Mai, Martin

Renal dysfunction is highly prevalent among patients with cirrhosis and has major implications for management, prognostication, and liver transplant decision-making. Both acute kidney injury (AKI) and chronic kidney disease (CKD) occur frequently in this population and are driven by a complex interplay of hemodynamic derangements, systemic inflammation, and intrinsic or functional renal injury. Accurate assessment of kidney function is essential, as serum creatinine and estimated glomerular filtration rate (eGFR) calculations directly influence MELD-based transplant allocation, eligibility for simultaneous liver–kidney transplantation (SLKT), and clinical decisions such as drug dosing and peri-transplant immunosuppression strategies. However, creatinine-based assessments are fundamentally limited in cirrhosis due to reduced creatinine production, sarcopenia, expanded volume of distribution, increased tubular secretion, and assay interference from hyperbilirubinemia, resulting in frequent overestimation of true GFR. Alternative methods, including cystatin C-based equations, combined creatinine–cystatin C equations, timed urine clearances, and direct GFR measurement using exogenous filtration markers (iohexol, iothalamate), offer potential advantages but also carry important limitations, particularly in decompensated disease with ascites or inflammation. Newer cirrhosis-specific eGFR equations such as the GRAIL and Royal Free Hospital formulas attempt to address these shortcomings, yet validation studies demonstrate inconsistent accuracy across patient cohorts. This review summarizes the pathophysiologic contributors to renal dysfunction in cirrhosis, evaluates the performance and pitfalls of existing kidney function assessment tools, and highlights the ongoing need for reliable, validated methods tailored to this unique population. Until improved approaches are widely accessible, serum creatinine remains the most practical—albeit imperfect—marker guiding clinical decision-making in cirrhotic patients.

ABSTRACTIntroductionThe incidence of mortality late in the pandemic, particularly after widespread vaccine availability, is not well understood. Herein, we elucidate the effect of this impact of the COVID pandemic as well as risk factors for mortality during it.MethodsThe primary end point was death with a functioning graft with secondary endpoints of mortality rates in subgroups and at different time intervals during the pandemic.ResultsDespite widespread vaccination, mortality rates for kidney transplant (KTx) recipients almost doubled during the COVID‐19 era (6.40 deaths per 100 person years vs. 3.54 pre‐COVID). Mortality increased in all racial/ethnic groups but increased more in Native Americans, Hispanics, and African Americans compared to non‐Hispanic Caucasians. The highest mortality rate occurred during the Delta and Omicron time frames. In contrast to the general population, mortality was more evenly spread across age groups in KTx recipients.ConclusionsMortality rates during the COVID‐19 era were extremely high, more than doubling in some racial/ethnic groups. We conclude that the KTx population was a particularly vulnerable group during the COVID‐19 era and suggests the need for further research into the management of variants in the future.

AbstractBackgroundThe aim of this study was to correlate peripheral blood gene expression profile (GEP) results during the first post‐transplant year with outcomes after kidney transplantation.MethodsWe conducted a prospective, multicenter observational study of obtaining peripheral blood at five timepoints during the first post‐transplant year to perform a GEP assay. The cohort was stratified based on the pattern of the peripheral blood GEP results: Tx‐all GEP results normal, 1 Not‐TX had one GEP result abnormal and >1 Not‐TX two or more abnormal GEP results. We correlated the GEP results with outcomes after transplantation.ResultsWe enrolled 240 kidney transplant recipients. The cohort was stratified into the three groups: TX n = 117 (47%), 1 Not‐TX n = 59 (25%) and >1 Not‐TX n = 64 (27%). Compared to the TX group, the >1 Not‐TX group had lower eGFR (p < .001) and more chronic changes on 1‐year surveillance biopsy (p = .007). Death censored graft survival showed inferior graft survival in the >1 Not‐TX group (p < .001) but not in the 1 Not‐TX group. All graft losses in the >1 Not‐TX group occurred after 1‐year post‐transplant.ConclusionsWe conclude that a pattern of persistently Not‐TX GEP assay correlates with inferior graft survival.

AbstractKidney paired donation (KPD) and the new kidney allocation system (KAS) in the United States have led to improved transplantation rates for highly sensitized candidates. We aimed to assess the potential need for other approaches to improve the transplantation rate of highly sensitized candidates such as desensitization. Using the UNOS STAR file, we analyzed transplant rates in a prevalent active waiting‐list cohort as of June 1, 2016, followed for 1 year. The overall transplantation rate was 18.9% (11 129/58769). However, only 9.7% (213/2204) of candidates with a calculated panel reactive antibody ≥99.9% received a transplant, and highly sensitized candidates were less likely to receive a living donor transplant. Among candidates with a CPRA ≥ 99.5% (ie. 100%), only 2.5% of transplants were from living donors (13 total, 7 from KPD). Nearly 4 years after KAS (6/30/2018), 1791 actively wait‐listed candidates had a CPRA of ≥99.9% and 34.6% (620/1791) of these had ≥5 years of waiting time. Thus, despite KPD and KAS, many sensitized candidates have not been transplanted even with prolonged waiting time. We conclude that candidates with a CPRA ≥ 99.9% and sensitized candidates with an incompatible living donor and prolonged waiting time may benefit from desensitization to improve their ability to receive a transplant.