prolonged seizure
		Polymyositis
		Trichinosis
		Haff disease