CNDP1 genotype and renal survival in pediatric nephropathies

• Published in: Journal of Pediatric Endocrinology & Metabolism Vol. 29; no. 7; pp. 827 - 833
• Main Authors: Peters, Verena, Kebbewar, Moustafa, Janssen, Bart, Hoffmann, Georg F., Möller, Kristina, Wygoda, Simone, Charbit, Marina, Fernandes-Teixeira, Ana, Jeck, Nikola, Zschocke, Johannes, Schmitt, Claus Peter, Schäfer, Franz, Wühl, Elke, for the ESCAPE Trial Group
• Format: Journal Article
• Language: English
• Published: Germany De Gruyter 01.07.2016; Walter de Gruyter GmbH
• Subjects: Adolescent; Alleles; carnosinase; Child; Cohort Studies; Combined Modality Therapy; Dipeptidases - genetics; Disease Progression; Female; Follow-Up Studies; Genetic Association Studies; Glomerulonephritis - genetics; Glomerulonephritis - physiopathology; Glomerulonephritis - therapy; Homozygote; Humans; Kidney Diseases - genetics; Kidney Diseases - physiopathology; Kidney Diseases - therapy; Male; non-diabetic glomerulopathies; pediatric kidney disease; Polymorphism, Genetic; Prospective Studies; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - physiopathology; Renal Insufficiency, Chronic - therapy; Severity of Illness Index; Survival Analysis
• ISSN: 0334-018X; 2191-0251
• DOI: 10.1515/jpem-2015-0262

The risk of developing type II diabetic nephropathy (DN) is lower in patients carrying the Mannheim polymorphism (homozygosity for the five leucine repeat), resulting in decreased activity of the histidine-dipeptide metabolizing enzyme carnosinase. The role of in other nephropathies is still unknown. To evaluate the impact of the Mannheim allele on pediatric chronic kidney disease (CKD), we prospectively followed the long-term clinical outcome of 272 children with non-diabetic kidney disease (glomerulopathies n=32, non-glomerular kidney disease n=240). Renal failure progression was independent of genotype in the total cohort of CKD children. However, in patients with glomerulopathies, only 39% of patients homozygous for the Mannheim polymorphism attained the primary renal endpoint as compared to 77% of patients with any other genotype (p=0.06). Our findings in pediatric CKD patients suggest that the nephroprotective effect of the Mannheim variant is not restricted to patients with diabetic nephropathy.