Hematuria

Epidemiology Hematuria Defn- presence of excessive numbers of red blood cells (RBCs) in the urine macroscopic-- gross microscopic-- visible with the aid of a microscope only

Epidemiology Hematuria Normal patients can excrete 104 to 105 RBC in a 12-hr period Corresponds to several RBCs in the sediment of a randomly collected, centrifuged specimen under high power magnification therefore hematuria is >4 RBC/hpf of urine sediment

Epidemiology Hematuria Children prevalence of microheme approximately 4% majority have normal UAs on f/u and do not develop urinary tract pathology therefore isolated microheme in children does not require extensive evaluation

Epidemiology Hematuria recall dipsticks detect globin pigments-- not RBCs, therefore a positive dipstick must be validated by microscopy r/o myoglobinuria (rhabdomyolysis) and severe hemolysis

Hematuria Where did the RBCs come from? Glomerulus Tubule bladder urethra ureter penis vagina prostate rectum

Hematuria Glomerulus Tubule Where did the RBCs come from? ureter Proliferative GN Primary IgA Post-infx GN MPGN Crescentic GN Fibrillary GN Secondary HSP SLE Anti-GBM (Good pasture's) Systemic Vasculitis Chronic Bacteremia Cryoglobulinemia Hepatitis B/C Non-Proliferative Minimal Change FSGS Membranous HUS Familial Glomerular Dz Alport's syndrome Thin basement membrane disease Fabry disease Nail-Patella ureter prostate

Hematuria - Where did the RBCs come from? Glomerulus Tubule Renal Causes-- Non-Glomerular Familial ADPKD Medullary Cystic Disease Medullary Sponge Kidney Papillary Necrosis Analgesic abuse Sickle Cell Disease and Trait Renal TB DM Obstructive uropathy Alcoholism Anklosing Spondyltis Hydronephrosis Drugs interstitial nephritis Trauma Renal Contusion or laceration Exercise hematuria Neoplasms renal cell cancer Wilms tumor benign cysts tuberous sclerosis multiple myeloma Vascular renal infarct renal vein thrombosis malignant hypertension AVM Loin-pain hematuria Metabolic Hypercalcuria Hyperoxaluria Hyperuricosuria Cystinuria ureter prostate

Hematuria-- non renal Glomerulus Tubule bladder urethra ureter penis Calculi ureter, bladder, prostate Neoplasms TCC prostate Ca/BPH squamous cell Infections cystitis, prostatitis, urethritis TB Schistosomiasis Drugs cyclophosphamide anticoagulants Trauma Contusion/laceration exercise induced hematuria foreign body decompression of severely distended bladder Genital or anal bleeding bladder urethra ureter penis vagina prostate rectum

Hematuria History frequency/dysuria - UTI hesitancy, weak stream, and dribbling - bladder obstruction 2nd stone/tumor/ prostate colicky flank pain that radiates to groin-- stone or renal papillary necrosis arthralgia/arthritis/rash - systemic inflammatory disorder-- HSP, SLE, or other systemic vasculitis s/p bloody diarrhea -- think HUS

Hematuria History 1-2 weeks s/p pharyngitis/skin infection - post-strep GN family h/o deafness/hematuria/renal failure -Alport's syndrome (hereditary nephritis) transient hematuria s/p exertion foreign travel--Schistosoma haematobium

Hematuria Type of bleeding Color Clots brown or cola-colored-- usually kidney pink or red usually suggests extra-renal Clots usually indicated a non-renal source

Hematuria Physical Exam Vitals-- hypertension-- esp new c/w renal pathology HEENT- CV- Resp- Abd-- Ext-- edema more c/w renal pathology arthritis-- SLE/inflammatory d/o GU-- vaginal/rectal source of blood. BPH? Skin-- rash

Hematuria UA proteinuria accompanying hematuria is glomerular disease until proven otherwise don’t send to Urology to r/o stones/TCC Potential error-- HgB is a protein -- nl Hgb (12grams/dl), therefore hematuria (if hemolyzed) can easily cause measurable proteinuria Pyuria-- frequently seen with UTI/STDs

Hematuria Urine microscopy Crystals Casts-- presence also points toward renal pathology dysmorphic RBCs presence confirms glomerular disease, absence has no diagnostic implications

Hematuria Glomerular Labs Chem 7 serum complement low-- MPGN, SLE, cryoglobulinemia ASO and anti-Dnase B HepBsAG, anti-HC ANA Other (depending upon clinical scenario) anti-gbm-- pulm hemorr or rpgn anca- s/s of vasculitis cryoglobulins pt/ptt sickle screen

Hematuria Glomerular Additional studies/info r/o hereditary nephropathy Alport’s, Thin Basement Membrane Disease (AKA benign familial hematuria), and ADPKD screen all available family members with UA if Alport’s suspected audiologic examination anterior lenticonus, yellowish perimacular flecks

