ACTIVITY DISCLAIMER Hematuria: Organizing Your Approach Charles Carter, MD, FAAFP The material presented here is being made available by the American Academy of Family Physicians for educational purposes only. Please note that medical information is constantly changing; the information contained in this activity was accurate at the time of publication. This material is not intended to represent the only, nor necessarily best, methods or procedures appropriate for the medical situations discussed. Rather, it is intended to present an approach, view, statement, or opinion of the faculty, which may be helpful to others who face similar situations. The AAFP disclaims any and all liability for injury or other damages resulting to any individual using this material and for all claims that might arise out of the use of the techniques demonstrated therein by such individuals, whether these claims shall be asserted by a physician or any other person. Physicians may care to check specific details such as drug doses and contraindications, etc., in standard sources prior to clinical application. This material might contain recommendations/guidelines developed by other organizations. Please note that although these guidelines might be included, this does not necessarily imply the endorsement by the AAFP. DISCLOSURE It is the policy of the AAFP that all individuals in a position to control content disclose any relationships with commercial interests upon nomination/invitation of participation. Disclosure documents are reviewed for potential conflict of interest (COI), and if identified, conflicts are resolved prior to confirmation of participation. Only those participants who had no conflict of interest or who agreed to an identified resolution process prior to their participation were involved in this CME activity. All individuals in a position to control content for this session have indicated they have no relevant financial relationships to disclose. The content of my material/presentation in this CME activity will not include discussion of unapproved or investigational uses of products or devices. Charles Carter, MD, FAAFP Program Director, Family Medicine Residency Program at Palmetto Health Richland, Columbia, South Carolina; Associate Professor, Department of Family and Preventive Medicine, University of South Carolina School of Medicine, Columbia Dr. Carter is a graduate of the University of South Carolina School of Medicine in Columbia. He completed his residency at Palmetto Health Richland in Columbia, and a fellowship at Georgetown University School of Medicine in Washington, DC. He practices in a residency teaching program and cares for mostly underserved patients. He has interests in diabetes, cardiovascular health, headache disorders, and urologic conditions. He feels family physicians are critical partners to help guide patients through complex evaluations and specialty care. Learning Objectives 1. Assess underlying conditions (including infections, kidney diseases and prostate enlargement in men) in patients with hematuria by taking a complete history and physical examination. Audience Engagement System Step 1 Step 2 Step 3 2. Perform appropriate urinalysis, using urine dipstick test or urinalysis microscopic exam, to determine the degree of severity of hematuria. 3. Interpret urinalysis results and establish a coordinated care plan for referral and follow-up to an urologist. 4. Counsel patients on modifying preventable factors for hematuria. 1
Hematuria Presence of blood in the urine Gross Hematuria Evident to patient and/or examiner Microhematuria Not apparent to patient and/or examiner Symptomatic Associated/caused by an evident condition Asymptomatic Detected on microscopic urinalysis No clear cause Key Principles Substantial overlap in differential for gross and microscopic hematuria Consider and assess patients for urinary malignancy risk factors Finding an evident cause doesn t necessarily rule out other co-existing causes Evaluation and follow-up often longitudinal Epidemiology Hematuria is a relatively common finding in ambulatory practice Prevalence estimates