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, 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.

Differentiating Hemoglobinuria from Myoglobinuria

Centrifuse Result

Sediment Red

Supernatant Red

Hematuria

Dipstick heme

Negative

Positive

❑ Beeturia ❑ Phenazopyridine ❑ Porphyria ❑ Other

❑ Myoglobin ❑ Hemoglobin

Plasma color

Clear

Red

Myoglobinuria

Hemoglobinuria

CATEGORY	EXAMPLES	COMMON CLINICAL PRESENTATION AND RISK FACTORS
Neoplasm	Any	Male gender, Age older than 35 years, Past or current smoking history, Occupational or other exposure to chemicals or dyes (benzenes or aromatic amines), Analgesic abuse, History of gross hematuria, History of urologic disorder or disease, History of Irritative voiding symptoms, History of pelvic irradiation, History of chronic urinary tract infection, Exposure to known carcinogenic agents or chemotherapy such as alkylating agents, History of chronic indwelling foreign body
	Bladder cancer	Older age, male predominance, tobacco, occupational exposures, Irritative voiding symptoms
	Ureteral or renal pelvis cancer	Family history of early colon cancers or upper tract tumors, flank pain
	Renal cortical tumor	Family history of early kidney tumors, flank pain, flank mass
	Prostate cancer	Older age, family history, African-American
	Urethral cancer	Obstructive symptoms, pain, bloody discharge
Infection/inflammation	Any	History of infection
	Cystitis	Female predominance, dysuria
	Pyelonephritis	Fever, flank pain, diabetes, female predominance
	Urethritis	Exposure to sexually transmitted infections, urethral discharge, dysuria
	Tuberculosis	Travel to endemic areas
	Schistosomiasis	Travel to endemic areas
Calculus	Nephroureterolithiasis	Flank pain, family history, prior stone
	Bladder stones	Bladder outlet obstruction
Prostatic cause	Benign prostatic enlargement	Male, older age, obstructive symptoms
Medical renal disease	Any	Hypertension, azotemia, dysmorphic erythrocytes, cellular casts, proteinuria
	IgA nephropathy	Upper respiratory tract infection, gastroenteritis, synchronous association of pharyngitis, children
Congenital or acquired anatomic abnormality	Polycystic kidney disease	Family history of renal cystic disease
	Uretero-pelvic junction obstruction	History of UTI, stone, flank pain
	Ureteral stricture	History of surgery or radiation, flank pain, hydronephrosis; stranguria, spraying urine
	Urethral diverticulum	Discharge, dribbling, dyspareunia, history of UTI, female predominance
	Fistula	Pneumaturia, Fecaluria, abdominal pain, recurrent UTI, history of diverticulitis or colon cancer
Other	Exercise-induced hematuria	Recent vigorous exercise
	Endometriosis	Cyclic hematuria in a menstruating woman
	Hematologic or thrombotic disease	Family history of personal history of bleeding or thrombosis
	Papillary necrosis	African-American, sickle cell disease, diabetes, analgesic abuse
	Interstitial cystitis	Voiding symptoms

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	CBC	Biomarkers	Urinalysis	Ultrasonography	CT scan	Other
				Dysuria	Frequency	Oliguria										Light microscopy	Electron microscopy	Immunoflourescence pattern
Differential Diagnosis 1
Differential Diagnosis 2
Differential Diagnosis 3
Diseases	Symptom 1	Symptom 2	Symptom 3				Physical exam 1	Physical exam 2	Physical exam 3	Lab 1	Lab 2	Lab 3	Imaging 1	Imaging 2	Imaging 3	Histopathology			Gold standard	Additional findings
Differential Diagnosis 4
Differential Diagnosis 5
Differential Diagnosis 6

