Kidney function and plasma copeptin levels in healthy kidney donors and autosomal dominant polycystic kidney disease patients

Abstract

Background and objectives: Plasma copeptin, a marker of arginine vasopressin, is elevated in patients with autosomal dominant polycystic kidney disease and predicts disease progression. It is unknown whether elevated copeptin levels result from decreased kidney clearance or as compensation for impaired concentrating capacity. Data from patients with autosomal dominant polycystic kidney disease and healthy kidney donors before and after donation were used, because after donation, overall GFR decreases with a functionally normal kidney.

Design, setting, participants, & measurements: Data were obtained between October of 2008 and January of 2012 from healthy kidney donors who visited the institution for routine measurements predonation and postdonation and patients with autosomal dominant polycystic kidney disease who visited the institution for kidney function measurement. Plasma copeptin levels were measured using a sandwich immunoassay, GFR was measured as (125)I-iothalamate clearance, and urine concentrating capacity was measured as urine-to-plasma ratio of urea. In patients with autosomal dominant polycystic kidney disease, total kidney volume was measured with magnetic resonance imaging.

Results: Patients with autosomal dominant polycystic kidney disease (n=122, age=40 years, men=56%) had significantly higher copeptin levels (median=6.8 pmol/L; interquartile range=3.4-15.7 pmol/L) compared with donors (n=134, age=52 years, men=49%) both predonation and postdonation (median=3.8 pmol/L; interquartile range=2.8-6.3 pmol/L; P<0.001; median=4.4 pmol/L; interquartile range=3.6-6.1 pmol/L; P<0.001). In donors, copeptin levels did not change after donation, despite a significant fall in GFR (from 105 ± 17 to 66 ± 10; P<0.001). Copeptin and GFR were significantly associated in patients with autosomal dominant polycystic kidney disease (β=-0.45, P<0.001) but not in donors. In patients with autosomal dominant polycystic kidney disease, GFR and total kidney volume were both associated significantly with urine-to-plasma ratio of urea (β=0.84, P<0.001; β=-0.51, P<0.001, respectively).

Conclusions: On the basis of the finding in donors that kidney clearance is not a main determinant of plasma copeptin levels, it was hypothesized that, in patients with autosomal dominant polycystic kidney disease, kidney damage and associated impaired urine concentration capacity determine copeptin levels.

Keywords: ADPKD; cystic kidney; urea; vasopressin.

Figure 1.

No association between plasma copeptin and GFR in donors whereas patients show a significant inverse association (β=−0.45, P<0.001).

Figure 2.

No significant association between change in GFR and change in copeptin in donors comparing predonation with postdonation values (β=-0.02, p=0.84).

Figure 3.

Significant inverse association between U/P urea and copeptin in patients with ADPKD (β=−0.32, P<0.001) whereas donors show a significant positive association predonation and postdonation (β=0.19, P=0.03; β=0.39, P<0.001). Because the units of the numerator and the denominator are similar in the U/P urea, this ratio has no unit by itself.

Figure 4.

Significant positive associations between GFR and U/P urea in patients with ADPKD and donors and significant positive associations between total kidney volume, U/P urea and plasma osmolality in patients with ADPKD. Significant positive associations between GFR and U/P urea in patients with ADPKD (β=0.84, P<0.001) and donors predonation and postdonation (β=0.32, P<0.001; β=0.27, P=0.02). Also shown is the association between total kidney volume and U/P urea and total kidney volume and plasma osmolality in patients with ADPKD (β=−0.51, P<0.001; β=0.44, P<0.001).