vary: 1%-18% Pretest likelihood of finding significant cause is >10% with gross hematuria Malignancy rates widely vary for microhematuria. Best evidence is 3.3% Davis R, Jones S, Barocas DA, et al. Diagnosis, Evaluation, and Follow up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline. American Urological Association, 2012. Limits of the Evidence Barriers to Practice Overall evidence base is limited Mostly observational studies, limited sample sizes Heterogeneity in study design, workups, definitions Some extrapolations from population data Most recommendations are low level and/or expert opinion Source is either Renal or Urinary Tract Image: wikimedia commons Malignancy Renal Bladder Prostate Differential Diagnosis Benign prostatic hyperplasia Infection Urethritis Cystitis Upper UTI Viral illness Menstruation Urolithiasis Trauma Extrinsic Iatrogenic (foley, procedure) Urinary anatomic Urethral stricture Inflammatory processes Medical renal disease Vigorous exercise Benign persistent hematuria 2
Which one of the following is the most common risk factor for bladder cancer in the U.S.? 1. Occupational chemical exposure 2. Chronic urinary tract infection 3. Smoking 4. Cancer chemotherapy Urinary Tract Malignancy Risk Factors Smoking Age >50 Cancer treatments: cyclophosphamide, ifosfamide, pelvic irradiation Chronic UTI, Schistosoma haematobium Chronic foreign body Gross hematuria, irritative voiding symptoms Aristolochic (AA) from Aristolochia fangchi (Chinese herbs) Family history and specific genetic mutations Occupational/environmental: Exposure to benzene, aromatic amines, aromatic hydrocarbons Aminobiphenyl Arsenic Image: wikimedia commons National Cancer Institute https://www.cancer.gov/types/bladder/hp/bladder treatment pdq#link/_17_toc Occupations Most relevant occupational carcinogens banned in U.S. at this point Textiles dyes Tire manufacturing Painters Leather workers and shoemakers Aluminum, iron, steelworkers National Cancer Institute https://www.cancer.gov/types/bladder/hp/bladder treatment pdq#link/_17_toc Irritative Voiding Symptoms Frequency Urgency Nocturia Urge incontinence However The only clinical finding predictive of urinary malignancy is gross hematuria Schmidt Hansen M, Berendse S, Hamilton W. Br J Gen Pract. 2015 Nov;65(640):e769 75. Should I screen for bladder cancer? USPSTF: Insufficient evidence available to assess balance of benefits and harms (USPSTF I) ACP: Don t use UA to screen for cancer in asymptomatic adults Final Update Summary: Bladder Cancer in Adults: Screening. U.S. Preventive Services Task Force. September 2016. Bladder Cancer 4.7% of all cancers ~ 79,030 new cases 16,870 deaths in 2017 19.8 per 100,000 men and women per year 77% 5-year survival rate Lifetime risk: ~ 2.4 percent of men and women diagnosed U.S. prevalence: 696,440 people (2014 data) National Cancer Institute https://seer.cancer.gov/statfacts/html/urinb.html 3
Large variation in approach to hematuria in primary care settings Retrospective review of 449 patients in Texas Only 36% of men and 8% of women were referred urology Advanced age, smoking, presence of urinary symptoms not associated increased urological referral Retrospective review in Tennessee of 2455 primary care patients from 2004-12 Significant variation between those who did and did not undergo evaluation in age, gender, and anticoagulant use GROSS HEMATURIA But also in Urology offices Inconsistent use of cystoscopy Excess use in low-risk patients Insufficient use in higher-risk patients Buteau A, et al. Urol Oncol 2014 Feb;32(2):128 34. Friedlander DF, Am J Med. 2014 Jul;127(7):633 640. David SA, et al. Urology. 2017 Feb;100:20 26. Edvard Munch, The Scream, public domain, wikimedia commons William is a 55-year-old man in your office reporting an episode of painless, gross hematuria that he sought emergency care for last week. He underwent non-contrast CT there and it showed at 4 mm stone in the renal pelvis. He has HTN, BPH, a history of kidney stones and has smoked for 20 years. Image: James Heilman, MD, wikimedia commons Which one of the following steps is most appropriate? 1. Urology consultation 2. Repeat urinalysis today 3. Urine culture 4. Reassurance 5. Contrast CT urography Gross Hematuria Patient generally brings to clinical attention May be symptomatic or asymptomatic History and exam may reveal clear cause Urologic evaluation imperative if benign cause not evident Even if benign likely still needed, particularly if patient has risk for urologic malignancy Gross Hematuria Image: wikimedia commons 4
