Endocrinol Metab.  2023 Feb;38(1):139-145. 10.3803/EnM.2022.1594.

Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients

• Jeon JY
• Han-Bit S
• Park BH
• Lee N
• Kim HJ
• Kim DJ
• Lee KW
• Han SJ

• KMID: 2539827
• DOI: http://doi.org/10.3803/EnM.2022.1594

Abstract

Background
Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients.
Methods
We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model.
Results
Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE.
Conclusion
Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

Keyword

Kidney transplantation; Diabetes mellitus; Cardiovascular diseases; Mortality; Graft survival

Figure

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  Fig. 1. Kaplan-Meier curves for all-cause mortality and four-point major adverse cardiovascular events according to post-transplant diabetes mellitus (PTDM) status (log-rank test, P=0.957 and P=0.079, respectively). (A) All-cause mortality. (B) Four-point major adverse cardiovascular events.

Reference

1. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, et al. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999; 341:1725–30.

2. Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ. Diabetes mellitus after kidney transplantation in the United States. Am J Transplant. 2003; 3:178–85.

3. Ahmed SH, Biddle K, Augustine T, Azmi S. Post-transplantation diabetes mellitus. Diabetes Ther. 2020; 11:779–801.

4. Jeon JY, Kim SJ, Ha KH, Park JH, Park B, Oh CK, et al. Trends in the effects of pre-transplant diabetes on mortality and cardiovascular events after kidney transplantation. J Diabetes Investig. 2021; 12:811–8.

5. Lim WH, Lok CE, Kim SJ, Knoll G, Shah BR, Naylor K, et al. Impact of pretransplant and new-onset diabetes after transplantation on the risk of major adverse cardiovascular events in kidney transplant recipients: a population-based cohort study. Transplantation. 2021; 105:2470–81.

6. Gaynor JJ, Ciancio G, Guerra G, Sageshima J, Hanson L, Roth D, et al. Single-centre study of 628 adult, primary kidney transplant recipients showing no unfavourable effect of new-onset diabetes after transplant. Diabetologia. 2015; 58:334–45.

7. Hariharan S, Israni AK, Danovitch G. Long-term survival after kidney transplantation. N Engl J Med. 2021; 385:729–43.

8. Choi JY, Kwon OJ. Post-transplant diabetes mellitus: is it associated with poor allograft outcomes in renal transplants? Transplant Proc. 2013; 45:2892–8.

9. Schnuelle P, Lorenz D, Trede M, Van Der Woude FJ. Impact of renal cadaveric transplantation on survival in end-stage renal failure: evidence for reduced mortality risk compared with hemodialysis during long-term follow-up. J Am Soc Nephrol. 1998; 9:2135–41.

10. Ying T, Shi B, Kelly PJ, Pilmore H, Clayton PA, Chadban SJ. Death after kidney transplantation: an analysis by era and time post-transplant. J Am Soc Nephrol. 2020; 31:2887–99.

11. Park S, Kim M, Kim JE, Kim K, Park M, Kim YC, et al. Characteristics of kidney transplantation recipients over time in South Korea. Korean J Intern Med. 2020; 35:1457–67.

12. Jardine AG, Fellstrom B, Logan JO, Cole E, Nyberg G, Gronhagen-Riska C, et al. Cardiovascular risk and renal transplantation: post hoc analyses of the Assessment of Lescol in Renal Transplantation (ALERT) Study. Am J Kidney Dis. 2005; 46:529–36.

13. Lentine KL, Brennan DC, Schnitzler MA. Incidence and predictors of myocardial infarction after kidney transplantation. J Am Soc Nephrol. 2005; 16:496–506.

14. Cosio FG, Pesavento TE, Kim S, Osei K, Henry M, Ferguson RM. Patient survival after renal transplantation: IV. Impact of post-transplant diabetes. Kidney Int. 2002; 62:1440–6.

15. Cole EH, Johnston O, Rose CL, Gill JS. Impact of acute rejection and new-onset diabetes on long-term transplant graft and patient survival. Clin J Am Soc Nephrol. 2008; 3:814–21.

16. Kuo HT, Sampaio MS, Vincenti F, Bunnapradist S. Associations of pretransplant diabetes mellitus, new-onset diabetes after transplant, and acute rejection with transplant outcomes: an analysis of the Organ Procurement and Transplant Network/United Network for Organ Sharing (OPTN/UNOS) database. Am J Kidney Dis. 2010; 56:1127–39.

17. Cosentino F, Grant PJ, Aboyans V, Bailey CJ, Ceriello A, Delgado V, et al. 2019 ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J. 2020; 41:255–323.

18. Wannamethee SG, Shaper AG, Whincup PH, Lennon L, Sattar N. Impact of diabetes on cardiovascular disease risk and all-cause mortality in older men: influence of age at onset, diabetes duration, and established and novel risk factors. Arch Intern Med. 2011; 171:404–10.

19. Kim JJ, Hwang BH, Choi IJ, Choo EH, Lim S, Kim JK, et al. Impact of diabetes duration on the extent and severity of coronary atheroma burden and long-term clinical outcome in asymptomatic type 2 diabetic patients: evaluation by Coronary CT angiography. Eur Heart J Cardiovasc Imaging. 2015; 16:1065–73.