Copeptin, a Surrogate Marker of Vasopressin, Is Associated with Disease Severity in Autosomal Dominant Polycystic Kidney Disease

Abstract

SummaryBackground 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 125 I-iothalamate and 131 I-hippuran, total renal volume by magnetic resonance imaging, and 24-hour urinary albumin excretion by nephelometry. ResultsIn these ADPKD patients, copeptin was associated with the various markers of disease severity in ADPKD (positively with total renal volume [R ϭ 0.47] and albuminuria [R ϭ 0.39] and negatively with GFR [R ϭ Ϫ0.58] and effective renal blood flow [R ϭ Ϫ0.52], all P Ͻ 0.001). These associations were independent of age, gender, and use of diuretics. Copeptin was furthermore associated with plasma osmolarity (P Ͻ 0.001) but not with 24-hour urinary volume, 24-hour urinary osmolarity or fractional urea excretion (P ϭ 0.7, 0.9, and 0.3, respectively). ConclusionsOn 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.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study

“…These data support earlier reports in ADPKD, 43 and the general population, although the significance levels were lower in our study. 49,50 This can be due to the higher number of patients in those studies, the fact that the PREVEND study used a cutoff of 10 mg/L albuminuria for inclusion, and the Malmo study analyzed ACR in spot urine instead of 24-hour urine collection.…”

“…This association has been observed in prospective studies involving patients with ADPKD as well as patients with a renal transplant and patients with diabetes. [43][44][45][46][47][48] Only two studies have used a populationbased sample to test the hypothesis that AVP might be involved in the development of albuminuria. In the Prevention of Renal and Vascular Endstage Disease (PREVEND) study, which includes 7593 nondiabetic participants with an urinary albumin concentration $10 mg/L, circulating copeptin was positively associated with albuminuria and negatively with renal function in a cross-sectional analysis.…”

“…51 Some studies have measured GFR using iothalamate, 99m Tc-DTPA, or inulin clearance. [43][44][45][46] Other studies estimated eGFR using the Modification of Diet in Renal Disease formula or cystatin C but not the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, which is known to be the most reliable formula. 47,[49][50][51] In our study, we observe an inverse linear association with copeptin levels even in participants with normal eGFR and confirm an almost 3 times increased odds of CKD in patients with higher copeptin levels.…”

Vasopressin, Copeptin, and Renal Concentrating Capacity in Patients with Autosomal Dominant Polycystic Kidney Disease without Renal Impairment

“…ddvap, desmopressin. study in 102 ADPKD patients, we found that copeptin levels were associated with various markers of disease severity, among which albuminuria, GFR, renal blood flow, and total renal volume (33). In a prospective study in 79 ADPKD patients, we subsequently showed that baseline copeptin levels were associated with faster kidney function decline when assessed as the change in either iothalamate clearance during short-term follow-up or eGFR during long-term follow-up (W.E.…”

Insights into autosomal dominant polycystic kidney disease by quantitative mass spectrometry-based proteomics

“…In ADPKD, several urinary (and plasma) markers have been recently reported, e.g., NGAL, CCL2 (MCP-1), CD14, AVP (copeptin) and HAVCR1 (KIM-1; Bolignano et al 2007;Kuehn et al 2007;Meijer et al 2010Meijer et al , 2011Zheng et al 2003). However, these markers have not made it into the clinic as yet and have also been reported to overlap with acute kidney injury patients and healthy controls thus raising concerns regarding their specificity (Kistler et al 2013).…”