CNDP1 genotype and renal survival in pediatric nephropathies

J Pediatr Endocrinol Metab. 2016 Jul 1;29(7):827-33. doi: 10.1515/jpem-2015-0262.

Abstract

Background: The risk of developing type II diabetic nephropathy (DN) is lower in patients carrying the CNDP1 Mannheim polymorphism (homozygosity for the five leucine repeat), resulting in decreased activity of the histidine-dipeptide metabolizing enzyme carnosinase. The role of CNDP1 in other nephropathies is still unknown.

Methods: To evaluate the impact of the CNDP1 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).

Results: Renal failure progression was independent of CNDP1 genotype in the total cohort of CKD children. However, in patients with glomerulopathies, only 39% of patients homozygous for the CNDP1 Mannheim polymorphism attained the primary renal endpoint as compared to 77% of patients with any other CNDP1 genotype (p=0.06).

Conclusions: Our findings in pediatric CKD patients suggest that the nephroprotective effect of the CNDP1 Mannheim variant is not restricted to patients with diabetic nephropathy.

MeSH terms

  • Adolescent
  • Alleles
  • 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
  • Polymorphism, Genetic*
  • Prospective Studies
  • Renal Insufficiency, Chronic / genetics
  • Renal Insufficiency, Chronic / physiopathology
  • Renal Insufficiency, Chronic / therapy
  • Severity of Illness Index
  • Survival Analysis

Substances

  • CNDP1 protein, human
  • Dipeptidases