Approach to Gross Hematuria Gross Hematuria Obvious benign cause Uncertain cause *Maintain a low threshold for Urology consultation Low risk for urinary malignancy Increased risk for urinary malignancy Evaluate based on history and physical exam Evaluate and address cause Reassess for resolution Address cause if found Reassess and/or obtain Urology consult*, especially if increased urologic malignancy risk Cystoscope. Photograph by Michael Reeve; wikimedia commons All patients 35 and older All patients with risk of urinary tract malignancy Under 35 at clinician s discretion Davis R, Jones S, Barocas DA, et al. Diagnosis, Evaluation, and Follow up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline. American Urological Association, 2012. MICROSCOPIC HEMATURIA Image: wikimedia commons Joan is a 55-year-old woman with complaint of urinary frequency and prior diagnosis of UTI last year. Dipstick urinalysis: Specific Gravity 1.025 Glucose Negative Protein 1+ Blood 2+ Nitrite Negative LE Trace RBCs on Microscopy What would be your next step? 1. Urine microscopy 2. Urine culture 3. Empiric treatment for UTI 4. Basic metabolic panel Image: wikimediacommons.org 5
This diagnoses microhematuria Image: Santiago Ramón y Cajal (1852 1934). Portrait in 1906, by R. Madrazo y Garreta. Madrid Athenaeum Public domain, wikimedia commons Frettie, Oil dipstick. Wikimedia commons US Navy, Public domain in US, wikimedia commons These don t Definitions Asymptomatic Microhematuria: Presence of 3 or more red blood cells per high power field on urinary microscopy Properly collected specimen No obvious benign cause Davis R, Jones S, Barocas DA, et al. Diagnosis, Evaluation, and Follow up of Asymptomatic Microhematuria (AMH) in Adults: AUA Guideline. American Urological Association, 2012. Obtaining Urinalysis Random, midstream clean catch 10 ml of urine 2000 rpm for 10 min 3000 rpm for 5 min Discard supernatant Re-suspend sediment and place on slide Examine 10-20 HPFs Davis R, et al. Diagnosis, evaluation, and follow up of asymptomatic microhematuria (AMH) in adults: AUA Guideline. 2012. American Urological Association Evaluation Asymptomatic Hematuria History and physical exam Urinalysis Renal function Other evaluations based on H&P Microhematuria No cause evident Findings of intrinsic renal disease No evident renal disease Concurrent renal evaluation Evaluate urinary tract CT Urography Urologic consultation Benign cause found Treat and reassess 6
Evaluation for Renal Disease Renal function testing Bun/Creatinine Proteinuria and Protein/Creatinine ratio Renal Ultrasound Consider Nephrology consultation Barriers to Practice Imaging CT Urography is the preferred method Alternatives MR Urography MR Urography with retrograde pyelogram Non-contrast CT with retrograde pyelogram Renal ultrasound with retrograde pyelogram Davis R, et al. Diagnosis, evaluation, and follow up of asymptomatic microhematuria (AMH) in adults: AUA Guideline. 2012. American Urological Association CT Urography Renal parenchymal mass SCiardullo via Wikimedia commons CT is the standard, but US emerging A cost-effectiveness analysis suggests: Combining renal US with cystoscopy is the most cost-effective approach vs. CT This wasn t a prospective trial Used literature i.e. simulated CT alone detects 221 cancers at $9,300,000 Ultrasound w/ cystoscopy detects 245 cancers and was most cost-effective at $53,810 per cancer detected Replacing ultrasound with CT detects 1 additional cancer at $6,480,484 per additional cancer detected Halpern JA, Chughtai B, Ghomrawi H. JAMA Intern Med. Published online April 17, 2017 Urologic Consultation Evaluation of a kidney lesion Evaluation of the urinary tract i.e. cystoscopy Alonzo is a 64-year-old man found to have microhematuria on urinalysis obtained as part of work-up for complaint increased voiding at night. He is on warfarin for atrial fibrillation and has a history of HTN, CAD, and tobacco use. His INR is 2.9. Which one of the following is the next most appropriate step? 1. Adjust warfarin to target INR of less than 2.5 2. Change warfarin to rivaroxaban 3. Repeat urinalysis in 4 weeks 4. Evaluate for microhematuria 5. Obtain bladder ultrasound and post-void residual 7
