1. Hematuria Dr Muzammil Koshish DCH, DNB Resident, JLN Hospital and Research Centre, Bhillai

2. Red or brown color change of urineIntermittent red or brown color urine a/w variety of clinical settingMedications (phenazopyridine, microbid, NSAID)Ingestion of beets or certain dyesMetabolitiesMyoglobinuria or hemoglobinuriaHematuria 3. Work upCentrifuge the specimen,Supernatant be tested forheme (hemoglobin or myoglobin) with a urine dipstick. 4. APPROACH TO A PATIENT WITH RED OR BROWN COLOURED URINE 5. CAUSES OF HEME-NEGATIVE RED URINEMedications Food dyesMetabolitiesDoxorubicin Beets (in selected patients) Bile pigmentsChloroquine Blackberries Homogentisic acidDesferoxamine Food coloringMelaninIbuprofenMethemoglobinIron sorbitolPorphyrinNitrofurantoin TyrosinosisPhenazopyridineUratesPhenolphthaleinRifampin 6. HematuriaMicroscopic hematuria> 50 RBCs / l ( 5 RBCs / HPF )Gross hematuria> 2500 RBCs / lAmerican Urological Association 7. The evaluation should address the following threequestions1. Are there any clues from the history or physical examination that suggest a particular diagnosis?2. Does the hematuria represent glomerular orextraglomerular bleeding?3. Is the hematuria transient or persistent? 8. a three-tube test may also help tolocate the source of bleeding inselected cases. Urethral: First 10-15 mL Bladder: Final 10-30 mL Upper urinary tract: Throughout 9. History and PhysicalExamination 10. History Abdominal or flank pain Dysuria, frequency, urgency Trauma Strenuous exercise Menstruation Recent URI/ sore throat Skin rashes/ skin infection Diarrhea (especially bloody) Joint pains/swellings Medications/toxins h/o sickle cell disease or sickle trait 11. Family history Hematuria ,Hearing loss,HTN,Stones,Renal disease,Dialysis or transplant,Sickle cell traitCoagulopathy, 12. Medication HxSubstances and Medications Affecting Urine ColorArtificial food coloringBeetsBerriesChloroquine (Aralen)Furazolidone (Furoxone)Hydroxychloroquine (Plaquenil)Nitrofurantoin (Furadantin)Phenazopyridine (Pyridium)PhenolphthaleinRifampin (Rifadin)Information from Restrepo NC, Carey PO. Evaluating hematuria in adults.Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood:Colo.: Micromedex, Inc., 1999. Accessed Sept. 24, 1998. 13. MECHANISM BY WHICH SELECTED DRUGS CAN CAUSE HEMATURIAInterstitial nephritis Captopril (Capoten) Cephalosporins Chlorothiazide (Diuril) Ciprofloxacin (Cipro) Furosemide (Lasix) NSAIDs Olsalazine (Dipentum) Omeprazole (Prilosec) Penicillins Rifampin (Rifadin) Silver sulfadiazine (Silvadene) Trimethoprim-sulfamethoxazole (Bactrim, SeptraPapillary necrosis Acetylsalicylic acid (aspirin) NSAIDsHemorrhagic cystitis Cyclophosphamide (Cytoxan) Ifosfamide (Ifex) Mitotane (Lysodren)Urolithiasis Carbonic anhydrase inhibitors Dichlorphenamide (Daranide) Indinavir (Crixivan) Mirtazapine (Remeron) Ritonavir (Norvir) Triamterene (Dyrenium) 14. Physical Exam Vital sign: BP, T, HR Skin: Rashes, evidence of trauma, bruising Abdomen for masses, tenderness (flank,suprapubics), bruits CVS: irregular irregular Edema (especially periorbital) Joint erythema, swelling, warmth Paleness, jaundice Careful inspection of external genitaliaIf BP is elevated, further evaluation is immediately warranted 15. Clues from the history and physical examinationthat point toward a specific diagnosis1. Concurrent pyuria and dysuria, indicate UTI.2. A recent URI, raise the possibility of either post infectiousglomerulonephritis or IgA nephropathy3. A positive family history of renal disease give suspicion of hereditarynephritis, polycystic kidney disease, or sickle cell disease.4. Unilateral flank pain radiating to the groin, suggesting ureteralobstruction. Flank pain that is persistent or recurrent can also occur inthe rare loin pain hematuria syndrome. 16. Clues from the history and physical examination thatpoint toward a specific diagnosis5. Recent vigorous exercise or trauma6. History of a bleeding disorder or bleeding from multiple sites due tocoagulopathy.7. Medications that might cause nephritis (usually with other findings,typically with renal insufficiency).8. All should be screened for sickle cell trait or disease, which can lead topapillary necrosis and hematuria.9.Sterile pyuria with hematuria, which may occur with renal tuberculosis,analgesic nephropathy and other interstitial diseases. 