Hematuria

1. Hematuria

2. 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

3. 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

4. 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

5. 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

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

7. Glomerulus Hematuria Tubule Where did the RBCs come from? • 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

8. 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

9. Glomerulus Hematuria-- non renal • 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 Tubule bladder urethra ureter penis vagina prostate rectum

10. 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

11. 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

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

13. 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

14. 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

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

16. HematuriaGlomerular • 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

17. HematuriaGlomerular • 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

18. HematuriaGlomerular • 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

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

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

21. Initial Evaluation • Rule out obvious benign causes • Infection • 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

22. 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

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

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

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

26. Imaging • CT • Current “Gold Standard” • 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

27. 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 ??

28. 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

29. 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

30. 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

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

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

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

34. 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

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

36. Follow-Up • Re-evaluate if: • 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

37. 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

38. 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 HematuriaPearls