Race-free estimated glomerular filtration rate equation in kidney transplant recipients:development and validation study

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. Performance of the GFR equations was assessed using P 30 (proportion of estimated GFR (eGFR) within 30% of measured GFR (mGFR)) and correct classification (agreement between eGFR and mGFR according to GFR stages). The race-free equation, based on creatinine level, age, and sex, was developed using additive and multiplicative linear regressions, and its performance was compared with the three current main GFR equations: Modification of Diet in Renal Disease (MDRD) equation, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation, and race-free CKD-EPI 2021 equation. RESULTS: The study included 15 489 participants, with 50 464 mGFR and eGFR values. The mean GFR was 53.18 mL/min/1.73m 2 (SD 17.23) in the development cohort and 55.90 mL/min/1.73m 2 (19.69) in the external validation cohorts. Among the current GFR equations, the race-free CKD-EPI 2021 equation showed the lowest performance compared with the MDRD and CKD-EPI 2009 equations. When race was included in the kidney recipient specific GFR equation, performance did not increase. The race-free kidney recipient specific GFR equation showed significantly improved performance compared with the race-free CKD-EPI 2021 equation and performed well in the external validation cohorts (P 30 ranging from 73.0% to 91.3%). The race-free kidney recipient specific GFR equation performed well in several subpopulations of kidney transplant recipients stratified by race (P 30 73.0-91.3%), sex (72.7-91.4%), age (70.3-92.0%), body mass index (64.5-100%), donor type (58.5-92.9%), donor age (68.3-94.3%), treatment (78.5-85.2%), creatinine level (72.8-91.3%), GFR measurement method (73.0-91.3%), and timing of GFR measurement post-transplant (72.9-95.5%). An online application was developed that estimates GFR based on recipient's creatinine level, age, and sex (https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/). CONCLUSION: A new race-free kidney recipient specific GFR equation was developed and validated using multiple, large, international cohorts of kidney transplant recipients. The equation showed high accuracy and outperformed the race-free CKD-EPI 2021 equation that was developed in individuals with native kidneys.TRIAL REGISTRATION: ClinicalTrials.gov NCT05229939.</p

Hepatorenal syndrome: pathophysiology and evidence-based management update

Hepatorenal syndrome (HRS) is a functional renal failure that develops in patients with advanced hepatic cirrhosis with ascites and in those with fulminant hepatic failure. The prevalence of HRS varies among studies but in general it is the third most common cause of acute kidney injury (AKI) in cirrhotic patients after pre-renal azotemia and acute tubular necrosis. HRS carries a grim prognosis with a mortality rate approaching 90% three months after disease diagnosis. Fortunately, different strategies have been proven to be successful in preventing HRS. Although treatment options are available, they are not universally effective in restoring renal function but they might prolong survival long enough for liver transplantation, which is the ultimate treatment. Much has been learned in the last two decades regarding the pathophysiology and management of this disease which lead to notable evolution in the HRS definition and better understanding on how best to manage HRS patients. In the current review, we will summarize the recent advancement in epidemiology, pathophysiology, and management of HRS

The Current Management of Hepatorenal Syndrome-Acute Kidney Injury in the United States and the Potential of Terlipressin

Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication of end-stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in critically ill patients. However, interventions have limited efficacy, and mortality rates remain high. In the US, the mainstay of pharmacologic therapy consists of the off-label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients since contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor, short-term prognosis in patients with HRS-AKI and, at best, serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS-AKI in the US is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS-AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS-AKI and supported by recommendations for first-line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS-AKI and the potential benefits if terlipressin was approved in the US

Simultaneous liver and kidney transplantation in elderly patients: Outcomes and validation of a clinical risk score for patient selection

Introduction and aim. Many transplant programs have expanded eligibility to include patients previously ineligible because of advanced age. Outcomes of simultaneous liver-kidney transplantation (SLK) in recipients with advanced age are not known.Material and methods. Data from patients undergoing transplantation between 2002 and 2015 were obtained from the UNOS Standard Analysis and Research file.Results. SLK recipients aged ≥ 65 years (N = 677), SLK recipients aged < 65 years (N = 4517), and recipients of liver transplant alone(LTA) aged ≥ 65 years(N = 8495) were compared. Recipient characteristics were similar between the SLK groups. Similar patient and graft survival were observed in SLK recipients aged ≥ 65 years compared to SLK recipients aged < 65 years and LTA recipients aged ≥ 65 years. Importantly, in a subgroup analysis, superior survival was seen in the SLK group aged ≥ 65 years compared to LTA recipients aged ≥ 65 years who underwent dialysis in the week prior to transplantation (p < 0.001). A prediction model of patient survival was developed for the SLK group aged ≥ 65 years with predictors including: age ≥ 70 years (3 points), calculated MELD score (-1 to 2 points), and recipient ventilator status at the time of SLK (4 points). The risk score predicted patient survival, with a significantly inferior survival seen in patients with a score ≥ 4 (p < 0.001).Conclusions. Age should not be used as a contraindication for SLK transplantation. The validated scoring system provides a guide for patient selection and can be used when evaluating elderly patients for SLK transplantation listing

