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hematuria

Blood in the urine. Generally > 3-5 RBC/hpf is considered abnormal. Etiology: 1) urinary tract infection a) cystitis - E coli - schistosomiasis b) pyelonephritis c) urethritis d) prostatitis 2) urinary stone - calcium stones most common - calcium oxalate stones & hyperoxaluria* 3) urogenital neoplasms a) bladder cancer (18% of gross hematuria in adults at a referral clinic) [6] b) renal cancer c) prostate cancer d) ureteral neoplasm 4) renal disease a) glomerulonephritis b) nephrolithiasis c) thin glomerular basement membrane disease (benign familial hematuria) d) hypertensive nephrosclerosis e) IgA nephropathy f) exercise-induced hematuria - lactic acidosis, generated during anaerobic conditions, causes passage of erythrocytes into the urine, through increased glomerular permeability [10] - proteinuria often accompanies the hematuria - exercise may exacerbate hematuria in patients with underlying glomerular disease such as IgA nephropathy [11] g) drug-induced hematuria h) papillary necrosis i) polycystic kidney disease j) renal infarct k) medullary sponge disease l) obstructive or reflux nephropathy m) tuberculosis n) renal vein thrombosis o) renal cancer 5) benign prostatic hypertrophy (BPH) 6) coagulopathy 7) sickle cell disease 8) trauma a) indwelling catheter b) meatal ulceration 9) endometriosis 10) pharmacologic agents a) cyclophosphamide b) penicillamine c) gold salts 11) false-positives may be due to: a) beets b) blackberries c) vaginal bleeding d) myoglobin e) drugs - rifampin - phenytoin - ibuprofen 12) idiopathic (50% of gross hematuria in adults at a referral clinic) [6] * see oxalate for food sources of oxalate History: - dysuria, frequency, pain, fever, bleeding between voidings, menstruation, renal stones & passage of stones, joint pain, color, timing, recent sore throat, streptococcal skin infection or upper respiratory tract infection, prior kidney infections, joint pain, travel, exposure to toxins - pattern: - initial hematuria (anterior urethral lesion) - terminal hematuria (bladder neck or prostate lesion) - hematuria throughout voiding (bladder or upper urinary tract) - family history (see management) Clinical manifestations: 1) otherwise asymptomatic hematuria is common 2) terminal hematuria (i.e. noted in later phase or with termination of urination) may arise from the bladder neck, posterior urethra or prostate (men) 3) blood arising independently of urine arises from the terminal urethra 4) brown or smokey urine arises from the kidney 5) gross hematuria is far more likely than microscopic hematuria to have a serious cause 6) manifestations of specific etiology Laboratory: 1) general investigation a) urinalysis with urine microscopy - dysmorphic RBC (especially acanthocytes), RBC casts & proteinuria suggest glomerulonephritis - serum complement may distinghish different glomerulonephritis [16] - isomorphic erythrocytes suggest urinary neoplasm, urinary stone, or UTI - pyuria suggests UTI - repeat microscopic hematuria - dipstick - detects > 5 RBC/hpf; >= 3 RBC/hpf [13] - detects hemoglobin & myoglobin - false positives - ascorbate > 5 mg/dL - contamination with povidone-iodine b) urine protein/creatinine ratio c) proteinuria & dysmorphic erythrocytes or RBC casts accompanying microscopic hematuria suggests glomerular etiology d) hematuria without proteinuria, dysmorphic erythrocytes or RBC casts suggests extraglomerular bleeding (i.e. nephrolithiasis, cancer, trauma, infections, medications) e) urine calcium for hypercalciuria - found is 1/3 of children referred for hematuria - found in some adults - 15% will develop nephrolithiasis - only after stone has been identified & hematuria has resolved [16] f) urine oxalate for hyperoxaluria g) serum chemistries - serum urea nitrogen - serum creatinine h) urine cytology for patients age > 50 years - not part of initial workup [13] - false positives may occur with nephrolithiasis - sensitivity & specificity