Decreased expression of AQP2 and AQP4 water channels and Na,K-ATPase in kidney collecting duct in AQP3 null mice

BACKGROUND INFORMATION: Phenotype analysis has demonstrated that AQP3 (aquaporin 3) null mice are polyuric and manifest a urinary concentration defect. In the present study, we report that deletion of AQP3 is also associated with an increased urinary sodium excretion. To investigate further the mechanism of the decreased urinary concentration and significant natriuresis, we examined the segmental and subcellular localization of collecting duct AQPs [AQP2, p-AQP2 (phosphorylated AQP2), AQP3 and AQP4], ENaC (epithelial sodium channel) subunits and Na,K-ATPase by immunoperoxidase and immunofluorescence microscopy in AQP3 null (-/-), heterozygous (+/-) mice, wild-type and unrelated strain of normal mice. RESULTS: The present study confirms that AQP3 null mice exhibit severe polyuria and polydipsia and demonstrated that they exhibit increased urinary sodium excretion. In AQP3 null mice, there is a marked down-regulation of AQP2 and p-AQP2 both in CNT (connecting tubule) and CCD (cortical collecting duct). Moreover, AQP4 is virtually absent from CNT and CCD in AQP3 null mice. Basolateral AQP2 was virtually absent from AQP3 null mice and normal mice in contrast with rat. Thus the above results demonstrate that no basolateral AQPs are expressed in CNT and CCD of AQP3 null mice. However, in the medullary-collecting ducts, there is no difference in the expression levels and subcellular localization of AQP2, p-AQP2 and AQP4 between AQP3 +/- and AQP3 null mice. Moreover, a striking decrease in the immunolabelling of the alpha1 subunit of Na,K-ATPase was observed in CCD in AQP3 null mice, whereas a medullary-collecting duct exhibited normal labelling. Immunolabelling of all the ENaC subunits in the collecting duct was comparable between the two groups. CONCLUSIONS: The results improve the possibility that the severe urinary concentrating defect in AQP3 null mice may in part be caused by the decreased expression of AQP2, p-AQP2 and AQP4 in CNT and CCD, whereas the increased urinary sodium excretion may in part be accounted for by Na,K-ATPase in CCD in AQP3 null mice.     

Postoperative Copeptin as a Biomarker for Development of Diabetes Insipidus Following Hypothalamic-Pituitary Surgery

ObjectiveCopeptin is a surrogate marker of arginine vasopressin release with better stability and simplicity of measurement. Postoperative copeptin levels may guide clinicians in stratifying patients who need close monitoring of fluid balance. The objective is to determine whether copeptin is a predictive marker of postoperative diabetes insipidus (DI).MethodsThis is a prospective diagnostic study. Patients who underwent neurosurgical intervention of the sellar-suprasellar regions were recruited. Serum copeptin levels were measured before and after surgery, within 24 hours. Logistic regression analysis and diagnostic performance measures were calculated to determine the relationship between postoperative copeptin levels and DI.ResultsOf 82 patients, 26 (31.7%) developed postoperative DI, with 7 patients (8.5%) having permanent DI. The samples for copeptin measurement were taken at 13 ± 2.1 hours postoperatively. From the receiver operating characteristic analysis, low postoperative copeptin levels (<2.5 pmol/L) demonstrated an acceptable ability to predict DI (area under the curve, 0.72; 95% CI, 0.60-0.84). Discriminative power was stronger in the permanent DI group (area under the curve, 0.82; 95% CI, 0.64-1.00). Postoperative copeptin levels <2.5 pmol/L were associated with DI (specificity > 91%). However, postoperative copeptin levels >20 pmol/L were rarely associated with DI, with a negative predictive value of 100%.ConclusionsIn patients undergoing sellar-suprasellar interventions, low postoperative copeptin levels within the first postoperative day predict postoperative DI, whereas high levels exclude it. Copeptin measurement should be applied in the clinical practice of postoperative care in patients following hypothalamic-pituitary surgery. This study may expand the potential use of copeptin, including in the Asian population.