The Vanderbilt Institute for Global Health (VIGH) and Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria have received a federal grant to study the factors associated with microalbuminuria among participants in an ongoing clinical trial of genetically at-risk HIV-positive adult Nigerians.
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant will provide $2.2 million over the next four years.
Microalbuminuria is an independent risk factor for cardiovascular and kidney disease and a predictor of end-organ damage, with persons living with HIV (PLWH) at higher risk.
During the Renal Risk Reduction (R3) Study, researchers unexpectedly discovered a high prevalence of microalbuminuria among screened study participants; specifically, 36.9% had microalbuminuria confirmed by measurements at 4 to 8 weeks apart.
“I am really looking forward to continuing to work with the exceptional research team we have in place on this new longitudinal study that we have entitled the P_MICRO study, short for “Etiology of Persistent Microalbuminuria in Nigeria,” said C. William (“Bill”) Wester, MD, MPH, professor of Medicine at Vanderbilt University and one of the project’s principal investigators. “
“This is an exciting opportunity to work with our Nigerian partners to elucidate why our study participants have such high rates of microalbuminuria. It is only by finding out why this is happening can we propose effective interventions,” said Muktar Aliyu, MBBS, DrPH, professor of Health Policy and Medicine at VUMC and one of the project’s principal investigators.
Given the high prevalence of Apolipoprotein-1 (APOL1) variants in prior studies in West Africa, the study team hypothesized genetics played an important role. However, genotyping in the R3 study revealed lower than anticipated prevalence (only 6.2%) of the high-risk APOL1 genotype (two copies of risk variants) were present.
The high rates of albuminuria observed in this study population may reflect a mix of reversible microvascular endothelial cell injury caused by inflammation, not APOL1 mediated and podocyte cell damage where APOL1 is dominant. To elucidate this further, the study team will evaluate additional potential contributors, including hypertension and pre-hypertension, immune activation from endemic co-infections including viral hepatitis, parasitic infestations, and Mycobacterium Tuberculosis. They will also evaluate if cumulative, long-term exposure to potentially nephrotoxic antiretroviral medications increases the risk for microalbuminuria in Nigeria and similar sub-Saharan African settings.
“The P_MICRO study provides a great opportunity to explore causes of microalbuminuria other than the traditional culprits. By leveraging the data provided from the R3 study, we feel that we are incredibly well poised to advance the field of HIV-associated kidney disease in resource-constrained settings globally,” added Baba Musa, MBBS, MPH, associate professor of Medicine, Bayero University Kano and multiple principal investigator.
The research study will compare the prevalence of albuminuria and established kidney disease risk factors in a large cohort of PLWH to age- and sex-matched HIV-negative adults presenting for routine medical care at AKTH in Nigeria.
The anticipated findings from this study will support the development of interventions to address microalbuminuria in PLWH to reduce kidney and cardiovascular morbidity and mortality.
Interventions may include intensive monitoring and treatment of traditional risk factors, provision of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, consideration of changes in antiretrovirals regimen, and screening and treatment for relevant co-infections.