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

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 ≤60 mL/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) was 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-h 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