Prospective evaluation of kidney and liver disease in autosomal recessive polycystic kidney disease-congenital hepatic fibrosis

Autor: Meral Gunay-Aygun, Nehna Abdul Majeed, Linda Lukose, Theo Heller, Joy Bryant, Esperanza Font-Montgomery, Peter L. Choyke, Peter Veppumthara, Ismail B. Turkbey, William A. Gahl
Rok vydání: 2020
Předmět:
Adult
Liver Cirrhosis
Male
0301 basic medicine
medicine.medical_specialty
Adolescent
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Receptors
Cell Surface
030105 genetics & heredity
Liver transplantation
Kidney
Compound heterozygosity
Biochemistry
Gastroenterology
Article
Cohort Studies
Young Adult
03 medical and health sciences
Liver disease
0302 clinical medicine
Endocrinology
Internal medicine
Hypertension
Portal
Genetics
medicine
Humans
Prospective Studies
Child
Molecular Biology
Kidney transplantation
Polycystic Kidney
Autosomal Recessive
business.industry
Genetic Diseases
Inborn
medicine.disease
Kidney Transplantation
Autosomal Recessive Polycystic Kidney Disease
Liver Transplantation
Cross-Sectional Studies
medicine.anatomical_structure
Liver
Disease Progression
Portal hypertension
Congenital hepatic fibrosis
Female
business
030217 neurology & neurosurgery
Zdroj: Mol Genet Metab
ISSN: 1096-7192
DOI: 10.1016/j.ymgme.2020.08.006
Popis: Background and objectives We have previously published the characteristics of kidney and liver disease in a cohort of 73 individuals with molecularly confirmed autosomal recessive polycystic kidney disease-congenital hepatic fibrosis, based upon cross-sectional data. Here, we present prospective data on the same cohort. Design, setting, participants, and measurements Comprehensive biochemical and imaging data on progression of kidney and liver disease in 60 of the 73 patients were prospectively collected at the NIH Clinical Center on multiple visits between 2003 and 2019. Results and conclusions Of the 73 patients, 23 received a renal allograft at an average age of 17.5 years and 10 underwent liver transplantation at an average age of 20.3 years. Patients who presented perinatally and those who had corticomedullary disease required kidney transplantation significantly earlier. The mean eGFR slope in patients with corticomedullary disease was −1.6 ml/min/1.73 m2/y, in comparison to −0.6 ml/min/1.73 m2/y in those with medullary disease. Kidney size remained the same over time and normalized to the upper limit of normal by 20–25 years of age. The extent of renal disease on ultrasound remained largely unchanged; no patient progressed from the “medullary” to the “corticomedullary” group. There was no correlation between eGFR slope and kidney size. The synthetic function of the liver remained largely intact even in patients with advanced portal hypertension. Based on spleen length/height ratio, two thirds of patients had portal hypertension which remained stable in 39% and worsened in 61%. Patients with portal hypertension had lower platelet counts and relatively higher levels of AST, GGT, direct bilirubin and ammonia. The progression rates of kidney and liver disease were independent of each other. Patients with bi-allelic non-truncating PKHD1 variants had similar progression of kidney and liver disease in comparison to those who were compound heterozygous for a non-truncating and a truncating variant.
Databáze: OpenAIRE
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