Evaluation of Microscopic Hematuria Alon Z. Weizer, MD, MS Division of Urologic Oncology Department of Urology University of Michigan

Microscopic Hematuria (MH) Objectives of Presentation Objectives of Presentation –Appreciate the importance & possible etiologies of MH –Understand the proper determination of MH –Consider the steps in evaluation of MH –Articulate recommended follow-up in cases of MH with negative initial evaluation

Why Evaluate MH? Gross hematuria is very often an indication of disease Although less ominous, MH also can be an indication of disease While many of these abnormalities are minor, some are significant and/or life-threatening

Possible Causes Life-Threatening – –Cancer Renal parenchyma Renal pelvic Ureteral Bladder Prostatic Urethral Penile – –AAA Require Treatment Require Treatment –Calculi –Vesico-ureteral reflux –Infection –Ureteral obstruction –Symptomatic urethral obstruction –Renal parenchymal disease –Symptomatic BPH –Renal artery stenosis –Renal vein thrombosis

Urothelial Tumors

Renal Mass

Prevalence of MH 0.2% to 16% in population studies 2.5% to 21% in screening programs 13% to 21% in men >60 years old Likelihood of finding etiology of MH varies with risk – –Low risk: Significant finding <5% – –High risk: Significant finding >50%

Updated Clinical Guidelines AUA Best Practices Panel: – –Urology, Nephrology, Family Medicine, Radiology – –Literature review & expert opinion – –Critique of document by other physicians – –Approval of AUA

Purpose of Recommendations Resource for urologists & PCPs Directed towards evaluation of asymptomatic MH in adults Not meant to address: – –Screening for hematuria – –Gross hematuria – –Symptomatic hematuria – –Pediatric age group

Determination of MH Freshly voided, clean-catch, midstream specimen Dipstick for Hb is screening test only – –95% sensitive, but only ~80% specific – –In population with 10% hematuria, PPV of Dipstick is only 35% Positive Dipstick must be confirmed by microscopy (>3 RBC/hpf)

Determination of MH >3 RBC/hpf is standard criterion >3 RBC/hpf is standard criterion –1 to 2 RBC/hpf doesn’t require evaluation in most –However, it might if risk factors present Just 1 specimen with hematuria should prompt evaluation Just 1 specimen with hematuria should prompt evaluation –Old rule: 2 of 3 properly collected specimens was standard criterion

Why the Change? There is substantial evidence that MH caused by a serious underlying condition can be highly intermittent Studies that evaluated patients after 1 positive sample, rates of malignancy in most were over 2% Non-life-threatening diagnoses that would benefit from active management or follow-up are frequently found

Risk Factors for Significant Disease Smoking history Occupational exposure to chemicals or dyes – –Benzenes or aromatic amines History of analgesic abuse Age >40 years Significant urological history – –Previous gross hematuria – –Irritative voiding symptoms – –Urinary tract infection – –Prior pelvic radiation

Determination of MH Hematuria cannot be determined in presence of squamous epithelial cells Hematuria cannot be determined in presence of squamous epithelial cells These cells may indicate contamination from source outside urinary tract These cells may indicate contamination from source outside urinary tract –Frequent in women Difficultly obtaining perfect clean-catch specimenDifficultly obtaining perfect clean-catch specimen –Occasionally in men Phimosis (cells from foreskin)Phimosis (cells from foreskin) –Squamous cells may be present in bladder urine

Determination of MH If there appears to be hematuria, but squamous cells are present, then get catheterized specimen If there appears to be hematuria, but squamous cells are present, then get catheterized specimen –Most common reason for “unnecessary” hematuria referral = contaminated specimen –Conversely, urine w/o RBCs is adequate for determination, even if there are squamous cells

Glomerular Hematuria Origin of blood from renal parenchymal disease can be suggested by UA Origin of blood from renal parenchymal disease can be suggested by UA –Dysmorphic RBCs (variable size & shape w/irregular outline) → sensitive –Plain microscopy, or may need inverted phase- contrast microscopy

Asymptomatic MH Rule Out Benign Causes: Menstruation Vigorous Exercise Sexual Activity Viral Illness Trauma Infection Rule Out Benign Causes: Menstruation Vigorous Exercise Sexual Activity Viral Illness Trauma Infection Resolved after Tx or delay Persistent No Evaluation Evaluation Required History and Physical Examination

Evaluation: H&P Gross or microscopic? – –Gross more often assoc w/significant disease Initial, terminal or total? – –Initial = urethra, terminal = bladder neck/prostate Pain, dysuria, bladder irritability – –Suspect infection or obstruction Anti-coagulated – –Still require evaluation

Evaluation: H&P Sickle cell, diabetes Family or personal history of calculi, PCKD, other GU/Neph diseases Trauma, physical or sexual activity Tobacco use, occupational exposure Association with menses Fever, palpable mass, atrial fibrillation, visible blood at meatus, CVAT

Confirmed MH (obtain Serum Cr) Confirmed MH (obtain Serum Cr) Suggestion of Primary Renal Disease? Proteinuria* (> 500 to 1000 mg / day) Dysmorphic RBCs or RBC casts Elevated Serum Cr Suggestion of Primary Renal Disease? Proteinuria* (> 500 to 1000 mg / day) Dysmorphic RBCs or RBC casts Elevated Serum Cr YesYesNoNo Urology Referral + Concurrent Nephrology Evaluation Urology Referral + Concurrent Nephrology EvaluationUrologicalEvaluationUrologicalEvaluation * Dipstick >1+ for protein prompts 24 hr urine

Purpose of Urological Eval Upper tract imaging – –Diseases of the kidney & ureter – –Most commonly &/or significantly: Calculi Urothelial lesions Obstruction Renal masses Cystoscopy – –Diseases of the bladder & urethra – –Most commonly &/or significantly: Bladder cancer BPH Urethral strictures

Urological Evaluation for Asymptomatic MH Upper Tract Imaging Multi-phasic CT urography Alternative1 : MR urography Alternative 2: RPGs w/MRI Upper Tract Imaging Multi-phasic CT urography Alternative1 : MR urography Alternative 2: RPGs w/MRI Follow-up Protocol Abnormal? Treat Cystoscopy In patients ≥35 years & Patients w/RFs regardless of age (Discretionary: those <35 w/o RFs) Cystoscopy In patients ≥35 years & Patients w/RFs regardless of age (Discretionary: those <35 w/o RFs) Yes Abnormal? Yes No Consider Urine Cytology

Imaging Modalities Computed Tomography – –Best modality for characterization of small renal masses – –More widely available & less expensive than MRI – –Best modality for calculi, renal and perirenal infection & associated complications – –Sensitivity for urothelial lesions not defined with certainty, but thought to be good with “urography” technique

Calculus

Renal Mass

CTUrogram

Other Options MR urography – –Pregnancy, patients with iodinated contrast allergy – –Risk of nephrogenic systemic fibrosis in patients with renal insufficiency Retrograde pyelograms combined w/magnetic resonance imaging

Follow-Up Protocol UA at 12 & 24 months – –If negative for 2 consecutive years, then D/C If persistent asympomatic MH, repeat urological evaluation w/in 3 – 5 years If gross hematuria or new voiding sx, repeat urological evaluation

Before Urological Referral Determine if this is real MH – –>3 RBC/hpf – –Catheterized urine if squamous cells Exclude benign causes w/H&P Likely glomerular → Refer to neph, too Obtain serum Cr Order imaging