The knowledge that the ratio of urinary albumin to creatinine, a prognostic marker used to improve the prediction of end-stage renal disease was increased, and chronic treatment with C21 in obese Zucker rats (OZR) prevented albuminuria (Patel et al., 2016), taken together, led to the hypothesis that combination therapy with the neprilysin inhibitor sacubitril (SAC) and AT2R agonist C21 will provide greater reno-protection as compared to the neprilysin inhibitor combined with the AT1R blocker valsartan (VAL). This evidence concerns the gene MME and chronic kidney disease.