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

BACKGROUND: Autosomal 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. METHODS: 15 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. RESULTS: Maximal 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. CONCLUSIONS: ADPKD 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

Characteristics of the overall population, and of ADPKD and IgA Nephropathy patients separately.

<p>Characteristics of the overall population, and of ADPKD and IgA Nephropathy patients separately.</p

Associations of copeptin and vasopressin concentration with plasma osmolality and urine osmolality in ADPKD patients (solid line) and IgA Nephropathy patients (IgAN, dashed line) at maximal urine concentration.

<p>Associations of copeptin and vasopressin concentration with plasma osmolality and urine osmolality in ADPKD patients (solid line) and IgA Nephropathy patients (IgAN, dashed line) at maximal urine concentration.</p

Univariate linear regression associations of the urine AQP2 to creatinine ratio with plasma copeptin or AVP (both log transformed) at maximal urine concentration and multivariable linear regression analyses testing the effect of having ADPKD on these associations.

<p>Univariate linear regression associations of the urine AQP2 to creatinine ratio with plasma copeptin or AVP (both log transformed) at maximal urine concentration and multivariable linear regression analyses testing the effect of having ADPKD on these associations.</p

Associations of plasma copeptin concentration with urine albumin to creatinine ratio in ADPKD (solid line) and IgA Nephropathy (IgAN, dashed line) patients at maximal urine concentration.

<p>Associations of plasma copeptin concentration with urine albumin to creatinine ratio in ADPKD (solid line) and IgA Nephropathy (IgAN, dashed line) patients at maximal urine concentration.</p

Measurements in plasma at baseline (5 p.m.) and at maximal urine concentration during a standard prolonged water deprivation test.

<p>Measurements in plasma at baseline (5 p.m.) and at maximal urine concentration during a standard prolonged water deprivation test.</p

Associations of maximal urine osmolality with baseline urine-to-plasma (U/P) urea ratio in ADPKD patients (solid line) and IgA Nephropathy patients (IgAN, dashed line).

<p>Associations of maximal urine osmolality with baseline urine-to-plasma (U/P) urea ratio in ADPKD patients (solid line) and IgA Nephropathy patients (IgAN, dashed line).</p

Univariate linear regression associations of plasma copeptin and AVP (log transformed) with plasma osmolality and multivariable linear regression analyses testing the effect of having ADPKD on the associations at baseline and at maximal urine concentration.

<p>Univariate linear regression associations of plasma copeptin and AVP (log transformed) with plasma osmolality and multivariable linear regression analyses testing the effect of having ADPKD on the associations at baseline and at maximal urine concentration.</p