Hematuria differential diagnosis

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Steven C. Campbell, M.D., Ph.D. Associate Editor(s)-in-Chief: Omer Kamal, M.D.[1], Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [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
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
  • 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
- - - - - Biopsy -
Fabry disease - - - - - - + + -
  • Hematuria
  • Proteinuria
- - - Non-specific+/- nephrotic picture - - -
Disease Low back pain Fever Nausea/

Vomiting

Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Ultrasonography CT scan Other Light microscopy Immunoflourescence pattern Gold standard Additional findings
Tubulointerstitial diseases + + + Rash N Rules out obstruction , if any
  • Edema and infiltration by mononuclear cells, (principally lymphocytes)
  • Eosinophils are present, often in large numbers.
Renal biopsy
Nephrolithiasis + ± + ± ± ±
  • Radiating pain to groin
Reflux nephropathy (hydronephrosis) + + - - - - - +
  • Elevated WBC count
  • Elevated BUN
  • Hyperkalemia
Malignancy Renal cell carcinoma (RCC)
Nephroblastoma
Transitional cell carcinoma (TCC)
Prostate cancer
Disease Low back pain Fever Nausea/

Vomiting

Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Ultrasonography CT scan Other Light microscopy Immunoflourescence pattern Gold standard Additional findings
Familial diseases Polycystic kidney disease + - - - - - + +
  • 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
  • Used as diagnostic screening
  • Renal venography: Gold standard
Polyarteritis nodosa - -/+ - - - + + -
  • CBC may show:
    • Leukocytosis
    • Normochromic anemia
    • thrombocytosis
Wegner's granulomatosis polyangiitis - - - - - - + +
  • URTI
  • CNS involvement
  • Ophthalmic involvement
  • Proteniuria
  • Microscopic hematuria
  • RBC casts
- CT chest +C ANCA antibodies - Biopsy
Henoch-Schönlein purpura
Disease Low back pain Fever Nausea/

Vomiting

Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Ultrasonography CT scan Other Light microscopy Immunoflourescence pattern Gold standard Additional findings
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
  • Rule out obstruction
  • Urine cytology to screen for bladder cancer
  • Biopsy to rule out cancer
Urolithiasis + +/- + +
Interstitial cystitis
Radiogenic cystitis
Systemic diseases Coagulopathy (hemophilia)
Sickle cell anemia
Abdominal aortic aneurysm
Lymphomas
Multiple myeloma
Disease Low back pain Fever Nausea/

Vomiting

Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Ultrasonography CT scan Other Light microscopy Immunoflourescence pattern Gold standard Additional findings
Infectious diseases Pyelonephritis + + + + + + - -
  • Enlarged kidneys

Contrast nephrograms

-
Cystitis - - - + + + - -
  • Presence of a gas in the bladder wall.
  • Also help to detect the presence of a tumor or a stone.
MRI
Prostatitis - + - + + + - -
  • Body aches
  • Focal hypoechoic region located in the peripheral part of the prostate
  • Hyperintense lesions on MRI
  • Neutrophils
  • Between the epithelial cells or inside the stroma.
Urethritis -/- + - + + + - -
  • Urethral discharge

-

  • Diffuse, circumferential urothelial wall thickening and contrast-enhancement
  • Periureteric or perinephric fat stranding.
-
Epididymitis -/+ + + - - - - -
Urogenital trauma Inserted bladder or ureteral catheters
Disease Low back pain Fever Nausea/

Vomiting

Dysuria Frequency Oliguria Hypertension Pitting edema Other Lab Findings Ultrasonography CT scan Other Light microscopy Immunoflourescence pattern Gold standard Additional findings
Hemoglobinuria Autoimmune hemolytic anemia
Microangiopathic hemolytic anemia
Thrombotic thrombocytopenic purpura
Paroxysmal nocturnal hemoglobinuria

References

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