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

HematuriaGlomerulus

Tubule

ureter

prostate

bladder

urethra

penisvaginarectum

Where did the RBCs come from?

HematuriaGlomerulus

Tubule

ureter

prostate

Where did the RBCs come from?

Proliferative GNPrimary

IgAPost-infx GNMPGNCrescentic GNFibrillary GN

SecondaryHSPSLEAnti-GBM (Good pasture's)Systemic VasculitisChronic BacteremiaCryoglobulinemiaHepatitis B/C

Non-Proliferative Minimal ChangeFSGSMembranousHUS

Familial Glomerular DzAlport's syndromeThin basement membrane diseaseFabry diseaseNail-Patella

Hematuria - Where did the RBCs come

from?Glomerulus

Tubule

ureter

prostate

Renal Causes-- Non-GlomerularNeoplasms

renal cell cancerWilms tumorbenign cyststuberous sclerosismultiple myeloma

Vascularrenal infarctrenal vein thrombosismalignant hypertensionAVMLoin-pain hematuria

MetabolicHypercalcuriaHyperoxaluriaHyperuricosuriaCystinuria

FamilialADPKDMedullary Cystic DiseaseMedullary Sponge Kidney

Papillary NecrosisAnalgesic abuseSickle Cell Disease and TraitRenal TBDMObstructive uropathyAlcoholismAnklosing Spondyltis

HydronephrosisDrugs

interstitial nephritisTrauma

Renal Contusion or laceration Exercise hematuria

Hematuria-- non renalGlomerulus

Tubule

ureter

prostate

bladder

urethra

penisvaginarectum

Calculiureter, bladder, prostate

NeoplasmsTCCprostate Ca/BPHsquamous cell

Infectionscystitis, prostatitis, urethritisTBSchistosomiasis

Drugscyclophosphamideanticoagulants

TraumaContusion/lacerationexercise induced hematuriaforeign bodydecompression of severely distended bladder

Genital or anal bleeding

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

• 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

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

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

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

HematuriaNonglomerular Hematuria

• If pyuria-– urine culture

– STD screen

• African-American– consider SICKLE CELL TRAIT OR DISEASE

• h/o cytoxan therapy– hemorrhagic cystitis

HematuriaNon-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• 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– 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.

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

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– 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– Urinalysis– Cytology x1– BP– Start in 6 months, continue for three years

• Modify based on risk

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

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

HematuriaPearls

• 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