Kidney after Liver Transplantation for All

Since the introduction of the Model for End-Stage Liver Disease (MELD) score in 2002, the number and percentage of simultaneous liver–kidney transplantation has continued to rise (Figure 1). This surge in simultaneous liver–kidney transplantation has been attributed to multiple reasons, including higher prevalence of CKD in liver transplant candidates, low pre–liver transplant estimated glomerular filtration rate (eGFR) associated with higher risk of death after liver transplant, and higher morbidity and mortality with CKD after liver transplant, which created the assumption that simultaneous liver–kidney transplantation will always translate into better outcomes, especially that there are no accurate tools to predict post–liver transplant kidney recovery.^2,3 Compounding the issue was lack of standardized criteria for allocation of kidney with a liver that resulted in wide variability in simultaneous liver–kidney transplantation among transplant centers in the United States. There are multiple drawbacks of the increase in simultaneous liver–kidney transplantation number on waitlisted kidney patients. One obvious drawback is the longer waiting time for the waitlisted kidney patients who on average will wait for years while patients receiving simultaneous liver–kidney transplant receive a kidney after a median of 39 days from listing.⁴ Another drawback is the diversion of lower kidney donor profile index (KDPI) kidneys to simultaneous liver–kidney transplantation (average KDPI of 36% for simultaneous liver–kidney versus 46% for kidney-alone recipients and almost 50% of the kidneys allocated to simultaneous liver–kidney having a KDPI <20%).⁵ There is also evidence that simultaneous liver–kidney transplant (and other multiorgan transplant) widens the gender and racial disparity gaps for waitlisted kidney patients.⁴ Although simultaneous kidney and liver transplant has the potential to significantly improve survival in selected individuals—the higher rate of post–simultaneous liver–kidney native kidney recovery, lower early kidney graft survival, and the lack of clear causation between post–liver transplant mortality and post–liver transplant low eGFR—the transplant community needed an urgent and fair solution that balances equity with utility in kidney allocation to liver transplant candidates with kidney dysfunction.⁶

Figure 1.

Number of simultaneous liver–kidney transplantation performed in the United States from 1993 to 2022. As demonstrated, since the introduction of the MELD score in 2002, the number of simultaneous liver–kidney transplants has increased exponentially. In 2017, the OPTN implemented the current simultaneous liver–kidney transplantation policy. Although the number of simultaneous liver–kidney transplants initially dropped immediately post-policy, simultaneous liver–kidney transplant numbers started to rise again in 2020 despite the COVID-19 pandemic. The percentage of simultaneous liver–kidney transplantation (number of simultaneous liver–kidney/number of liver transplant), however, has declined from 9.7% pre-policy to 8% in 2022 (source: www.unos.org). There is also evidence of post-policy increase in kidney-after-liver transplantation.¹ COVID-19, coronavirus disease 2019; MELD, Model for End-Stage Liver Disease; OPTN, Organ Procurement and Transplantation Network; SLK, simultaneous liver–kidney.

In 2017, the Organ Procurement and Transplantation Network implemented the current simultaneous liver–kidney transplantation policy. Standardized criteria for simultaneous liver–kidney transplant allocation were implemented along with creation of a safety net rule that prioritizes liver transplant recipients who are on dialysis or with eGFR <20 ml/min and listed between 60 and 365 days from liver transplant for a subsequent kidney transplantation. Initial analysis of the effect of this policy on simultaneous liver–kidney and liver transplant outcomes was very encouraging, with evidence of decrease in percent simultaneous liver–kidney transplantation from 9.7% pre-policy to 8% in 2022 (Figure 1), increase in liver transplant–alone listing for liver transplant candidates on dialysis, decrease in simultaneous liver–kidney transplant listing, increase in kidney-after-liver listing and transplantation while maintaining comparable waitlist and liver transplant outcomes, comparable patient and kidney survivals between simultaneous liver–kidney and kidney-after-liver recipients, comparable kidney outcomes in kidney-after-liver versus kidney-alone transplants, and a signal toward improvement in liver graft survival in kidney-after-liver transplant recipients, post-policy.^1,7–9 Despite these welcoming results, the transplant community is still skeptical regarding the kidney-after-liver transplantation under the safety net policy.

