Dysglycemia and Dyslipidemia Models in Nonhuman Primates: Part V. Diabetic Nephropathy and Effects of Angiotensin
Published on Jan 1, 2021in Journal of diabetes & metabolism
ong-term hyperglycemia can impair renal microvessels and lead to diabetic nephropathy (DN). Early treatment can delay or prevent its progression. Efficacy of monoclonal antibody (mAb) therapies for human diseases can often be tested only in nonhuman primates (NHPs) but no other species due to lack of human mAb cross-reactivity. To test if DN in NHPs is similar to the human disease, this study analyzed the blood and urine biochemistry data from a large pool (n=129) of cynomolgus monkeys (Macacafascicularis). Compared with the normoglycemic monkeys, the diabetic animals were significantly aged and showed significantly higher levels of blood glucose, HbA1c, TC, TG, LDL and ALT. DN monkeys (n=47) significantly increased urine (24h) volume, glucose, albumin, total protein, bilirubin and albumin/creatinine ratio (ACR). The data showed significant correlations between age and 24h-urine glucose (p<0.05) and between age and urine creatinine (negative, p<0.05). Plasma glucose correlated well with 24h-urine volume, glucose, albumin, total protein, creatinine, and ACR (p<0.01). Treatment with the angiotensin �?� antagonist losartan significantly improved proteinuria in DN monkeys, which is consistent with the clinical observations in nephropathy patients. Our data indicate that DN in NHPs can be a highly valuable translational model for studying pathophysiological mechanisms and novel therapies of human nephropathy.