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HEMATURIA: Brenner and RectorThe Kidney

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HEMATURIA: Rakel and BopeConns Current Therapy, 2008

Microscopic hematuria in a patient with an apparent UTIshould be carefully observed and should disappear aftertherapy of the UTI. If the microscopic hematuria

disappears, then the physician can safely assume it wasrelated to the UTI. Particularly in elderly patients, if themicroscopic hematuria persists after eradication of theUTI, then the patient should be investigated for abladder or renal source of the microscopic hematuria.

(p. 668)

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P.T.:A Hard Case

53 YO man who works in highway construction presentsto various physicians over a one year period withmicroscopic hematuria associated with intermittentburning dysuria.

He smokes one PPD and has mild controlled HBP. He is diagnosed with cystitis and bladder infections,

given various antibiotics with varying relief.

He develops gross painful hematuria and after a failure

of antibiotics is referred to a urologist. What do you think he is most likely to have?

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P.T.:A Hard Case

53YO manwho works in highway constructionpresentsto various physicians over a one year period withmicroscopic hematuriaassociated with intermittentburning dysuria.

He smokesone PPD and has mild controlled HBP. He is diagnosed with cystitis and bladder infections,

given various antibiotics with varying relief.

He develops gross painful hematuria and after a failure

of antibiotics is referred to a urologist.= risk factors for bladder CA

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P.T.:A Hard Case continued

He is diagnosed with adenocarcinoma of the bladder andhas transurethral resection.

His symptoms resolve and he does well for about sixmonths, but they recur and require cystectomy and an

ileal conduit. He comes to you to see what else can be done.

Over the next year he develops multiple areas of longbone pain with metastases on imaging.

He becomes unable to care for his aging mother. Spinal metastases result in paraplegia.

Five years after diagnosis, he dies with home hospice.

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M.P.:An Easier Case?

48 YO AAF sees you for routine examination and healthmaintenance. She has HBP controlled with HCTZ.

Her BP is normal. General examination is normal, pelvicexam is normal, and there is no edema.

UA shows 5 RBC/hpf, 0-2 WBC, no proteinuria

Creatinine 0.8 mg/dL

How should she be evaluated?

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Causes of heme-negative red urine

Medications: Doxorubicin, Chloroquine,Deferoxamine, Ibuprofen, Iron, sorbitol, Nitrofurantoin,Phenazopyridine, Phenolphthalein, Rifampin

Food dyes: Beets (in selected patients), Blackberries,Food coloring

Metabolites: Bile pigments, Homogentisic acid,Melanin, Methemoglobin, Porphyrin, Tyrosinosis, Urates

2008 UpToDate www.uptodate.com

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CAUSES OF HEMATURIA BY AGE

2008 UpToDate

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REPORTED CAUSES OF ASYMPTOMATIC MICROSCOPIC HEMATURIA

Highly SignificantBladder cancer

Renal cell carcinomaCA prostateUreteral calculusRenal calculusHydronephrosisRenal artery stenosisRenal lymphomaRenal transitional cell CAUreteral trans.call CAMetastatic carcinomaAbd. aortic aneurysmRenal parenchymal ds.

Moderately SignificantRenal calculus

Bacterial cystitisVesicoureteral refluxInterstitital cystitisBladder diverticulumBladder calculusUreteropelvic junction obstr.Radiation cystitisPapillary necrosisRenal parenchymal diseaseAtrophic kidneyRenal AV fistulaRenal contusionBladder neck contracture

Symptomatic BPHUrethral stricture/meatal stenosisPolycystic kidneyProstatitisBladder papillomaMycobacterial cystitisPyelonephritis

InsignificantAsymptomatic BPH

UrethrotrigonitisRenal cystDuplicated collecting systemCystoceleNeurogenic bladderProstatic calculusUreteroceleBladder neck polypsUrethral polypsCystitis cystica/glandularisBladder varices/telangiectasiaScarred kidneyTrabeculated bladder

Urethral carunclePseudomembranous trigonitisUrethritisPelvic kidneyCaliceal diverticulumExercise hematuriaVerumontanitis

Adapted from Urol Clin N Am 1998; 25(4):661

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Cohen R and Brown R. N Engl J Med 2003;348:2330-2338

Findings in Urinary Sediment

Hematuria(Crenated RBCs arenonspecific.)

RBC Cast= glomerular

Dysmorphic RBCs(acanthocytes)

suggest glomerular

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URINALYSIS IN ACUTE KIDNEY INJURY

Prerenal Normal or hyaline casts

Intrarenal

Tubular cell injury Muddy-brown, granular, epithelial casts

Interstitial nephritis Pyuria, hematuria, mild proteinuria,granular and epithelial casts, eosinophils

Glomerulonephritis Hematuria, marked proteinuria, redblood cell casts,granular casts

Vascular disorders Normal or hematuria, mild proteinuria

Postrenal Normal or hematuria,granular casts,pyuria

from Goldman: Cecil Medicine, 23rd ed.

