Relative risk of renal disease among people living with HIV: a systematic review and meta-analysis

Abstract

Background: Antiretroviral therapy (ART) has substantially decreased mortality and HIV-related morbidity. However, other morbidities appear to be more common among PLHIV than in the general population. This study aimed to estimate the relative risk of renal disease among people living with HIV (PLHIV) compared to the HIV-uninfected population.

Methods: We conducted a systematic review and meta-analysis of relative risks of renal disease among populations of PLHIV reported in studies from the peer-reviewed literature. We searched Medline for relevant journal articles published before September 2010, yielding papers published during or after 2002. We also searched conference proceedings of the International AIDS Society (IAS) and Conference on Retroviruses and Opportunistic Infections (CROI) prior to and including 2010. Eligible studies were observational studies reporting renal disease defined as acute or chronic reduced renal function with glomerular filtration rate less than or equal to 60 ml/min/1.73 m2 among HIV-positive adults. Pooled relative risks were calculated for various groupings, including class of ART drugs administered.

Results: The overall relative risk of renal disease was 3.87 (95% CI: 2.85-6.85) among HIV-infected people compared to HIV-uninfected people. The relative risk of renal disease among people with late-stage HIV infection (AIDS) was 3.32 (1.86-5.93) compared to other PLHIV. The relative risk of renal disease among PLHIV who were receiving antiretroviral therapy (ART) was 0.54 (0.29-0.99) compared to treatment-naïve PLHIV; the relative risk of renal disease among PLHIV who were treated with tenofovir was 1.56 (0.83-2.93) compared to PLHIV who were treated with non-tenofovir therapy. The risk of renal disease was also found to significantly increase with age.

Conclusion: PLHIV are at increased risk of renal disease, with greater risk at later stages of infection and at older ages. ART prolongs survival and decreases the risk of renal disease. However, less reduction in renal disease risk occurs for Tenofovir-containing ART than for other regimens.

Figure 1

Information flow diagram of the systematic review. a Qualitative synthesis: results of primary studies are summarized but not statistically combined; b Quantitative synthesis: Statistical methods applied to combine the results of two or more studies c includes conference proceedings (7).

Figure 2

Forest plot of studies and pooled estimate of relative risk of renal disease. In (a) HIV-infected versus HIV-uninfected people; (b) HIV-infected people exposed to antiretroviral treatment versus treatment-naïve PLHIV; (c) HIV-infected people exposed to tenofovir-based ART versus non-tenofovir-based ART; (d) HIV-infected people per year of exposure to TDF-based ART. (e)Relative risk of renal disease in PLHIV according to CD4 count. Mid-values of the range of reported CD4 categories are plotted; each point/bar presents data from a single study, illustrating the RR/95% CI of CKD < 60 for the low CD4 group (CD4 value shown on the abscissa) compared to the high CD4 group (presented in Table 3). (f)Forest plot of studies and pooled estimate of relative risk of renal disease among people in AIDS stage versus non-AIDS HIV infection. (g)Relative risk of renal disease in HIV-infected people in various age groups (presented in Table 2). ¹Crane, 2007; compared with < 30, ²Lucas, 2007; compared with < 30, ³Ganesan, 2010; compared with < 35 ⁴Franey, 2009; compared with < 30; ⁵Lucas, 2007; compared with < 50; ⁶Campbell, 2009; compared with < 50. (h)Forest plot of studies and pooled estimate of relative risk of renal disease in HIV-infected people by 10-year increment in age.