Effects of Aging, Baseline Renal Function and Stage of HIV Infection on Post-treatment Changes in Renal Function Among HIV-Infected Patients

A Retrospective Cohort Study

Y Ding; S Duan; R Ye; S Yao; D Cao; Y Yang; J Wang; Y Shi; Y Zhang; P Li; Y Xu; H Wei; C Yin; X Liu; N He

Disclosures

HIV Medicine. 2019;20(9):591-600. 

In This Article

Abstract and Introduction

Abstract

Objectives: The use of combination antiretroviral therapy (cART) increases clinical uncertainty about changes in renal function. Specifically, little is known regarding the interaction of the effects of aging, baseline renal impairment, and stages of HIV infection on post-treatment changes in renal function.

Methods: This analysis included 5533 HIV-infected patients on cART in 2004–2016. Progression to chronic kidney disease (CKD) was defined as either two consecutive estimated glomerular filtration rate (eGFR) measurements < 60 mL/min/1.73 m2 for baseline eGFR ≥ 60 mL/min/1.73 m2 (mild renal impairment or normal renal function) or a 25% decline for baseline eGFR < 60 mL/min/1.73 m2 (moderate renal impairment).

Results: During follow-up (median 4.8 years), 130 (2.3%) of the patients progressed to CKD. A total of 20.1% of patients with baseline normal renal function progressed to mild renal impairment, while 74.0% of patients with baseline mild or moderate renal impairment improved to normal renal function. In multivariable analysis, a significant positive baseline-eGFR-by-World Health Organization (WHO)-stage interaction effect on progression to CKD in all patients was identified, indicating a cross-over effect from a reduced risk to an increased risk. A significant negative baseline-age-by-WHO-stage interaction effect on progression to mild renal impairment in patients with baseline normal renal function was identified, with adjusted hazard ratios progressively lower at older ages. In addition, there were significant associations with older age, lower baseline eGFR, Dai ethnic minority, and anaemia for both outcomes, hyperglycaemia for CKD only, and higher CD4 count, tenofovir and ritonavir-boosted lopinavir use for mild renal impairment only.

Conclusions: Our data suggest a complex pattern of renal function dynamics in patients on cART, which requires precise management with systematic monitoring of the interaction of the effects of sociodemographic, nephrological and HIV-specific clinical characteristics.

Introduction

The widespread use of combination antiretroviral therapy (cART) among HIV-positive individuals has transformed HIV infection into a chronic condition, resulting in improved life expectancy. The prevalence of HIV-associated nephropathy (HIVAN) – a leading cause of HIV-associated kidney diseases during the early HIV epidemic – has greatly declined.[1] However, HIV-infected individuals continue to have much higher rates of chronic kidney disease (CKD) than HIV-uninfected individuals,[2,3] increasing their risk of cardiovascular disease, end-stage renal disease and premature mortality.[4]

Exposure to some antiretroviral agents, such as tenofovir disoproxil fumarate (TDF), indinavir (IDV) and ritonavir-boosted lopinavir (LPV/r), has been associated with an increased risk of CKD as a consequence of their nephrotoxicity.[5,6] cART itself also increases the risk of metabolic disorders, which in turn increases the risk of CKD.[7] In addition, an elevated risk of CKD may be linked to 'normal' aging and potentially 'accelerated' aging as an indirect consequence of cART.[7–11] Aging is an important risk factor for CKD associated with hypertension and diabetes in the general population.[12] The prevalence of these CKD risk factors is increased in older HIV-infected adults,[3] and older age has been linked to increased risk of CKD in the HIV-infected population.[6,13]

Previous studies have shown that changes in renal function differ by the level of baseline renal function, with improvement in patients with baseline renal impairment but deterioration in patients with baseline normal renal function.[14] Studies have also shown that cART could improve renal function among patients with advanced HIV stage at baseline.[6,15] However, a recent study of patients with baseline normal renal function has revealed that prior AIDS-defining illness is an independent risk factor for CKD development.[16] Chronic immune activation was a key feature of AIDS pathogenesis in the pre-cART era.[10] Chronic immune activation and inflammation have been implicated in accelerating the aging process as well as elevating the risks of age-related comorbidities such as renal impairment during suppressive cART.[3,10,17,18] cART partially reverses pro-inflammatory pathways, but inflammation persists particularly among people who have a late HIV clinical stage prior to their treatment.[10]

The independent effects of age, baseline renal function and HIV clinical stage have been evaluated, as previously described, but the possible interactions between these risk factors have not been systematically examined. A fuller evaluation of their interactions will shed light on their impact on changes in renal function, and further help evaluate CKD risk and provide guidance on clinical monitoring, particularly in the context of current guidelines recommending the early initiation of cART regardless of CD4 cell count and of medications needing to be taken life-long. In particular, there are few data on the impact of cART on renal function changes among HIV-infected individuals in China,[19] where, at the end of 2017, 609 829 out of a total of 758 610 persons reported to be living with HIV were receiving cART.

The aim of this study was therefore to assess the possible interactions between aging, baseline renal function and stage of HIV infection in their effects on post-cART changes in renal function (effect modifications), as measured by the estimated glomerular filtration rate (eGFR), among HIV-infected patients in China.

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