Pre-liver transplant renal dysfunction is associated with decreased survival following transplantation and is also a prognostic indicator of posttransplant chronic kidney disease. Selection of patients for combined liver/kidney transplantation versus orthotopic liver transplantation alone (OLTa) is often difficult given the lack of a reliable method to predict which patients will have ongoing severe renal dysfunction in the absence of concomitant kidney transplantation. We hypothesized that most patients with pretransplant renal dysfunction (serum creatinine Ն 1.5 mg/dL for at least 2 weeks prior to and at time of transplant) will not experience a rapid decline in estimated glomerular filtration rates (eGF) post-OLTa to the point of necessitating consideration for kidney transplantation, even in the setting of calcineurin inhibitor-based immunosuppression. We performed a single-center retrospective study of 60 OLTa patients with pretransplant renal dysfunction transplanted between 2000 and 2005. Kaplan-Meier analysis was performed of the time interval to develop eGFR Ͻ 20 mL/minute post-OLTa. At OLTa, the mean patient age was 59 years, and median serum creatinine was 1.8 mg/dL; 42% patients were hepatitis C-positive, 32% were diabetic, 38% had kidney dysfunction Ͼ 12 weeks, and 5% were receiving hemodialysis. After 36 months median follow-up post-OLTa, only 8 patients (13%) with significant renal dysfunction pre-OLTa achieved eGFR Ͻ 20 mL/minute. Patients with pretransplant kidney dysfunction Ͼ 12 weeks were at increased risk for eGFR Ͻ 20 mL/minute (hazard ratio ϭ 5.3, P ϭ 0.04), a risk that escalated after adjustment for age and serum creatinine at transplant (hazard ratio ϭ 8.9, P ϭ 0.01). Significant predictors of eGFR Ͻ 20 mL/minute post-OLTa in this patient cohort were the presence of diabetes and the serum creatinine level at transplant. In conclusion, few patients with preexisting renal dysfunction, especially if Ͻ12 weeks duration, experience a significant drop in eGFR post-OLTa. Liver Transpl 14: 665-671, 2008.

SUMMARY BackgroundHepatocellular adenoma is a benign tumour associated with bleeding and malignant transformation. Obesity has been linked to hepatic tumourigenesis.

Guidelines recommend restricting simultaneous liverkidney (SLK) transplant to candidates with prolonged dialysis or estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m 2 for 90 days. However, few studies exist to support the latter recommendation. Using Scientific Registry of Transplant Recipients and Medicare dialysis data, we assembled a cohort of 4997 liver transplant recipients from February 27, 2002-January 1, 2008. Serial eGFRs were calculated from serum creatinines submitted with MELD reports. We categorized recipients by eGFR patterns in the 90 days pretransplant: Group 1 (eGFR always >30), Group 2 (eGFR fluctuated), Group 3 (eGFR always <30) and Group 4 (short-term dialysis). For Group 2, we characterized fluctuations in renal function using time-weighted mean eGFR. Among liver-alone recipients in Group 3, the rate of end-stage renal disease (ESRD) by 3 years was 31%, versus <10% for other groups (p < 0.001). In multivariable Cox regression, eGFR Group, diabetes (HR 2.65, p < 0.001) and black race (HR 1.83, p = 0.02) were associated with ESRD. Among liver-alone recipients in Group 2, only diabetics with time-weighted mean eGFR <30 had a substantial ESRD risk (25.6%). In summary, among liver transplant candidates not on prolonged dialysis, SLK should be considered for those whose eGFR is always <30 and diabetic candidates whose weighted mean eGFR is <30 for 90 days.

Estimation of glomerular filtration rate (eGFR) in patients with liver disease is suboptimal in the presence of renal dysfunction. We developed a model for GFR assessment in liver disease (GRAIL) before and after liver transplantation (LT). GRAIL was derived using objective variables (creatinine, blood urea nitrogen, age, gender, race, and albumin) to estimate GFR based on timing of measurement relative to LT and degree of renal dysfunction (www.bswh.md/grail). The measured GFR (mGFR) by iothalamate clearance (n = 12,122, 1985‐2015) at protocol time points before/after LT was used as reference. GRAIL was compared with the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and Modification of Diet in Renal Disease (MDRD‐4, MDRD‐6) equations for mGFR < 30 mL/min/1.73 m2. Prediction of development of chronic kidney disease (mGFR < 20 mL/min/1.73 m2, initiation of chronic dialysis) and listing or receipt of kidney transplantation within 5 years was examined in internal cohort (n = 785) and external validation (n = 68,217, 2001‐2015). GRAIL had less bias and was more accurate and precise as compared with CKD‐EPI, MDRD‐4, and MDRD‐6 at time points before/after LT for low GFR. For mGFR < 30 mL/min/1.73 m2, the median difference (eGFR–mGFR) was GRAIL: 5.24 (9.65) mL/min/1.73 m2 as compared with CKD‐EPI: 8.70 (18.24) mL/min/1.73 m2, MDRD‐4: 8.82 (17.38) mL/min/1.73 m2, and MDRD‐6: 6.53 (14.42) mL/min/1.73 m2. Before LT, GRAIL correctly classified 75% as having mGFR < 30 mL/min/1.73 m2 versus 36.1% (CKD‐EPI), 36.1% (MDRD‐4), and 52.8% (MDRD‐6) (P < 0.01). An eGFR < 30 mL/min/1.73 m2 by GRAIL predicted development of CKD (26.9% versus 4.6% CKD‐EPI, 5.9% MDRD‐4, and 10.5% MDRD‐6) in center data and needing kidney after LT (48.3% versus 22.0% CKD‐EPI versus 23.1% MDRD‐4 versus 48.3% MDRD‐6, P < 0.01) in national data within 5 years after LT. Conclusion: GRAIL may serve as an alternative model to estimate GFR among patients with liver disease before and after LT at low GFR.

Key Points 1. Chronic kidney disease is a common complication after liver transplantation and has a major impact on graft and patient survival. 2. Pretransplant renal dysfunction is the most important determinant of posttransplant chronic kidney disease; other factors include the presence of diabetes/hypertension, acute kidney injury pre‐transplant and post‐transplant, and the use of calcineurin inhibitor–based immunosuppression. 3. The most common cause of end‐stage renal disease post–orthotopic liver transplantation is calcineurin inhibitor toxicity, and this emphasizes the need for calcineurin inhibitor minimization protocols post‐transplant. 4. The presence of chronic kidney disease post–orthotopic liver transplantation not only is important with respect to the need for renal replacement therapy and kidney transplantation but also increases cardiovascular risk dramatically. 5. The Model for End‐Stage Liver Disease score is partly driven by creatinine, and it is not uncommon to have an elevated creatinine level in those who have a high Model for End‐Stage Liver Disease score and are close to having an organ allocated. Thus, evaluating patients with advanced liver disease and pretransplant acute kidney injury is challenging. It is important to identify pre–liver transplant patients at high risk for early evolution of chronic kidney disease post‐transplant in order to appropriately select patients for combined liver/kidney transplantation. Liver Transpl 15:S70–S74, 2009. © 2009 AASLD.