In this issue of CJASN, Schold and colleagues describe outcomes in 3053 paired donors to kidney-alone and simultaneous liver–kidney recipients and another 516 paired donors to kidney-alone and kidney-after-liver transplant recipients transplanted after the implementation of the safety net policy from August 2017 to August 2022.¹⁰ Kidney-after-liver transplants were restricted to those listed between 60 and 365 days from liver transplant to match the safety net policy. They used univariable and multivariable Cox models to evaluate time to overall kidney graft survival as defined by the composite outcome of death or kidney graft loss. They report no difference in 1- and 3-year kidney graft survival for kidney-alone versus kidney-after-liver transplant. The adjusted delayed graft function was lower, and length of hospital stay was similar in kidney-after-liver compared with kidney-alone recipients. On the other hand, the 1- and 3-year kidney allograft survival was lower for simultaneous liver–kidney transplant recipients compared with paired kidney-alone recipients with an adjusted hazard ratio of graft loss of 1.43 (95% confidence interval, 1.2 to 1.7) for simultaneous liver–kidney transplant, with the highest risk of kidney graft loss being observed in the first 90 days from simultaneous liver–kidney transplant (hazard ratio, 1.95; 95% confidence interval, 1.4 to 2.6), which was mainly explained by early patient death. Death with functioning graft was almost two-folds higher in paired simultaneous liver–kidney versus kidney-alone recipients (n=305 versus 143), while it was slightly better in paired kidney-after-liver transplant compared with kidney-alone (17 versus 28) recipients. An important finding of this study is that compared with simultaneous liver–kidney recipients, kidney-alone recipients enjoyed 21 additional graft years/100 transplants with comparable mean graft years between kidney-after-liver and kidney-alone recipients. Finally, simultaneous liver–kidney transplant was associated with more resource utilization with a higher adjusted delayed graft function rate and longer length of hospital compared with kidney-alone recipients.

We should congratulate the authors for their work that used paired kidney donation to alleviate donor-related factors. They demonstrate worse kidney survival in simultaneous liver–kidney transplant patients (mainly due to early patient death) and show the number of kidney graft years lost had these kidneys been used in kidney-alone recipients who waited much longer while suffering dialysis complications while 75% of simultaneous liver–kidney transplantation were performed within 6 months from listing. This study also gives us proof that the safety net policy achieved its goals of providing timely kidney transplantation for those liver transplant recipients in need for a kidney because most of these patients (72%) waited <6 months on the kidney waitlist without compromising kidney allograft survival. The study also sheds light on the persistent disparities in transplant access, with higher proportion of Black and female patients who received kidney-alone than kidney-after-liver transplant.

Some questions remain unanswered. We do not know the mortality of patients who were listed for kidney-after-liver but never received a kidney transplant. Is the reason for similar outcomes between kidney-after-liver and kidney-alone transplant because a selected healthy cohort receives kidney-after-liver transplant? Could patients who were listed for kidney-after-liver but never got a kidney due to loss of eligibility or death have benefited from simultaneous liver–kidney transplant in the first place? Owing to the nature of the paired donor analysis, direct comparison of outcomes between kidney-after-liver and simultaneous liver–kidney groups was not performed in this study. Although these two groups are fundamentally different, previous studies suggested similar outcomes between simultaneous liver–kidney and kidney-after-liver transplants.⁹ Simultaneous liver–kidney transplant recipients in this study had higher 1- and 3-year mortality. Is the higher risk in this subset of simultaneous liver–kidney transplant recipients attributable to kidney failure or due to systemic causes leading to higher risk of death, irrespective of number of organs transplanted? Actionable characteristic of recipients who survived the first 90 days after transplant might be important information to ascertain because this may help develop better medical eligibility criteria because futility of transplant would have largely been answered in this group.

As a transplant community, we need to be cautious not to overinterpret these results, but this well-executed analysis adds to the ongoing debate regarding the kidney allocation to liver transplant candidates. It demonstrates that kidney-after-liver transplant appears to be a win-win situation by offering the opportunity to judiciously and timely allocate a scarce resource (kidney) to liver transplant recipients who did not recover kidney function and those who developed new-onset kidney failure after liver transplant, while maintaining equal kidney graft survival rates had this kidney been transplanted in a kidney-alone recipient. This study, as well as previous work that showed that outcomes remained unchanged after implementing the safety net rule,^7–9 begs the question: Has the time come to maximally use the safety net and do away with simultaneous liver–kidney transplant while keeping the Organ Procurement and Transplantation Network monitoring and reporting systems in place for future modifications in multiorgan allocation policies?

Disclosures

H.M. Wadei reports employment with Mayo Clinic, consultancy for Mallinckodt Pharmaceutical, and advisory or leadership role for Medical Advisory Board with Mallinckodt Pharmaceutical. The remaining author has nothing to disclose.

Funding

None.

Author Contributions

Conceptualization: Abhishek Kumar, Hani M. Wadei.

Writing – original draft: Abhishek Kumar, Hani M. Wadei.

Writing – review & editing: Abhishek Kumar, Hani M. Wadei.