Yuri Genyk

Working Party proposal for a revised classification system of renal dysfunction in patients with cirrhosis

Objectives To propose an improvement on the current classification of renal dysfunction in cirrhosis. Clinicians caring for patients with cirrhosis recognize that the development of renal dysfunction is associated with significant morbidity and mortality. While most cases of renal dysfunction in cirrhosis are functional in nature, developed as a result of changes in haemodynamics, cardiac function, and renal auto-regulation, there is an increasing number of patients with cirrhosis and structural changes in their kidney as a cause of renal dysfunction. Therefore, there is a need for a newer classification to include both functional and structural renal diseases. Design A working party consisting of specialists from multiple disciplines conducted literature search and developed summary statements, incorporating the renal dysfunction classification used in nephrology. These were discussed and revised to produce this proposal. Setting Multi-disciplinary international meeting. Patients None. Interventions Literature search using keywords of cirrhosis, renal dysfunction, acute kidney injury (AKI), chronic kidney injury (CKD), and hepatorenal syndrome. Results Acute kidney injury will include all causes of acute deterioration of renal function as indicated by an increase in serum creatinine of >50% from baseline, or a rise in serum creatinine of ≥26.4µmol/L (≥0.3mg/dL) in <48hours. Chronic renal disease will be defined as an estimated glomerular filtration rate (GFR) of <60ml/min calculated using the Modification of Diet in Renal Disease 6 (MDRD6) formula, recognising that the MDRD6 formula is not perfect for the cirrhotic patients and this may change as improved means of estimating GFR becomes available. Acute on chronic kidney disease will be defined as AKI superimposed on existing chronic renal disease using the above definitions for AKI and CKD. Conclusions Accepting this new classification will allow studies into the epidemiology, incidence, prevalence, natural history and the development of new treatments for these subtypes of renal dysfunction in cirrhosis.

Risk Factors for Graft Survival After Liver Transplantation from Donation After Cardiac Death Donors: An Analysis of OPTN/UNOS Data

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low‐risk recipients (RCRR ≤ 1.5) with low‐risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log‐rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low‐risk grafts are transplanted in a low‐risk setting. Whether transplantation of these organs in low‐risk recipients provides a survival benefit compared to the waiting list is unknown.

Simultaneous Liver-Kidney Transplantation Summit: Current State and Future Directions

Although previous consensus recommendations have helped define patients who would benefit from simultaneous liver–kidney transplantation (SLK), there is a current need to reassess published guidelines for SLK because of continuing increase in proportion of liver transplant candidates with renal dysfunction and ongoing donor organ shortage. The purpose of this consensus meeting was to critically evaluate published and registry data regarding patient and renal outcomes following liver transplantation alone or SLK in liver transplant recipients with renal dysfunction. Modifications to the current guidelines for SLK and a research agenda were proposed.

Management of the critically ill patient with cirrhosis: A multidisciplinary perspective.

a r Management of the critically ill patient with cirrhosis: A multidisciplinary perspective Mitra K. Nadim1,⇑, Francois Durand, John A. Kellum, Josh Levitsky, Jacqueline G. O’Leary, Constantine J. Karvellas, Jasmohan S. Bajaj, Andrew Davenport, Rajiv Jalan, Paolo Angeli, Stephen H. Caldwell, Javier Fernández, Claire Francoz, Guadalupe Garcia-Tsao, Pere Ginès, Michael G. Ison, David J. Kramer, Ravindra L. Mehta, Richard Moreau, David Mulligan, Jody C. Olson, Elizabeth A. Pomfret, Marco Senzolo, Randolph H. Steadman, Ram M. Subramanian, Jean-Louis Vincent, Yuri S. Genyk

Impact of the etiology of acute kidney injury on outcomes following liver transplantation: acute tubular necrosis versus hepatorenal syndrome†

Acute kidney injury (AKI) at the time of liver transplantation (LT) has been associated with increased morbidity and mortality. In patients with potentially reversible renal dysfunction, predicting whether there will be sufficient return of native kidney function is sometimes difficult. Previous studies have focused mainly on the effect of the severity of renal dysfunction or the duration of pretransplant dialysis on posttransplant outcomes. We performed a retrospective analysis of patients who underwent LT at our center after Model for End‐Stage Liver Disease–based allocation so that we could determine the impact of the etiology of AKI [acute tubular necrosis (ATN) versus hepatorenal syndrome (HRS)] on post‐LT outcomes. The patients were stratified according to the severity of AKI at the time of LT as described by the Risk, Injury, Failure, Loss, and End‐Stage Kidney Disease (RIFLE) classification: risk, injury, or failure. The RIFLE failure group was further subdivided according to the etiology of AKI: HRS or ATN. The patient survival and renal outcomes 1 and 5 years after LT were significantly worse for those with ATN. At 5 years, the incidence of chronic kidney disease (stage 4 or 5) was statistically higher in the ATN group versus the HRS group (56% versus 16%, P < 0.001). A multivariate analysis revealed that the presence of ATN at the time of LT was the only variable associated with higher mortality 1 year after LT (P < 0.001). Our study is the first to demonstrate that the etiology of AKI has the greatest impact on patient and renal outcomes after LT. Liver Transpl, 2012.

