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Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus

Cherney, David Z.I ; Perkins, Bruce A ; Soleymanlou, Nima ; Maione, Maria ; Lai, Vesta ; Lee, Alana ; Fagan, Nora M ; Woerle, Hans J ; Johansen, Odd Erik ; Broedl, Uli C ; von Eynatten, Maximilian

Circulation (New York, N.Y.), 2014-02, Vol.129 (5), p.587-597 [Periódico revisado por pares]

Hagerstown, MD: by the American College of Cardiology Foundation and the American Heart Association, Inc

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Título:
Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus
Autor: Cherney, David Z.I ; Perkins, Bruce A ; Soleymanlou, Nima ; Maione, Maria ; Lai, Vesta ; Lee, Alana ; Fagan, Nora M ; Woerle, Hans J ; Johansen, Odd Erik ; Broedl, Uli C ; von Eynatten, Maximilian
Assuntos: Adult ; Associated diseases and complications ; Benzhydryl Compounds - pharmacology ; Benzhydryl Compounds - therapeutic use ; Biological and medical sciences ; Blood and lymphatic vessels ; Cardiology. Vascular system ; Diabetes Mellitus, Type 1 - blood ; Diabetes Mellitus, Type 1 - drug therapy ; Diabetes Mellitus, Type 1 - physiopathology ; Diabetes. Impaired glucose tolerance ; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Glomerular Filtration Rate - drug effects ; Glomerular Filtration Rate - physiology ; Glucose Clamp Technique - methods ; Glucosides - pharmacology ; Glucosides - therapeutic use ; Hemodynamics - drug effects ; Hemodynamics - physiology ; Humans ; Kidney - drug effects ; Kidney - physiology ; Kidneys ; Male ; Medical sciences ; Nephrology. Urinary tract diseases ; Sodium-Glucose Transporter 2 - antagonists & inhibitors ; Sodium-Glucose Transporter 2 - physiology ; Treatment Outcome ; Urinary system involvement in other diseases. Miscellaneous ; Young Adult
É parte de: Circulation (New York, N.Y.), 2014-02, Vol.129 (5), p.587-597
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SourceType-Scholarly Journals-1
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Descrição: 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, n=27) or normal GFR (T1D-N, GFR 90–134 mL/min/1.73m, 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 with empagliflozin in T1D-H, (GFR 172±23–139±25 mL/min/1.73 m, 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—URLhttp://www.clinicaltrials.gov. Unique identifierNCT01392560.
Editor: Hagerstown, MD: by the American College of Cardiology Foundation and the American Heart Association, Inc
Idioma: Inglês

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Renal Hemodynamic Effect of Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 1 Diabetes Mellitus

Cherney, David Z.I ; Perkins, Bruce A ; Soleymanlou, Nima ; Maione, Maria ; Lai, Vesta ; Lee, Alana ; Fagan, Nora M ; Woerle, Hans J ; Johansen, Odd Erik ; Broedl, Uli C ; von Eynatten, Maximilian

Hagerstown, MD: by the American College of Cardiology Foundation and the American Heart Association, Inc

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