Publications

BACKGROUND

Chronic kidney disease (CKD) is common among HIV-infected individuals but serum creatinine is insensitive for detecting kidney damage at early stages. We hypothesized that HIV infection would be associated with elevations in subclinical markers of kidney injury and fibrosis in a contemporary cohort of men.

METHODS

In this cross-sectional study, we measured urine levels of interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), pro-collagen type III N-terminal pro-peptide (PIIINP) and albumin-creatinine ratio (ACR) in 813 HIV-infected and 331 uninfected men enrolled in the Multicenter AIDS Cohort Study.

RESULTS

Median eGFR was 95 ml/min/1.73 m among African-Americans (n=376) and 87 ml/min/1.73 m among Caucasians (n=768). Among HIV-infected men, the median CD4 lymphocyte count was 572 cells/mm and 76% of men had undetectable HIV RNA levels. After multivariable adjustment for traditional CKD risk factors including eGFR, HIV infection was associated with 52% higher urine IL-18 (95% CI, 33%, 73%), 44% higher KIM-1 (27%, 64%), 30% higher PIIINP (15%, 47%) and 84% higher ACR (54%, 120%), with similar effect sizes among African-Americans and Caucasians (P>0.2 for tests of interaction by race). These associations remained statistically significant in analyses that excluded persons with detectable HIV RNA levels and in models that adjusted for cumulative exposure to tenofovir disoproxil fumarate.

CONCLUSIONS

Compared with uninfected men, HIV-infected men had more extensive glomerular and tubulointerstitial damage, as assessed by urine biomarkers. Future studies should evaluate whether combinations of biomarkers can be used to monitor stages of kidney injury and to predict CKD risk in HIV-infected individuals.

Under the U.S. Lung Allocation Score (LAS) system, older and sicker patients are prioritized for lung transplantation (LT). The impact of these changes on health-related quality of life (HRQL) after transplant has not been determined. In a single-center prospective cohort study from 2010 to 2016, we assessed HRQL before and repeatedly after LT for up to 3 years using the SF12-Physical and Mental Health, the respiratory-specific Airway Questionnaire 20-Revised, and the Euroqol 5D/Visual Analog Scale utility measures by multivariate linear mixed models jointly modeled with death. We also tested changes in LT-Valued Life Activities disability, BMI, allograft function, and 6-min walk test exercise capacity as predictors of HRQL change. Among 211 initial participants (92% of those eligible), LT improved HRQL by all 5 measures (p < 0.05) and all but SF12-Mental Health improved by threefold or greater than the minimally clinically important difference. Compared to younger participants, those aged ≥65 improved less in SF12-Physical and Mental Health (p < 0.01). Improvements in disability accounted for much of the HRQL improvement. In the LAS era, LT affords meaningful and durable HRQL improvements, mediated by amelioration of disability. Identifying factors limiting HRQL improvement in selected subgroups, especially those aged ≥65, are needed to maximize the net benefits of LT.

OBJECTIVE

Liver disease markers have been associated with mortality in HIV-infected individuals in the modern era of effective antiretroviral therapy. Our objective was to determine which markers are most predictive of mortality in HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected persons.

RESEARCH DESIGN AND METHODS

We measured serum albumin, total protein, calculated globulin, aspartate transaminase (AST), and alanine transaminase in 193 HIV/HCV-coinfected and 720 HIV-monoinfected persons in the study of Fat Redistribution and Metabolic Change in HIV Infection. We evaluated associations of each marker with 5-year, all-cause mortality, adjusting for cardiovascular, HIV-related factors, inflammation, renal disease, muscle, and adiposity.

RESULTS

After 5 years of follow-up, overall mortality was 21% in HIV/HCV-coinfected and 12% in HIV-monoinfected participants. After multivariable adjustment, lower albumin and higher AST were independently associated with increased mortality. Lower albumin was associated with 49% increased odds of mortality overall [per 0.5 g/dl decrease, 95% confidence interval (CI): 1.2-1.9]; the association was stronger in HIV/HCV-coinfected [odds ratio (OR) = 2.1, 95% CI: 1.4-3.2] vs. HIV-monoinfected (OR = 1.3, 95% CI: 1.0-1.7; HCV-by-albumin interaction: P = 0.038). Higher AST was associated with 41% increased odds of mortality (per AST doubling; 95% CI: 1.1-1.8); associations were much stronger among HIV/HCV-coinfected (OR = 2.5, 95% CI: 1.5-4.1) than HIV-monoinfected (OR = 1.1, 95% CI: 0.8-1.5; HCV-by-AST interaction: P = 0.0042).

CONCLUSION

Lower serum albumin and higher AST appear to be important mortality risk factors in HIV/HCV-coinfection, but much less so in HIV-monoinfected individuals. The association of low albumin with mortality may reflect its role as a negative acute phase response protein. AST levels do not appear to be useful in predicting mortality in HIV-monoinfection and should be considered primarily in the context of HCV-coinfection.