Copyright 2007 Saunders, Chapter 121

EVALUATION OF

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Cohen R and Brown R.N Engl J Med 2003;348:2330-2338

EVALUATION OFMICROSCOPIC HEMATURIA

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

IV pyelogram

Ultrasound

Non-contrasted CT

Four phase contrasted helical CT

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

IV pyelogram

Mostly outdated

OK for stone disease if CT not available

Ultrasound Non-contrasted CT

Four phase contrasted helical CT

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

IV pyelogram Mostly outdated

OK for stone disease if CT not available

Ultrasound

Good option in pregnancy, children, acute renal failure Similar sensitivity/specificity to non-con CT

Operator-dependent

FUTURE: US contrast (bubble study)

Non-contrasted CT Best for stone disease

Not as sensitive for renal or other tumors

Four phase contrasted helical CT

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

IV pyelogram Mostly outdated

OK for stone disease if CT not available

Ultrasound

Good option in pregnancy, children, acute renal failure Similar sensitivity/specificity to non-con CT

Operator-dependent

FUTURE: US contrast (bubble study)

Non-contrasted CT Best for stone disease

Not as sensitive for renal or other tumors

Four phase contrasted helical CT: BEST/RISKIEST/$$$

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

IV pyelogram

Ultrasound

Non-contrasted CT

Four phase contrasted helical CT

Most sensitive and specific (0.92/0.94)

Involves contrast exposure approx. 15 X annual baseline

Most expensive current option

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

Four-sequence helical CT Pre-enhancement: calculi or parenchymal

calcifications in the genitourinary tractArterial early corticomedullary: vascular tumors, such

as renal cell carcinoma, inflammatory conditions,infarcts and vascular anomalies, such as a retro-aorticleft renal vein or the nutcracker phenomenon

Nephrographic phase: hypervascular andhypovascular lesions such as infarcts, inflammatorylesions of the medulla and certain neoplastic lesions

Excretory phase: transitional cell carcinoma,medullary sponge kidney, caliceal diverticula, andlesions of the ureter and urethra

FUTURE: MR Urography

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MICROSCOPIC HEMATURIA:IMAGING OPTIONS

IV pyelogram

Ultrasound

Non-contrasted CT

Four phase contrasted helical CT

FUTURE: MR Urography

RADIATION DOSE IS BECOMING MAJOR CONCERN

Patients with recurrent stones can get up to 10 CTs infive years = threshhold associated with CA breast

Litigation trends

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MICROSCOPIC HEMATURIA:WHEN TO REFER

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MICROSCOPIC HEMATURIA:WHEN TO REFER

With proteinuria/casts/renal insufficiency:possible renal Bx

Lesion on CT

Positive urine cytology: Cystoscopy +/- moreimaging

Neg imaging, neg cytology but >50 yo or other

risk for CA bladder: Cystoscopy(AUA recommends >40 yo)

Cohen R and Brown R. N Engl J Med 2003;348:2330-2338

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MICROSCOPIC HEMATURIA:PATIENTS ON ANTICOAGULANTS

243 pts on warfarin in 2-yr prospective study Hematuria incidence on warfarin (3.2%) same as controls (4.8%)

G-U disease found in 81% of patients with >1 episode of microscopichematuria

Causes of hematuria did not vary between groups (mostly infection,

also bladder CA, cysts, pap. nec.) Arch Int Med 1994;154:649 30 pts new onset gross or microscopic hematuria on anticoagulation

6 microscopic, 24 gross

9/30 = 30% had sig. disease (stones, bladder CA)J Urol 1995;153:1594

These observations indicate that hematuria in an anticoagulatedpatient should generally be evaluated in the same fashion as inother patients unless there is evidence of bleeding from multiplesites with markedly abnormal coagulation studies. (Rose, UTD)

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UNEXPLAINED MICROSCOPIC HEMATURIA:POSSIBLE CAUSES

Glomerular (50%): IgA Nephrop., thin B. memb. Ds. Nutcracker Syndrome(Left Renal Vein compressed

between aorta and SMA) Left RV and gonadal varices Hematuria, left flank pain can be intermittent Can have nephrotic range proteinuria Dx by CT or MRA

Loin Pain-Hematuria Syndrome Hypercalciuria/Hyperuricosuria: thiazide or allopurinol

can cure Factitious Hematuria: usually gross Exercise Hematuria March Hematuria Undiagnosed

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MICROSCOPIC HEMATURIA:IS SCREENING INDICATED?

The U.S. Preventive Services Task Force (USPSTF)recommends AGAINST screening for Bladder Cancer

Bladder CA 2-3 X more in men

Smoking increases risk, about 50% occur in smokers

Unusual before age 50

UA, cytology, bladder tumor antigen (BTA) or nuclear matrixantigen (NMP22) can detect silent tumors

Low prevalence of bladder CA makes PPV of tests low.

Occupational exposure not addressed (chemicals in dye andrubber industries)

USPSTF: AHRQ June 2004. http://www.ahrq.gov/clinic/

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M.P.:An Easier Case?

48 YO AAF sees you for routine examination and healthmaintenance. She has HBP controlled with HCTZ.

Her BP is normal. General examination is normal, pelvicexam is normal, and there is no edema.

UA shows 5 RBC/hpf, 0-2 WBC, no proteinuria

Creatinine 0.8 mg/dL

How should she be evaluated?

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SELECTED REFERENCES

1. Cohen R and Brown R. Clinical practice: Microscopic hematuria.N Engl J Med 2003; 348:2330.

2. Grossfeld, BD, Wolf, JS Jr et al. Asymptomatic microscopichematuria in adults: Summary of the AUA best practice policyrecommendations. Am Fam Physician 2001; 63:1145.

3. Lang, EK, Macchia, RJ et al. Computerized tomography tailoredfor the assessment of microscopic hematuria. J Urol 2002;167:547.

4. Rose, BD and Fletcher RH. Evaluation of hematuria in adults.UpToDate; July 17, 2007.