ESPN 54th Annual Meeting

ESPN 2022


 
Hepatic phenotype and complications in patients with autosomal recessive polycystic kidney disease (ARPKD)
KATHRIN BURGMAIER 1 ILSE J. BROEKAERT 1 SAMUEL KILIAN 2 BENJAMIN LEIDIG 1 ANJA BÜSCHER 3 ISMAIL DURSUN 4 MARC FILA 5 IBRAHIM GOKCE 6 NAKYSA HOOMAN 7 MATKO MARLAIS 8 LAURA MASSELLA 9 ANTONIO MASTRANGELO 10 DJALILA MEKAHLI 11 MONIKA MIKLASZEWSKA 12 LUKASZ OBRYCKI 13 LARISA PRIKHODINA 14 BRUNO RANCHIN 15 LUTZ T. WEBER 1 ELKE WÜHL 16 JÖRG DÖTSCH 1 FRANZ SCHAEFER 16 MAX C. LIEBAU 17

1- DEPARTMENT OF PEDIATRICS, UNIVERSITY HOSPITAL COLOGNE AND UNIVERSITY OF COLOGNE, FACULTY OF MEDICINE, COLOGNE, GERMANY
2- INSTITUTE OF MEDICAL BIOMETRY, UNIVERSITY OF HEIDELBERG, HEIDELBERG, GERMANY
3- DEPARTMENT OF PEDIATRICS II, UNIVERSITY HOSPITAL ESSEN, ESSEN, GERMANY
4- DEPARTMENT OF PEDIATRIC NEPHROLOGY, ERCIYES UNIVERSITY, FACULTY OF MEDICINE, KAYSERI, TURKEY
5- PEDIATRIC NEPHROLOGY UNIT, CHU ARNAUD DE VILLENEUVE-UNIVERSITé DE MONTPELLIER, MONTPELLIER, FRANCE
6- RESEARCH AND TRAINING HOSPITAL, DIVISION OF PEDIATRIC NEPHROLOGY, MARMARA UNIVERSITY, ISTANBUL, TURKEY
7- DEPARTMENT OF PEDIATRIC NEPHROLOGY, ALI-ASGHAR CHILDREN HOSPITAL, ALI-ASGHAR CLINICAL RESEARCH DEVELOPMENT CENTER (AACRDC), IRAN UNIVERSITY OF MEDICAL SCIENCES, TEHRAN, IRAN
8- UCL GREAT ORMOND STREET HOSPITAL FOR CHILDREN INSTITUTE OF CHILD HEALTH, UCL, LONDON, UK
9- DIVISION OF NEPHROLOGY, DEPARTMENT OF PEDIATRIC SUBSPECIALTIES, BAMBINO GESù CHILDREN’S HOSPITAL, IRCCS, ROME, ITALY
10- PEDIATRIC NEPHROLOGY, DIALYSIS AND TRANSPLANT UNIT, FONDAZIONE IRCCS Cà GRANDA, OSPEDALE MAGGIORE POLICLINICO, MILAN, ITALY
11- DEPARTMENT OF PEDIATRIC NEPHROLOGY, UNIVERSITY HOSPITALS LEUVEN AND DEPARTMENT OF DEVELOPMENT AND REGENERATION, PKD RESEARCH GROUP, KU LEUVEN, LEUVEN, BELGIUM
12- DEPARTMENT OF PEDIATRIC NEPHROLOGY AND HYPERTENSION, FACULTY OF MEDICINE, JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE, KRAKOW, POLAND
13- THE CHILDRENS MEMORIAL HEALTH INSTITUTE, WARSAW, POLAND
14- DEPARTMENT OF INHERITED AND ACQUIRED KIDNEY DISEASES, RESEARCH CLINICAL INSTITUTE FOR PEDIATRICS N.A. ACAD. Y. E. VELTISHEV, PIROGOV RUSSIAN NATIONAL RESEARCH MEDICAL UNIVERSITY, MOSCOW, RUSSIA
15- PEDIATRIC NEPHROLOGY UNIT, HôPITAL FEMME MèRE ENFANT, HOSPICES CIVILS DE LYON, CENTRE DE RéFéRENCE MALADIES RéNALES RARES, BRON, FRANCE
16- DIVISION OF PEDIATRIC NEPHROLOGY, CENTER FOR PEDIATRICS AND ADOLESCENT MEDICINE, UNIVERSITY OF HEIDELBERG, HEIDELBERG, GERMANY
17- DEPARTMENT OF PEDIATRICS, UNIVERSITY HOSPITAL COLOGNE; CENTER FOR MOLECULAR MEDICINE, UNIVERSITY HOSPITAL COLOGNE AND UNIVERSITY OF COLOGNE, FACULTY OF MEDICINE, COLOGNE, GERMANY
 
Introduction:

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but severe early-onset hepatorenal fibrocystic disease and mainly caused by variants in the PKHD1 gene. Ductal plate malformation as mandatory aspect of the disease is the pathophysiologic basis for development of congenital hepatic fibrosis, which leads to clinical signs of portal hypertension. Here, we aimed to describe the hepatic phenotype of ARPKD patients.

Material and methods:

We analysed clinical datasets of 605 ARPKD patients from the ARegPKD registry study for their hepatic characteristics and complications. Portal hypertension was defined as splenomegaly on ultrasound, thrombocytopenia (<150 000/ul), proof of collateral blood flow or a substantial hepatic complication, substantial hepatic complication was defined as occurrence of variceal bleeding, presence of TIPS/surgical portosystemic shunt or isolated liver or combined liver-kidney transplantation (LTx, CLKTx).

Results:

Of the 605 analyzed patients with ≥1 follow-up visit, median (Q1-Q3) age at initial diagnosis was 0.2 (0.1-1.6) years, median (Q1-Q3) age at first visit was 1.3 (0.2-7.2) years. Most patients initially presented with kidney-related symptoms, but 14/537 patients (3%) presented with gastrointestinal bleeding and 4/557 (1%) with cholangitis. The 5 (10; 20) year survival without signs of portal hypertension was 77% (55%; 25%), without substantial hepatic complication 94% (79%; 58%). In total, 42 children underwent at least one LTx or CLKTx. Median (Q1-Q3) age at first LTx was 8.7 (5.3-22.4) years and at first CLKTx 8.1 (5.4-14.6) years.

Conclusions:

Only a small fraction of patients initially presented with gastrointestinal symptoms. However, 20-year-survival without signs of portal hypertension was only 25%, without substantial hepatic complication 58%, indicating that a relevant fraction of patients suffers from hepatic symptoms in childhood and adolescence. Further analyses aim to delineate early clinical or biochemical risk markers for a substantial hepatic phenotype to counsel wisely this at-risk group and to improve clinical decision-making.