Updates and Perspectives on Aquaporin-2 and Water Balance Disorders.

Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules.

Asymptomatic sinusitis as an origin of infection-related glomerulonephritis manifesting steroid-resistant nephrotic syndrome: A case report.

Rationale: Infection is a major trigger or pathogenic origin in a substantial proportion of glomerulonephritis (GN) patients, typically manifesting infection-related GN (IRGN). Various microorganisms, infection sites, and clinical and histopathological features are involved in IRGN. Once an infectious origin is identified and successfully eradicated, nephrotic syndrome or kidney dysfunction is spontaneously resolved.

Phosphorylation profile of human AQP2 in urinary exosomes by LC-MS/MS phosphoproteomic analysis.

Background: Aquaporin-2 (AQP2) is a key water channel protein which determines the water permeability of the collecting duct. Multiple phosphorylation sites are present at the C-terminal of AQP2 including S256 (serine at 256 residue), S261, S264 and S/T269, which are regulated by vasopressin (VP) to modulate AQP2 trafficking. As the dynamics of these phosphorylations have been studied mostly in rodents, little is known about the phosphorylation of human AQP2 which has unique T269 in the place of S269 of rodent AQP2.

Prognosis of chronic kidney disease with normal-range proteinuria: The CKD-ROUTE study.

Background: Although lower estimated glomerular filtration rate (eGFR) and higher proteinuria are high risks for mortality and kidney outcomes, the prognosis of chronic kidney disease (CKD) in patients with normal-range proteinuria remains unclear.

Methods: In this prospective cohort study, 1138 newly visiting stage G2-G5 CKD patients were stratified into normal-range and abnormal-range proteinuria groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of dialysis), cardiovascular events, and all-cause death.

The use of vitamin D analogs is independently associated with the favorable renal prognosis in chronic kidney disease stages 4-5: the CKD-ROUTE study.

Background: Vitamin D analogs have generally been recommended for treatment of mineral bone disease in chronic kidney disease (CKD). However, the association between this treatment and CKD progression has not yet been established.

Methods: We designed a post hoc propensity score-matched cohort analysis derived from 3-year follow-up data of a prospective cohort.

Association of serum chloride level with mortality and cardiovascular events in chronic kidney disease: the CKD-ROUTE study.

Background: Electrolyte abnormalities, particularly dysnatremia, are independent predictors of adverse outcome in individuals with and without renal failure. However, the association of serum chloride level (Cl) with mortality or risk of cardiovascular (CV) events in chronic kidney disease (CKD) remains unclear.

Methods: This prospective cohort study included 923 pre-dialysis CKD G2-G5 patients among the participants of the CKD Research of Outcomes in Treatment and Epidemiology (CKD-ROUTE) study, who newly visited 16 nephrology centers.

Combination of low body mass index and serum albumin level is associated with chronic kidney disease progression: the chronic kidney disease-research of outcomes in treatment and epidemiology (CKD-ROUTE) study.

Background: The relationship between protein-energy wasting and chronic kidney disease (CKD) progression is unknown. In the present prospective cohort study, we evaluated the hypothesis that a combination of low body mass index (BMI) and serum albumin level is associated with rapid CKD progression.

Methods: The study cohort comprised 728 predialysis Japanese patients with CKD (stages 2-5) enrolled from 2010 to 2011.

Anaemia management and mortality risk in newly visiting patients with chronic kidney disease in Japan: The CKD-ROUTE study.

Aim: To investigate the association between iron deficiency anaemia and mortality risk and assess the changes in anaemia and iron status after primary management by a nephrologist.

Methods: In this prospective cohort study, we stratified 951 non-dialysis chronic kidney disease (CKD) G2-G5 patients newly visiting 16 nephrology centres into four groups according to the presence of anaemia with or without iron deficiency. All-cause mortality, cardiovascular (CV)-related mortality, and a change in anaemia and iron status after specialized primary care were the endpoints evaluated.

Dynamic regulation and dysregulation of the water channel aquaporin-2: a common cause of and promising therapeutic target for water balance disorders.

The human body is two-thirds water. The ability of ensuring the proper amount of water inside the body is essential for the survival of mammals. The key event for maintenance of body water balance is water reabsorption in the kidney collecting ducts, which is regulated by aquaporin-2 (AQP2).

Baseline characteristics and prevalence of cardiovascular disease in newly visiting or referred chronic kidney disease patients to nephrology centers in Japan: a prospective cohort study.

Background: About 39,000 patients were newly prescribed renal replacement therapy in Japan in 2011, resulting in a total of more than 300,000 patients being treated with dialysis. This high prevalence of treated end stage kidney disease (ESKD) patients is an emergent problem that requires immediate attention. We launched a prospective cohort study to evaluate population specific characteristics of the progression of chronic kidney disease (CKD).

Actin directly interacts with different membrane channel proteins and influences channel activities: AQP2 as a model.

