Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Oct 27, 2020; 12(10): 722-737
Published online Oct 27, 2020. doi: 10.4254/wjh.v12.i10.722
Combined liver-kidney transplantation for rare diseases
Mladen Knotek, Rafaela Novak, Alemka Jaklin-Kekez, Anna Mrzljak
Mladen Knotek, Department of Medicine, Tree Top Hospital, Hulhumale 23000, Maldives
Mladen Knotek, Anna Mrzljak, Department of Medicine, Merkur University Hospital, Zagreb 10000, Croatia
Mladen Knotek, Rafaela Novak, Anna Mrzljak, School of Medicine, University of Zagreb, Zagreb 10000, Croatia
Alemka Jaklin-Kekez, Clinic for Pediatric Diseases Helena, Zagreb 10000, Croatia
Author contributions: Knotek M and Mrzljak A contributed to the study design and wrote the manuscript; Novak R and Jaklin-Kekez A contributed to the data acquisition and wrote the manuscript; All authors read and approved the final manuscript.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Anna Mrzljak, FEBG, MD, PhD, Associate Professor, Department of Medicine, Merkur University Hospital, Zajčeva 19, Zagreb 10000, Croatia.
Received: May 12, 2020
Peer-review started: May 12, 2020
First decision: July 29, 2020
Revised: July 30, 2020
Accepted: September 18, 2020
Article in press: September 18, 2020
Published online: October 27, 2020

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.