The effect of Empagliflozin on alleviating C4d over-activation in Diabetic kidney disease

Empagliflozin was associated with a slower progression of kidney disease. We aimed to investigate the effect of empagliflozin on alleviating complement over-activation in DKD.

100 patients with DKD were recruited, they were divided into three groups: group I, 50 patients type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) stage I-II; group II, 50 patients T2DM with CKD stage III; and the control group, which included 50 healthy, age-matched volunteers. Groups I and II received empagliflozin, while Group III received a placebo. Before and after six months on empagliflozin, the patients in both groups underwent tests for serum creatinine, uric acid, fasting blood glucose (FBG), glycated hemoglobin (HbA1c) urine albumin/creatinine ratio, and blood levels of human complement fragment 4d (C4d).

The optimal cut off value of C4d was ascertained to be 17.55 U/L with a sensitivity of about 68 % and specificity of about 68 %. There were statistically significant differences in Group I after empagliflozin treatment (p < 0.001): HbA1c (6.5 to 5.7), C4d (16 to 7U/l). Whereas serum creatinine (1.9 to 1.7mg/dl), HbA1c (9.9 to 6.7 %), urine albumin/creatinine ratio (115 to 49), and C4d (18 to 11U/l) were significantly improved in Group II after using empagliflozin (p < 0.001). There was a negative correlation between C4d levels and the percent change in uric acid (r -0.647-, p < 0.001).

Empagliflozin may have a beneficial effect on mitigating complement over-activation in DKD. Further research is needed to confirm our findings.