17. Glomerular or Extra Glomerular bleeding? 18. Microscopic hematuria DDxGlomerular primary nephritis (post streptococcal glomerulonephritis, Ig Anephropathy, Anti-GBM disease) IInd nephritis (SLE, goodpastures syndrome, ANCA related vasculitis) Alports syndrome (hereditary nephritis) Thin basement membrane nephropathy (benign familial hematuria) 19. Microscopic hematuria DDx Non-glomerular Renal Malignancy vascular disease (malignant hypertension, AVM,nutcracker syndrome, renal veinthrombosis, sickle cell trait/disease, papillary necrosis) infection (pyelonephritis, TB, CMV, EBV) Hypercalciuria hereditary disease (polycystic kidney disease, medullarysponge kidney) 20. Nonrenal Nephrolithiasis Coagulopathy Trauma 21. Rare cause of Microscopic Hematuria Arteriovenous malformations and fistulas Nutcracker syndrome Loin pain-hematuria syndrome 22. Arteriovenous malformations and fistulas An AVmalformation (AVM) or fistula of the urologic tract may be either congenital oracquired. The primary presenting sign is gross hematuria, but high-output heartfailure and hypertension also may be seen . The latter is presumably due toactivation of the renin-angiotensin system resulting from ischemia distal to theAVMNutcracker syndrome The nutcracker syndrome refers to compressionof the left renal vein between the aorta and proximal superior mesenteric artery.Nutcracker syndrome can cause both microscopic and gross hematuria, primarily inchildren (but also adults) in Asia . The hematuria is usually asymptomatic but may beassociated with left flank pain. Nutcracker syndrome has also been associated withorthostatic proteinuria.Loin pain-hematuria syndrome The loin pain-hematuria syndromeis a poorly defined disorder characterized by loin or flank pain that is often severeand unrelenting, and hematuria with dysmorphic red cell features suggesting aglomerular origin. Affected patients usually have normal kidney function. 23. Extraglomerular vs Glomerular Extraglomerular GlomerularColor (if Red or pink Red, smoky brown, or "Coca-Cola"macroscopic)ClotsMay be presentAbsentProteinuria500 mg/dayRBC morphology NormalDysmorphicRBC castsAbsentMay be present 24. Dysmorphic erythrocytes are characterized by an irregular outer cell membrane andsuggest hematuria of glomerular origin.Red blood cell casts are also associated with a glomerular cause of hematuria. FIGURE 2. Dysmorphic erythrocytes from a urine specimen. These cells suggest a glomerular cause of microscopic hematuria. (phase contrast microscopy, 3 100) 25. Transient or persistent hematuria 26. Transient hematuriaTransient microscopic hematuria is a common problem inadultsFever, infection, trauma, and exercise are potential causesIt is reasonable to repeat an abnormal urinalysis in a fewdays 27. Persistent hematuriaWhen persistent hematuria is essentially the only manifestation of glomerulardisease, one of three disorders is most likelyIgA nephropathy, in which there is often gross hematuria, and sometimes apositive family history but without any clear pattern of autosomal inheritance Alport syndrome (hereditary nephritis), in which gross hematuria can occurin association with a positive family history of renal failure, and sometimesdeafness or corneal abnormalities.Thin basement membrane nephropathy (also called thin basementmembrane disease or benign familial hematuria), in which gross hematuria isunusual and the family history may be positive (with an autosomal dominantpattern of inheritance) for microscopic hematuria but not for renal failure . 