Risks and Benefits of Combined versus Solitary Organ Transplantation

Acute kidney disease or CKD is highly prevalent among patients with various organ dysfunctions. With liver failure, heart failure, or lung dysfunction, there can be hemodynamic changes associated with portal hypertension, reduced kidney perfusion, or disease processes that affect both the kidney and other organs. CKD and nonkidney organ failure have a complex bidirectional interaction, meaning one organ failure can lead to an acute or chronic worsening of another organ. To assess kidney function, creatinine-based estimated equations are commonly used. However, this calculation has various limitations, particularly among those with chronic medical conditions and low muscle mass. In liver disease, creatinine and creatinine-based equations are likely to overestimate the eGFR. In chronic liver disease, the reduction in serum creatinine can be secondary to decreased hepatic production of creatinine, increased volume of distribution due to the accumulation of extracellular fluid, malnutrition, and loss of muscle mass.¹ Moreover, the interaction of bilirubin with creatinine in jaundiced patients results in falsely low serum creatinine, leading to an overestimation of the eGFR.² Similarly, overestimation of eGFR is common among patients with heart failure or lung disease.^3,4 The best methods for assessment of GFR in patients with organ failure depend on the clearance of exogenous markers, such as iothalamate, ⁵¹Cr-EDTA, and inulin, but these measurements are costly, complex to perform, and not widely available.²

Similarly, the prevalence of CKD and ESKD among nonkidney solid organ transplant recipients is very high.⁵ The current literature has identified an extensive list of potential risk factors for the progression of CKD or ESKD; however, most of the risk factors are unclear, inconsistently identified among studies, or contradicted from study to study.^1,5 Outcomes of nonkidney solid organ transplant recipients on dialysis are associated with increased risk of morbidity and mortality. Given the uncertainty in assessing pretransplant kidney function, the presence of weak predictors of post-transplant ESKD, and the significant risk of morbidity and mortality with kidney failure, there is a large dilemma regarding which recipients will benefit from combined solid organ transplant with kidney versus nonkidney solid organ transplant alone (solitary transplant). Both combined and solitary organ transplants have several advantages and disadvantages. One thought process supporting combined organ transplant is that combined transplant often maximizes grafts and patient survival. On the other hand, an argument in support of solitary nonkidney transplant is that patients with pure kidney failure due to other solid organ failure (e.g., hepatorenal or cardiorenal) should recover kidney function after just receiving the primary organ without a kidney. Advantages and disadvantages of solitary nonkidney transplant versus combined solid organ transplantation with kidney¹ are presented in Figure 1.

Figure 1.

Debate of combined with kidney versus solitary nonkidney transplant. ICU, intensive care unit.

Although there are long-term advantages to underdoing combined solid organ transplantation, there are also several consequences associated with this. The kidney allocation system is a wait time–based system, whereas allocation systems for other organs, such as heart, lung, and liver, are largely based on illness severity and medical urgency. Given that patients who undergo combined organ transplant follow nonkidney organ allocation systems, these patients often receive kidneys quicker than patients who have ESKD and require solitary kidney transplantation. Moreover, patients undergoing combined organ transplant often receive the highest quality kidneys with lower kidney donor profile index, disadvantaging ESKD patients who require solitary kidney transplantation by further prolonging their time to transplant. These challenges combined with a limited pool of kidney donors will continue to allocate lower quality kidneys to patients with ESKD, worsening their morbidity and mortality. In addition, combined transplantation is associated with a greater risk of early kidney graft failure.⁶

To overcome some of these challenges, in this current issue of Kideny360, Jan et al.⁷ reported a retrospective cross-sectional study of all adult liver, heart, or lung transplant recipients between 2008 and 2018 using two databases from the Scientific Registry of Transplant Recipients and the United States Renal Data System. The eGFR was calculated at listing for primary organ transplant and at follow-up time points using the race-adjusted CKD Epidemiology Collaboration equation. Post-transplant ESKD was defined as a new inclusion in the United States Renal Data System database after transplant, indicating the start of dialysis, eGFR of <25 ml/min in the Scientific Registry of Transplant Recipients transplant follow-up file, a new waitlisting for a kidney transplant, or receipt of a kidney transplant. This large cohort of 86,350 recipients included 53,620 livers, 22,042 hearts, and 10,688 lung transplant recipients. The rate of ESKD ranged between 2.4% and 3.4% in the first-year post-transplant and 1.4%–1.8% in the second-year post-transplant. In the first-year post-transplant, the probability of ESKD was comparable among heart (0.036; 95% confidence interval [CI], 0.033 to 0.038) and liver transplant (0.033; 95% CI, 0.031 to 0.035) recipients but was markedly lower in lung transplant recipients (0.024; 95% CI, 0.021 to 0.027). In the second-year post-transplant, the probability of ESKD was comparable among liver (0.016; 95% CI, 0.015 to 0.017), lung (0.018; 95% CI, 0.015 to 0.021), and heart transplant recipients (0.014; 95% CI, 0.013 to 0.016). Although the risk of ESKD within the first year of transplant at a rate of 2.4%–3.4% may not seem markedly high, the most striking finding was that at the time of listing, these recipients had excellent kidney function with mean eGFR of more than 70 ml/min in all three groups of organ transplant. Likely, all recipients had gone through extensive workup and consideration by experts in the field and decided only to offer a liver, heart, or lung transplant without a kidney. They concluded thoracic transplant candidates may also benefit from the safety net policy like that of the kidney after liver allocation. Effective June 29, 2023, new safety net policies were implemented for kidney after heart and kidney after lung allocation. The new policies are similar to the safety net provision already in effect for kidney after liver allocation since 2017.⁸

Since the implementation of the kidney after liver allocation safety net policy, there have been some positive outcomes among liver transplant recipients, including rapid access to kidney transplantation along with better patient survival for those who were able to take advantage of it.⁹ In addition, there has been a net negative kidney utilization in end-stage liver disease, which is consistent with a more efficient system with increasingly appropriate allocation of organs.¹⁰ Currently, with these new safety net policies implemented for kidney after heart and kidney after lung allocation, we anticipate seeing similar positive reports. Until then, we can only hope that this policy will help to solve some of the dilemmas regarding performing combined versus solitary organ transplants.

Disclosures

S. Parajuli reports the following: Research Funding: CareDx and Veloxis Pharmaceuticals; and Advisory or Leadership Role: CareDx, Eurofin, and Horizon Pharmaceuticals. The remaining author has nothing to disclose.

Funding

None.

Author Contributions

Data curation: Ban Dodin, Sandesh Parajuli.

Methodology: Ban Dodin, Sandesh Parajuli.

Writing – original draft: Ban Dodin.

Writing – review & editing: Sandesh Parajuli.