Research Article| Volume 27, ISSUE 11, P1175-1184, November 2021

Download started.


Estimated Glomerular Filtration Rate Variability in Patients With Heart Failure and Chronic Kidney Disease


      • Variability in the estimated glomerular filtration rate was higher in those with heart failure and chronic kidney disease relative to those with only chronic kidney disease.
      • Patients with heart failure with reduced ejection fraction displayed the greatest amount of variability in the estimated glomerular filtration rate.
      • Variability in the estimated glomerular filtration rate was associated with a greater risk of death in all participants.
      • The risk of death was independent of heart failure phenotype.



      Greater variability in the estimated glomerular filtration rate (eGFR) is associated with higher mortality in patients with chronic kidney disease (CKD). Heart failure (HF) is common in CKD and may increase variability through changes in hemodynamic and volume regulation. We sought to determine if patients with vs without HF have higher kidney function variability in CKD, and to define the association with mortality.

      Methods and Results

      Patients undergoing coronary angiography from 2003 to 2013 with an eGFR of less than 60 mL/min/1.73 m2 were evaluated from the Duke Databank for Cardiovascular Disease. Variability in the eGFR, measured as the coefficient of variation (CV) of residuals from the regression of eGFR vs time, was calculated spanning 3 months to 2 years after catheterization. Mortality was assessed 2 to 7 years after catheterization. Patients were grouped into 3 HF phenotypes: HF with reduced ejection fraction, HF with preserved ejection, and no HF. Regression was used to evaluate associations between HF phenotypes and variability in the eGFR and between variability in the eGFR and mortality rate with stratification by HF phenotype. Among 3767 participants, the median eGFR at baseline was 45 mL/min/1.73 m2 (interquartile range 33-53 mL/min/1.73 m2), and longitudinal measures of eGFR over 21 months had within-patient residual variability (CV) of 14% (9%–20%). In adjusted analyses, variability in the eGFR was greater in those with HF with preserved ejection (n = 695, CV difference 0.98%, 95% confidence interval 0.14%–1.81%) or HF with reduced ejection fraction (n = 800, CV difference 2.51%, 95% confidence interval 1.66%–3.37%) relative to no HF (n = 2272). In 3068 participants eligible for mortality analysis, the presence of HF and greater variability in the eGFR were each associated independently with higher mortality, but there was no evidence of interaction between variability in the eGFR and any HF phenotype (all P for interaction ≥.49).


      Variability in the eGFR is greater in patients with HF and associated with mortality. Prediction algorithms and classification schemes should consider not only static, but also dynamic eGFR variability in HF and CKD prognostication.

