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]

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			Type of hematuria	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)	Microscopic		+	-	-	-	+	+	+	-	-
		Hereditary nephritis (Alport syndrome)	Microscopic	-	-	-	-	-	-	+	-	Cataract Hearing loss	Pyuria Red cell casts Cylindrical casts		-	-	Renal Biopsy Irregularly thin and attenuated GBM Splitting of GBM Scarring
		Poststreptococcal glomerulonephritis	Microscopic
		Mesangioproliferative glomerulonephritis	Microscopic
		Focal segmental glomerular sclerosis	Microscopic
		Rapidly progressive glomerulonephritis	Microscopic
		Lupus nephritis	Microscopic
		Thin basement membrane disease	Microscopic
		Fabry disease	Microscopic
	Tubulointerstitial diseases	Renal papillary necrosis	Gross
		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	Micro/Gross	+	-	-	-	-	-	+	+	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	Micro/Gross	+	+	+	-	-	-	-	-	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
		Malignant hypertension
		Polyarteritis nodosa
		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	Gross	+	+	+	+	+	+	-	-	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
		Urethritis
		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
		Prosthetic heart valve
	Myoglobinuria	Crush injury
		Vigorous muscle exercise
		Hyperthermia (Heat stroke)
		Electric shock
		Prolonged seizure
		Polymyositis
		Trichinosis
		Haff disease
		Animal venom bite
	Chemicals	Phenazopyridine
		Beet (Beeturia)