Urine Concentrating Capacity, Vasopressin and Copeptin in ADPKD and IgA Nephropathy Patients with Renal Impairment.

Debbie Zittema,Niek F Casteleijn,Stephan J L Bakker,Carlo A J M Gaillard,Casper F M Franssen,Lianne S M Boesten,Ron T Gansevoort,A A Margreeth Duit

doi:10.1371/journal.pone.0169263

Debbie Zittema, Niek F Casteleijn + Show 6 more

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https://doi.org/10.1371/journal.pone.0169263

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Abstract

BackgroundAutosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. Increased circulating vasopressin (AVP) concentrations are supposed to play a role in the progression of ADPKD. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with consequently an enhanced AVP response to water deprivation with higher circulating AVP concentrations.Methods15 ADPKD (eGFR<60) patients and 15 age-, sex- and eGFR-matched controls with IgA nephropathy (IgAN), underwent a water deprivation test to determine maximal urine concentrating capacity. Plasma and urine osmolality, urine aquaporin-2 (AQP2) and plasma AVP and copeptin (a surrogate marker for AVP) were measured at baseline and after water deprivation (average 16 hours). In ADPKD patients, height adjusted total kidney volume (hTKV) was measured by MRI.ResultsMaximal achieved urine concentration was lower in ADPKD compared to IgAN controls (533±138 vs. 642±148 mOsm/kg, p = 0.046), with particularly a lower maximal achieved urine urea concentration (223±74 vs. 299±72 mmol/L, p = 0.008). After water deprivation, plasma osmolality was similar in both groups although change in plasma osmolality was more profound in ADPKD due to a lower baseline plasma osmolality in comparison to IgAN controls. Copeptin and AVP increased significantly in a similar way in both groups. AVP, copeptin and urine AQP2 were inversely associated with maximal urine concentrating in both groups.ConclusionsADPKD patients have a more severely impaired maximal urine concentrating capacity with a lower maximal achieved urine urea concentration in comparison to IgAN controls with similar endogenous copeptin and AVP responses.

Highlights

One of the first clinical features in autosomal dominant polycystic kidney disease (ADPKD) is an impaired urine concentrating capacity that occurs prior to kidney function decline [1,2,3]
Plasma osmolality was similar in both groups change in plasma osmolality was more profound in ADPKD due to a lower baseline plasma osmolality in comparison to IgA nephropathy (IgAN) controls
Baseline characteristics with respect to age, sex and estimated GFR (eGFR) were similar between ADPKD patients and the IgAN controls, indicating that matching was successful (Table 1)

Summary

Introduction

One of the first clinical features in autosomal dominant polycystic kidney disease (ADPKD) is an impaired urine concentrating capacity that occurs prior to kidney function decline [1,2,3]. We found that already in the early stages of disease there is an impaired maximal urine concentrating capacity, which is accompanied by increased plasma osmolality and vasopressin (AVP) levels during water deprivation, in comparison to healthy controls [4]. Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients have an impaired urine concentrating capacity. We hypothesized that ADPKD patients have a more severely impaired urine concentrating capacity in comparison to other patients with chronic kidney disease at a similar level of kidney function, with an enhanced AVP response to water deprivation with higher circulating AVP concentrations

Methods

Results

Conclusion