Morbidity from Congenital Hepatic Fibrosis after Renal Transplantation for Autosomal Recessive Polycystic Kidney Disease

Abstract

Presentation of autosomal recessive polycystic kidney disease (ARPKD) ranges from severe renal impairment and a high mortality rate in infancy to older children and adolescents with minimal renal disease and complications of congenital hepatic fibrosis (CHF), cholangitis and portal hypertension. Renal transplantation improves prognosis but it is unclear whether CHF in transplanted children follows the same clinical course as in older children with less severe renal disease. The aim of this study was to evaluate morbidity from CHF in ARPKD post renal transplantation. Data were analyzed for six males and eight females, transplanted for ARPKD (mean age 8.3years, range 1-22.3years) at the University of Minnesota between 1972 and 1998. Follow-up was for a mean of 14.5years (range 3.1-33.6years). One and 5years patient survival rates were 93% and 86%, respectively. Overall five patients (36%) died; 4/5 deaths were related to CHF. Causes of death were hepatic failure immediately post transplant (n Ω 1), septicemia related to bile duct dilatation (n Ω 3) and multiorgan failure (n Ω 1). One and 5years graft survival rates were 87% and 70%, respectively. One patient had a combined liver-kidney transplant and two were re-transplanted. Initial signs of CHF were splenomegaly (n Ω 5), hepatosplenomegaly (n Ω 4) and gastrointestinal bleed (n Ω 2). Progression of CHF through childhood included hypersplenism (n Ω 7), esophageal varices with gastrointestinal bleeding (n Ω 5) and bile duct dilatation (n Ω 5). Portal hypertension was treated with portosystemic shunt (n Ω 3), sclerotherapy (n Ω 2), banding of varices (n Ω 1) and transjugular intrahepatic portosystemic shunt (n Ω 1). Of the nine survivors (mean age 12.8years) 78% have functioning grafts (one liver-kidney transplant), 63% have portal hypertension and 22% have asymptomatic biliary dilatation. Complications of CHF developed in 79% of children who received a renal transplant for ARPKD. Mortality related to CHF occurred in 29% and accounted for 80% (4/5) of the deaths.

A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD)

“…4,13 Therefore, liver and kidney serum parameters were measured in wild-type and Pkhd1ex40-mutated mice. We found that the mean values and standard deviation of serum creatinine, phosphate, potassium, creatine kinase, urea, glutamic oxaloacetic acid, glutamic pyruvic transaminase, alkaline phosphatase, gamma-glutamyltransferase, total protein, and bilirubin values when measured at different ages between 8 weeks to 14 months did not differ between wildtype and homozygous mutant littermates (data not shown).…”

“…For reverse transcription, 1 g total RNA was primed with 1 g oligo d(T) [12][13][14][15][16][17][18] , and transcription was performed by Superscript II RT following the manufacturer's description (Invitrogen). PCR was run with 35 cycles (1 minute at 94°C, 45 seconds at 53°C to 55°C, and 1 to 2 minutes at 72°C).…”

Transplantation in autosomal recessive polycystic kidney disease: liver and/or kidney?

“…Fever, right upper quadrant pain, icterus, and abnormal transaminases could indicate cholangitis but often the presentation can be subtle. A significant number of children have succumbed to the complications of biliary disease after transplantation [18][19][20][21]. Extrahepatic biliary disease as the predominant manifestation has also been reported [9].…”

Combined liver and kidney transplantation in children

“…Although the patients have large liver and portal hypertension, the liver function often remains satisfactory for a long time, and the indications for LT or CLKT are not clear. When isolated KT is performed, hepatic disease can worsen the outcome, especially by increasing the risk for cholangitis and sepsis [47,48]. In a retrospective analysis of 203 patients with polycystic kidney disease and isolated KT, nine patients (4.4 %) died from sepsis posttransplant, which is a high frequency among KT patients.…”

“…Placement of a portosystemic shunt may help but carries a risk for hepatic encephalopathy, especially in uremic patients. Also, the shunt may need revision because of thrombosis or growth of the child [46,47,49].…”