Vasopressin associated with renal vascular resistance in adults with longstanding type 1 diabetes with and without diabetic kidney disease.

ABSTRACT Objective Arginine vasopressin (AVP) and its surrogate, copeptin, have been implicated in diabetic kidney disease (DKD) pathogenesis, which develops in a subset of people with longstanding type 1 diabetes, but not in others (DKD Resistors). We hypothesized that patients with DKD would exhibit higher copeptin concentrations vs. DKD Resistors. Methods Participants with type 1 diabetes (n=62, duration ≥50 years) were stratified into 42 DKD Resistors and 20 with DKD (eGFR ≤60mL/min/1.73m2 or ≥30 mg/day urine albumin), and age/sex-matched controls (HC, n=74) were included. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were calculated by inulin and p-aminohippurate clearance before and after angiotensin II (ang II) infusion. Renal vascular resistance (RVR) were calculated as mean arterial pressure / renal blood flow. Plasma copeptin, renin, aldosterone, neutrophil gelatinase-associated lipocalin (NGAL), and urea concentrations were measured, along with 24-hour urine volume. Results DKD resistors had lower copeptin (95% CI: 4.0 [3.4-4.8] pmol/l) compared to DKD (5.8 [4.5-7.6] pmol/l, p=0.02) and HC (4.8 [4.1-5.5] pmol/l, p=0.01) adjusting for age, sex and HbA1c. In type 1 diabetes, higher copeptin correlated with lower GFR (r: -0.32, p=0.01) and higher renin concentration (r: 0.40, p=0.002) after multivariable adjustments. These relationships were not evident in HC. Copeptin inversely associated with RVR change following exogenous ang II only in participants with type 1 diabetes (β±SE: -6.9±3.4, p=0.04). Conclusions In longstanding type 1 diabetes, copeptin was associated with intrarenal renin–angiotensin–aldosterone system (RAAS) activation and renal hemodynamic function, suggesting interplay between AVP and RAAS in DKD pathogenesis.