Relationship of copeptin, a surrogate marker for arginine vasopressin, with change in total kidney volume and GFR decline in autosomal dominant polycystic kidney disease: results from the CRISP cohort

Abstract

Background: Experimental studies indicate that arginine vasopressin (AVP) may have deleterious effects in the pathogenesis of autosomal dominant polycystic kidney disease (ADPKD). However, the significance of AVP in human ADPKD is unclear.

Study design: 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 patients with ADPKD with creatinine clearance >70 mL/min.

Predictor: Plasma copeptin concentration, a surrogate marker for AVP.

Outcomes: Change in measured glomerular filtration rate (mGFR, assessed by iothalamate clearance) and total kidney volume (measured by magnetic resonance imaging).

Measurements: Baseline copeptin level, plasma and urinary osmolality, and measurements of total kidney volume and mGFR during follow-up.

Results: In these patients (median age, 34 [IQR, 25-40] years; 38% men; median mGFR, 94 [IQR, 79-145] mL/min/1.73 m(2); median total kidney volume, 859 [IQR, 577-1,299] 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 associated significantly with change in total kidney volume during follow-up (P < 0.001). This association remained significant after adjusting for sex, age, cardiovascular risk factors, and diuretic use (P = 0.03). Copeptin level was associated borderline significantly with change in mGFR after adjusting for these variables (P = 0.09).

Limitations: No standardization of hydration status at time of copeptin measurement.

Conclusions: These data show that in ADPKD, copeptin level, as a marker for AVP, is not correlated with plasma osmolality. Most importantly, high copeptin levels are associated independently with disease progression in early ADPKD. This is in line with experimental studies that indicate a disease-promoting role for AVP.

Figure 1

Mean measured glomerular filtration rate (GFR) at all time points in the three gender stratified strata of copeptin (panel A) and mean percentage change in measured GFR from baseline (panel B). Numbers of patients per time point: baseline, n=222; after 1 yea, n=213; after 2 years, n=208; after 3 years, n=211; after 6 years, n=188; after 8 years, n= 163.Error bars represent 95% confidence interval.

Figure 2

Mean total kidney volume (TKV) at all time points in the three gender stratified strata of copeptin (panel A) and mean percentage change in TKV from baseline (panel B). Numbers of patients per time point: baseline, n=225; after 1 year, n=216; after 2 years, n=204; after 3 years, n=214; after 6 years, n=181; after 8 years, n=152. Error bars represent 95% confidence interval.