Combined liver-kidney transplantation for rare diseases

Abstract

Combined liver and kidney transplantation (CLKT) is indicated in patients with failure of both organs, or for the treatment of end-stage chronic kidney disease (ESKD) caused by a genetic defect in the liver. The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT. They are major indications for CLKT in children. However, in some of them (e.g., atypical hemolytic uremic syndrome or primary hyperoxaluria), CLKT may be required in adults as well. Primary hyperoxaluria is divided into three types, of which type 1 and 2 lead to ESKD. CLKT has been proven effective in renal function replacement, at the same time preventing recurrence of the disease. Nephronophthisis is associated with liver fibrosis in 5% of cases and these patients are candidates for CLKT. In alpha 1-antitrypsin deficiency, hereditary C3 deficiency, lecithin cholesterol acyltransferase deficiency and glycogen storage diseases, glomerular or tubulointerstitial disease can lead to chronic kidney disease. Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality. In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H, successful CLKT has been reported in a small number of patients. However, for this indication, CLKT has been largely replaced by eculizumab, an anti-C5 antibody. CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA, facilitating transplantation in a highly sensitized recipient.

Keywords: Combined liver-kidney transplantation; Methylmalonic aciduria; Hereditary complement C3 deficiency; Glycogen storage diseases; Homozygous protein C deficiency; Primary hyperoxaluria; Atypical hemolytic uremic syndrome; Sensitization; Donor-specific antibodies

Core Tip: Combined liver and kidney transplantation (CLKT) provides replacement of both liver and kidney function in both organ end-stage diseases, or in end-stage kidney disease with origin in the genetic defect in the liver. It has been proven as an invaluable treatment option in the range of rare diseases such as primary hyperoxalurias, atypical hemolytic uremic syndrome, lecithin cholesterol acyltransferase deficiency, alpha 1-antitrypsin deficiency, hereditary complement C3 deficiency, nephronophthisis glycogen storage diseases. In this review, we provide an overview of rare indications for CLKT.