Mayo Clinic Proceedings Home

Association of Slopes of Estimated Glomerular Filtration Rate With Post–End-Stage Renal Disease Mortality in Patients With Advanced Chronic Kidney Disease Transitioning to Dialysis



      To investigate the association of estimated glomerular filtration rate (eGFR) slopes before dialysis initiation with cause-specific mortality after dialysis initiation.

      Patients and Methods

      In this retrospective cohort study of 18,874 US veterans who had transitioned to dialysis from October 1, 2007, through September 30, 2011, we examined the association of pre–end-stage renal disease (ESRD) eGFR slopes with all-cause, cardiovascular, and infection-related mortality during the post-ESRD period over a median follow-up of 2.0 years (interquartile range, 1.1-3.2 years). Associations were examined using Cox models with adjustment for potential confounders.


      Before the 18,874 patients transitioned to dialysis, 4485 (23.8%), 5633 (29.8%), and 7942 (42.1%) experienced fast, moderate, and slow eGFR decline, respectively, and 814 (4.3%) had increasing eGFR (defined as eGFR slopes of less than −10, −10 to less than −5, −5 to <0, and ≥0 mL/min per 1.73 m2 per year). During the study period, a total of 9744 all-cause, 2702 cardiovascular, and 604 infection-related deaths were observed. Compared with patients with slow eGFR decline, those with moderate and fast eGFR decline had a higher risk of all-cause mortality (adjusted hazard ratio [HR], 1.06; 95% CI, 1.00-1.11; and HR, 1.11; 95% CI, 1.04-1.18, respectively) and cardiovascular mortality (HR, 1.11; 95% CI, 1.01-1.23 and HR, 1.13; 95% CI, 1.00-1.27, respectively). In contrast, increasing eGFR was only associated with higher infection-related mortality (HR, 1.49; 95% CI, 1.03-2.17).


      Rapid eGFR decline is associated with higher all-cause and cardiovascular mortality, and increasing eGFR is associated with higher infection-related mortality among incident dialysis cases.

      Abbreviations and Acronyms:

      AKI (acute kidney injury), BMI (body mass index), CKD (chronic kidney disease), CMS (Centers for Medicare and Medicaid Services), eGFR (estimated glomerular filtration rate), ESA (erythropoiesis-stimulating agent), ESRD (end-stage renal disease), HR (hazard ratio), IQR (interquartile range), NDD (non–dialysis dependent), PY (patient-year), USRDS (United States Renal Data System), VA (Veterans Affairs)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • United States Renal Data System
        2014 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States.
        National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD2014
        • Robinson B.M.
        • Zhang J.
        • Morgenstern H.
        • et al.
        Worldwide, mortality risk is high soon after initiation of hemodialysis.
        Kidney Int. 2014; 85: 158-165
        • Bradbury B.D.
        • Fissell R.B.
        • Albert J.M.
        • et al.
        Predictors of early mortality among incident US hemodialysis patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS).
        Clin J Am Soc Nephrol. 2007; 2: 89-99
        • Rhee C.M.
        • Kalantar-Zadeh K.
        Transition to dialysis: controversies in its timing and modality.
        Semin Dial. 2013; 26 ([published correction appears in Semin Dial. 2014;27(1):60]): 641-643
        • Turin T.C.
        • Coresh J.
        • Tonelli M.
        • et al.
        Short-term change in kidney function and risk of end-stage renal disease.
        Nephrol Dial Transplant. 2012; 27: 3835-3843
        • Coresh J.
        • Turin T.C.
        • Matsushita K.
        • et al.
        • CKD Prognosis Consortium
        Decline in estimated glomerular filtration rate and subsequent risk of end-stage renal disease and mortality.
        JAMA. 2014; 311: 2518-2531
        • Matsushita K.
        • Selvin E.
        • Bash L.D.
        • Franceschini N.
        • Astor B.C.
        • Coresh J.
        Change in estimated GFR associates with coronary heart disease and mortality.
        J Am Soc Nephrol. 2009; 20: 2617-2624
        • Shlipak M.G.
        • Katz R.
        • Kestenbaum B.
        • et al.
        Rapid decline of kidney function increases cardiovascular risk in the elderly.
        J Am Soc Nephrol. 2009; 20: 2625-2630
        • Rifkin D.E.
        • Shlipak M.G.
        • Katz R.
        • et al.
        Rapid kidney function decline and mortality risk in older adults.
        Arch Intern Med. 2008; 168: 2212-2218
        • Lambers Heerspink H.J.
        • Weldegiorgis M.
        • Inker L.A.
        • et al.
        Estimated GFR decline as a surrogate end point for kidney failure: a post hoc analysis from the Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan (RENAAL) study and Irbesartan Diabetic Nephropathy Trial (IDNT).
        Am J Kidney Dis. 2014; 63: 244-250
        • Al-Aly Z.
        • Zeringue A.
        • Fu J.
        • et al.
        Rate of kidney function decline associates with mortality.
        J Am Soc Nephrol. 2010; 21: 1961-1969
        • Perkins R.M.
        • Bucaloiu I.D.
        • Kirchner H.L.
        • Ashouian N.
        • Hartle J.E.
        • Yahya T.
        GFR decline and mortality risk among patients with chronic kidney disease.
        Clin J Am Soc Nephrol. 2011; 6: 1879-1886
        • Turin T.C.
        • Coresh J.
        • Tonelli M.
        • et al.
        One-year change in kidney function is associated with an increased mortality risk.
        Am J Nephrol. 2012; 36: 41-49
        • Turin T.C.
        • Coresh J.
        • Tonelli M.
        • et al.
        Change in the estimated glomerular filtration rate over time and risk of all-cause mortality.
        Kidney Int. 2013; 83: 684-691
        • O'Hare A.M.
        • Batten A.
        • Burrows N.R.
        • et al.
        Trajectories of kidney function decline in the 2 years before initiation of long-term dialysis.
        Am J Kidney Dis. 2012; 59: 513-522
        • US Department of Veterans Affairs
        • Health Services Research and Development Service
        • VA Information Resource Center
        VIReC Resource Guide: VA Corporate Data Warehouse.
        VA Information Resource Center, Hines, IL2012
        • US Department of Veterans Affairs
        • Health Services Research and Development Service
        • VA Information Resource Center
        VIReC Research User Guide: VHA Decision Support System Clinical National Data Extracts.
        2nd ed. VA Information Resource Center, Hines, IL2009
        • US Department of Veterans Affairs
        • Health Services Research and Development Service
        • VA Information Resource Center
        VIReC Research User Guide: VHA Pharmacy Prescription Data.
        2nd ed. VA Information Resource Center, Hines, IL2008
        • US Department of Veterans Affairs
        • Health Services Research and Development Service
        • VA Information Resource Center
        VIReC Research User Guide: VHA Medical SAS Inpatient Datasets FY2006-2007.
        VA Information Resource Center, Hines, IL2007
        • Deyo R.A.
        • Cherkin D.C.
        • Ciol M.A.
        Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases.
        J Clin Epidemiol. 1992; 45: 613-619
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        • CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150 ([published correction appears in Ann Intern Med. 2011;155(6):408]): 604-612
        • Levin A.
        • Stevens P.E.
        Summary of KDIGO 2012 CKD Guideline: behind the scenes, need for guidance, and a framework for moving forward.
        Kidney Int. 2014; 85: 49-61
        • Fine J.P.
        • Gray R.J.
        A proportional hazards model for the subdistribution of a competing risk.
        J Am Stat Assoc. 1999; 94: 496-509
        • Onuigbo M.A.
        Syndrome of rapid-onset end-stage renal disease: a new unrecognized pattern of CKD progression to ESRD.
        Ren Fail. 2010; 32: 954-958
        • Onuigbo M.
        • Agbasi N.
        Syndrome of rapid onset ESRD accounted for high hemodialysis catheter use—results of a 13-year Mayo Clinic incident hemodialysis study.
        Ren Fail. 2015; 37: 1486-1491
        • Manjunath G.
        • Tighiouart H.
        • Ibrahim H.
        • et al.
        Level of kidney function as a risk factor for atherosclerotic cardiovascular outcomes in the community.
        J Am Coll Cardiol. 2003; 41: 47-55
        • Sarnak M.J.
        • Levey A.S.
        • Schoolwerth A.C.
        • et al.
        Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American Heart Association Councils on Kidney in Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology, and Epidemiology and Prevention.
        Circulation. 2003; 108: 2154-2169
        • Kottgen A.
        • Russell S.D.
        • Loehr L.R.
        • et al.
        Reduced kidney function as a risk factor for incident heart failure: the Atherosclerosis Risk in Communities (ARIC) study.
        J Am Soc Nephrol. 2007; 18: 1307-1315
        • Shlipak M.G.
        • Stehman-Breen C.
        • Fried L.F.
        • et al.
        The presence of frailty in elderly persons with chronic renal insufficiency.
        Am J Kidney Dis. 2004; 43: 861-867
        • Odden M.C.
        • Chertow G.M.
        • Fried L.F.
        • et al.
        • HABC Study
        Cystatin C and measures of physical function in elderly adults: the Health, Aging, and Body Composition (HABC) Study.
        Am J Epidemiol. 2006; 164: 1180-1189
        • Kovesdy C.P.
        • George S.M.
        • Anderson J.E.
        • Kalantar-Zadeh K.
        Outcome predictability of biomarkers of protein-energy wasting and inflammation in moderate and advanced chronic kidney disease.
        Am J Clin Nutr. 2009; 90: 407-414
        • Lee P.S.
        • Waxman A.B.
        • Cotich K.L.
        • Chung S.W.
        • Perrella M.A.
        • Stossel T.P.
        Plasma gelsolin is a marker and therapeutic agent in animal sepsis.
        Crit Care Med. 2007; 35: 849-855
        • Goetzl E.J.
        • Lee H.
        • Azuma T.
        • Stossel T.P.
        • Turck C.W.
        • Karliner J.S.
        Gelsolin binding and cellular presentation of lysophosphatidic acid.
        J Biol Chem. 2000; 275: 14573-14578
        • Bucki R.
        • Georges P.C.
        • Espinassous Q.
        • et al.
        Inactivation of endotoxin by human plasma gelsolin.
        Biochemistry. 2005; 44: 9590-9597
        • Osborn T.M.
        • Dahlgren C.
        • Hartwig J.H.
        • Stossel T.P.
        Modifications of cellular responses to lysophosphatidic acid and platelet-activating factor by plasma gelsolin.
        Am J Physiol Cell Physiol. 2007; 292: C1323-C1330
        • Lee P.S.
        • Sampath K.
        • Karumanchi S.A.
        • et al.
        Plasma gelsolin and circulating actin correlate with hemodialysis mortality.
        J Am Soc Nephrol. 2009; 20: 1140-1148
        • Kovesdy C.P.
        • Kalantar-Zadeh K.
        Why is protein-energy wasting associated with mortality in chronic kidney disease?.
        Semin Nephrol. 2009; 29: 3-14