Gross hematuria	Causes of hematuria		Sub-entity	Causes and associations	History and Symtoms											Laboratory Findings
					History	Shaking, chills and rigors	Fever	Nausea/vomiting	Dysuria	Frequency	Pitting edema	Hypertension	Hemoptysis	Oliguria	Peri-orbital edema (Facial puffiness)	Urinalysis	Cystoscopy	Hyperlipidemia and hypercholesterolemia	Nephrotic features	Nephritic features	ANCA	Anti-glomerular basement membrane antibody (Anti-GBM antibody)	Immune complex formation	Light microscope	Electron microscope	Immunoflourescence pattern
	Urolithiasis (Renal stones)- may be microscopic		Calcium oxalate stones Calcium phosphate stones Uric acid stones Magnesium ammonium phosphate stones Cysteine stones	Low calcium diet Hyperparathyroidism Hypocalcemic hypercalciuria Anatomic abnormalities of the urinary tract Obesity Dehydration Diets rich in oxalate Urinary tract infection Increased or decreased urinary pH	Episodic lower back pain radiating to the groin	+/-	+/-	+	+	-	-	-	-	+	-	> 5 RBCs/hpf (exaggerated in gross hematuria)	-	-	-	-	-	-	-	-	-	-
	Renal tumors- may be microscopic
	Renal cysts
	Prostatitis
	Benign prostatic hyperplasia (BPH)- may be micrscopic
	Anti-coagulant use- may be microscopic		Oral anticoagulant use
			Heparin
			Aspirin
			Clopidogrel
			Ticlopidine
			Factor Xa inhibitors
	Bladder tumors- may be micrscopic		Transitional cell carcinoma	Male sex Past or current smoking Exposure to known carcinogenic agents or alkylating chemotherapeutic agents	Age older than 35 years Exposure to chemicals or dyes (benzenes or aromatic amines) Chronic indwelling foreign body Chronic urinary tract infection Pelvic irradiation	-	-		+/-	+/-	-	-	-	-	-
	Urinary tract infection- may be microscopic
	Tuberculosis
	Schistomsomiasis
	Hemorrhagic cystitis
	Renal infarction
	Recent urologic procedure
Microscopic hematuria	Glomerulonephritides	Non-proliferative	Minimal change disease	Idiopathic Protein tyrosine phosphatase receptor type O (glomerular epithelial protein 1- GLEPP1)	Young children Recent infection and immunization Atopy Hodgkin lymphoma Thrombosis (due to urinary loss of antithrombin-III)						+	-	-	+/-	-			+	+	-	-	-	-	Normal	Fusion of podocytes	-
			Focal segmental glomerulosclerosis	Idiopathic HIV Heroine use Sickle cell disease Interferon Severe obesity Mixed cryoglobunemia (Hepatitis C)	Adults						+	-	-	+/-	-			+	+	-	-	-	-	Focal (some glomeruli) and segmental (only part of glomerulus)	Effacement of podocytes	-
			Membranous glomerulonephritis	Idiopathic Hepatitis B and C Solid tumors Systemic lupus erythmatosus Drugs (NSAIDS, penclliamine, gold, captopril)							+	-	-	+/-	-			+	+	-	-	-	+	Thick glomerular basement membrance	Sub-epithelial immune complex depositis with 'spike and dome' appearance	-
		Proliferative	IgA nephropathy	Idiopathic Viral infections	Young children History of mucosal infections (e.g. gastroenteritis) and upper respiratory tract infection 2-3 days after infection (synpharyngitic)						+/-	+	-	+	+/-			-	-	+	-	-	+	Crescent formation	Mesangial proliferation	-
			Rapidly progressive glomerulonephritis	Goodpasture syndrome	Young adults						+/-	+	+	+	+			-	-	+	-	+	+	Hypercellular and inflamed glomeruli (Crescent formation)	Diffuse thickening of the glomerular basement membrane with absence of subepithelial and subendothelial deposits	+ (Linear)
				Post infectious glomerulonephritis	Streptococcal skin infections Streptococcal pharyngitis 2-3 weeks after infection						+/-	+	+	+	+			-	-	+	-	-	+	Hypercellular and inflamed glomeruli	Sub-epithelial immune complex deposits	+ (Granular)
				Granulomatosis with polyangitis (Wegner's granulomatosis)	Necrotizing granulomas (Nasopharynx, lungs, kidneys) Conjunctivitis Ulceration of the cornea Episcleritis Peripheral neuropathy						+/-	+	+	+	+			-	-	+	+ (C-ANCA)	-	-	Hypercellular and inflamed glomeruli (Crescent formation)	- (pauci-immune)	+/-
				Churg Strauss syndrome	Necrotizing granulomas (Lungs and kidneys) Asthma Peripheral neuropathy						+/-	+	+	+	+			-	-	+	+ (C-ANCA)	-	-	Hypercellular and inflamed glomeruli (Crescent formation)	- (pauci-immune)	-
				Microscopic polyngitis	Necrotizing vasculitis (no granuloma)						+/-	+	+	+	+			-	-	+	+ (P-ANCA)	-	-	Hypercellular and inflamed glomeruli (Crescent formation)	- (pauci-immune)	-
			Membranoproliferative glomerulonephritis	Idiopathic Hepatitis B and C (Type 1) C3 nepritic factor (Type2)	hematuria Oliguria Periorbital edema Hypertension						+/-	+	+	+	+			-	+	-	-	-	+	Thick glomerular basement membrane (Tram-track appearance)	Mesangial proliferation and leukocyte infiltration	+ (Granular)
	Henoch-Schonlein purpura
	Alport's syndrome
	Diabetic glomerulosclerosis
	Interestitial nephritis
	Renal papillary necrosis
	Renal artery stenosis