The interplay between actin and 10 membrane channel proteins that have been shown to directly bind to actin are reviewed. The 10 membrane channel proteins covered in this review are aquaporin 2 (AQP2), cystic fibrosis transmembrane conductance regulator (CFTR), ClC2, short form of ClC3 (sClC3), chloride intracellular channel 1 (CLIC1), chloride intracellular channel 5 (CLIC5), epithelial sodium channel (ENaC), large-conductance calcium-activated potassium channel (Maxi-K), transient receptor potential vanilloid 4 (TRPV4), and voltage-dependent anion channel (VDAC), with particular attention to AQP2. In regard to AQP2, most reciprocal interactions between actin and AQP2 occur during intracellular trafficking, which are largely mediated through indirect binding.

Claudin-4 deficiency results in urothelial hyperplasia and lethal hydronephrosis.

Claudin (Cld)-4 is one of the dominant Clds expressed in the kidney and urinary tract, including selective segments of renal nephrons and the entire urothelium from the pelvis to the bladder. We generated Cldn4(-/-) mice and found that these mice had increased mortality due to hydronephrosis of relatively late onset. While the renal nephrons of Cldn4(-/-) mice showed a concomitant diminution of Cld8 expression at tight junction (TJ), accumulation of Cld3 at TJ was markedly enhanced in compensation and the overall TJ structure was unaffected.

Type II diabetes mellitus is a risk factor for heart failure in pre-dialysis patients.

Chronic kidney disease (CKD) increases the risk of developing cardiovascular diseases such as heart failure (HF) and ischemic heart disease (IHD). The characteristics of patients with CKD complicated with HF at the time of starting hemodialysis have not yet been evaluated. We enrolled 347 patients in this study and compared gender, age, body mass index, laboratory data, causative disease, complications, and echocardiographic findings between groups with (n = 105) and without (n = 242) HF.

Splenic artery ligation: A protection against hepatic ischemia/reperfusion injury in partially hepatectomized rats.

Aim:   In liver resection, the temporary occlusion of the hepatoduodenal ligament (Pringle maneuver) is often used. However, the maneuver causes ischemia/reperfusion (I/R) injury in the remnant liver. Heme oxygenase (HO)-1 has a cytoprotective role against this injury.

Severe hyperparathyroidism in a pre-dialysis chronic kidney disease patient treated with a very low protein diet.

The present report describes a case of a 64-year-old pre-dialysis woman with chronic kidney disease (CKD) stage 5, who developed severe hyperparathyroidism. This patient had been on a very low protein diet (VLPD) to delay the progression of CKD and the need for renal replacement therapy (RRT). Her serum calcium levels were high-normal to slightly high during this time.

Phosphorylation of aquaporin-2 regulates its water permeability.

Vasopressin-regulated water reabsorption through the water channel aquaporin-2 (AQP2) in renal collecting ducts maintains body water homeostasis. Vasopressin activates PKA, which phosphorylates AQP2, and this phosphorylation event is required to increase the water permeability and water reabsorption of the collecting duct cells. It has been established that the phosphorylation of AQP2 induces its apical membrane insertion, rendering the cell water-permeable.

Calcium-alkali syndrome-like symptoms manifested by daily alphacalcidol and thiazide.

A 73-year-old man was admitted with complaints of a 2-month history of generalized weakness and numbness. Laboratory examination revealed hypercalcemia, metabolic alkalosis, and kidney injury, similar to the traditional milk-alkali syndrome. The clinical history and the response to therapy indicated that alphacalcidol and thiazide taken daily were the cause.

Aquaporins in kidney pathophysiology.

Seven aquaporin water channels are expressed in human kidneys, and they have key roles in maintaining body water homeostasis. Impairment of their function can result in nephrogenic diabetes insipidus and other water-balance disorders. A lot of data have increased understanding of the functions and mechanisms of regulation of aquaporins both at the molecular and the clinical level.

FAPP2 is required for aquaporin-2 apical sorting at trans-Golgi network in polarized MDCK cells.

FAPP2 is an adaptor protein of phosphatidylinositol-4-phosphate and is involved in the transport of some apical cargos from the trans-Golgi network (TGN). To investigate whether the regulated apical transport of aquaporin-2 (AQP2) is involved in the FAPP2-dependent apical protein-sorting machinery, we measured apical sorting of AQP2 in Madin-Darby canine kidney (MDCK) cells with or without FAPP2 knockdown. We established MDCK cell lines that stably express rat AQP2 without any tag sequence.

Aquaporin-2 regulates cell volume recovery via tropomyosin.

Cell volume regulation is particularly important for kidney collecting duct cells. These cells are the site of water reabsorption regulated by vasopressin and aquaporin-2 (AQP2) trafficking to the apical membrane, and subject to changes in osmolality. Here, we examined the role of AQP2 in regulatory volume decrease (RVD), which is a cellular defensive process against hypotonic stress.