Renal insufficiency (RI) is a common finding with end-stage liver disease. RI is generally not regarded as a contraindication to liver transplantation. However, the impact of RI on outcome following transplantation and the role of combined liver-kidney transplant are not well understood. The effect of RI on patients with fulminant hepatic failure (FHF) or chronic liver disease (cirrhosis) was investigated using the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Liver Transplantation Database. Patients were analyzed based on the presence of RI, defined as creatinine >1.6 mg/dl, or on dialysis. Patients undergoing liver-kidney transplantation were analyzed separately. For patients with FHF, the RI group had a lower patient survival rate at 1 year (50% vs. 83%, P=0.04) and tended to have a lower graft survival rate (50% vs. 71%). Stay in the intensive care unit (ICU) was prolonged in the RI group but hospital stay was not. Among patients with cirrhosis, RI did not affect patient survival, except for patients on dialysis or those with liver-kidney transplants. One-year patient and graft survival rates were 65% and 60% for the dialysis group, 74% and 70% for the liver-kidney transplant group, 89% and 86% for RI patients not on dialysis, and 89 and 84% for non-RI patients. ICU and hospital stays were prolonged for all of the RI groups compared with the non-RI patients. Patients with RI had higher rates of posttransplant dialysis; however, the differences tended to equalize after 4 weeks. We conclude that RI in FHF and RI requiring dialysis or liver-kidney transplantation in cirrhosis predict lower posttransplant patient and graft survival rates. Patients with RI have longer hospital and ICU stays and an increased need for dialysis, which likely increases the cost of transplantation. Whether liver-kidney transplantation improves outcome and thus represents an appropriate use of cadaver kidneys requires further study.