Experimental studies indicate that arginine vasopressin (AVP) may have deleterious effects in the pathogenesis of ADPKD. The significance of AVP in human ADPKD, however, is yet unclear.
Longitudinal, observational study with 8.5 (IQR, 7.7-9.0) years follow-up (CRISP; Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease).
Setting & Participants
241 ADPKD patients with creatinine clearance >70 mL/min.
Plasma copeptin concentration, a surrogate marker for vasopressin.
Change in measured glomerular filtration rate (mGFR, assessed by iothalamate clearance), and total kidney volume (TKV, measured by MRI).
Baseline copeptin, plasma and urinary osmolality, and measurements of TKV and mGFR during follow-up.
In these patients (median age, 34; [IQR, 25-40] years; 38% male; median mGFR, 94 [IQR, 79-145] mL/min/1.73 m2; median total kidney volume, 859 [IQR, 577-1299] mL) median copeptin level was 2.9 (IQR, 1.8-5.1) pmol/L. Copeptin was not associated with plasma osmolality (p=0.3), the physiologic stimulus for AVP release, but was significantly associated with change in TKV during follow-up (p<0.001). This association remained significant after adjusting for gender, age, cardiovascular risk factors and diuretic use (p=0.03). Copeptin level was borderline significantly associated with change in mGFR after adjusting for these variables (p=0.09).
No standardization of hydration status at time of copeptin measurement.
These data show that in ADPKD copeptin levels, as a marker for AVP, are not correlated with plasma osmolality. Most importantly, high copeptin levels are independently associated with disease progression in early ADPKD. This is in line with experimental studies that indicate a disease-promoting role for AVP.