MO625: Effects of Dietary Sodium and Protein Intake on Early DIP of GFR Levels in Subjects with Type 2 Diabetes Treated with SGLT2 Inhibitors

Abstract

BACKGROUND AND AIMS SGLT2 inhibitors (SGLT2i) are able to decrease proteinuria and slow down eGFR decline in DKD patients. The effect is mainly obtained by increase of natriuresis and glucose-induced osmotic diuresis, resulting in a reduction in intraglomerular pressure. These hemodynamic changes are beneficial in long-term period, but up to 28% of patients treated with SGLT2i experience an acute, usually transient, eGFR reduction of more than 10% [1]. Moreover, in some case, the decrease of eGFR can be more pronounced and compromise the maintenance of therapy. High sodium and protein intake can lead to intraglomerular pressure increase and predispose to a deeper fall of eGFR. We aimed at investigating whether measured creatinine clearance (CrCl) is a more sensitive method to detect the initial dip of GFR in patients with T2D treated with SGLT2i, and if dietary sodium and protein intake can influence the extent of the early change in GFR. METHOD Subjects with type 2 diabetes (T2D) were consecutively recruited among those referring to the inpatients of combined Nephrology and Diabetology clinic in years 2020–2021. Those eligible for treatment with SGLT2i were asked to collect 24-h urinary samples for sodium and urea determination, to estimate sodium and protein intake, respectively, before and 1, 3 and 6 months after treatment initiation. RESULTS At baseline, 27 patients (M 23/F 4; age 69 ± 7 years; BMI 28.2 ± 3.6 kg/m2; HbA1c 56 ± 16 mmol/mol) had a CrCl of 83.23 ± 25.52 mL/min/1.73 m2 (eGFR 67.32 ± 16.07), which dropped by 19% at month 1 (eGFR by 6%, although not significantly) and then increased to comparable baseline values at month 6. Exploring the potential correlation between changes in renal function and salt intake, ΔCrCl and baseline urinary sodium were inversely related at month 1 (r = −0.61; P <0.01), at month 3 (r = −0.51; P = 0.01) and month 6 (r= −0,48; P < 0.05) (Fig. 1). Likewise, an inverse correlation between ΔCrCl and baseline urinary urea (Fig. 2) was demonstrated at month 1 and 3 (r = −0.46; P <0.05 for both), at month 6 a similar, not significant, trend was observed (r = −0.47; P = 0.054). Proteinuria showed a significant reduction from baseline (P < 0.05); no significant relationship between change in proteinuria and urinary sodium or urea was observed. CONCLUSION The present study suggests that a higher dietary sodium and protein intake may amplify the extent of early dip in glomerular filtration rate, detected with measured CrCl, in diabetic patients undergoing SGLT2i treatment. We believe that measured creatinine clearance is a very sensitive method to detect it. Further studies are needed to confirm the results of our pilot study.