Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss

Amali Samarasinghe¹, Germaine Wong^{2

3

4}, Armando Teixeira-Pinto^{2

3}, David W Johnson^{5

6

7}, Carmel Hawley^{5

6

7}, Helen Pilmore^{8

9}, William R Mulley^{10

11}, Matthew A Roberts¹², Kevan R Polkinghorne^{13

14}, Neil Boudville^{1

15}, Christopher E Davies^{16

17}, Andrea K Viecelli^{5

6}, Esther Ooi¹⁸, Nicholas G Larkins^{19

20}, Charmaine Lok^{21

22}, Wai H Lim^{1

15}

Affiliations

¹ Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
² School of Public Health, Faculty of Medicine and Health, Sydney University, Sydney, Australia.
³ Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
⁴ Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, Australia.
⁵ Department of Kidney and Transplant Services, Princess Alexandra Hospital, Queensland, Australia.
⁶ Australasian Kidney Trials Network, University of Queensland, Queensland, Australia.
⁷ Translational Research Institute, Queensland, Australia.
⁸ Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand.
⁹ Department of Medicine, Auckland University, Auckland, New Zealand.
¹⁰ Department of Nephrology, Monash Medical Centre, Melbourne, Australia.
¹¹ Department of Medicine, Monash University, Melbourne, Australia.
¹² Eastern Health Clinical School, Monash University, Victoria, Australia.
¹³ Department of Nephrology and Medicine, Monash Medical Centre, Melbourne, Australia.
¹⁴ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
¹⁵ Internal Medicine, University of Western Australia Medical School, Perth, Australia.
¹⁶ Faculty of Health and Medical Science, Adelaide University Medical School, South Australia, Australia.
¹⁷ Australia and New Zealand Dialysis and Transplant Registry, South Australian Health and Medical Research Institute, Adelaide, Australia.
¹⁸ School of Biomedical Sciences, University of Western Australia, Western Australia, Australia.
¹⁹ Department of Nephrology, Perth Children's Hospital, Perth, Western Australia, Australia.
²⁰ School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
²¹ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
²² Division of Nephrology, Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada.

PMID: 38468698
PMCID: PMC10926326
DOI: 10.1093/ckj/sfad245

Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss

Amali Samarasinghe et al. Clin Kidney J. 2024.

. 2024 Mar 7;17(3):sfad245.

doi: 10.1093/ckj/sfad245. eCollection 2024 Mar.

Authors

Affiliations

¹ Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia.
² School of Public Health, Faculty of Medicine and Health, Sydney University, Sydney, Australia.
³ Centre for Kidney Research, The Children's Hospital at Westmead, Sydney, Australia.
⁴ Department of Renal Medicine and National Pancreas Transplant Unit, Westmead Hospital, Sydney, Australia.
⁵ Department of Kidney and Transplant Services, Princess Alexandra Hospital, Queensland, Australia.
⁶ Australasian Kidney Trials Network, University of Queensland, Queensland, Australia.
⁷ Translational Research Institute, Queensland, Australia.
⁸ Department of Renal Medicine, Auckland City Hospital, Auckland, New Zealand.
⁹ Department of Medicine, Auckland University, Auckland, New Zealand.
¹⁰ Department of Nephrology, Monash Medical Centre, Melbourne, Australia.
¹¹ Department of Medicine, Monash University, Melbourne, Australia.
¹² Eastern Health Clinical School, Monash University, Victoria, Australia.
¹³ Department of Nephrology and Medicine, Monash Medical Centre, Melbourne, Australia.
¹⁴ Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia.
¹⁵ Internal Medicine, University of Western Australia Medical School, Perth, Australia.
¹⁶ Faculty of Health and Medical Science, Adelaide University Medical School, South Australia, Australia.
¹⁷ Australia and New Zealand Dialysis and Transplant Registry, South Australian Health and Medical Research Institute, Adelaide, Australia.
¹⁸ School of Biomedical Sciences, University of Western Australia, Western Australia, Australia.
¹⁹ Department of Nephrology, Perth Children's Hospital, Perth, Western Australia, Australia.
²⁰ School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia.
²¹ Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
²² Division of Nephrology, Department of Medicine, University Health Network-Toronto General Hospital, Toronto, Ontario, Canada.

PMID: 38468698
PMCID: PMC10926326
DOI: 10.1093/ckj/sfad245

Abstract

Background: Diabetes mellitus (DM) is associated with a greater risk of mortality in kidney transplant patients, primarily driven by a greater risk of cardiovascular disease (CVD)-related mortality. However, the associations between diabetes status at time of first allograft loss and mortality on dialysis remain unknown.

