In patients with long-standing type 1 diabetes, higher copeptin levels were associated with higher intrarenal renin-angiotensin activity and progression of diabetic kidney disease.81 In fact a provocative study showed that in diabetic patients with severe fluid retention despite treatment with loop diuretics, the addition of a V2R antagonist (tolvaptan) resulted in significant diuresis and improved decongestion.82 This supports the notion that vasopressin plays a key role in volume retention associated with diabetic nephropathy. Here, REN is linked to diabetic kidney disease.