28. Persistent hematuriaUnderlying malignancy is greater in patients with persistent hematuria inwhom there is no obvious cause from the historyThe primary underlying cancers are bladder, renal, and, much lessoften, prostate 29. Laboratory Tests (initial work up) UA andmicroscopy to determine the number and morphology ofRBC, crystal and casts Consider urine Cx CBC, PT, INR, electrolytes, kidney function Serum chemistries and serologic studies for glomerular causes ofhematuria as directed by the medical history Repeat UA in a few daysFurther urologic evaluation is warranted if more than fiveRBC/phf are found on at least two of three properlycollected urine specimens or if high-grade microscopichematuria (more than 100 red blood cells per high-powerfield) is found on a single urinalysis.17 30. Further Work upGlomerular causes: Consider a refer to nephrology for further evaluation and possible renal biopsy 31. Renal BiopsyA biopsy is not usually performed for isolatedglomerular hematuria (i.e., no proteinuria or renalinsufficiency,) since there is no specific therapy forthese conditionsHowever, biopsy should be considered if there isevidence of progressive disease as manifested by anelevation in the plasma creatinine concentration,increasing protein excretion, or an otherwiseunexplained rise in blood pressure, even when thevalues remain within the normal range 32. Further Work upNon-glomerular causes: CT, renal US, and/or IVP: to search for lesions in the kidney, collecting system, ureters, and bladder Consider a referral to urology for cystoscopy 33. RADIOLOGIC AND OTHER TESTS FOR THE EVALUATION OF HEMATURIATestAdvantagesDisadvantagesExcellent visualization of theMay miss bladder lesions; canIntravenous pyelogram (IVP) kidney, collecting system, andcause nephrotoxicity,ureteridiosyncratic reactions (1/10,000)Best way to examine the bladder,Invasive, uncomfortable andCystoscopywhich is not as well visualized byexpensiveIVP or ultrasoundIf of good quality, as sensitive asLess sensitive than IVP for ureterUltrasoundIVP for renal lesions, with lessand bladdermorbidity and costThe best test for examing the Invasive, not useful forRetrograde pyelographyureters, can be combined with examining other parts of thecystoscopyurinary collecting systemSensitivity 67 percent, specificityUseful only for cancer, mainly ofUrinary cytology96 percent for uroepithelialthe bladdercancerExcellent for examining theCT scan, DTPA, DMSA renal parenchyma andExpensivefunctioningUseful for gross hematuria whenother tests have not revealed theAngiography Invasive, expensivecause; the only good test forvascular malformations 34. SCREENING FOR HEMATURIA Not recommended 35. Reference:1.Significance of microhaematuria in young adults. AU Froom P; Ribak J; Benbassat J SO Br Med J (Clin Res Ed)1984 Jan 7;288(6410):20-2.2. Asymptomatic microhematuria and urologic disease. A population-based study3. Asymptomatic microscopic hematuria in adults: summary of the AUA best practice policy recommendations. AUGrossfeld GD; Wolf JS Jr; Litwan MS; Hricak H; Shuler CL; Agerter DC; Carroll PR SO Am Fam Physician 2001Mar 15;63(6):1145-54.U Mohr DN; Offord KP; Owen RA; Melton LJ 3d SO JAMA 1986 Jul 11;256(2):224-94. The left renal entrapment syndrome: diagnosis and treatment. AU Zhang H; Li M; Jin W; San P; Xu P; Pan S SOAnn Vasc Surg. 2007 Mar;21(2):198-203.5. Heavy phenacetin use and bladder cancer in women aged 20 to 49 years. AU Piper JM; Tonascia J; Matanoski GMSO N Engl J Med 1985 Aug 1;313(5):292-5.6. Recent advances in the diagnosis and treatment of renal arteriovenous malformations and fistulas. AU Crotty KL;Orihuela E; Warren MM SO J Urol 1993 Nov;150(5 Pt 1):1355-9.7. Evaluation of Asymptomatic Microscopic Hematuria in Adults. TIMOTHY R. THALLER, M.DUniversity of Kansas Medical Center, Kansas City, Kansas LESTER P. WANG, M.D. Valley UrologyCenter, Renton, Washington8. Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood: Colo.: Micromedex, Inc., 1999.Accessed Sept. 24, 1998.9. Am Fam Physician 1989; 40(2):149-56, and Drugdex system. Englewood: Colo.: Micromedex, Inc., 1999.Accessed Sept. 24, 1998.10. Urothelial tumors of the urinary tract. In: Walsh PC, ed. Campbells Urology. 7th ed. Philadelphia:Saunders, 1998:2327-410.11. A quick reference for urologist, AUA 200612. Up to date 2008 36. Thank you