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Renal HemodynamicEffect ofSodium-GlucoseCotransporter 2Inhibition inPatients With Type 1Diabetes Mellitus David Z.I. CherneyBruce A. PerkinsNima Soleymanlou2013 год

Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus
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Аннотация: Background— The primary objective of this mechanistic open-label, stratified clinical trial was to determine the effect of 8 weeks’ sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D). Methods and Results— Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m 2 , n=27) or normal GFR (T1D-N, GFR 90–134 mL/min/1.73m 2 , n=13) at baseline. Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic (4–6 mmol/L) and hyperglycemic (9–11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by −33 mL/min/1.73m 2 with empagliflozin in T1D-H, (GFR 172±23–139±25 mL/min/1.73 m 2 , P <0.01). This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P <0.01). Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal function parameters, and plasma NO were not altered by empagliflozin. Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower insulin doses in each group ( P ≤0.04). Conclusions— In conclusion, short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D, likely by affecting tubular-glomerular feedback mechanisms. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01392560.
Год издания: 2013
Авторы: David Z.I. Cherney, Bruce A. Perkins, Nima Soleymanlou, M Maione, Vesta Lai, Alana Lee, Nora Fagan, Hans J. Woerle, Odd Erik Johansen, Uli C. Broedl, Maximilian von Eynatten
Издательство: Lippincott Williams & Wilkins
Источник: Circulation
Ключевые слова: Diabetes Treatment and Management, Chronic Kidney Disease and Diabetes, Diabetes Management and Research
Другие ссылки: Circulation (PDF)
Circulation (HTML)
PubMed (HTML)