Hematuria Glomerular Biopsy considered on a case by case basis risks-- 1/2000 - 1/5000 risk of death, defining disease often will NOT result in a change in therapy avoid if s/p recent sore throat, acute nephritis, and low complements usually performed if associated with renal insufficiency, proteinuria, or low complement

Hematuria Nonglomerular Hematuria If pyuria- urine culture STD screen African-American consider SICKLE CELL TRAIT OR DISEASE h/o cytoxan therapy hemorrhagic cystitis

Hematuria Non-glomerular Hematuria If initial evaluation unremarkable: renal US KUB and >40yo, consider urology referral urine cytology cystoscopy

Initial Evaluation Rule out obvious benign causes Infection Activity Irritative sx’s or WBCs on U/A  Culture Treat appropriately Men – 30 days of quinolone & consider GU evaluation Repeat U/A in 6 weeks Activity Vigorous exercise, sex, virus, trauma, menses Repeat U/A 48+ hours after cessation External lesions Examine penis or perineum & vagina

Initial Evaluation Rule out nephrologic hematuria Proteinuria 1+ on dipstick, >500-1000 mg on 24 hr urine RBC Casts Pathognomonic for glomerular bleeding Dysmorphic RBCs Variation in size & shape, irregular/distorted outline Predominance suggest glomerular origin Renal insufficiency New rise in creatinine

General Evaluation Imaging upper tracts Cytology Cystoscopy Modify based on risk factors

Imaging Looking for: Renal tumors Collecting system tumors Stones Other – UPJO, infection

Imaging IVP Ultrasound Old standard Misses smaller stones and masses Misses smaller solid masses Operator & body habitus dependent OK for screening low-risk pts Good in combo with retrograde pyelograms for contrast allergic pts.

Imaging CT Current “Gold Standard” “Hematuria protocol” Stones: 94-99% sensitive Masses: excellent down to ~1 cm “Hematuria protocol” No oral or rectal contrast Non-contrast spiral CT full GU tract Renal dedicated IV contrast view(s) Early (arterial) and nephrographic Excretory phase of full GU tract

Imaging CT How to order 3 separate orders CT, ABDOMEN WO/W CONTRAST 74170 8120 CT, PELVIS WO/W CONTRAST 72194 8142 CT, KIDNEYS W/WO CONTRAST 74170 8114 “Hematuria protocol” in comments at NNMC ?? CHCS order line coming soon ??

Imaging Retrograde pyelogram Collecting system anatomy only In conjunction with non-contrast CT or ultrasound for contrast allergic patients To confirm abnormality on initial imaging Performed at the the time of clinic cystoscopy !! Best to have imaging results prior to cystoscopy

Cytology Examination of exfoliated cells in the urine Looking for malignant cells Sensitivity for urothelial cancer Excellent (90+%) for high-grade Poor (40%) for low-grade “Reactive” cells often suggest a stone “Atypical” or “Suspicious” Only 15% truly malignant

Cytology How to order Lab CYTOLOGIC NON-GYN # Container Specimen Description Frozen = ====== =================== ====== 1 A Voided urine NO 2 B Voided urine NO 3 C Voided urine NO

Cytology Patient instructions Well hydrated & active Not first morning void Fill container Refrigerate immediately Turn in <24 hrs

Cystoscopy Complete visualization of the bladder mucosa Anatomy of urethra, prostate, ureteral orifices

Low-Risk Evaluation No risk factors CT Either cystoscopy or cytology Stop after non-contrast phase if cause found Ultrasound also reasonable Either cystoscopy or cytology

Benign Hematuria Benign/Isolated/Idiopathic Hematuria Negative full workup ~2/3 have mild structural abnormality if biopsied At risk for mild nephropathy with low risk of progression <3% have missed malignancy

Follow-Up Follow-Up Protocol Annual Modify based on risk Urinalysis Cytology x1 BP Start in 6 months, continue for three years Modify based on risk

Follow-Up Re-evaluate if: Nephrology Evaluation Significant increase in hematuria Ex. 5-10 now 25-50 RBC/HPF Abnormal urinary cytology Irritative voiding symptoms develop in the absence of infection Nephrology Evaluation HTN, Proteinuria, RBC Casts, Dysmorphic RBCs

Take Home Messages Dx: 3 RBC/HPF, 2/3 samples, properly collected R/o benign & nephrologic causes Begin w/u with CT & cytology x3 Consult Urology Cystoscopy F/u yearly for 3 years with Hx, BP, U/A, cytology

Hematuria Pearls Hematuria (<4rbc/phpf) is normal Strenuous exercise can induce hematuria Hematuria accompanied by proteinuria usually represents a renal source Only RBC casts or dysmorphic RBCs reliably localize hematuria to the kidney Microheme is the most common presentation of sickle trait