Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD

doi:10.1053/j.ajkd.2013.12.010

Randomized Controlled Trial

. 2014 May;63(5):806-15.

doi: 10.1053/j.ajkd.2013.12.010. Epub 2014 Feb 6.

Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD

Deidra C Crews¹, Julia J Scialla², L Ebony Boulware³, Sankar D Navaneethan⁴, Joseph V Nally Jr⁴, Xiaobo Liu⁵, Susana Arrigain⁵, Jesse D Schold⁵, Patti L Ephraim⁶, Stacey E Jolly⁷, Stephen M Sozio⁸, Wieneke M Michels⁹, Dana C Miskulin¹⁰, Navdeep Tangri¹¹, Tariq Shafi⁸, Albert W Wu¹², Karen Bandeen-Roche¹³; DEcIDE Network Patient Outcomes in End Stage Renal Disease Study Investigators

Collaborators, Affiliations

Collaborators

DEcIDE Network Patient Outcomes in End Stage Renal Disease Study Investigators:
L Ebony Boulware, Karen Bandeen-Roche, Courtney Cook, Josef Coresh, Deidra Crews, Patti Ephraim, Bernard Jaar, Jeonyoung Kim, Yang Liu, Jason Luly, Aidan McDermott, Wieneke Michels, Paul Scheel, Tariq Shafi, Stephen Sozio, Albert Wu, Jing Zhou, Neil Powe, Allan Collins, Robert Foley, David Gilbertson, Haifeng Guo, Joseph Grill, Charles Herzog, Jiannong Liu, Wendy St Peter, Joseph Nally, Susana Arrigain, Stacey Jolly, Vicky Konig, Xiaobo Liu, Sankar Navaneethan, Jesse Schold, Karen Majchrzak, Philip Zager, Dana Miskulin, Klemens Meyer, Julia Scialla, Navdeep Tangri, Wieneke Michels

Affiliations

¹ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD. Electronic address: dcrews1@jhmi.edu.
² Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
³ Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC.
⁴ Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.
⁵ Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
⁶ Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁷ Department of General Internal Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH.
⁸ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD.
⁹ Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Nephrology, Department of Medicine, Academic Medical Center, Amsterdam, the Netherlands.
¹⁰ Division of Nephrology, Tufts University School of Medicine, Boston, MA.
¹¹ Division of Nephrology, Department of Medicine, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
¹² Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Health, Policy, and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
¹³ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

PMID: 24508475
PMCID: PMC4117406
DOI: 10.1053/j.ajkd.2013.12.010

Randomized Controlled Trial

Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD

Deidra C Crews et al. Am J Kidney Dis. 2014 May.

. 2014 May;63(5):806-15.

doi: 10.1053/j.ajkd.2013.12.010. Epub 2014 Feb 6.

Authors

Collaborators

DEcIDE Network Patient Outcomes in End Stage Renal Disease Study Investigators:
L Ebony Boulware, Karen Bandeen-Roche, Courtney Cook, Josef Coresh, Deidra Crews, Patti Ephraim, Bernard Jaar, Jeonyoung Kim, Yang Liu, Jason Luly, Aidan McDermott, Wieneke Michels, Paul Scheel, Tariq Shafi, Stephen Sozio, Albert Wu, Jing Zhou, Neil Powe, Allan Collins, Robert Foley, David Gilbertson, Haifeng Guo, Joseph Grill, Charles Herzog, Jiannong Liu, Wendy St Peter, Joseph Nally, Susana Arrigain, Stacey Jolly, Vicky Konig, Xiaobo Liu, Sankar Navaneethan, Jesse Schold, Karen Majchrzak, Philip Zager, Dana Miskulin, Klemens Meyer, Julia Scialla, Navdeep Tangri, Wieneke Michels

Affiliations

¹ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD. Electronic address: dcrews1@jhmi.edu.
² Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.
³ Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Duke University School of Medicine, Durham, NC.
⁴ Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH; Cleveland Clinic, Lerner College of Medicine of Case Western Reserve University, Cleveland, OH.
⁵ Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH.
⁶ Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
⁷ Department of General Internal Medicine, Medicine Institute, Cleveland Clinic, Cleveland, OH.
⁸ Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD.
⁹ Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, MD; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Division of Nephrology, Department of Medicine, Academic Medical Center, Amsterdam, the Netherlands.
¹⁰ Division of Nephrology, Tufts University School of Medicine, Boston, MA.
¹¹ Division of Nephrology, Department of Medicine, Seven Oaks General Hospital, University of Manitoba, Winnipeg, Manitoba, Canada.
¹² Division of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Health, Policy, and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD.
¹³ Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

PMID: 24508475
PMCID: PMC4117406
DOI: 10.1053/j.ajkd.2013.12.010

Abstract

Background: Previous observational studies examining outcomes associated with the timing of dialysis therapy initiation in the United States have often been limited by lead time and survivor bias.

Study design: Retrospective cohort study comparing the effectiveness of early versus later (conventional) dialysis therapy initiation in advanced chronic kidney disease (CKD). The analysis used inverse probability weighting to account for an individual's contribution to different exposure groups over time in a pooled logistic regression model. Patients contributed risk to both exposure categories (early and later initiation) until there was a clear treatment strategy (ie, dialysis therapy was initiated early or estimated glomerular filtration rate [eGFR] decreased to <10mL/min/1.73m(2)).

