Nitric oxide (NO) is synthesized within the adult and developing kidney and plays a critical role in the regulation of renal hemodynamics and tubule function. In the adult kidney, the regulation of NO synthesis is very cell type specific and subject to distinct control mechanisms of NO synthase (NOS) isoforms. Endothelial NOS (eNOS) is expressed in the endothelial cells of glomeruli, peritubular capillaries, and vascular bundles. Neuronal NOS (nNOS) is expressed in the tubular epithelial cells of the macula densa and inner medullary collecting duct. Furthermore, in the immature kidney, the expression of eNOS and nNOS shows unique patterns distinct from that is observed in the adult. This review will summarize the localization and presumable function of NOS isoforms in the adult and developing kidney.

• Kidney
• Development
• Renal hemodynamics
• Nitric oxide

The kidney is an important organ for controlling the volume of body fluids, electrolytic balance and excretion/reabsorption of endogenous and exogenous compounds. Among these renal functions, excretion/reabsorption of endogenous and exogenous substance is very important for the maintenance of physiological homeostasis in the body. Recently discovered organic anion transporters (OAT or SLC22A) have important roles for renal functions. It is well known as drug transporter. Several isoforms belong to SLC22A family. They showed different transport substrate spectrums and different localizations within the kidney. Their gene expressions are changed by some stimulus. The functional transport properties are regulated by protein kinase C. In addition, the function of organic anion transporters are also regulated by protein-protein interaction, such as caveolin which is compositional protein of caveolae structure. In this review, we will give an introduction of organic anion transporters and its regulatory mechanisms.

• Kidney
• Organic anion
• Multispecific organic anion transporter
• Tubular secretion
• Xenobiotics
• Renal Localization
• Caveolin

To produce a concentrated urine, the renal medulla needs hypertonicity for the reabsorption of free water from collecting duct. The single effect that increases interstitial tonicity in the outer medulla is the active NaCl reabsorption in the thick ascending limb, while the single effect in the inner medulla is the passive efflux of NaCl through the thin ascending limb. The passive mechanism in the inner medulla requires high interstitial urea concentration. Two main groups of urea transporters (UT-A, UT-B) are present in the kidney, which maintains the high concentration of urea in the deepest portion of the inner medulla by intra-renal urea recycling. Recent studies suggest that UT-A1 in the terminal inner medullary collecting duct is up-regulated when urine or inner medullary interstitial urea is depleted in order to enhance the reabsorption of urea, while UT-A2 in the descending thin limb of loops of Henle and UT-B in the descending vasa recta are increased when outer medullary interstitial urea concentration is high, in order to prevent the loss of urea from the medulla to the systemic circulation, thereby increasing intra-renal urea recycling. This review will summarize the functions of the renal urea transporters in urine concentration mechanism and the recent knowledge about their long-term regulation.

• Urine concentration
• Water
• Urea
• Urea transporters

Nephrotic syndrome and liver cirrhosis are common clinical manifestations, and are associated with avid sodium retention leading to the development of edema and ascites. However, the mechanism for the sodium retention is still incompletely understood and the molecular basis remains undefined. We examined the changes of sodium (co)transporters and epithelial sodium channels (ENaCs) in the kidneys of experimental nephrotic syndrome and liver cirrhosis. The results demonstrated that puromycin- or HgCl2?induced nephrotic syndrome was associated with 1) sodium retention, decreased urinary sodium excretion, development of ascites, and increased plasma aldosterone level; 2) increased apical targeting of ENaC subunits in connecting tubule and collecting duct segments; and 3) decreased protein abundance of type 2 11β-hydroxysteroid dehydrogenase (11βHSD2). Experimental liver cirrhosis was induced in rats by CCl4 treatment or common bile duct ligation. An increased apical targeting of alpha-, beta-, and gamma-ENaC subunits in connecting tubule, and cortical and medullary collecting duct segments in sodium retaining phase of liver cirhosis but not in escape phase of sodium retention. Immunolabeling intensity of 11βHSD2 in the connecting tubule and cortical collecting duct was significantly reduced in sodium retaining phase of liver cirrhosis, and this was confirmed by immunoblotting. These observations therefore strongly support the view that the renal sodium retention associated with nephrotic syndrome and liver cirrhosis is caused by increased sodium reabsorption in the aldosterone sensitive distal nephron including the connecting tubule and collecting duct, and increased apical targeting of ENaC subunits plays a role in the development of sodium retention in nephrotic syndrome and liver cirrhosis.

