This transcript has been edited for clarity.
Linda, a 50-year-old hedge fund manager, consults you in clinic after her recent annual company health screen detected 2+ blood on her urine dipstick test. She is asymptomatic. She has no past medical history of note and takes no prescribed medications or any over-the-counter medications. Linda's health screen also revealed a blood pressure of 126/72 mm Hg and normal renal function, with an estimated glomerular filtration rate (eGFR) over 60 mL/min. She is a nonsmoker and drinks alcohol within recommended limits.
Linda has asymptomatic nonvisible hematuria (NVH), the current preferred terminology for what many of us used to call microscopic hematuria. As we all know, NVH can herald serious pathology, such as urologic cancer or vasculitis. However, no cause is found for around half of all cases of NVH, and so investigation needs to focus, as is so often the case in primary care, on spotting those individuals with pathology while not overinvestigating those without.
How should we manage Linda? Should I tell her to stop attending her annual company health screen? More seriously, should I simply repeat her dipstick urine test in a few weeks? Should I refer a routinely to urology or renal medicine for further investigation? Should I refer her urgently to urology or renal medicine?
NVH is common in primary care. However, there is no compelling evidence to support population screening for NVH in asymptomatic people. The prevalence of asymptomatic NVH in the United Kingdom is around 2.5%. Studies suggest that 1%-4% of individuals who screen positive for NVH will have serious underlying pathology, such as bladder cancer.
Spurious causes of NVH include menstruation; physical exertion (especially long-distance running); sexual activity; certain foods, such as beetroot; and certain drugs, including rifampicin. A key message for all of us in primary care is that individuals with persistent NVH require primary care follow-up to exclude progressive kidney disease. Persistent NVH is defined as asymptomatic NVH that persists on at least two out of three samples separated by at least 2-6 weeks.
We can ignore any trace of blood on urine dipstick. There must be at least 1+ blood on urine dipstick for NVH to be present. Additionally, it is of no significance whether hemolyzed or nonhemolyzed blood is present on dipstick testing. Remember also not to leave the top off the dipstick container or oxidation may occur, resulting in false-positive results.
If NVH persists, we need to undertake further history, examination, and investigation using our clinical judgment. This might include an abdominal examination to exclude an enlarged bladder, a digital rectal examination to exclude an enlarged prostate gland, or pelvic examination to exclude pelvic pathology in women.
Investigations should include a complete blood cell count to exclude anemia or other bleeding diathesis; urine culture to exclude urinary tract infection; and assessment of baseline renal status, comprising blood pressure, eGFR, and urinary albumin-to-creatinine ratio (ACR) or protein-to-creatinine ratio (PCR). Importantly, individuals on aspirin, warfarin, or direct oral anticoagulants should be managed in exactly the same way as those not on these drugs. We should not attribute NVH to these drugs until more serious causes have been excluded.
Linda hands in a repeat urine sample 6 weeks later, which is also positive for blood. What do we do next? As discussed, she needs further history examination and investigation using our clinical judgment. We already have a full blood count, urine culture, and baseline renal status results from her company medical exam, which were all reassuring.
What we do next depends on the age of the individual. Current UK guidance recommends that persons younger than 45 years with normal baseline renal function need annual primary care monitoring of blood pressure, eGFR, and urinary ACR or PCR for as long as the NVH persists.
We should consider referral to our renal colleagues if urinary ACR rises above 30 mg/mmol or urinary PCR rises above 50 mg/mmol. We should also consider referral if eGFR declines below 30 mL/min; if there is a decline in eGFR of over 25% over the preceding 12 months; or if the patient has a family history of hereditary renal disease, such as polycystic kidney disease. This, of course, has workload implications for all of us working in primary care.
For persons older than 45 years, UK guidance recommends referral to urology to exclude cancer, though the urgency of referral varies. Individuals aged 45-60 years with persistent NVH require a routine referral to urology, whereas those aged 60 or older with persistent NVH in the absence of a urinary tract infection require an urgent referral to urology to exclude cancer. There is no need for us to arrange primary care imaging.
Linda was subsequently referred for private urologic assessment, which did not reveal any evidence of cancer. However, she requires annual primary care monitoring of her baseline renal function for as long as her NVH persists.
Linda needs to be under annual recall to check her blood pressure, eGFR, and urinary ACR or PCR, and she should be referred to renal medicine if any abnormalities develop, as I discussed earlier. I should also inform Linda to report any new urologic symptoms: for example, visible hematuria, which would trigger a further referral to urology, with urgency depending on the clinical situation.
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Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: Nonvisible Hematuria: Management Guidance in Primary Care - Medscape - Jun 06, 2024.
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