      Graphical Abstract

      Key Words

      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 Journal of Cardiac Failure
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lofman I
        • Szummer K
        • Hagerman I
        • Dahlström U
        • Lund LH
        • Jernberg T.
        Prevalence and prognostic impact of kidney disease on heart failure patients.
        Open Heart. 2016; 3e000324
        • Lofman I
        • Szummer K
        • Dahlstrom U
        • Jernberg T
        • Lund LH.
        Associations with and prognostic impact of chronic kidney disease in heart failure with preserved, mid-range, and reduced ejection fraction.
        Eur J Heart Fail. 2017; 19: 1606-1614
        • Galil AG
        • Pinheiro HS
        • Chaoubah A
        • Costa DM
        • Bastos MG.
        Chronic kidney disease increases cardiovascular unfavourable outcomes in outpatients with heart failure.
        BMC Nephrol. 2009; 10: 31
        • Smith DH
        • Thorp ML
        • Gurwitz JH
        • McManus DD
        • Goldberg RJ
        • Allen LA
        • et al.
        Chronic kidney disease and outcomes in heart failure with preserved versus reduced ejection fraction: the Cardiovascular Research Network PRESERVE Study.
        Circ Cardiovasc Qual Outcomes. 2013; 6: 333-342
        • McCullough PA
        • Franklin BA
        • Leifer E
        • Fonarow GC.
        Impact of reduced kidney function on cardiopulmonary fitness in patients with systolic heart failure.
        Am J Nephrol. 2010; 32: 226-233
        • Perkins RM
        • Tang X
        • Bengier AC
        • Kirchner HL
        • Bucaloiu ID.
        Variability in estimated glomerular filtration rate is an independent risk factor for death among patients with stage 3 chronic kidney disease.
        Kidney Int. 2012; 82: 1332-1338
        • Al-Aly Z
        • Balasubramanian S
        • McDonald JR
        • Scherrer JF
        • O'Hare AM
        Greater variability in kidney function is associated with an increased risk of death.
        Kidney Int. 2012; 82: 1208-1214
        • Uehara K
        • Yasuda T
        • Shibagaki Y
        • Kimura K.
        Estimated glomerular filtration rate variability independently predicts renal prognosis in advanced chronic kidney disease patients.
        Nephron. 2015; 130: 256-262
        • Schefold JC
        • Filippatos G
        • Hasenfuss G
        • Anker SD
        • von Haehling S.
        Heart failure and kidney dysfunction: epidemiology, mechanisms and management.
        Nat Rev Nephrol. 2016; 12: 610-623
        • Rosati RA
        • McNeer JF
        • Starmer CF
        • Mittler BS
        • Morris Jr., JJ
        • Wallace AG
        A new information system for medical practice.
        Arch Intern Med. 1975; 135: 1017-1024
        • Harris PJ
        • Lee K
        • Harrell Jr F
        • Behar V
        • Rosati R
        Outcome in medically treated coronary artery disease. Ischemic events: nonfatal infarction and death.
        Circulation. 1980; 62: 718-726
        • Banks A
        • Broderick S
        • Chiswell K
        • Shaw L
        • Devore A
        • Fiuzat M
        • et al.
        Comparison of clinical characteristics and outcomes of patients with versus without diabetes mellitus and with versus without angina pectoris (from the Duke Databank for Cardiovascular Disease).
        Am J Cardiol. 2017; 119: 1703-1709
        • Levey AS
        • Stevens LA
        • Schmid CH
        • Zhang YL
        • Castro AF
        • Feldman HI
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Boyle CA
        • Decouflé P.
        National sources of vital status information: extent of coverage and possible selectivity in reporting.
        Am J Epidemiol. 1990; 131: 160-168
        • Ronco C
        • Bellasi A
        • Di Lullo L.
        Cardiorenal Syndrome: an overview.
        Adv Chronic Kidney Dis. 2018; 25: 382-390
        • Zannad F
        • Rossignol P.
        Cardiorenal syndrome revisited.
        Circulation. 2018; 138: 929-944
        • Rangaswami J
        • Mathew RO.
        Pathophysiological mechanisms in cardiorenal syndrome.
        Adv Chronic Kidney Dis. 2018; 25: 400-407
        • Abudiab MM
        • Redfield MM
        • Melenovsky V
        • Olson TP
        • Kass DA
        • Johnson BD
        • et al.
        Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction.
        Eur J Heart Fail. 2013; 15: 776-785
        • Reddy YNV
        • Andersen MJ
        • Obokata M
        • Koepp KE
        • Kane GC
        • Melenovsky V
        • et al.
        Arterial stiffening with exercise in patients with heart failure and preserved ejection fraction.
        J Am Coll Cardiol. 2017; 70: 136-148
        • Triposkiadis F
        • Butler J
        • Abboud FM
        • Armstrong PW
        • Adamopoulos S
        • Atherton JJ
        • et al.
        The continuous heart failure spectrum: moving beyond an ejection fraction classification.
        Eur Heart J. 2019; 40: 2155-2163
        • House AA
        • Wanner C
        • Sarnak MJ
        • Piña IL
        • McIntyre CW
        • Komenda P
        • et al.
        Heart failure in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.
        Kidney Int. 2019; 95: 1304-1317
        • Shah SJ
        • Katz DH
        • Selvaraj S
        • Burke MA
        • Yancy CW
        • Gheorghiade M
        • et al.
        Phenomapping for novel classification of heart failure with preserved ejection fraction.
        Circulation. 2015; 131: 269-279
        • Testani JM
        • McCauley BD
        • Chen J
        • Coca SG
        • Cappola TP
        • Kimmel SE.
        Clinical characteristics and outcomes of patients with improvement in renal function during the treatment of decompensated heart failure.
        J Card Fail. 2011; 17: 993-1000