Nehna Abdul Majeed1, Esperanza Font-Montgomery2, Linda Lukose3, Joy Bryant4, Peter Veppumthara5, Peter L Choyke6, Ismail B Turkbey6, Theo Heller7, William A Gahl8, Meral Gunay-Aygun9. 1. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA; MedStar Health, Internal Medicine, Baltimore, MD, USA. 2. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; University of Missouri, Department of Pediatrics and Medical Genetics, Columbia, MO 65212, USA. 3. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; RBK Pediatrics, Commack, NY 11725, USA. 4. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. 5. Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA. 6. Molecular Imaging Program, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 7. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 8. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; NIH Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA. 9. Section on Human Biochemical Genetics, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA; Johns Hopkins University School of Medicine, McKusick-Nathans Department of Genetic Medicine, Department of Pediatrics, Baltimore, MD 21287, USA. Electronic address: mgaygun@mail.nih.gov.
Abstract
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.
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.
Authors: Meral Gunay-Aygun; Esperanza Font-Montgomery; Linda Lukose; Maya Tuchman Gerstein; Katie Piwnica-Worms; Peter Choyke; Kailash T Daryanani; Baris Turkbey; Roxanne Fischer; Isa Bernardini; Murat Sincan; Xiongce Zhao; Netanya G Sandler; Annelys Roque; Daniel C Douek; Jennifer Graf; Marjan Huizing; Joy C Bryant; Parvathi Mohan; William A Gahl; Theo Heller Journal: Gastroenterology Date: 2012-10-03 Impact factor: 22.682
Authors: Baris Turkbey; Iclal Ocak; Kailash Daryanani; Esperanza Font-Montgomery; Linda Lukose; Joy Bryant; Maya Tuchman; Parvathi Mohan; Theo Heller; William A Gahl; Peter L Choyke; Meral Gunay-Aygun Journal: Pediatr Radiol Date: 2008-12-17
Authors: Magdalena Adeva; Mounif El-Youssef; Sandro Rossetti; Patrick S Kamath; Vickie Kubly; Mark B Consugar; Dawn M Milliner; Bernard F King; Vicente E Torres; Peter C Harris Journal: Medicine (Baltimore) Date: 2006-01 Impact factor: 1.889