Hepatorenal syndrome: the 8th international consensus conference of the Acute Dialysis Quality Initiative (ADQI) Group

IntroductionRenal dysfunction is a common complication in patients with end-stage cirrhosis. Since the original publication of the definition and diagnostic criteria for the hepatorenal syndrome (HRS), there have been major advances in our understanding of its pathogenesis. The prognosis of patients with cirrhosis who develop HRS remains poor, with a median survival without liver transplantation of less than six months. However, a number of pharmacological and other therapeutic strategies have now become available which offer the ability to prevent or treat renal dysfunction more effectively in this setting. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies.MethodsWe undertook a systematic review of the literature using Medline, PubMed and Web of Science, data provided by the Scientific Registry of Transplant Recipients and the bibliographies of key reviews. We determined a list of key questions and convened a two-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research.ResultsOf the 30 questions considered, we found inadequate evidence for the majority of questions and our recommendations were mainly based on expert opinion. There was insufficient evidence to grade three questions, but we were able to develop a consensus definition for acute kidney injury in patients with cirrhosis and provide consensus recommendations for future investigations to address key areas of uncertainty.ConclusionsDespite a paucity of sufficiently powered prospectively randomized trials, we were able to establish an evidence-based appraisal of this field and develop a set of consensus recommendations to standardize care and direct further research for patients with cirrhosis and renal dysfunction.

Expanding the Donor Kidney Pool: Utility of Renal Allografts Procured in a Setting of Uncontrolled Cardiac Death

The chronic shortage of deceased kidney donors has led to increased utilization of donation after cardiac death (DCD) kidneys, the majority of which are procured in a controlled setting. The objective of this study is to evaluate transplantation outcomes from uncontrolled DCD (uDCD) donors and evaluate their utility as a source of donor kidneys.

Live donor liver transplantation without blood products: strategies developed for Jehovah's Witnesses offer broad application.

Objective:Developing strategies for transfusion-free live donor liver transplantation in Jehovahs Witness patients. Summary Background Data:Liver transplantation is the standard of care for patients with end-stage liver disease. A disproportionate increase in transplant candidates and an allocation policy restructuring, favoring patients with advanced disease, have led to longer waiting time and increased medical acuity for transplant recipients. Consequently, Jehovahs Witness patients, who refuse blood product transfusion, are usually excluded from liver transplantation. We combined blood augmentation and conservation practices with live donor liver transplantation (LDLT) to accomplish successful LDLT in Jehovahs Witness patients without blood products. Our algorithm provides broad possibilities for blood conservation for all surgical patients. Methods:From September 1998 until June 2001, 38 LDLTs were performed at Keck USC School of Medicine: 8 in Jehovahs Witness patients (transfusion-free group) and 30 in non-Jehovahs Witness patients (transfusion-eligible group). All transfusion-free patients underwent preoperative blood augmentation with erythropoietin, intraoperative cell salvage, and acute normovolemic hemodilution. These techniques were used in only 7%, 80%, and 10%, respectively, in transfusion-eligible patients. Perioperative clinical data and outcomes were retrospectively reviewed. Data from both groups were statistically analyzed. Results:Preoperative liver disease severity was similar in both groups; however, transfusion-free patients had significantly higher hematocrit levels following erythropoietin augmentation. Operative time, blood loss, and postoperative hematocrits were similar in both groups. No blood products were used in transfusion-free patients while 80% of transfusion-eligible patients received a median of 4.5+/− 3.5 units of packed red cell. ICU and total hospital stay were similar in both groups. The survival rate was 100% in transfusion-free patients and 90% in transfusion-eligible patients. Conclusions:Timely LDLT can be done successfully without blood product transfusion in selected patients. Preoperative preparation, intraoperative cell salvage, and acute normovolemic hemodilution are essential. These techniques may be widely applied to all patients for several surgical procedures. Chronic blood product shortages, as well as the known and unknown risk of blood products, should serve as the driving force for development of transfusion-free technology.

A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation

Background  Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well‐described.

Simultaneous Liver–Kidney Transplantation: A Survey of US Transplant Centers

Consensus recommendations have been published to help better define those patients who would benefit from simultaneous liver–kidney transplantation (SLK). We conducted a survey of transplant centers that perform SLK (n = 88, 65% response rate) to determine practice patterns in the United States. The majority of centers (73%) stated that they use dialysis duration whereas only 30% of centers use acute kidney injury duration as a criterion for determining need for SLK. Dialysis duration >4 weeks was used by 32% of centers, >6 weeks by 37% and >8 weeks by 32% of centers. Glomerular filtration rate (GFR) was estimated using the modified diet in renal disease (MDRD)‐4 equation in roughly half of centers whereas the MDRD‐6 equation was used by only 6%. In patients with chronic kidney disease, GFR < 40 mL/min was used by 24% of centers as a criterion for SLK transplants instead of the recommended threshold of < 30 mL/min. Regional differences in practices were also observed. This survey demonstrates significant variation in the criteria used for SLK among transplant centers, with few centers following the current published recommendations, and emphasizes the need for evidence‐based guidelines and uniformity in studying renal dysfunction in liver transplant candidates.