While anticoagulation may exacerbate bleeding, hematuria should not be attributed solely to the patient being on anticoagulation. Look for an underlying cause. Persistent Microhematuria Persistent asymptomatic microhematuria Microhematuria Negative urologic workup Yearly urinalysis Repeat evaluation in 3 5 years Negative urinalysis Stop UA if negative two consecutive years Davis R, et al. Diagnosis, evaluation, and follow up of asymptomatic microhematuria (AMH) in adults: AUA Guideline. 2012. American Urological Association Urine Cytology Previously part of long-term surveillance Now recommending against routine use May still play a role in high-risk patients Urine cytology Urinary biomarkers NMP22 BTA-stat Urovysion FISH ImmunoCyt Davis R, et al. Diagnosis, evaluation, and follow up of asymptomatic microhematuria (AMH) in adults: AUA Guideline. 2012. American Urological Association Practice Recommendations Confirm urine dipstick heme with microscopic urinalysis Gross hematuria warrants thorough evaluation Don t attribute hematuria to anticoagulants Follow hematuria longitudinally. The initial diagnosis isn t necessarily the final one. Include as a problem on your problem list. Questions Thank you! 8
ICD 10 Codes Supplemental Billing and Coding Slides Code Descriptor Additional Considerations N02. Recurrent and persistent hematuria Excludes: acute cystitis with hematuria (N30.01); hematuria NOS (R31.9); hematuria not associated with specified morphologic lesions (R31. ) N18. Chronic kidney disease (CKD) Code first any associated: diabetic chronic kidney disease (E08.22, E09.22, E10.22, E11.22, E13.22); hypertensive chronic kidney disease (I12., I13. ) Use additional code to identify kidney transplant status, if applicable, (Z94.0) N28. Other disorders of kidney and ureter, not elsewhere classified N28.89 Other specified disorders of kidney and ureter N28.9 Disorder of kidney and ureter, unspecified Nephropathy NOS; Renal disease (acute) NOS; Renal insufficiency (acute) Excludes: chronic renal insufficiency (N18.9); unspecified nephritic syndrome (N05. ) N29 Other disorders of kidney and ureter in diseases Code first underlying disease, such as: amyloidosis (E85. ); nephrocalcinosis (E83.5); classified elsewhere schistosomiasis (B65.0 B65.9) Excludes disorders of kidney and ureter in: cystinosis (E72.0); gonorrhea (A54.21); syphilis (A52.75); tuberculosis (A18.11) N40. Benign prostatic hyperplasia Includes: adenofibromatous hypertrophy of prostate; benign hypertrophy of the prostate; benign prostatic hypertrophy; BPH; enlarged prostate; nodular prostate; polyp of prostate Excludes: benign neoplasms of prostate (adenoma, benign) (fibroadenoma) (fibroma) (myoma) (D29.1) Excludes: malignant neoplasm of prostate (C61) Q61. Cystic kidney disease Excludes: acquired cyst of kidney (N28.1); Potter's syndrome (Q60.6) R31. Hematuria Excludes: hematuria included with underlying conditions, such as: acute cystitis with hematuria (N30.01); recurrent and persistent hematuria in glomerular diseases (N02. ) 49 Lab CPT Code 81000 Labs Urinalysis, by dip stick or tablet reagent for bilirubin, glucose, hemoglobin, ketones, leukocytes, nitrite, ph, protein, specific gravity, urobilinogen, any number of these constituents; non automated, with microscopy 81001 ; automated, with microscopy 81002 ; non automated, without microscopy 81003 ; automated, without microscopy 81005 Urinalysis; qualitative or semiquantitative, except immunoassays 81007 Urinalysis; bacturiuria screen, except by culture or dipstick 81015 Urinalysis; microscopic only 81050 Volume measurement for timed collection, each 9