Trends in the survival benefit of repeat kidney transplantation over the past 3 decades

Abstract

Repeat kidney transplantation (re-KT) is the preferred treatment for patients with graft failure. Changing allocation policies, widening the risk profile of recipients, and improving dialysis care may have altered the survival benefit of a re-KT. We characterized trends in re-KT survival benefit over 3 decades and tested whether it differed by age, race/ethnicity, sex, and panel reactive assay (PRA). By using the Scientific Registry of Transplant Recipient data, we identified 25 419 patients who underwent a re-KT from 1990 to 2019 and 25 419 waitlisted counterfactuals from the same year with the same waitlisted time following graft failure. In the adjusted analysis, a re-KT was associated with a lower risk of death (adjusted hazard ratio [aHR] = 0.63; 95% confidence interval [CI], 0.61-0.65). By using the 1990-1994 era as a reference (aHR = 0.77; 95% CI, 0.69-0.85), incremental improvements in the survival benefit were noted (1995-1999: aHR = 0.72; 95% CI, 0.67-0.78: 2000-2004: aHR = 0.59; 95% CI, 0.55-0.63: 2005-2009: aHR = 0.59; 95% CI, 0.56-0.63: 2010-2014: aHR = 0.57; 95% CI, 0.53-0.62: 2015-2019: aHR = 0.64; 95% CI, 0.57-0.73). The survival benefit of a re-KT was noted in both younger (age = 18-64 years: aHR = 0.63; 95% CI, 0.61-0.65) and older patients (age ≥65 years: aHR = 0.66; 95% CI, 0.58-0.74; P_interaction = .45). Patients of all races/ethnicities demonstrated similar benefits with a re-KT. However, it varied by the sex of the recipient (female patients: aHR = 0.60; 95% CI, 0.56-0.63: male patients: aHR = 0.66; 95% CI, 0.63-0.68; P_interaction = .004) and PRA (0-20: aHR = 0.69; 95% CI, 0.65-0.74: 21-80: aHR = 0.61; 95% CI, 0.57-0.66; P_interaction = .02; >80: aHR = 0.57; 95% CI, 0.53-0.61; P_interaction< .001). Our findings support the continued practice of a re-KT and efforts to overcome the medical, immunologic, and surgical challenges of a re-KT.

Introduction

When compared with dialysis, a repeat kidney transplantation (re-KT) is a superior treatment option for patients with a history of graft failure. A landmark article in 1998 reported that in a cohort of 19 208 patients with graft failure, a re-KT led to 23% to 45% of reduction in the 5-year mortality risk.¹ These results were replicated in a Canadian cohort² and later by other scholars analyzing the US registry data.3, 4, 5 These findings of a survival benefit have been extended to third and even fourth transplantations.⁶ Thus, approximately 15% of the current waitlist in the United States includes kidney transplant recipients (KTRs) with a history of graft failure.⁷

Although gradual improvements in KTR survival have been reported over time,^7,8 the age, risk profiles, and lifetime immunosuppression burden of patients undergoing a re-KT have changed dramatically since these initial reports.^7,9,10 Simultaneously, the survival of patients on dialysis is improving.⁷ Therefore, it remains to be seen whether a re-KT is associated with a survival benefit in the recent eras, particularly following the kidney allocation system (KAS) implementation.¹¹ KAS was introduced in 2014 by the United Network for Organ Sharing with the goals of longevity matching and prioritizing sensitized patients.¹¹ However, this often entails allocating grafts with a higher kidney donor profile index to those with a history of graft failure. A re-KT with higher risk donors, such as expanded criteria donors, may not be associated with a survival advantage.⁵ Thus, KAS may have diminished the survival benefit of a re-KT. On the other hand, increasing the waiting time before a re-KT is associated with an increased risk of death,¹² and KAS may have shortened the wait time to a re-KT, potentially improving the outcomes. Overall, exploring the trends in the survival benefit of a re-KT after 2014 is needed to assess the impact of this policy change.

In addition to the era changes, a more granular evaluation of the survival benefit of a re-KT by age, race/ethnicity, sex, and panel reactive assay (PRA) of the KTR has yet to be conducted. Among the first KTRs, many studies have shown inferior outcomes in women and in patients of non-White race/ethnicity^13,14; this has yet to be explored in recipients of a re-KT. In addition, each previous transplant leads to sensitization, and higher PRA confers an incremental mortality risk in KTRs.¹⁵ High PRA after graft failure and its association with the survival benefit of a re-KT is not known. Most importantly, the survival advantage of a re-KT in older patients has not been explored, despite this being rapidly increasing in a cohort of patients.¹⁰ Older patients are known to be more frail, have cognitive impairment, and have multiple comorbidities; all are risk factors for mortality. Determining the importance of a re-KT in these specific populations therefore will have clinical and policy implications.

Thus, we sought to estimate the survival benefit of a re-KT over the past 3 decades and test whether it has changed over time, particularly during the KAS era. We also aimed to quantify the survival benefit of a re-KT by age, race/ethnicity, sex, and PRA.