• Edema
• Sodium retention
• Epithelial sodium channel
• Aldosterone sensitive distal nephron

Tubulointerstitial (TI) fibrosis is a final common pathway to progressive renal injury of all forms of renal disease. However, once renal damage reaches a certain threshold, progression of renal disease is consistent, irreversible, and largely independent of the initial injury. Angiotensin (AT) II is the main effector of the renin angiotensin system (RAS) and effects that may contribute to the onset and progression of renal damage. AT II may also directly contribute to accelerate renal damage by sustaining cell growth, inflammation, and fibrosis. Interventions that inhibit the activity of the RAS are renoprotective and may retard or even halt the progression of chronic nephropathies. Unilateral ureteral obstruction suggested as a well-stablished experimental model of progressive interstitial expansion and fibrosis. Although technically challenging, some investigators have successfully relieved the obstruction and reported significant reduction in interstitial fibrosis severity. Drugs that modulate the RAS, such as ACE inhibitors and angiotensin type 1 (AT1) receptor antagonists, have demonstrated protective renal effects and can ameliorate fibrosis. However, neither ACE inhibitor nor AT1 receptor blockade completely suppresses progression of renal disease. Dual blockade of the RAS with ACE inhibitors and AT1 receptor blockers may provide renal benefit beyond therapy with either drug alone, due to their potential additive beneficial effect.

• Fibrosis
• Unilateral ureteral obstruction
• Angiotensin inhibition

The anion gap in the serum is useful in the interpretation of acid-base disorders and in the diagnosis of other conditions. In the early 1980s, ion-selective electrodes for specific ionic species were introduced for the measurement of serum electrolytes. This new method has caused a shift of the anion gap from 12±4 mEq/L down 6±3 mEq/L. It is worthy for clinicians to understand the range of normal anion gap and the measuring methods for serum sodium and chloride in the laboratories that support their practice. While an increase in the anion gap is almost always caused by retained unmeasured anions, a decrease in the anion gap can be generated by multiple mechanisms.

• Anion gap
• Ion-selective electrode

In end-stage renal disease (ESRD) patients regardless of dialysis modes, i.e. maintenance hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD), potassium (K) homeostasis is regulated primarily via dialysis and extrarenal K regulation in the diverse daily K intake. However, K metabolism has been known to differ greatly between the two main methods of dialysis. Hyperkalemia is a common complication (10-24%) and the most common cause of the death (3-5%) among electrolyte disorders in patients on maintenance HD. On the contrary, hypokalemia (10-36%) is responsible for a rather common complication and independent prognostic factor on CAPD. Although excessive K intake or inadequate dialysis on maintenance HD and poor nutritional K intake on CAPD are accused without doubts upto 50% of ESRD patients as a primary cause of the K-imbalance, i.e. hyperkalemia on HD and hypokalemia on CAPD, other contributory factors including certain medications and unknown causes remain still to be resolved. Accordingly, the effects of medications as another source of K-imbalance on HD with RAS blockades and beta blockers as well as those of conventional and glucose-free dialysates (Icodextrin) for internal K-redistribution on CAPD were evaluated with reviewing the literatures and our data. Furthermore, new developments in the clinical managements of hyperkalemia on HD following the exclusion of pseudohyperkalemia before the initiation of dialysis were suggested, especially, by the comparison of the effects between mono- and dual-therapy with medications for transcellular K shifting in the emergent situation. Also, the intraperitoneal K administration via conventional glucose-containing (2.5%) and glucose-free dialysates (Icodextrin) as a specific route of K-supplementation for hypokalemia on CAPD was examined for its efficiency and the degree of intracellular K shift between these two different types of dialysates.

• Hyperkalemia
• Hypokalemia
• Hemodialsysis
• Continuous ambulatory peritoneal dialysis

D-Lactic acidosis has been well documented in ruminants. In humans, D-lactic acidosis is very rare, but D-lactic acidosis may be more common than generally believed and should be looked for in a case of metabolic acidosis in which the cause of acidosis is not apparent. The clinical presentation of D-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The entity should be considered as a diagnosis in a patient who presents with metabolic acidosis accompanied by high anion gap, normal lactate level, negative Acetest, history of short bowel syndrome or malabsorption, and characteristic neurologic manifestations. Low carbohydrate diet, bicarbonate treatment, rehydration, and oral antibiotics would be helpful in controlling symptoms.

• D-Lactic acidosis
• Metabolic acidosis
• Humans