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  • Review Article
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Timing of dialysis initiation in transplant-naive and failed transplant patients

Nature Reviews Nephrology volume 8, pages 284–292 (2012)Cite this article

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Abstract

Over the past two decades, most guidelines have advocated early initiation of dialysis on the basis of studies showing improved survival in patients starting dialysis early. These recommendations led to an increase in the proportion of patients initiating dialysis with an estimated glomerular filtration rate (eGFR) >10 ml/min/1.73 m2, from 20% in 1996 to 52% in 2008. During this period, the percentage of patients starting dialysis with an eGFR ≥15 ml/min/1.73 m2 increased from 4% to 17%. However, recent studies have failed to substantiate a benefit of early dialysis initiation and some data have suggested worse outcomes for patients starting dialysis with a higher eGFR. Several reasons for this seemingly paradoxical observation have been suggested, including the fact that patients requiring early dialysis are likely to have more severe symptoms and comorbidities, leading to confounding by indication, as well as biological mechanisms that causally relate early dialysis therapy to adverse outcomes. Patients with a failing renal allograft who reinitiate dialysis encounter similar problems. However, unique factors associated with a failed allograft means that the optimal timing of dialysis initiation in failed transplant patients might differ from that in transplant-naive patients with chronic kidney disease. In this Review, we discuss studies of dialysis initiation and compare risks and benefits of early versus late initiation and reinitiation of dialysis therapy.

Key Points

  • Late initiation of dialysis is not associated with worse mortality in transplant-naive patients with chronic kidney disease compared with mortality in patients who start dialysis early

  • Current guidelines suggest that the majority of transplant-naive patients will be symptomatic and need to start dialysis with an estimated glomerular filtration rate (eGFR) in the 6–9 ml/min/1.73 m2 range

  • In patients with a failing kidney transplant, there is a paucity of evidence for or against early reinitiation of dialysis treatment

  • Factors such as predialysis care, late referral, dialysis dose, timing of immunosuppression reduction and residual function of the renal allograft might modify the association between dialysis reinitiation and outcomes in failed transplant recipients

  • Several biological factors, including hemodynamic instability, loss of residual renal function and a high infection rate, might contribute to the increased mortality risk associated with dialysis initiation

  • Starting dialysis early solely based on eGFR is not justified and could in fact be harmful in some cases; therefore, alternative and more reliable measures of a patient's clinical condition are required

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Figure 1: Landmark studies of early versus late initiation of dialysis treatment in transplant-naive patients with chronic kidney disease and in failed kidney transplant patients.
Figure 2: Potential factors associated with early initiation of dialysis treatment.
Figure 3: Outcomes associated with early versus late dialysis initiation in transplant-naive and failed kidney transplant patients.
Figure 4: Number of patients returning to dialysis therapy after renal transplant failure.

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Acknowledgements

M. Z. Molnar received grants from the National Development Agency (KTIA-OTKA-EU 7KP-HUMAN-MB08-A-81231) from the Research and Technology Innovation Fund, and was also supported by the Hungarian Kidney Foundation. K. Kalantar-Zadeh was supported by research grants from the National Institute of Diabetes, Digestive and Kidney Diseases of the National Institutes of Health (K24 DK091419 and R01 DK078106) and a philanthropic grant from H. Simmons.

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Authors and Affiliations

  1. Harold Simmons Center for Chronic Disease Research and Epidemiology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, 90502, CA, USA

    Miklos Z. Molnar & Kamyar Kalantar-Zadeh

  2. Department of Internal Medicine, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, 48109, MI, USA

    Akinlolu O. Ojo

  3. David Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, Los Angeles, 90095, CA, USA

    Suphamai Bunnapradist

  4. Division of Nephrology, Salem VA Medical Center, 1970 Roanoke Boulevard, Salem, 24153, VA, USA

    Csaba P. Kovesdy

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M. Z. Molnar and K. Kalantar-Zadeh researched data to include in the manuscript. M. Z. Molnar, C. P. Kovesdy and K. Kalantar-Zadeh contributed to discussion of content for the article. All authors contributed equally to the writing of the article and to the reviewing and editing of the manuscript before submission.

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Correspondence to Kamyar Kalantar-Zadeh.

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Molnar, M., Ojo, A., Bunnapradist, S. et al. Timing of dialysis initiation in transplant-naive and failed transplant patients. Nat Rev Nephrol 8, 284–292 (2012). https://doi.org/10.1038/nrneph.2012.36

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