Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33)

Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort. Samples from 1,328 patients were available; 349 were analysed separately because they used renin-angiotensin-aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58-75], ACR 1.8 mg/mmol [0.9-5.7], eGFR 67 +/- 14 ml min(-1) 1.73 m(-2)) baseline copeptin (5.3 pmol/l [3.2-9.5]) was significantly associated with log (e) [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] beta 0.13, p < 0.001, std beta -0.20, p < 0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1-9.6]). Baseline copeptin was associated with increase in ACR (std beta 0.09, p = 0.02), but lost significance after adjustment (std beta 0.07, p = 0.08). Copeptin was associated with a decrease in eGFR after adjustment (std beta -0.09, p = 0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA(1c)). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR. In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.