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Podcast Recap | Hematuria with Dr. Derek Fine

July 27, 2023

In this episoide of The Curbsiders Podcast, internal medicine physicians Dr. Matthew Frank Watto and Dr. Paul Nelson Williams interview Dr. Derek Fine, Clinical Director of the Division of Nephrology at Johns Hopkins University School of Medicine to discuss how to work-up hematuria with confidence. They review what to look out for, what tests are worth considering, and how to decide if this is a job for a urologist or nephrologist. Below are key highlights from the interview.

Podcast length - 51:53 min.

Key Clinical Considerations

1. How do you differentiate between glomerular and nonglomerular bleeding hematuria?

• The major thrust of a hematuria w/u should be evaluating whether the source of the blood is a nonglomerular or a glomerular etiology.  
• The presence of clots in the urine is more suggestive of a urologic or nonglomerular cause of bleeding. Although gross hematuria is more commonly associated with urologic causes, it can be seen in IGA nephropathy and thin basement disease, where the hematuria typically manifests without proteinuria.
• Hematuria with proteinuria or a rising creatinine should prompt concern for glomerular bleeding or referral to a nephrologist.
• Point-of-care urinalysis is generally not accurate enough to truly quantify proteinuria. A protein:creatinine ratio or albumin:creatinine ratio can be used to do this. In practice, it's helpful to get both, especially as they come back quickly and UPEP may take a while. Albumin is more sensitive and accurate and can be suggestive of glomerular protein. For CKD and risk stratification, the abluminuria is a much better measure. If there's a big difference between the two, it may suggest tubular proteins in the urine.
• Red blood cells suggest a glomerular source, but may not be reported in routine lab analysis.

2. Which risk factors make urothelial cancer more likely?

• Risk factors for urothelial malignancy include tobacco use, older age (above 35-40), prior pelvic radiation, and benzene exposure, hair dye exposure, among others.
• Gross hematuria with clots is more suggestive of malignancy vs. microscopic hematuria and those patients should get a urologic w/u for malignancy.
• Big picture: Think urology and cancer to start. Quickly decide if a nephrologist needs to be involved. If the albuminuria and creatinine are normal, the cause is more likely urologic. Always obtain a good verbal history from the patient. Always take gross hematuria seriously.

3. How do you best utilize imaging to evaluate for cause of hematuria?

• For gross hematuria and concern for malignancy, imaging is typically the first step— typically CT urography to identify masses/tumors, stones, cysts as well as any anatomical abnormalities. CT will pick up small cancers and cysts that are hemorrhagic vs. not hemorrhagic.
• AUA recommends renal ultrasound for patients at low and intermediate risk for malignancy. Generally obtain an ultrasound if there's no alternative explanation for hematuria. It will show cysts (if the masses are large enough), hydronephrosis, and anatomical abnormalities. If there's obstruction, one might possibly see stones, but those could also be missed as they may also be lower. Ultrasounds also have good definition of the arterial venous flow, although resolution on the CT is far greater.
• Intermediate and high-risk patients will also typically undergo cystoscopy, as well as low-risk patients who have prior negative imaging. If a clear etiology can't be found, consider additional angiographic imaging to r/o vascular anomalies.
• Imaging w/u for patient with asymptomatic microscopic hematuria vs. gross hematuria. The w/u is the same but having gross hematuria immediately puts patients in that high-risk category, so it's important to obtain both a CT and cystoscopy.

4. What are steps to promptly identify glomerular sources of bleeding and begin an appropriate work-up?

Proteinuria or a rising creatinine are suggestive of a renal process that should prompt a thorough w/u for glomerular causes of hematuria. Most important considerations are albumin in the urine, serum creatinine, and GFR. If creatinine is going up without obstructions, then renal process is a major concern and requires urgent evaluation.

• Most serious of the nephrologic issues: Is there rapidly progressive glomerulonephritis? If not caught early, patient can lose a kidney.
• Proteinuria and systemic symptoms (eg, new hypertension) will lead towards a nephrologic vs. urologic disease pathway.
• Recurrent gross hematuria may prompt consideration of papillary necrosis, sickle cell, vascular abnormalities, or renal arterial venous malformations. Consider obtaining angiography, CT, or actual angiogram for patients with gross hematuria.
• F/U. If patient has only one episode of gross hematuria: AUA guidelines say in the low-risk patients you can check again in a year; but Dr. Fine prefers six month intervals. If it's recurrent, then consider more serious w/u and biopsy to r/o malignancies.

5. When might a renal biopsy not be needed?

Generally, it's valuable for diagnostic confirmation unless patient refuses or has high bleeding risk. However, if patient has very little proteinuria, stable disease, and hematuria for a long time, think possible thin basement membrane disease or very low-level IgA—not renal biopsy.

6. How do you differentiate between all the glomerulonephritis (GN) possibilities?

GN can broadly be divided into 3 categories: anti-GBM disease, ANCA GN, and immune complex GN, with dx all made on immunofluorescence.

• Anti-GBMs (formerly Goodpasture's). Anti-GBM is unlikely in the absence of rapidly progressive renal failure.
• ANCA GNs (formerly pauci-immune glomerulonephritis). Contrary to popular belief, they are not necessarily rapidly progressive. Initial w/u includes testing for ANCA antibodies, which include anti-MPO and anti-PR3 antibodies. If both present, consider drug-type induced ANCA GNs.
• Immune complex GNs. The differential for immune complex GNs are longer. Dr. Fine sub-categorizes these into low- and normal-complement disease. For low-complement disease, Dr. Fine considers three broad groups: infection-related GNs, lupus, and membranoproliferative glomerulonephritis. If normal-complement disease, Dr. Fine considers IgA vasculitis (formerly Henoch-Schonlein). However, all of these disease states can present with normal complement levels.

The C3 serum test is basic. The C4 serum will help identify hypocomplementemia diseases: postinfectious GN, ANA, anti-double stranded DNA, generally lupus, ANCAs, vasculitis and drug-induced anti-GBMs, hepatitis B, and hepatitis C.

Also consider several mimickers of RPGN, including HIV nephropathy and hepatitis C-related disease, although these do not typically present with hematuria. Scleroderma can cause thrombotic microangiopathy with hemolytic anemia and thrombocytopenia.

Any views, thoughts, and opinions expressed in this podcast recap are solely that of the host and guests and do not reflect the views, opinions, policies, or position of epocrates and athenahealth.

Source:

Williams, PN, Fine DM, Watto MF. (2023, July 17). The Curbsiders Internal Medicine Podcast. "#404 Hematuria with Dr. Derek Fine." https://thecurbsiders.com/curbsiders-podcast/404-hematuria-with-dr-derek-fine