Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation.

• kidney tubules
• collecting
• ubiquitination
• vasopressin
• aquaporin 2

Acquired renal tubular disorder can be observed in various disease processes, especially autoimmune diseases. Gitelman syndrome is an autosomal recessive disease characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. This disorder is caused by mutation in the SLC12A3 gene, which encodes the thiazide-sensitive NaCl cotransporter (NCCT). Acquired Gitelman syndrome has been reported and the majority has been associated with Sjogren`s syndrome. The presence of circulating auto-antibodies to NCCT was suggested as a mechanism of acquired Gitelman syndrome. Treatment of acquired Gitelman syndrome was done with supplements of potassium and magnesium and prednisone was effective in some cases. Acquired Gitelman syndrome should be included in the differential diagnosis of renal involvement in patients with autoimmune diseases, especially Sjogren`s syndrome.

• Gitelman syndrome
• Sjogren`s syndrome
• thiazide-sensitive NaCl cotransporter

Renal ammonium metabolism is the primary component of net acid excretion and thereby is critical for acid-base homeostasis. Briefly, ammonium is produced from glutamine in the proximal tubule in a series of biochemical reactions that result in equimolar bicarbonate. Ammonium is predominantly secreted into the luminal fluid via the apical Na+/H+ exchanger, NHE3. The thick ascending limb of the loop of Henle reabsorbs luminal ammonium, predominantly by transport of NH4+ by the apical Na+/K+/2Cl- cotransporter, BSC1/NKCC2. This process results in renal interstitial ammonium accumulation. Finally, the collecting duct secretes ammonium from the renal interstitium into the luminal fluid. Although in past ammonium was believed to move across epithelia entirely by passive diffusion, an increasing number of studies demonstrated that specific proteins contribute to renal ammonium transport. Recent studies have yielded important new insights into the mechanisms of renal ammonium transport. In this review, we will discuss renal handling of ammonium, with particular emphasis on the transporters involved in this process.

• ammonia
• kidney
• kidney tubules
• collecting
• acidosis

Ammonia metabolism is a fundamental process in the maintenance of life in all living organisms. Recent studies have identified ammonia transporter family proteins in yeast (Mep), plants (Amt), and mammals (Rh glycoproteins). In mammalian kidneys, where ammonia metabolism and transport are critically important for the regulation of systemic acid-base homeostasis, basolateral Rh B glycoprotein and apical/basolateral Rh C glycoprotein are expressed along the distal nephron segments. Data from experimental animal models and knockout mice suggest that the Rh glycoproteins appear to mediate important roles in urinary ammonia excretion.

• ammonia
• kidney tubules
• collecting
• kidney

Pendrin (SLC26A4) is a Na+ -independent Cl-/HCO3- exchanger which is expressed in the apical membranes of type B and non-A, non-B intercalated cells within the distal convoluted tubule, the connecting tubule, and the cortical collecting duct. In those segments it mediates HCO3- secretion and chloride (Cl-) absorption. In mice, no renal abnormalities are observed under basal conditions, and individuals with genetic disruption of the pendrin (SLC26A4) gene (Pendred syndrome) have normal acid-base balance. In contrast, there are definite differences under conditions wherein the transporter is stimulated. In animal studies, pendrin (SLC26A4) is upregulated with aldosterone analogues, Cl- restriction, and metabolic alkalosis, and is down-regulated with Cl loading and metabolic acidosis, independently. However, the exact role of pendrin in humans has not been established to date, and further examinations are necessary.

• pendrin
• SLC26A4
• acidosis
• renal tubular
• metabolic alkalosis

This study aimed to compare the increment in plasma potassium concentration ([K+]) as well as the role of internal K+ balance for its changes following acute K+ supplementation between conventional 2.5% glucose (GD) and non-glucose containing dialysate (icodextrin, ID) in continuous ambulatory peritoneal dialysis (CAPD) patients. A total of 9 stable CAPD patients (5 men and 4 women; age, 56±13 years; 7 type-2 diabetics and 2 non-diabetics) on daily 4 exchanges of 2 L of glucose dialysate underwent the 6-hr dwell on fasting in the morning with 2 L of 2.5% glucose mixed with 20 mEq/L of KCl, and then the same regimen was repeated with icodextrin after 1-wk interval. The degree of intraperitoneal absorption was comparable, 65±2% in GD and 68±2% in ID, respectively (p=NS). However, despite the similar plasma K+ levels at the baseline of both regimens, its increment was significantly less in GD than ID, which was accompanied by more marked increase in the calculated intracellular K+ redistribution (68±3% vs. 52±3%, p<0.05). The basal levels of insulin were similar between the GD and ID groups. However, the change, checked up after 2 hours` dwell, from the basal insulin levels was much lower on ID. ID with a lesser degree of transcelluar K+ shift by the decreased secretion of insulin is more effective than the conventional glucose solution for acute K+ repletion via dialysate during CAPD. Furthermore, these results suggested that the role of insulin for the internal K+ balance was intact even in type-2 diabetic patients on CAPD.

• hypokalemia
• peritoneal dialysis
• continuous ambulatory
• potassium supplementation
• icodextrin