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Multicenter Study
. 2024 Aug 16;79(2):469-476.
doi: 10.1093/cid/ciae065.

Incident Proteinuria by HIV Serostatus Among Men With Pre--Diabetes Mellitus: The Multicenter AIDS Cohort Study

Laurence Slama  1   2   3 , Benjamin W Barrett  4 , Alison G Abraham  5 , Frank J Palella Jr  3 , Jared W Magnani  6 , Jean Paul Viard  1 , Jordan E Lake  7 , Todd T Brown  4
Affiliations
Multicenter Study

Incident Proteinuria by HIV Serostatus Among Men With Pre--Diabetes Mellitus: The Multicenter AIDS Cohort Study

Laurence Slama et al. Clin Infect Dis. .

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.

Keywords: HIV; MACS; diabetes; incident proteinuria; pre-diabetes.

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Conflict of interest statement

Potential conflicts of interest. L. S. declares consulting fees, support for attending meetings, and payment for presentation from Gilead Sciences, ViiV Healthcare, and Merck, outside the present work. A. G. A. declares a National Heart, Lung, and Blood Institute grant paid to her institution. F. J. P. declares payment from ViiV, Gilead Sciences, Janssen, Merck, and EMD Serono, outside the present work. J. W. M. declares a NIH/NHLBI research grant to the University of Pittsburgh and is an American Heart Association committee member. J. E. L. declares research support from Gilead Sciences, Pfizer, Oncoimmune, and CytoDyn, all paid to her institution; consulting fees for Theratechnologies; and stock options from CytoDyn. T. T. B. declares consulting fees from Merck, Janssen, Gilead Sciences, and ViiV Healthcare, outside the present work. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Incident proteinuria among men with pre–diabetes mellitus (DM) over a median of 10 years of follow-up Differences by human immunodeficiency virus (HIV) serostatus. (Percentages displayed in the figure differ slightly from those reported in the text owing to HIV seroconversion over follow-up.)
Figure 2.
Figure 2.
Multivariable regression model for incident proteinuria among 1276 men with pre–diabetes mellitus (DM). Forest plot of multivariate Poisson regression model results, among 1276 men with pre-DM between 1 April 2006 and 30 September 2019. Incident proteinuria is the outcome, human immunodeficiency virus (HIV) serostatus is the main exposure, and controls are age, race/ethnicity, education, smoking status, categorical estimated glomerular filtration rate (eGFR; determined using the race-free CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equation), body mass index (BMI; calculated as weight in kilograms divided by height in meters squared), dyslipidemia, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) use, high blood pressure (BP), and hepatitis C virus (HCV) infection. Error bars represent 95% confidence intervals; dashed vertical line, incidence rate ratio (IRR) of 1.0 (no difference in proteinuria risk by exposure). Abbreviation: Ref, reference.
Figure 3.
Figure 3.
Multivariable regression model for incident proteinuria among 613 men with pre–diabetes mellitus (DM) and human immunodeficiency virus (HIV). Forest plot of multivariate Poisson regression model results, among 613 men with pre-DM and HIV between 1 April 2006 and 30 September 2019. Incident proteinuria is the outcome, and covariates are age, race/ethnicity, education, smoking status, categorical estimated glomerular filtration rate (eGFR; determined using the race-free CKD-EPI [Chronic Kidney Disease Epidemiology Collaboration] equation), body mass index (BMI), dyslipidemia, angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) use, high blood pressure (BP), hepatitis C virus (HCV) infection, suppressed HIV viral load (VL), history of clinical AIDS, current CD4 cell count <500/µL, CD4 cell count nadir <200/µL, and cumulative years of antiretroviral therapy (ART) and highly active ART (HAART) use before the baseline visit. Error bars represent 95% confidence intervals (CIs); dashed vertical line, incidence rate ratio (IRR) of 1.0 (no difference in proteinuria risk by exposure). Abbreviation: Ref, reference.
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