Cystatin C, albuminuria, and 5-year all-cause mortality in HIV-infected persons

Abstract

Background: Compared with controls, human immunodeficiency virus (HIV)-infected persons have a greater prevalence of kidney disease, assessed according to high cystatin C level and albuminuria, but not according to creatinine level. However, the clinical importance of increased cystatin C level and albuminuria in the HIV-infected population has not been studied.

Study design: We conducted an observational cohort study to determine the association of kidney disease (measured according to albuminuria, cystatin C, and serum creatinine) with mortality.

Setting & participants: 922 HIV-infected persons enrolled in the FRAM (Fat Redistribution and Metabolic Change in HIV Infection) Study.

Predictor: Serum cystatin C and serum creatinine levels were used to estimate glomerular filtration rates (eGFR(SCysC) and eGFR(SCr), respectively). Albuminuria was defined as a positive urine dipstick result (≥ 1+) or urine albumin-creatinine ratio >30 mg/g.

Outcome: 5-Year mortality.

Results: At baseline, decreased kidney function (eGFR(SCysC) <60 mL/min/1.73 m(2)) or albuminuria was present in 28% of participants. After 5 years of follow-up, mortality was 48% in those with both eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria, 23% in those with eGFR(SCysC) < 60 mL/min/1.73 m(2) alone, 20% in those with albuminuria alone, and 9% in those with neither condition. After multivariable adjustment for demographics, cardiovascular risk factors, HIV-related factors, and inflammatory marker levels, eGFR(SCysC) < 60 mL/min/1.73 m(2) and albuminuria were associated with a nearly 2-fold increase in mortality, whereas eGFR(SCr) < 60 mL/min/1.73 m(2) did not appear to have a substantial association with mortality. Together, eGFR(SCysC) <60 mL/min/1.73 m(2) and albuminuria accounted for 17% of the population-level attributable risk of mortality.

Limitations: Vital status was unknown in 261 participants from the original cohort.

Conclusions: Kidney disease marked by albuminuria or increased cystatin C level appears to be an important risk factor for mortality in HIV-infected individuals. A substantial proportion of this risk may be unrecognized because of the current reliance on serum creatinine to estimate kidney function in clinical practice.

FIGURE 1

Unadjusted 5-year mortality rates in HIV-infected participants, stratified by presence of reduced serum cystatin C-based estimated glomerular filtration rate (eGFR_Cys <60 mL/min/1.73m²) or albuminuria. In Panel (A), mortality rates in all 922 HIV-infected FRAM (Fat Redistribution and Metabolic Change in HIV Infection) participants are shown. In Panel (B), mortality rates in 877 HIV-infected individuals with normal kidney function, defined as a serum creatinine-based eGFR ≥60 mL/min/1.73m², are displayed.*

FIGURE 1

Unadjusted 5-year mortality rates in HIV-infected participants, stratified by presence of reduced serum cystatin C-based estimated glomerular filtration rate (eGFR_Cys <60 mL/min/1.73m²) or albuminuria. In Panel (A), mortality rates in all 922 HIV-infected FRAM (Fat Redistribution and Metabolic Change in HIV Infection) participants are shown. In Panel (B), mortality rates in 877 HIV-infected individuals with normal kidney function, defined as a serum creatinine-based eGFR ≥60 mL/min/1.73m², are displayed.*

FIGURE 2

Population-Level Risk of Mortality Attributable to Kidney Disease in HIV-Infected Persons. eGFR_Cys (serum cystatin C-based estimated glomerular filtration rate) reported in mL/min/1.73m². “Combined” category includes those with either eGFR_Cys <60 mL/min/1.73m² or microalbuminuria.