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	CBC	Biomarkers	Urinalysis	Ultrasonography	CT scan	Other
							Dysuria	Frequency	Oliguria										Light microscopy	Electron microscopy	Immunoflourescence pattern
Hematuria	Glomerular diseases	IgA nephropathy (Berger nephropathy)	Microscopic
		Hereditary nephritis (Alport syndrome)	Microscopic
		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
		Medullary sponge kidney
	Vascular diseases	Arteriovenous renal malformations
		Renal vein thrombosis
		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
		Cystitis
		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)

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