COMMON AMBULATORY TOPICS: HEMATURIA

William A. Curry, MD UAB General Internal Medicine April 1, 2008

HEMATURIA: Bennett and Plum Cecil Textook of Medicine

HEMATURIA: Brenner and Rector The Kidney

HEMATURIA: Rakel and Bope Conns Current Therapy, 2008

Microscopic hematuria in a patient with an apparent UTI should be carefully observed and should disappear after therapy of the UTI. If the microscopic hematuria disappears, then the physician can safely assume it was related to the UTI. Particularly in elderly patients, if the microscopic hematuria persists after eradication of the UTI, then the patient should be investigated for a bladder or renal source of the microscopic hematuria. (p. 668)

MICROSCOPIC HEMATURIA:

Cohen, RA and Brown, RS. NEJM 2003; 348:233 Since bleeding may arise from any site along the urinary tract, it has a broad differential diagnosis, possibly reflecting an entirely benign cause, such as vigorous exercise just before urine collection, or a malignant, potentially lethal disease, such as bladder or renal cancer. Even with a thorough investigation, the source of the microscopic hematuria frequently is not found.

P.T.: A Hard Case

53 YO man who works in highway construction presents to various physicians over a one year period with microscopic hematuria associated with intermittent burning 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?

P.T.: A Hard Case

53 YO man who works in highway construction presents to various physicians over a one year period with microscopic hematuria associated with intermittent burning 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.

= risk factors for bladder CA

P.T.: A Hard Case continued

He is diagnosed with adenocarcinoma of the bladder and has transurethral resection. His symptoms resolve and he does well for about six months, 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 long bone 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.

M.P.: An Easier Case?

48 YO AAF sees you for routine examination and health maintenance. She has HBP controlled with HCTZ. Her BP is normal. General examination is normal, pelvic exam 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?

ETIOLOGY OF RED URINE

Hemolysis March Hemoglobinuria

Adapted from 2008 UpToDate

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,

2008 UpToDate www.uptodate.com

Melanin, Methemoglobin, Porphyrin, Tyrosinosis, Urates

CAUSES OF HEMATURIA BY AGE

2008 UpToDate

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

REPORTED CAUSES OF ASYMPTOMATIC MICROSCOPIC HEMATURIA

Highly Significant Moderately Significant
Asymptomatic BPH Urethrotrigonitis Renal cyst Duplicated collecting system Cystocele Neurogenic bladder Prostatic calculus Ureterocele Bladder neck polyps Urethral polyps Cystitis cystica/glandularis Bladder varices/telangiectasia Scarred kidney Trabeculated bladder Urethral caruncle Pseudomembranous trigonitis Urethritis Pelvic kidney Caliceal diverticulum Exercise hematuria Verumontanitis

Insignificant

Bladder cancer Renal cell carcinoma CA prostate Ureteral calculus Renal calculus Hydronephrosis Renal artery stenosis Renal lymphoma Renal transitional cell CA Ureteral trans.call CA Metastatic carcinoma Abd. aortic aneurysm Renal parenchymal ds.

Renal calculus Bacterial cystitis Vesicoureteral reflux Interstitital cystitis Bladder diverticulum Bladder calculus Ureteropelvic junction obstr. Radiation cystitis Papillary necrosis Renal parenchymal disease Atrophic kidney Renal AV fistula Renal contusion Bladder neck contracture Symptomatic BPH Urethral stricture/meatal stenosis Polycystic kidney Prostatitis Bladder papilloma Mycobacterial cystitis Pyelonephritis

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

Findings in Urinary Sediment

RBC Cast = glomerular

Hematuria (Crenated RBCs are nonspecific.)

Dysmorphic RBCs (acanthocytes) suggest glomerular

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

URINALYSIS IN ACUTE KIDNEY INJURY

Prerenal Intrarenal
Tubular cell injury
Interstitial nephritis Glomerulonephritis Vascular disorders Normal or hyaline casts

Muddy-brown, granular, epithelial casts

Pyuria, hematuria, mild proteinuria, granular and epithelial casts, eosinophils Hematuria, marked proteinuria, red blood cell casts, granular casts Normal or hematuria, mild proteinuria Normal or hematuria, granular casts, pyuria
from Goldman: Cecil Medicine, 23rd ed. Copyright 2007 Saunders, Chapter 121

Postrenal

EVALUATION OF MICROSCOPIC HEMATURIA

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

MICROSCOPIC HEMATURIA: IMAGING OPTIONS

IV pyelogram Ultrasound Non-contrasted CT Four phase contrasted helical CT

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

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 Four phase contrasted helical CT

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

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/$$$

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

MICROSCOPIC HEMATURIA: IMAGING OPTIONS

Four-sequence helical CT

FUTURE: MR Urography

Pre-enhancement: calculi or parenchymal calcifications in the genitourinary tract Arterial early corticomedullary: vascular tumors, such as renal cell carcinoma, inflammatory conditions, infarcts and vascular anomalies, such as a retro-aortic left renal vein or the nutcracker phenomenon Nephrographic phase: hypervascular and hypovascular lesions such as infarcts, inflammatory lesions of the medulla and certain neoplastic lesions Excretory phase: transitional cell carcinoma, medullary sponge kidney, caliceal diverticula, and lesions of the ureter and urethra

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 in five years = threshhold associated with CA breast Litigation trends

MICROSCOPIC HEMATURIA: WHEN TO REFER

EVALUATION OF MICROSCOPIC HEMATURIA

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

MICROSCOPIC HEMATURIA: WHEN TO REFER

With proteinuria/casts/renal insufficiency: possible renal Bx Lesion on CT Positive urine cytology: Cystoscopy +/- more imaging 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

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 microscopic hematuria 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 anticoagulated patient should generally be evaluated in the same fashion as in other patients unless there is evidence of bleeding from multiple sites with markedly abnormal coagulation studies. (Rose, UTD)

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

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 matrix antigen (NMP22) can detect silent tumors Low prevalence of bladder CA makes PPV of tests low. Occupational exposure not addressed (chemicals in dye and rubber industries)
USPSTF: AHRQ June 2004. http://www.ahrq.gov/clinic/

M.P.: An Easier Case?

48 YO AAF sees you for routine examination and health maintenance. She has HBP controlled with HCTZ. Her BP is normal. General examination is normal, pelvic exam 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?

SELECTED REFERENCES
1. 2.

3.

4.

Cohen R and Brown R. Clinical practice: Microscopic hematuria. N Engl J Med 2003; 348:2330. Grossfeld, BD, Wolf, JS Jr et al. Asymptomatic microscopic hematuria in adults: Summary of the AUA best practice policy recommendations. Am Fam Physician 2001; 63:1145. Lang, EK, Macchia, RJ et al. Computerized tomography tailored for the assessment of microscopic hematuria. J Urol 2002; 167:547. Rose, BD and Fletcher RH. Evaluation of hematuria in adults. UpToDate; July 17, 2007.