PEGylation renders carnosine resistant to hydrolysis by serum carnosinase and increases renal carnosine levels.

Carnosine's protective effect in rodent models of glycoxidative stress have provided a rational for translation of these findings in therapeutic concepts in patient with diabetic kidney disease. In contrast to rodents however, carnosine is rapidly degraded by the carnosinase-1 enzyme. To overcome this hurdle, we sought to protect hydrolysis of carnosine by conjugation to Methoxypolyethylene glycol amine (mPEG-NH).

Serum and urinary carnosinase-1 correlate with kidney function and inflammation.

The carnosinase dipeptidase 1 (CNDP1) gene has been reported as a susceptibility locus for the development of diabetic kidney disease (DKD). While the (CTG) allele affords protection in the Caucasian population, we have previously shown that this allele is less frequently present in the Chinese population and therefore a protective role for the (CTG) allele is difficult to demonstrate. In the present study, we sought to assess if carnosinase-1 (CN-1) concentrations in serum and/or urine are associated with progression of DKD and to what extent CN-1 influences diabetes-associated inflammation.