The effect of various drug treatments on the progression of kidney disease in patients with diabetic kidney disease

Introduction: Diabetic kidney disease is a serious complication of diabetes mellitus and one of the leading causes of end-stage renal disease. Guidelines strongly recommend the use of medications with proven efficacy in preventing and treating diabetic kidney disease. This study investigates the effects of treatment approaches such as renin-angiotensin system (RAS) blockers and sodium-glucose cotransporter-2 (SGLT2) inhibitors on disease progression in patients with type 2 diabetes mellitus and diabetic kidney disease. Objective: To evaluate the effects of RAS blockers and SGLT2 inhibitors on creatinine levels, glomerular filtration rate (GFR), and albuminuria, as well as secondary outcomes such as mortality, doubling of creatinine levels, need for supportive therapy, and A2 to A3 albuminuria progression in patients with diabetic kidney disease. Methods: This retrospective study included 200 patients followed at Akdeniz University Faculty of Medicine Hospital Nephrology Outpatient Clinic with a diagnosis of diabetic chronic kidney disease between January 1, 2018, and December 31, 2023. Patients were divided into three groups based on their treatment regimens: untreated, treated with RAS blockers only, and treated with a combination of RAS blockers and SGLT2 inhibitors. Demographic and clinical data such as age, sex, comorbidities (hypertension, cardiovascular diseases, hyperlipidemia, cerebrovascular diseases), and medications used were evaluated. Laboratory parameters including creatinine, GFR, urine albumin/creatinine and protein/creatinine ratios, fasting glucose, HbA1C, low-density lipoprotein (LDL), and uric acid levels were retrospectively analyzed. Reasons for discontinuation of RAS blockers were also recorded. Results: Significant differences were observed between treatment groups in terms of creatinine increase and moderate GFR decline. Patients treated with a combination of RAS blockers and SGLT2 inhibitors had higher GFR levels and lower creatinine levels compared to other groups. While no significant differences in albuminuria levels were found between groups, albuminuria was lower in the group using both RAS blockers and SGLT2 inhibitors. Mortality rates did not differ significantly among the groups. Regarding secondary outcomes, the need for supportive therapy was lowest in the combination therapy group, indicating a potential renal protective effect. However, no significant differences were observed in albuminuria progression between groups. Conclusion: The combination of RAS blockers and SGLT2 inhibitors is associated with higher GFR levels, lower creatinine levels, and reduced need for supportive therapy, highlighting the potential renal protective effects of SGLT2 inhibitors. Although no significant differences were found in albuminuria progression, the lower albuminuria levels observed in the combination therapy group are noteworthy. Larger studies are needed to confirm these findings and guide clinical practice. Keywords: Diabetes Mellitus, Chronic Kidney Disease, Glomerular Filtration Rate, Sodium-Glucose Cotransporter-2 Inhibitors, Proteinuria