of abnormal cytology for bladder cancer = 45 & 89%, respectively, thus not sufficiently sensitive to be clinically useful [7] 2) investigation guided by history, physical exam, urinalysis a) urine culture if indicated by urinalysis b) complete blood count (CBC) c) PT/PTT d) prostate-specific antigen (PSA) e) electrolytes f) serologies - antinuclear antibodies (ANA) - antistreptolysin O (ASO) - rapid plasma reagin (RPR) - antiglomerular basement membrane Ab - ANCA, c-ANCA, p-ANCA g) urine protein electrophoresis h) hemoglobin electrophoresis i) tuberculin skin test j urine for acid-fast bacilli k) immunohistochemical staining of erythrocytes for Tamm-Horsfall protein suggests renal origin l) renal biopsy Special laboratory: - renal biopsy for glomerular hematuria [3] - hematuria, proteinuria & progressive renal failure [18] - cystoscopy for adults > 35 years of age or risk factors for urologic malignancy [3] - not useful for glomerular hematuria [18] Radiology: 1) renal ultrasound (includes ureters & urinary bladder) - gross hematuria or confirmed microscopic hematuria - first line test in child, pregnant woman [16] - unable to detect renal neoplasms < 3 cm [18] 2) computed tomography (CT) - if ultrasound negative, pain suggesting urolithiasis [3] - if ultrasound shows solid or complex renal mass - contraindicated in pregnancy [3] - CT urography for unexplained post-glomerular hematuria [3] - first line in men, non-pregnant women - high radiation dose - risk of contrast-induced nephropathy - evaluation of asymptomatic microscopic hematuria unless pregnant, renal failure or contrast hypersensitivity [3] - abdominal CT with contrast delineates renal vasculature, renal neoplasms & renal cysts [3] - helical abdominal CT with without contrast for diagnosis of nephrolithiasis [3] - routine CT associated with increased costs, harms of secondary cancers, procedural complications, & false positives, with only a marginal increase in cancer detection [15] 3) intravenous pyelogram (IVP) for gross hematuria in the absence of infection - diagnosis uncertain or needs clarification after renal ultrasound - less radiation exposure than CT (~ 1/2) but less sensitive than CT (~1/2) [3] 4) magnetic resonance imaging (MRI) - avoid if GFR < 30 mL/min/1.73 m2 [3] - risk of gadolinium-induced nephrogenic systemic fibrosis - CT urography generally preferred as diagnostic test of choice [3] 5) plain film (X-ray) of abdomen (KUB) of uncertain value Differential diagnosis: - hemoglobinuria - myoglobinuria - porphyria - betanin from beets - pharmaceuticals - rifampicin - phenazopyridine Complications: - 0.7% of patients with persistent microscopic hematuria will develop end-stage renal disease [5] - bladder cancer - 0.8% in women eiyh microscopic hematuria, 1.9% in men - no patient < 50 years with bladder cancer on cystoscopy [14] Management: 1) hematuria should be evaluated even if patients are taking antiplatelet agents or anticoagulants [3,13] 2) confirmed microscopic hematuria a) renal ultrasound (includes ureters & urinary bladder) b) refer to urology for cystoscopy c) asymptomatic microcopic hematuria in children with otherwise normal exams may not require diagnostic evaluation [4] 3) gross hematuria (not cystitis or pyelonephritis) a) refer to urology for cystoscopy b) renal ultrasound (includes ureters & urinary bladder) vs CT urography c) see radiology d) carcinoma of the bladder is the most serious cause 4) high risk: treat as gross hematuria a) smoking b) exposure to benzene or aromatic amines c) age > 40 years d) history of urologic disorder e) dysuria f) analgesic abuse g) pelvic irradiation 5) idiopathic hematuria a) patient education - incidence of future serious disease is low b) follow up: - age > 50 years - urine cytology every 6 months - yearly cystoscopy - age < 50 years: observation 6) isolated hematuria with family history of hematuria may require monitoring of renal function & urine protein - renal failure may occur later in life [3]

