pituitrin and Glomerulonephritis--IGA

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.. 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.. 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.. 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.

Topics: Adolescent; Adult; Aged; Aquaporin 2; Female; Glomerulonephritis, IGA; Glycopeptides; Humans; Kidney Concentrating Ability; Magnetic Resonance Imaging; Male; Middle Aged; Polycystic Kidney, Autosomal Dominant; Vasopressins

Patients with autosomal dominant polycystic kidney disease (ADPKD) are treated with a vasopressin V2 receptor antagonist (V2RA) to slow disease progression. This drug increases vasopressin considerably in these patients with already elevated baseline levels. Vasopressin is known to stimulate the hypothalamic-pituitary-adrenal (HPA) axis through V1 and V3 receptor activation. It is unknown whether this increase in vasopressin during V2RA treatment affects glucocorticoid production.. Twenty-seven ADPKD patients were studied on and off treatment with a V2RA and compared to age- and sex-matched healthy controls and IgA nephropathy patients, the latter also matched for kidney function. Vasopressin was measured by its surrogate copeptin. Twenty-four-hour urinary excretions of cortisol, cortisone, tetrahydrocortisone, tetrahydrocortisol, allotetrahydrocortisol, and the total glucocorticoid pool were measured.. At baseline, ADPKD patients demonstrated a higher copeptin concentration in comparison with healthy controls, while urinary excretion of cortisol and cortisone was lower (medians of 0.23 vs. 0.34 μmol/24 h, p = 0.007, and 0.29 vs. 0.53 μmol/24 h, p < 0.001, respectively). There were no differences in cortisol and cortisone excretion compared to IgA nephropathy patients. Cortisol, cortisone, and total glucocorticoid excretions correlated with kidney function (R = 0.37, 0.58, and 0.19, respectively; all p < 0.05). Despite that V2RA treatment resulted in a 3-fold increase in copeptin, only cortisone excretion increased (median of 0.44 vs. baseline 0.29 μmol/24 h, p < 0.001), whereas no changes in cortisol or total glucocorticoid excretion were observed.. Increased concentration of vasopressin in ADPKD patients at baseline and during V2RA treatment does not result in activation of the HPA axis. The impaired glucocorticoid production in these patients is related to their degree of kidney function impairment.

Topics: Adult; Aged; Antidiuretic Hormone Receptor Antagonists; Case-Control Studies; Cortisone; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Glycopeptides; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal System; Polycystic Kidney, Autosomal Dominant; Receptors, Vasopressin; Renal Elimination; Severity of Illness Index; Vasopressins

Topics: Animals; Blood Pressure; Disease Progression; Diuresis; Endothelins; Female; Glomerulonephritis, IGA; Humans; Kidney Failure, Chronic; Kidney Tubules; Male; Nitric Oxide; Oxidative Stress; Polycystic Kidney, Autosomal Dominant; Retrospective Studies; Risk Factors; Sex Factors; Smoking; Vasopressins