SAN FRANCISCO—Microalbuminuria (MA) predicts the development of overt proteinuria at two years in patients with HIV infection, data suggest.


In addition, markers for the stage of HIV infection—lower CD4-cell counts and higher plasma HIV RNA levels—may have a similar association with the development of proteinuria.

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“Our findings are really a screening message,” said lead investigator Lynda Szczech, MD, an associate professor of medicine at Duke University Medical Center in Durham, N.C. 


“Nephrologists are going to be seeing more patients with HIV and a better understanding of the aggressiveness this disease can have and of the heterogeneity of the disease, the better off we will be. Just like with diabetic nephropathy, small amounts of albumin predict the development of big amounts of protein down the road.”


In diabetic nephropathy, however, this predictive factor extends over 7-18 years; in HIV-infected individuals with MA, overt proteinuria developed in 6-12 months, she said.


Survival among HIV-infected individuals has significantly improved over the past 10 years, but their prolonged lifespan has been accompanied by an increase in the proportion of deaths from kidney and liver disease, Dr. Szczech observed.


She and her colleagues studied 948 patients receiving care at two academic centers between 2000 and 2003. The mean age of the patients was 43 years and approximately two thirds (674 patients) were male. Random urine specimens were collected at baseline and every six months for two years.


All measurements for urine albumin, protein, and creatinine were performed by a single laboratory. The researchers defined MA as albumin-to-creatinine ratio of greater than 30 mg/g and proteinuria as protein-to-creatinine ratio of 350 mg/mg or greater. Patients without urinary abnormalities, MA, and proteinuria were compared at baseline and progression to proteinuria was examined.


At baseline 69.4% of subjects had no urinary abnormalities, 20.1% had MA, and 10.5% had proteinuria, Dr. Szczech reported here during Renal Week 2007. The individuals with MA and proteinuria were more likely to be African-American, have a lower CD4-cell count and have a higher HIV RNA level compared with individuals without MA and proteinuria. Among the 658 patients without urinary abnormalities at baseline, 82.7% continued to have no abnormalities. However, 14.3% progressed to MA and 3.0% progressed to proteinuria at six months.


Among the 191 patients with MA at baseline, 40.0% showed no abnormalities, 48.8% continued to have MA and 11.2% progressed to proteinuria at six months. Patients without proteinuria at baseline who went on to develop proteinuria were more likely to have MA, a lower CD4 count, and a higher HIV RNA level than those who did not develop proteinuria.


Among subjects without proteinuria at baseline, MA was associated with a 2.9-fold increased risk of developing of proteinuria over a period of two years. Older age and lower glomerular filtration rate were both associated with an increased risk of persistent abnormal urine examinations on follow-up.


“We don’t know the process yet,” Dr. Szczech said. “It may be endothelial cell dysfunction or maybe direct viral infection into endothelial cells or other kinds of cells.  We do know it is an incredibly accelerated process. Odds are that this story is going to be very similar to diabetes, but it may be that additional factors, such as starting antiretroviral medications early, may be very important.”