Setting & participants: Patients with CKD who had at least one face-to-face outpatient encounter with a Cleveland Clinic health care provider as of January 1, 2005, and at least 3 eGFRs in the range of 20-30mL/min/1.73m(2) measured at least 180 days apart.

Predictors: Timing of dialysis therapy initiation as determined using model-based interpolation of eGFR trajectories over time. Timing was defined as early (interpolated eGFR at dialysis therapy initiation≥10mL/min/1.73m(2)) or later (eGFR < 10mL/min/1.73m(2)) and was time-varying.

Outcomes: Death from any cause occurring from the time that eGFR was equal to 20mL/min/1.73m(2) through September 15, 2009.

Results: The study population consisted of 652 patients meeting inclusion criteria. Most (71.3%) of the study population did not initiate dialysis therapy during follow-up. Patients who did not initiate dialysis therapy (n=465) were older, more likely to be white, and had more favorable laboratory profiles than those who started dialysis therapy. Overall, 146 initiated dialysis early and 80 had eGFRs decrease to <10mL/min/1.73m(2). Many participants (n=426) were censored prior to attaining a clear treatment strategy and were considered undeclared. There was no statistically significant survival difference for the early compared with later initiation strategy (OR, 0.85; 95% CI, 0.65-1.11).

Limitations: Interpolated eGFR, moderate sample size, and likely unmeasured confounders.

Conclusions: In patients with advanced CKD, timing of dialysis therapy initiation was not associated with mortality when accounting for lead time bias and survivor bias.

Keywords: Kidney disease trajectory; decreased glomerular filtration rate (GFR); dialysis initiation; early-start dialysis; end-stage renal disease (ESRD); prognosis; renal disease progression; renal replacement therapy (RRT); timing of dialysis.

PubMed Disclaimer

Conflict of interest statement

Potential Conflicts of Interest

All other authors report no relevant conflicts of interest.

Figures

**Figure 2**
Kaplan-Meier Survival Curves of the Three Dialysis Initiation Strategies

**Figure 3**
Distribution of the Estimated Weights (W) for the Inverse Probability Weighting Method

See this image and copyright information in PMC

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References

1. O'Hare AM, Choi AI, Boscardin WJ, et al. Trends in timing of initiation of chronic dialysis in the United States. Arch Intern Med. 2011 Oct 10;171(18):1663–1669. - PMC - PubMed
1. Rosansky SJ, Clark WF, Eggers P, Glassock RJ. Initiation of dialysis at higher GFRs: is the apparent rising tide of early dialysis harmful or helpful? Kidney Int. 2009 Aug;76(3):257–261. - PubMed
1. Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010 Aug 12;363(7):609–619. - PubMed
1. Beddhu S, Samore MH, Roberts MS, et al. Impact of timing of initiation of dialysis on mortality. Journal of the American Society of Nephrology : JASN. 2003 Sep;14(9):2305–2312. - PubMed
1. Kazmi WH, Gilbertson DT, Obrador GT, et al. Effect of comorbidity on the increased mortality associated with early initiation of dialysis. Am J Kidney Dis. 2005 Nov;46(5):887–896. - PubMed

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[1] O'Hare AM, Choi AI, Boscardin WJ, et al. Trends in timing of initiation of chronic dialysis in the United States. Arch Intern Med. 2011 Oct 10;171(18):1663–1669. - PMC - PubMed

[2] O'Hare AM, Choi AI, Boscardin WJ, et al. Trends in timing of initiation of chronic dialysis in the United States. Arch Intern Med. 2011 Oct 10;171(18):1663–1669. - PMC - PubMed

[3] Rosansky SJ, Clark WF, Eggers P, Glassock RJ. Initiation of dialysis at higher GFRs: is the apparent rising tide of early dialysis harmful or helpful? Kidney Int. 2009 Aug;76(3):257–261. - PubMed

[4] Rosansky SJ, Clark WF, Eggers P, Glassock RJ. Initiation of dialysis at higher GFRs: is the apparent rising tide of early dialysis harmful or helpful? Kidney Int. 2009 Aug;76(3):257–261. - PubMed

[5] Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010 Aug 12;363(7):609–619. - PubMed

[6] Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med. 2010 Aug 12;363(7):609–619. - PubMed

[7] Beddhu S, Samore MH, Roberts MS, et al. Impact of timing of initiation of dialysis on mortality. Journal of the American Society of Nephrology : JASN. 2003 Sep;14(9):2305–2312. - PubMed

[8] Beddhu S, Samore MH, Roberts MS, et al. Impact of timing of initiation of dialysis on mortality. Journal of the American Society of Nephrology : JASN. 2003 Sep;14(9):2305–2312. - PubMed

[9] Kazmi WH, Gilbertson DT, Obrador GT, et al. Effect of comorbidity on the increased mortality associated with early initiation of dialysis. Am J Kidney Dis. 2005 Nov;46(5):887–896. - PubMed

[10] Kazmi WH, Gilbertson DT, Obrador GT, et al. Effect of comorbidity on the increased mortality associated with early initiation of dialysis. Am J Kidney Dis. 2005 Nov;46(5):887–896. - PubMed

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Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD

Collaborators

Affiliations

Comparative effectiveness of early versus conventional timing of dialysis initiation in advanced CKD

Authors

Collaborators

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Abstract

Conflict of interest statement

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References

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