Persistent asymptomatic isolated microscopic hematuria in adolescence and young adulthood appears to be a strong predictor of end-stage renal disease in later adulthood, independent of other risk factors, according to a report in the Aug. 17 JAMA.
Such hematuria is frequently an incidental finding on routine examination in this age group, but its significance has been unclear. Short-term prognosis is favorable, and the condition is generally considered benign. But long-term data are lacking, and uncertainty about the implications has prompted "considerable controversy over appropriate evaluation, management, and prognosis," said Dr. Asaf Vivante of the Israeli Defense Forces Medical Corps and the Edmond and Lily Safra Children’s Hospital, Tel Hashomer, Israel, and his associates.
"The most recent American Academy of Pediatrics guidelines rescinded the recommendation for urine screening during the second decade of life," they noted.
They conducted a nationwide retrospective cohort study to assess the long-term outcomes of persistent asymptomatic isolated microscopic hematuria, which by definition is unaccompanied by proteinuria or kidney abnormalities and unrelated to any systemic condition. By using mandatory military service records, the researchers assessed medical data on over 1.2 million Israelis who were aged 16-25 years at induction in 1975-1997 and who were followed for about 22 years.
Study subjects were initially screened by urinary dipstick test. In those with positive results for hematuria, urinary sediment was examined by microscopy. A total of 3,690 of these young men and women (0.3% of the cohort) were found to have persistent asymptomatic isolated hematuria.
The investigators then used a national end-stage renal disease (ESRD) database to identify all patients receiving any form of renal replacement therapy from 1980 through 2010. During follow-up, 565 members of the study cohort were treated for ESRD.
The incidence of ESRD was 34 per 100,000 person-years for subjects who had had hematuria in adolescence and young adulthood, a strikingly higher rate than the 2.05 cases per 100,000 person-years for subjects who had not had hematuria, Dr. Vivante and his associates said (JAMA 2011;306:729-36).
A total of 0.7% of subjects with hematuria in adolescence developed ESRD, compared with 0.04% of those without hematuria, yielding an unadjusted hazard ratio of 19.5. When the data were adjusted to account for factors that might influence kidney function, such as subject age, sex, BMI, and blood pressure, there was no significant change in the estimated HR (18.5).
In addition, study subjects who had hematuria in adolescence were considerably younger at the onset of ESRD (34 years) than were subjects without hematuria during their youth (38 years).
When the cases of ESRD were categorized by nine possible causes – diabetes, hypertension, glomerulonephritis, hereditary nephritis, interstitial nephritis, cystic kidney disease, secondary glomerulonephritis, drug-induced, and other causes – the clear majority of cases among subjects who had hematuria in adolescence were found to be due to glomerular disease.
"Our findings suggest that persistent asymptomatic isolated microscopic hematuria detected during adolescence and young adulthood is an early marker for primary glomerular injury and may be the first sign of an occult renal disease," the researchers said.
They added that follow-up in this study ended well before subjects reached the age at which ESRD incidence peaks, so their calculations likely underestimate the true significance of hematuria as a predictor for the disease.
Since this study involved only Jewish subjects, the results may not be generalizable to other racial/ethnic groups, and confirmation of these results should be sought in other populations.
"Future studies [also] are warranted to evaluate the utility of population screening in improving clinical outcomes," they noted.
This study was supported by the Israel Defense Forces Medical Corps and the Israeli Ministry of Health. No financial conflicts of interest were reported.