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      Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex: a meta-analysis

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          Abstract

          Objective To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease.

          Design Random effects meta-analysis using pooled individual participant data.

          Setting 46 cohorts from Europe, North and South America, Asia, and Australasia.

          Participants 2 051 158 participants (54% women) from general population cohorts (n=1 861 052), high risk cohorts (n=151 494), and chronic kidney disease cohorts (n=38 612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m 2) and urinary albumin-creatinine ratio (mg/g).

          Results Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (P interaction<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (P interaction<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk.

          Conclusions Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

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          Most cited references21

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          Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts.

          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(2) 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.
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            Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts.

            We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.
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              CIRCULATION

              SS Chugh (1964)
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                Author and article information

                Contributors
                Role: clinical senior lecturer
                Role: assistant professor
                Role: biostatistician
                Role: senior clinical lecturer
                Role: associate professor
                Role: corporate director
                Role: director
                Role: clinical professor
                Role: assistant professor
                Role: professor
                Role: associate professor
                Role: professor
                Role: professor
                Role: professor
                Role: associate professor
                Journal
                BMJ
                BMJ
                bmj
                BMJ : British Medical Journal
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2013
                2013
                29 January 2013
                : 346
                : f324
                Affiliations
                [1 ]Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK
                [2 ]Department of Medicine, Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore MD, USA
                [3 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore MD, USA
                [4 ]Chronic Disease Research Group, Medical School, Aberdeen, UK
                [5 ]Department of Medicine (Nephrology), University of Salerno, Baronissi (SA), Italy
                [6 ]Provincial Health Services Authority, Vancouver BC, Canada
                [7 ]Division of Nephrology UBC, St.Pauls Hospital, Vancouver BC, Canada
                [8 ]Dialysis Unit, University Hospital of the Ryukyus, Okinawa, Japan
                [9 ]VA San Diego Healthcare System, Division of GIM/G, San Diego CA, USA
                [10 ]Institute for Health Promotion, Department of Epidemiology and Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea
                [11 ]Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
                [12 ]St Olavs Hospital, Department of Medicine, Section of Nephrology, Trondheim, Norway
                [13 ]Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston MA, USA
                [14 ]George Institute for Global Health, Camperdown NSW, Australia
                [15 ]Division of Nephrology, Foothills Medical Centre, Calgary AB, Canada
                Author notes
                Correspondence to: A S Levey, Chronic Kidney Disease Prognosis Consortium. 615 N Wolfe Street, Baltimore, MD 21205, USA ckdpc@ 123456jhmi.edu
                Article
                nitd006437
                10.1136/bmj.f324
                3558410
                23360717
                b8821165-3cef-412b-953f-c1cd337b0ecb
                © Nitsch et al 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: http://creativecommons.org/licenses/by-nc/2.0/ and http://creativecommons.org/licenses/by-nc/2.0/legalcode.

                History
                : 28 December 2012
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                Medicine
                Medicine

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