Methods: All patients with failed first kidney allografts transplanted in Australia and New Zealand between 2000 and 2020 were included. The associations between diabetes status at first allograft loss, all-cause and cause-specific mortality were examined using competing risk analyses, separating patients with diabetes into those with pre-transplant DM or post-transplant diabetes mellitus (PTDM).

Results: Of 3782 patients with a median (IQR) follow-up duration of 2.7 (1.1-5.4) years, 539 (14%) and 390 (10%) patients had pre-transplant DM or developed PTDM, respectively. In the follow-up period, 1336 (35%) patients died, with 424 (32%), 264 (20%) and 199 (15%) deaths attributed to CVD, dialysis withdrawal and infection, respectively. Compared to patients without DM, the adjusted subdistribution HRs (95% CI) for pre-transplant DM and PTDM for all-cause mortality on dialysis were 1.47 (1.17-1.84) and 1.47 (1.23-1.76), respectively; for CVD-related mortality were 0.81 (0.51-1.29) and 1.02 (0.70-1.47), respectively; for infection-related mortality were 1.84 (1.02-3.35) and 2.70 (1.73-4.20), respectively; and for dialysis withdrawal-related mortality were 1.71 (1.05-2.77) and 1.51 (1.02-2.22), respectively.

Conclusions: Patients with diabetes at the time of kidney allograft loss have a significant survival disadvantage, with the excess mortality risk attributed to infection and dialysis withdrawal.

Keywords: allograft loss; diabetes; dialysis; kidney failure; mortality.

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Conflict of interest statement

There are no conflicts of interest.

Figures

**Figure 1:**
Flow diagram of the study cohort of 3782 patients who commenced on dialysis following failed first kidney allografts in Australia and New Zealand, comprising of 2853 (75%) patients without diabetes, 539 (14%) patients with pre-transplant diabetes mellitus (DM), and 390 (10%) patients who developed post-transplant diabetes mellitus (PTDM).

**Figure 2:**
Bar graph showing the clinical outcomes of patients who commenced dialysis following failed first kidney allografts, stratified by diabetes status. For the outcome of ‘deaths’, the proportion of deaths from cardiovascular disease, infection, dialysis withdrawal, and other causes are shown. CVA: cerebrovascular accident.

**Figure 3:**
Forest plots showing the adjusted hazard ratios (HR) and subdistribution HR and 95% confidence intervals (95% CI) of the association between diabetes status at time of first allograft loss, all-cause, and cause-specific [cardiovascular disease (CVD), dialysis withdrawal, and infection] mortality.

**Figure 4:**
Adjusted cumulative incidence curves for all-cause mortality on dialysis (A), cardiovascular disease (CVD)-related mortality (B), dialysis withdrawal-related mortality (C) and infection-related mortality (D) post-dialysis initiation following first kidney allograft loss. The solid black line represents patients without diabetes, discontinuous black line represents patients with pre-transplant diabetes mellitus and the solid grey line represents patients with post-transplant diabetes mellitus (PTDM).

**Figure 5:**
Forest plots showing the adjusted hazard ratios (HR) and subdistribution HR and 95% confidence intervals (95% CI) of the association between diabetes status at time of first allograft loss and all-cause mortality, stratified by patient age (< and ≥50 years at time of allograft loss).

See this image and copyright information in PMC

References

1. Australia and New Zealand Dialysis and Transplant Registry . ANZDATA Registry 43rd Report, Chapter 1: Incidence of Renal Replacement Therapy for End Stage Kidney Disease. Adelaide, Australia, 2020.
1. Grace B, Excell L, Dent H et al. Australia and New Zealand Dialysis and Transplant Registry. ANZDATA Registry 43rd Report, Chapter 2: New Patients. Adelaide, Australia, 2010.
1. United States Renal Data System . 2019 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, MD, 2019.
1. United States Renal Data System . 2014 USRDS Annual Data Report Volume 2: End-Stage Renal Disease. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2014.
1. Lim WH, Johnson DW, Hawley C et al. Type 2 diabetes in patients with end-stage kidney disease: influence on cardiovascular disease-related mortality risk. Med J Aust 2018;209:440–6. 10.5694/mja18.00195 - DOI - PubMed

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Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss

Affiliations

Association between diabetic status and risk of all-cause and cause-specific mortality on dialysis following first kidney allograft loss

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources