Elevated Serum Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Intrarenal Hemodynamic Dysfunction in Type 1 Diabetes (T1D)

Abstract

Little is known about how tubular injury relates to intrarenal hemodynamic dysfunction in T1D. We sought to define the relationships between serum NGAL, a marker of tubular injury, and intrarenal hemodynamic function (glomerular filtration rate [GFR], effective renal plasma flow [ERPF], renal vascular resistance [RVR]) in T1D adults. The cohort consisted of patients with longstanding T1D (≥50 years duration); 44 Diabetic Nephropathy (DN) Resistors (eGFR >60mL/min/1.73m2 and <30mg/day urine albumin excretion) and 22 with DN. GFRINULIN and ERPFPAH were measured, and afferent arteriolar resistance (RA), efferent arteriolar resistance (RE), and RVR were derived from Gomez equations. Serum NGAL was measured using immunoassay kits from MSD. Serum NGAL was higher in DN vs. DN Resistors (median, IQR: 224[136, 355] vs. 138[106, 191]ng/ml, p=.001). Serum NGAL inversely correlated with GFR (r:-0.33, p=.006), ERPF (r:-0.34, p=.006) and positively with RA (r:0.26, p=.03) and RVR (r:0.31, p=.01). Subjects in the highest NGAL tertile had lower GFR and ERPF, and greater RAand RVR vs. those in the lowest tertile (Figure). Differences remained significant after adjusting for age, sex, HbA1c, SBP and LDL. DN Resistors had significantly lower serum NGAL vs. those with DN. Elevated NGAL is related to intrarenal hemodynamic dysfunction and afferent vasoconstriction in longstanding T1D. Disclosure P. Bjornstad: Consultant; Self; Boehringer Ingelheim GmbH. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation. J.A. Lovshin: Other Relationship; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Research Support; Self; Sanofi, Merck Sharp & Dohme Corp.. Other Relationship; Self; Novo Nordisk Inc.. S.K. Singh: None. L. Lovblom: None. J.M. Tse: None. A. Orszag: None. Y. Lytvyn: None. M.H. Brent: Research Support; Self; Novartis Canada. Advisory Panel; Self; Novartis Canada. Research Support; Self; Bayer Canada. Advisory Panel; Self; Bayer Canada, Allergan Canada. Research Support; Self; Roche Canada. N. Paul: None. A. Weisman: None. H.A. Keenan: Research Support; Self; Sanofi. Employee; Self; Sanofi Genzyme. L. Cham: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc. D. Cherney: Consultant; Self; AbbVie Inc.. Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company. Consultant; Self; Sanofi. Other Relationship; Self; Merck & Co., Inc.. Consultant; Self; Mitsubishi Tanabe Pharma Corporation. Other Relationship; Self; Janssen Pharmaceuticals, Inc..