The Current Management of Hepatorenal Syndrome-Acute Kidney Injury in the United States and the Potential of Terlipressin

Acute kidney injury in the setting of cirrhosis (hepatorenal syndrome-acute kidney injury [HRS-AKI]) is a severe and often fatal complication of end-stage liver disease. The goals of treatment are to reverse renal failure and prolong survival in critically ill patients. However, interventions have limited efficacy, and mortality rates remain high. In the US, the mainstay of pharmacologic therapy consists of the off-label use of vasoconstrictive agents in combination with plasma expanders, a strategy that produces modest effects. Liver transplantation is the ultimate solution but is only an option in a minority of patients since contraindications to transplantation are common and organ availability is limited. Renal replacement therapy is a temporary option but is known to confer an extremely poor, short-term prognosis in patients with HRS-AKI and, at best, serves as a bridge to liver transplantation for the minority of patients who are transplantation candidates. The high mortality rate associated with HRS-AKI in the US is a reflection of the suboptimal standard of care. Improved therapeutic options to treat HRS-AKI are sought. Terlipressin is a drug approved in Europe for treatment of HRS-AKI and supported by recommendations for first-line therapy by some liver societies and experts around the world. This review article will discuss the substantial unmet medical need associated with HRS-AKI and the potential benefits if terlipressin was approved in the US

Predictors of disease severity and outcome of hospitalized renal transplant recipients with COVID-19 infection: a systematic review of a globally representative sample

Introduction. COVID-19 presents a special challenge to the kidney transplant population

Acute Pancreatitis in Advanced Chronic Kidney Disease and Kidney Transplant Recipients: Results of a US Nationwide Analysis

Objective: To study the prevalence, etiology, and outcome of acute pancreatitis (AP) in kidney transplant and stage 5 chronic kidney disease (CKD) populations in comparison to a non-CKD cohort. Patients and Methods: Using the Nationwide Inpatient Sample database, we identified patients with acute pancreatitis as the primary discharge diagnosis, after which propensity scores were used to create 2 cohorts of patients: 1 with CKD (n=13,425) and 1 without CKD (n=13,425). The CKD group was subsequently subdivided into dialysis-independent stage 5 CKD (n=690), dialysis-dependent stage 5 CKD (n=11,415), and kidney transplant recipients (n=1320). Patients younger than 18 years old, those who received a kidney transplant during the incident admission, and pancreas transplant recipients were excluded. Results: The adjusted odds ratios (ORs) of AP were comparable between the no CKD, stage 5 CKD, and kidney transplant populations. Adjusted inpatient mortality was highest in patients with dialysis-dependent stage 5 CKD (OR, 2.72; 95% CI, 2.2-3.3; P<.01), followed by kidney transplant recipients (OR, 2.29; 95% CI, 1.12-4.51; P=.02), compared to the non-CKD group. Patients with stage 5 CKD experienced higher rates of shock and intensive care unit admission and had more prolonged and costly hospitalizations than the non-CKD group (P<.01 for all). Hypercalcemia was the most common cause of AP in both dialysis-dependent and dialysis-independent patients with stage 5 CKD, while viral and drug-induced pancreatitis were more prevalent in the transplant recipients. Conclusion: Despite comparable adjusted prevalence of AP among the stage 5 CKD, transplant, and non-CKD populations, mortality, morbidity, and resource utilization were higher in the patients with stage 5 CKD and transplant recipients. Hypercalcemia is the most common cause of AP in the stage 5 CKD population irrespective of dialysis requirement

Early Allograft Dysfunction Is Associated With Higher Risk of Renal Nonrecovery After Liver Transplantation

Abstract. Early allograft dysfunction (EAD) identifies allografts with marginal function soon after liver transplantation (LT) and is associated with poor LT outcomes. The impact of EAD on post-LT renal recovery, however, has not been studied. Data on 69 primary LT recipients (41 with and 28 without history of renal dysfunction) who received renal replacement therapy (RRT) for a median (range) of 9 (13-41) days before LT were retrospectively analyzed. Primary outcome was renal nonrecovery defined as RRT requirement 30 days from LT. Early allograft dysfunction developed in 21 (30%) patients, and 22 (32%) patients did not recover renal function. Early allograft dysfunction was more common in the renal nonrecovery group (50% vs 21%, P = 0.016). Multivariate logistic regression analysis demonstrated that EAD (odds ratio, 7.25; 95% confidence interval, 2.0-25.8; P = 0.002) and baseline serum creatinine (odds ratio, 3.37; 95% confidence interval, 1.4-8.1; P = 0.007) were independently associated with renal nonrecovery. History of renal dysfunction, duration of renal dysfunction, and duration of RRT were not related to renal recovery (P > 0.2 for all). Patients who had EAD and renal nonrecovery had the worst 1-, 3-, and 5-year patient survival, whereas those without EAD and recovered renal function had the best outcomes (P < 0.001). Post-LT EAD was independently associated with renal nonrecovery in LT recipients on RRT for a short duration before LT. Furthermore, EAD in the setting of renal nonrecovery resulted in the worst long-term survival. Measures to prevent EAD should be undertaken in LT recipients on RRT at time of LT