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Hematuria in Primary Care: The Bloody Truth Ashlyn Bruning, MMS, PA-C NCAPA Summer Conference Disclosure: I Have No Financial or Non-financial Relationships or Conflicts of Interest to Disclose OBJECTIVES 1. Define Hematuria 2. Differentiate dipstick positive hematuria vs. microscopic hematuria vs. gross hematuria 3. Recognize common causes of microscopic hematuria and gross hematuria 4. Identify risk factors associated with hematuria 5. Describe a systematic approach to hematuria evaluation in primary care 6. Recognize when to refer to a specialist for further evaluation 7. Discuss common hematuria work-up in Urology (for patient education purposes) HEMATURIA The abnormal presence of blood or red blood cells in the urine hematuria. (n.d.) Farlex Partner Medical Dictionary. (2012). Retrieved July 1 2015 from http://medical-dictionary.thefreedictionary.com/hematuria Take Home Message: Hematuria, visible or not, is a red flag and warrants further evaluation. Dipstick Positive Heme/ hemoglobinuria: finding on dipstick urinalysis. Does not constitute MH; should be confirmed or refuted with Microscopic urinalysis. Ensure that this was a clean catch, midstream voided specimen. What do we do with a dipstick positive heme urine…. Take home message ALL dipstick positive heme urines warrant microscopic urinalysis for confirmation of true or false positive Microscopic hematuria: > 3 red blood cells per high powered field (rbc/hpf) on two of three specimens. (AUA) Take Home Message: Microscopic hematuria without a clear etiology (UTI/BPH/Prostatitis/Nephrolithiasis) warrants referral to Urology for further evaluation if patient is deemed at risk Microscopic hematuria with identifiable etiology (UTI/BPH/Prostatitis/Nephrolithiasis) should have follow up repeat microscopic urinalysis post treatment to verify resolution. Gross…So what does that mean? Gross Hematuria = Visible blood in the urine Bright red blood in the urine is typically of lower urinary tract origin Smoky, hazy or reddish-brown coloration of urine is typically of upper urinary tract origin (renal parenchymal) False Positives Myogobinuria Hemoglobinuria Medications that may cause red urine: • Pyridium Phenytoin (Dilantin) • Sulfamethoxazole Levodopa • Nitrofurantoin Methyldopa • Rifampin Quinine • Ibuprofen Chloroquine • Phenacetin Foods that may cause RED pigmenturia Rhubarb Blackberries Blueberries Paprika Beets Fava Beans *Cleveland Clinic* Glomerular Hematuria Arising from the kidney itself (medical renal or parenchymal) and typically evaluated/treated by nephrology. • IgA nephropathy (Berger's disease) • Thin glomerular basement membrane disease • Hereditary nephritis (Alport's syndrome) Findings suggestive of glomerular hematuria are: significant proteinuria (2+ or greater), RBC casts and dysmorphic RBCs. Evidence of Glomerular Hematuria Non Glomerular Hematuria A condition arising from the upper or lower urinary tract resulting from a structural or pathologic condition Lower Tract Upper Tract • Urolithiasis • Bacterial cystitis (UTI) • Pyelonephritis • Benign prostatic hyperplasia • Renal cell carcinoma • • Transitional cell carcinoma (kidney or ureters) Strenuous exercise ("marathon runner's hematuria") • Transitional cell carcinoma of the bladder • Spurious hematuria (e.g. menses) • Instrumentation • Benign hematuria • Urinary obstruction • Benign hematuria Common Causes of Microscopic hematuria Urinary Tract Infection (UTI) Benign Prostatic Hyperplasia (BPH) Urinary Calculi Idiopathic familial microhematuria (43%) Always consider urinary tract malignancy until proven otherwise Up to 5% of patients with asymptomatic microscopic hematuria will have a urinary tract malignancy Kidney Cancers Renal Cell Carcinoma (RCC): The most common type of kidney cancer. 