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CNDP1 and Diabetic Kidney Disease: From Genetic Susceptibility to Therapeutic Targeting.

  • 2026-03-24
  • Genes 17(4)
    • Bulent Tolga Delibasi
    • Michael Ismail Sarisen
    • Matthew Thomas Belitsos
    • Halil Kutlu Erol
    • Tuncay Delibasi

Study Design

Type
Review
Diabetic kidney disease (DKD) affects a substantial proportion of individuals with diabetes mellitus and represents the leading cause of end-stage renal disease worldwide. Familial aggregation studies consistently demonstrate that genetic factors contribute significantly to DKD susceptibility beyond metabolic and hemodynamic determinants. The carnosine dipeptidase 1 (CNDP1) gene on chromosome 18q22.3 has emerged as a compelling susceptibility locus, with a trinucleotide (CTG) repeat polymorphism in exon 2 that encodes the Mannheim variant, which has demonstrated protective associations in selected populations. Individuals homozygous for the shorter (CTG)5 allele exhibit reduced serum carnosinase-1 concentrations and activity, resulting in elevated tissue carnosine levels. Carnosine exerts multiple renoprotective effects, including antioxidant activity, inhibition of advanced glycation end-product formation, and attenuation of profibrotic signaling. Experimental models demonstrate that genetic or pharmacological reduction in carnosinase activity attenuates diabetic kidney injury. Early clinical studies of carnosine supplementation report improvements in albuminuria and oxidative stress markers, though available trials are limited in size, duration, and population scope. Therapeutic targeting of CNDP1 via carnosinase inhibition, therefore, represents a biologically grounded yet still emerging pharmacological strategy. This review synthesizes genetic, molecular, and translational evidence supporting CNDP1 as a model for genetics-informed therapeutic development in DKD, while highlighting important population-specific variation in allele frequencies that constrain universal clinical applicability.

Research Insights

  • Carnosine→Improved Albuminuria

    Early clinical studies of carnosine supplementation report improvements in albuminuria and oxidative stress markers, though available trials are limited in size, duration, and population scope.

    Effect
    Beneficial
    Effect size
    Small
  • Carnosine→Reduced Oxidative Stress Markers

    Early clinical studies of carnosine supplementation report improvements in albuminuria and oxidative stress markers, though available trials are limited in size, duration, and population scope.

    Effect
    Beneficial
    Effect size
    Small
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