16 TI Clinical practice. Microscopic hematuria. AU Cohen RA; Brown RS SO N Engl J Med 2003 Jun 5;348(23):2330-8.
Concurrent pyuria and dysuria, which are usually indicative of a urinary tract infection, but may also occur with bladder malignancy. A recent upper respiratory infection, suggesting either postinfectious glomerulonephritis or IgA nephropathy (see "Hematuria following an upper respiratory infection"). A positive family history of renal disease, as in hereditary nephritis, polycystic kidney disease, or sickle cell disease. Unilateral flank pain, which may radiate to the groin, suggesting ureteral obstruction due to a calculus or blood clot, but can occasionally be seen with malignancy. Flank pain that is persistent or recurrent can also occur in the rare loin pain hematuria syndrome. (See "Loin pain hematuria syndrome"). Symptoms of prostatic obstruction in older men such as hesitancy and dribbling. The cellular proliferation in benign prostatic hyperplasia (BPH) is associated with increased vascularity, and the new vessels can be fragile. There is some controversy about whether hematuria is more common in these patients than in age-matched controls [11,17] . However, there is general agreement that the presence of BPH should not dissuade the clinician from pursuing further evaluation of hematuria, particularly since older men are more likely to have more serious disorders such as cancer of the prostate or bladder. Among those with gross hematuria in whom no other cause can be identified, finasteride usually suppresses the hematuria [18,19] . (See "Medical treatment of benign prostatic hyperplasia"). Recent vigorous exercise or trauma (see "Exercise-induced hematuria"). History of a bleeding disorder or bleeding from multiple sites due to uncontrolled anticoagulant therapy. In contrast, it should not be assumed that hematuria alone can be explained by chronic warfarin therapy. In one report of 243 patients prospectively followed for two years, the incidence of hematuria was similar to that in a control group not receiving warfarin  . Furthermore, evaluation of patients who developed hematuria revealed a genitourinary cause in 81 percent of cases. Infection was most common, but papillary necrosis, renal cysts, and several malignancies of the bladder were also found. A smaller study found significant urinary tract disease in nine of 30 patients, two of whom had bladder cancer  . These observations indicate that hematuria in an anticoagulated patient should generally be evaluated in the same fashion as in other patients unless there is evidence of bleeding from multiple sites with markedly abnormal coagulation studies.Cyclic hematuria in women that is most prominent during and shortly after menstruation, suggesting endometriosis of the urinary tract  . Contamination with menstrual blood is always a possibility, and should be ruled out by repeating the urinalysis when menstruation has ceased. Medications that might cause nephritis (usually with other findings, typically with renal insufficiency). Black patients should be screened for sickle cell trait or disease, which can lead to papillary necrosis and hematuria. (See "Renal manifestations of sickle cell disease"). Travel or residence in areas endemic for Schistosoma hematobium, or tuberculosis. Sterile pyuria with hematuria, which may occur with renal tuberculosis, analgesic nephropathy and other interstitial diseases. 22 Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 33-1992. A 34-year-old woman with endometriosis and bilateral hydronephrosis. N Engl J Med 1992; 327:481.
Hematuria Dr Muzammil Koshish DCH, DNB Resident, JLN Hospital and Research Centre, Bhillai
Red or brown color change of urineIntermittent red or brown color urine a/w variety of clinical setting Medications (phenazopyridine, microbid, NSAID) Ingestion of beets or certain dyes Metabolities Myoglobinuria or hemoglobinuria Hematuria
Work upCentrifuge the specimen,Supernatant be tested forheme (hemoglobin or myoglobin) with a urine dipstick.
APPROACH TO A PATIENT WITH RED OR BROWN COLOURED URINE
CAUSES OF HEME-NEGATIVE RED URINEMedications Food dyes MetabolitiesDoxorubicin Beets (in selected patients) Bile pigmentsChloroquine Blackberries Homogentisic acidDesferoxamine Food coloring MelaninIbuprofen MethemoglobinIron sorbitol PorphyrinNitrofurantoin TyrosinosisPhenazopyridine UratesPhenolphthaleinRifampin
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?
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
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 genitalia•If BP is elevated, further evaluation is immediately warranted
Clues from the history and physical examination that point toward a specific diagnosis1. Concurrent pyuria and dysuria, indicate UTI.2. A recent URI, raise the possibility of either post infectious glomerulonephritis or IgA nephropathy3. A positive family history of renal disease give suspicion of hereditary nephritis, polycystic kidney disease, or sickle cell disease.4. Unilateral flank pain radiating to the groin, suggesting ureteral obstruction. Flank pain that is persistent or recurrent can also occur in the rare loin pain hematuria syndrome.
Clues from the history and physical examination that point 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.
Rare cause of Microscopic Hematuria Arteriovenous malformations and fistulas Nutcracker syndrome Loin pain-hematuria syndrome
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.
Extraglomerular vs Glomerular Extraglomerular GlomerularColor (if Red or pink Red, smoky brown, or "Coca-Cola"macroscopic)Clots May be present AbsentProteinuria <500 mg/day May be >500 mg/dayRBC morphology Normal DysmorphicRBC casts Absent May be present
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)
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
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 .
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
Laboratory Tests (initial work up)• UA and microscopy to determine the number and morphology of RBC, crystal and casts• Consider urine Cx• CBC, PT, INR, electrolytes, kidney function• Serum chemistries and serologic studies for glomerular causes of hematuria as directed by the medical history• Repeat UA in a few days Further urologic evaluation is warranted if more than five RBC/phf are found on at least two of three properly collected urine specimens or if high-grade microscopic hematuria (more than 100 red blood cells per high-power field) is found on a single urinalysis.17
Further Work up•Glomerular causes: Consider a refer to nephrology for further evaluation and possible renal biopsy
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
Further Work up•Non-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
RADIOLOGIC AND OTHER TESTS FOR THE EVALUATION OF HEMATURIATest Advantages Disadvantages Excellent visualization of the May miss bladder lesions; canIntravenous pyelogram (IVP) kidney, collecting system, and cause nephrotoxicity, ureter idiosyncratic reactions (1/10,000) Best way to examine the bladder, Invasive, uncomfortable andCystoscopy which is not as well visualized by expensive IVP or ultrasound If of good quality, as sensitive as Less sensitive than IVP for ureterUltrasound IVP for renal lesions, with less and bladder morbidity and cost The best test for examing the Invasive, not useful forRetrograde pyelography ureters, can be combined with examining other parts of the cystoscopy urinary collecting system Sensitivity 67 percent, specificity Useful only for cancer, mainly ofUrinary cytology 96 percent for uroepithelial the bladder cancer Excellent for examining theCT scan, DTPA, DMSA renal parenchyma and Expensive functioning Useful for gross hematuria when other tests have not revealed theAngiography Invasive, expensive cause; the only good test for vascular malformations
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. AU Grossfeld GD; Wolf JS Jr; Litwan MS; Hricak H; Shuler CL; Agerter DC; Carroll PR SO Am Fam Physician 2001 Mar 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 SO Ann 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 GM SO 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.D University of Kansas Medical Center, Kansas City, Kansas LESTER P. WANG, M.D. Valley Urology Center, 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