9 out of 10 kidney cancers are RCC Transitional Cell Carcinoma (TCC): AKA Urothelial carcinomas, account for 5-10% of kidney cancers Wilm’s tumors: almost always occur in children, very rare in adults. 9 of 10 tumors will have favorable histology (nonanaplastic)and high cure rate. Renal Sarcoma: Rare (less than 1% of all kidney cancers) Gross Hematuria Commonly associated with: • Urinary calculi- kidney, ureteral or bladder stones (irritative voiding sxs) • Severe UTI (irritative voiding sxs) • Strenuous exercise, especially long distance running and cyclists • Hemorrhagic cystitis- persistent or recurrent hematuria caused by bladder inflammation. Often radiation or chemotherapy induced. Bleeding can be severe. • Kidney trauma • Malignancy- renal, ureteral, prostatic, bladder, urethral (up to 23%) • BPH with bladder outlet obstruction MNEUMONIC: PP ON THIS (with 4 Ts) Differential Diagnosis P- Period (menses) aka: pseudohematuria P- Prostate- Prostatitis, BPH, prostate ca O- Obstructive Uropathy N- Nephritis- glomerulonephritis, Alport’s syndrome, Berger’s, interstitial nephritis T- Trauma T- Tumor T- Tuberculosis T- Thrombosis- renal vein thrombosis H- Hematologic- anticoagulation, coag disorders, sickle cell disease I- Infection/inflammation- UTI, pyelonephritis, interstitial cystitis, radiation cystitis S- Stones Risk Factors Associated with Hematuria Age: > 40 Sex: Male, esp. > 50 due to BPH Pelvic radiation Previous history of urologic disease and treatment Cigarette smokers: increased risk for urinary tract malignancy Irritative voiding symptoms (urgency, frequency, dysuria) Chemical exposures (cyclophosphamide, benzenes, aromatic amines) American Urological Association Guidelines: www.auanet.org It’s the Aspirin….. Or is it? Medications such as anticoagulants, Aspirin, NSAIDs, chemotherapy and some abx such as PCN may influence the duration and severity of hematuria from another cause but ARE NOT THE CAUSE Evaluation in Primary Care A thorough Medical History: • • • • Renal colic (ureteral stones, pyelonephrosis, ureteral obstruction) fever (infection) Irritative voiding symptoms (UTI, bladder or urethral stricture, bladder tumor) Obstructive voiding sxs ( BPH, tumor) • Recent infection: Kidney inflammation after a viral or bacterial infection (post-infectious glomerulonephritis) is one of the leading causes of gross hematuria in children. • Asymptomatic: menses, trauma, malignancy, medications, bleeding disorder, dietary factors, vigorous physical activity Prior pelvic radiation or chemotherapy • History continued Timing Initial hematuria indicates anterior urethral bleeding (urethritis, stricture, meatal stenosis) Terminal hematuria is more consistent with posterior urethral bleeding (prostatitis, posterior urethritis, tumors of bladder neck or trigone, polyps) Total hematuria indicates bleeding at or above the level of the bladder (stones, tumors, cystitis, nephritis, tuberculosis) Social History Cigarette smoking Occupational exposures to aniline dyes or aromatic amines used in certain manufacturing processes which increase the risk of bladder cancer Family History Hereditary diseases: Alport’s syndrome, Berger’s IgA nephropathy, Sickle cell disease, nephrolithiasis, urologic cancers Idiopathic familial microscopic hematuria Physical Exam CVA tenderness without fever may indicate kidney stone CVA tenderness with fever is more indicative of pyelonephritis Palpate abdomen for masses Palpable kidneys indicate hydronephrosis or renal mass Palpable bladder may indicate obstruction or retention Rectal exam may reveal tender, boggy prostate indicating prostatitis Edema: nephrotic syndrome Cardiac arrhythmia: atrial fibrillation; in the presence of flank pain and hematuria should raise the possibility of renal embolic infarction Diagnostics Microscopic urinalysis Urine culture if indicated Renal function testing if indicated (red cell casts=suspect glomerular hematuria) Patients with gross hematuria or