Copeptin, a surrogate marker of vasopressin, is associated with disease severity in autosomal dominant polycystic kidney disease

Abstract

Background and objectives: Experimental studies suggest a detrimental role for vasopressin in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, it is unknown whether endogenous vasopressin concentration is associated with disease severity in patients with ADPKD.

Design, setting, participants, & measurements: Plasma copeptin concentration (a marker of endogenous vasopressin levels) was measured in 102 ADPKD patients (diagnosis based on Ravine criteria) by an immunoassay. Plasma and urinary osmolarity were also measured. To assess disease severity, GFR and effective renal blood flow were measured by continuous infusion of 125I-iothalamate and 131I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry.

Results: In these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R=0.47] and albuminuria [R=0.39] and negatively with GFR [R=-0.58] and effective renal blood flow [R=-0.52], all P<0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P<0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P=0.7, 0.9, and 0.3, respectively).

Conclusions: On cross-sectional analysis, copeptin is associated with disease severity in ADPKD patients, supporting the results of experimental studies that suggest that vasopressin antagonists have a renoprotective effect in ADPKD and offering a good prospect for clinical studies with these agents.

Figure 1.

Association between plasma osmolarity and copeptin (overall R = 0.53, P < 0.001; males ▴ and —, R = 0.40, P = 0.003; and females ○ and – –, R = 0.46, P = 0.002).

Figure 2.

VP in association with markers of disease severity in ADPKD (males ▴ and —; females ○ and – –). On the left, associations between copeptin and TRV (upper left; overall: R = 0.47, P < 0.001; males: R = 0.37, P = 0.006; females: R = 0.37, P = 0.01) and 24-hour UAE (lower left; overall: R = 0.39, P < 0.001; males: R = 0.30, P = 0.03; females: R = 0.29, P = 0.07). On the right, associations between log copeptin and ERBF (upper right; overall R = −0.52, P < 0.001; males: R = −0.57, P < 0.001; females: R = −0.61, P < 0.001) and GFR (lower right; overall R = −0.58, P < 0.001, males: R = −0.58, P < 0.001; females: R = −0.61, P < 0.001).