Related

causes of hematuria hemoglobinuria pharmaceutical agents associated with hematuria red urine urine blood

Specific

exercise-induced hematuria microscopic hematuria

General

sign/symptom hemorrhage (bleeding)

References

  1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
  2. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 518-519
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Journal Watch 25(11):90-91, 2005 Bergstein J, Leiser J, Andreoli S. The clinical significance of asymptomatic gross and microscopic hematuria in children. Arch Pediatr Adolesc Med. 2005 Apr;159(4):353-5. PMID: 15809388 - Stapleton FB. Asymptomatic microscopic hematuria: time to look the other way? Arch Pediatr Adolesc Med. 2005 Apr;159(4):398-9. No abstract available. PMID: 15809399
  5. Vivante A et al. Persistent asymptomatic isolated microscopic hematuria in Israeli adolescents and young adults and risk for end-stage renal disease. JAMA 2011 Aug 17; 306:729 PMID: 21846854
  6. Mishriki SF et al. Half of visible and half of recurrent visible hematuria cases have underlying pathology: Prospective large cohort study with long-term followup. J Urol 2012 May; 187:1561. PMID: 22425074
  7. Mishriki SF et al. Routine urine cytology has no role in hematuria investigations. J Urol 2013 Apr; 189:1255. PMID: 23079371
  8. Margulis V, Sagalowsky AI. Assessment of hematuria. Med Clin North Am. 2011 Jan;95(1):153-9 PMID: 21095418
  9. Cohen RA, Brown RS. Clinical practice. Microscopic hematuria. N Engl J Med. 2003 Jun 5;348(23):2330-8. PMID: 12788998
  10. Bellinghieri G, Savica V, Santoro D Renal alterations during exercise J Ren Nutr. 2008 Jan;18(1):158-64. PMID: 18089464
  11. Mercieri A Exercise-induced hematuria UpToDate http://www.uptodate.com/contents/exercise-induced-hematuria
  12. Ganapathi L, Somers M A Child with Gross Hematuria. N Engl J Med 2015; 373:e11. August 27, 2015 PMID: 26308700 http://www.nejm.org/doi/full/10.1056/NEJMicm1410250
  13. Nielsen M, Qaseem A, for the High Value Care Task Force of the American College of Physicians. Hematuria as a Marker of Occult Urinary Tract Cancer: Advice for High-Value Care From the American College of Physicians. Ann Intern Med. Published online 26 January 2016 PMID: 26811233 http://annals.org/article.aspx?articleid=2484287
  14. Gonzalez AN, Lipsky MJ, Li G et al. The prevalence of bladder cancer during cystoscopy for asymptomatic microscopic hematuria. Urology 2019 Apr; 126:34 PMID: 30677457 https://www.goldjournal.net/article/S0090-4295(19)30073-1/fulltext
  15. Georgieva MV, Wheeler SB, Erim D et al Comparison of the Harms, Advantages, and Costs Associated With Alternative Guidelines for the Evaluation of Hematuria. JAMA Intern Med. Published online July 29, 2019. PMID: 31355874 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2739056 - Bauer SR, Carroll PR, Grady D. Hematuria Practice Guidelines That Explicitly Consider Harms and Costs. JAMA Intern Med. Published online July 29, 2019. PMID: 31355847 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2739052
  16. NEJM Knowledge+ Question of the week. Oct 15, 2019 https://knowledgeplus.nejm.org/question-of-week/4388 - Greenfield SP et al. Gross hematuria in children: a ten-year review. Urology 2007 Feb 3; 69:166 PMID: 17270642 - Johnson EK et al. Are stone protocol computed tomography scans mandatory for children with suspected urinary calculi? Urology 2011 Jul 5; 78:662 PMID: 21722946 - American College of Radiology. ACR appropriateness criteria: hematuria - child. 2012. https://acsearch.acr.org/docs/69440/Narrative/ - Viteri B, Reid-Adam J. Hematuria and proteinuria in children. Pediatr Rev 2018 Dec; 39:573 PMID: 30504250 Free PMC Article
  17. Ingelfinger JR Hematuria in Adults N Engl J Med 2021; 385:153-163. July 8 PMID: 34233098 https://www.nejm.org/doi/full/10.1056/NEJMra1604481
  18. NEJM Knowledge+ Nephrology/Urology
  19. Hematuria (Blood in the Urine) http://kidney.niddk.nih.gov/kudiseases/pubs/hematuria/index.htm