those with any of the risk factors are considered high risk and should undergo a thorough urologic evaluation. Patients with asymptomatic hematuria and no associated risk factors are classified as low risk but still warrant urologic evaluation. The diagnostic studies selected depend on the risk factors for significant disease. Imaging studies are used to evaluate the upper urinary tract (kidneys and ureters) Urine cytology or direct endoscopic (cystoscopy) visualization of the bladder and urethra can be used to evaluate the lower urinary tract Low risk patients: Renal U/S and voided urine cytology (urine cytology does not screen for renal cancer thus the renal U/S) High Risk patients: (gross hematuria or associated risk factors) should undergo contrast-enhanced imaging of the kidneys and ureters ( CT A&P) in addition to cystourethroscopy and urine cytology. Case Study: 22 y/o female HPI: Sudden onset of severe pain (10/10) in the right lower back. Associated nausea and vomiting. No fever or chills. No history of recent injury or illness. Has never had back pain like this before. Feelings of extreme urgency and voiding small amounts frequently. Denies gross hematuria. PE: A+O x3. In obvious discomfort/distress. + CVA tenderness on the right. Abdomen is unremarkable. No suprapubic tenderness. Lab: Dipstick urinalysis is heme positive Clinical Suspicion for Nephrolithiasis If nephrolithiasis is suspected, various imaging studies can be helpful. What test should we order for further evaluation ( after r/o pregnancy of course!)?? Plain Abdominal film (KUB)is quick and noninvasive but beware that small stones (less than 2mm) are easily missed. Uric acid stones are radiolucent and will be missed. Overlying bowel gas and stool can hide stones as can bony pelvic structures. Gold Standard for diagnosing urolithiasis is CT A&P without contrast Management: depends on size and location of stone and/or ability to control patient’s pain- ultimately, need to repeat microscopic urinalysis once stone resolved Case Study: 46 y/o male 46 y/o male presents with complaints of painless, gross hematuria intermittently x 2 weeks. Denies irritative voiding symptoms- dysuria, frequency, urgency. Denies passage of clots. Blood is bright red in color and present throughout the stream. He has not had similar symptoms previously. History of cigarette smoking- quit 6 years ago with a prior 2ppd history. No prior history of prostatitis but has been told that his prostate is mildly enlarged. PE: Unremarkable Lab: dipstick positive urinalysis for heme, microscopic hematuria confirmed. No bacteria or significant proteinuria. What would you do next??? This patient is high risk Male gender >40 Previous smoker Refer to Urology for thorough evaluation! Highly suspicious for urologic malignancy Referral to Urology Symptomatic or Not: It is appropriate to refer to Urology any patient with gross hematuria Any at risk patient with proven Microscopic Hematuria without a proven benign cause (UTI, prostatitis) Urine C&S negative Patient’s with persistent microhematuria despite treatment of suspected UTI or prostatitis Questions??? References Farlex Partner Medical Dictionary. (2012). Retrieved July 9 2015 from http://medical-dictionary.thefreedictionary.com/hematuria Assessment of Asymptomatic Microscopic Hematuria in Adults VICTORIA J. SHARP, MD, MBA; KERRI T. BARNES, MD, MPH; and BRADLEY A. ERICKSON, MD, MS, University of Iowa Hospitals and Clinics, Iowa City, Iowa, Am Fam Physician. 2013 Dec 1;88(11):747-754. http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/ne phrology/evaluation-of-hematuria/Default.htm Urology: House Officer Series, 4th edition. Michael Macfarlane. Lippincott Williams & Wilkins. 2007. Smith’s General Urology, 17th edition. Tanagho, Emil, McAninch, Jack. Lange. 2008. http://www.auanet.org/education/hematuria.cfm http://www.cancer.org/cancer/wilmstumor