DYNAMICS OF NEPHRIN AND CYSTATIN C DURING DIFFERENT GLUCOSE-LOWERING THERAPIES IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
Abstract
Background. Diabetic kidney disease is a major complication of type 2 diabetes mellitus (T2DM). Current evidence supports the kidney-protective effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with diabetes and chronic kidney disease [1–4]. Nephrin reflects podocyte injury, whereas cystatin C is a sensitive marker of changes in glomerular filtration. Their combined assessment may provide information on both structural and functional renal changes during treatment.
Objective. To compare changes in nephrin and cystatin C during different glucose-lowering treatment regimens in patients with T2DM.
Materials and Methods. The study included 140 patients with T2DM receiving combination glucose-lowering therapy. Of these, 62 patients received a DPP-4 inhibitor plus metformin and 78 patients received an SGLT2 inhibitor plus metformin. After 12 months, patients were evaluated according to three treatment regimens: DPP-4 inhibitor + metformin, SGLT2 inhibitor + metformin, and SGLT2 inhibitor + DPP-4 inhibitor + metformin. Clinical, metabolic and renal parameters were assessed, with particular attention to serum nephrin and cystatin C.
Results. At baseline, serum nephrin was 8.10 ± 0.78 ng/mL in the DPP-4 inhibitor + metformin group and 6.85 ± 0.95 ng/mL in the SGLT2 inhibitor + metformin group (p<0.05). Serum cystatin C was 16.0 ± 1.03 versus 16.5 ± 0.93 mg/L, respectively (p>0.05).
After 12 months, nephrin levels were 6.92 ± 0.64, 4.98 ± 0.58 and 3.86 ± 0.47 ng/mL in the DPP-4 inhibitor + metformin, SGLT2 inhibitor + metformin and triple-therapy groups, respectively (p<0.05). Cystatin C levels were 14.8 ± 0.84, 13.2 ± 0.76 and 12.4 ± 0.69 mg/L, respectively.
The greatest reduction in nephrin was observed with triple therapy (43.6%), compared with 27.3% with SGLT2 inhibitor + metformin and 14.6% with DPP-4 inhibitor + metformin. Cystatin C decreased by 24.8%, 20.0% and 7.5%, respectively.
Conclusion. Treatment regimens containing an SGLT2 inhibitor were associated with greater reductions in nephrin and cystatin C. The most pronounced biomarker changes were observed with triple therapy combining an SGLT2 inhibitor, DPP-4 inhibitor and metformin. These findings suggest that simultaneous measurement of nephrin and cystatin C may be useful for monitoring structural and functional renal biomarker responses during therapy in patients with T2DM..
