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Incident Proteinuria by HIV Serostatus Among Men With Pre-Diabetes Mellitus: The Multicenter AIDS Cohort Study
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Download the PDF here
Download the PDF here
Clinical Infectious Diseases, 15 August 2024
Our findings suggest the need for implementation of early screening and prevention strategies among men with HIV and pre-DM in order to reduce the risk of incident proteinuria and long-term kidney disease.
we showed that the risk of incident proteinuria in men with pre-DM was 3 times greater among PWH than among PWOH after adjustment for traditional risk factors. Given that proteinuria is strongly associated with subsequent declines in glomerular filtration rate and chronic kidney disease, our findings suggest that persons with pre-DM and HIV may particularly benefit from interventions to preserve kidney function and that further study is warranted....... The central finding of our study was that HIV serostatus was the factor second-most strongly associated with incident proteinuria in men with pre-DM, with a relative risk of 3.3
lower CD4 cell count and certain ART exposures were associated with incident proteinuria. Similar to the MACS prevalence analysis, we found that a current CD4 cell count <500/μL was associated with a 2-fold increase in incident proteinuria among PWH with pre-DM, although no statistically significant association was seen with nadir CD4 cell count, history of AIDS, or other markers of immunologic function. In previous MACS analyses, proteinuria and renal dysfunction have been associated with markers of systemic inflammation [4, 20]. We hypothesize that immunologic dysfunction and resulting systemic inflammation in those with incomplete T-cell recovery is also driving the risk of proteinuria in PWH with pre-DM.
We found that current protease inhibitor use was associated with incident proteinuria, as seen in previous studies, while INSTI use was associated with a lower risk of proteinuria
hypertension, a well-known risk factor for proteinuria, had an IRR of 2.0
HCV was also a strong risk factor, as seen in previous analyses. Early evidence suggests that HCV treatment and cure may decrease the risk of proteinuria and renal disease
Taken together, our findings suggest that PWH with pre-DM may represent an important target population for prevention strategies. This may include recommendations that promote more aggressive lifestyle changes or metformin use to reduce the progression to overt DM and its related complications, such as renal disease. The use of sodium glucose transporter 2 inhibitor treatment, which has favorable effects on protein excretion and glycemic control, should be evaluated in this population [25], as well as blockade of the renin-angiotensin-aldosterone system, which has been shown to be activated in PWH
Abstract
Background
Pre-diabetes mellitus (DM) is associated with proteinuria, a risk factor for chronic kidney disease. While people with human immunodeficiency virus (HIV; PWH) have a higher risk of proteinuria than people without HIV (PWOH), it is unknown whether incident proteinuria differs by HIV serostatus among prediabetic persons.
Methods
The urine protein-to-creatinine ratio was measured at semiannual visits among men in the Multicenter AIDS Cohort Study since April 2006. Men with pre-DM on or after April 2006 and no prevalent proteinuria or use of antidiabetic medications were included. Pre-DM was defined as a fasting glucose level of 100-125 mg/dL confirmed within a year by a repeated fasting glucose or hemoglobin A1c measurement of 5.7%-6.4%. Incident proteinuria was defined as a urine protein-to-creatinine ratio (UPCR) >200 mg/g, confirmed within a year. We used Poisson regression models to determine whether incident proteinuria in participants with pre-DM differed by HIV serostatus and, among PWH, whether HIV-specific factors were related to incident proteinuria.
Results
Between 2006 and 2019, among 1276 men with pre-DM, proteinuria developed in 128 of 613 PWH (21%) and 50 of 663 PWOH (8%) over a median 10-year follow-up. After multivariable adjustment, the incidence of proteinuria in PWH with pre-DM was 3.3 times (95% confidence interval, 2.3-4.8 times) greater than in PWOH (P < .01). Among PWH, current CD4 cell count <50/μL (P < .01) and current use of protease inhibitors (P = .03) were associated with incident proteinuria, while lamivudine and integrase inhibitor use were associated with a lower risk.
Conclusions
Among men with pre-DM, the risk of incident proteinuria was 3 times higher in PWH. Strategies to preserve renal function are needed in this population.
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