Abstract and Introduction
Abstract
Both a low estimated glomerular filtration rate (eGFR) and albuminuria are known risk factors for end-stage renal disease (ESRD). To determine their joint contribution to ESRD and other kidney outcomes, we performed a meta-analysis of nine general population cohorts with 845,125 participants and an additional eight cohorts with 173,892 patients, the latter selected because of their high risk for chronic kidney disease (CKD). In the general population, the risk for ESRD was unrelated to eGFR at values between 75 and 105 ml/min per 1.73 m but increased exponentially at lower levels. Hazard ratios for eGFRs averaging 60, 45, and 15 were 4, 29, and 454, respectively, compared with an eGFR of 95, after adjustment for albuminuria and cardiovascular risk factors. Log albuminuria was linearly associated with log ESRD risk without thresholds. Adjusted hazard ratios at albumin-to-creatinine ratios of 30, 300, and 1000 mg/g were 5, 13, and 28, respectively, compared with an albumin-to-creatinine ratio of 5. Albuminuria and eGFR were associated with ESRD, without evidence for multiplicative interaction. Similar associations were found for acute kidney injury and progressive CKD. In high-risk cohorts, the findings were generally comparable. Thus, lower eGFR and higher albuminuria are risk factors for ESRD, acute kidney injury and progressive CKD in both general and high-risk populations, independent of each other and of cardiovascular risk factors.
Introduction
This is the third in a series of four manuscripts to report the results of collaborative meta-analyses of estimated GFR (eGFR) and albuminuria on outcomes of chronic kidney disease (CKD) undertaken by the CKD Prognosis Consortium. These analyses were undertaken in conjunction with the 2009 Controversies Conference sponsored by Kidney Disease Improving Global Outcomes (KDIGO) to evaluate the current definition and classification of CKD and proposed alternatives. The report of the Consensus Conference is included in this issue of Kidney International.
Widespread implementation of the definition and classification of CKD, as proposed by Kidney Disease Outcomes Quality Initiative (KDOQI) in 2002 and subsequently endorsed by KDIGO in 2004, has promoted increased attention to CKD in clinical practice, research, and public health. It has also generated substantial debate about the appropriateness of recommending the same GFR thresholds for people of all ages, the optimal level of albuminuria for diagnosing kidney damage, and about the value of the 5-stage classification system based on eGFR without consideration of albuminuria. It was the position of KDOQI and KDIGO that a comprehensive analysis of mortality and kidney outcomes according to eGFR and albuminuria was needed to answer key questions underlying the debate.
Until recently, most of the data on kidney outcomes were from studies of patients with later stages of CKD rather than from general population cohorts or cohorts at increased risk for CKD. Reports from the general population and high-risk cohorts focused mainly on all-cause and cardiovascular mortality, with fewer data available on kidney outcomes. In this manuscript, we describe a collaborative meta-analysis of nine general population and eight high-risk cohorts. The outcomes reported in this manuscript include kidney failure treated by dialysis or transplantation (end-stage renal disease (ESRD)) or coded on the death certificate. In addition, we also included acute kidney injury, because it is increasingly recognized as a major cause for and consequence of CKD, and kidney disease progression, based on fast eGFR decline (progressive CKD), because of its clinical importance and potential to lead to ESRD or other complications.
Other papers in this series deal with all-cause and cardiovascular mortality in general population cohorts and high-risk cohorts. This report describes the kidney outcomes from these cohorts. A fourth manuscript reports mortality and kidney outcomes in CKD cohorts.A priori we hypothesized that both eGFR and albuminuria would be associated with these outcomes, independent of traditional cardiovascular risk factors and independent of each other, and despite inclusion of diverse study populations.