Altered regulation of renal sodium transporters in salt-sensitive hypertensive rats induced by uninephrectomy.

Uninephrectomy (uNx) in young rats causes salt-sensitive hypertension (SSH). Alterations of sodium handling in residual nephrons may play a role in the pathogenesis. Therefore, we evaluated the adaptive alterations of renal sodium transporters according to salt intake in uNx-SSH rats.

Hyponatremia in patients with neurologic disorders.

The kidney and the brain play a major role in maintaining normal homeostasis of the extracellular fluid by neuroendocrine regulation of sodium and water balance. Therefore, disturbances of sodium balance are common in patients with central nervous system (CNS) disorders and clinicians should focus not only on the CNS lesion, but also on the potentially deleterious complications. Hyponatremia is the most common and important electrolyte disorder affecting patients with critical neurologic diseases.

Activation of hypoxia-inducible factor attenuates renal injury in rat remnant kidney.

Background: Chronic hypoxia in the kidney has been suggested as a final common pathway to end-stage renal disease. Hypoxia-inducible factor (HIF) is a transcription factor that regulates cellular hypoxic responses, and it is a promising target with therapeutic potential in various kidney disease models. In this study, we investigated whether HIF activation could attenuate renal injury in the rat remnant kidney model.

Genetic polymorphisms of hypoxia-inducible factor-1 alpha and cardiovascular disease in hemodialysis patients.

Background: Hemodialysis patients are prone to ischemic events potentially aggravated by hypoxia. The key player in adaptation to hypoxia is hypoxia-inducible factor-1 alpha (HIF-1alpha). Therefore, we investigated the association of HIF-1alpha polymorphisms with ischemia/hypoxia-related events in hemodialysis patients.

Clinicopathologic characteristics of IgA nephropathy with steroid-responsive nephrotic syndrome.

Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN). Some cases respond to steroid treatment. Here we describe a case-series of IgAN patients with steroid-responsive nephrotic syndrome.

The mildly elevated serum bilirubin level is negatively associated with the incidence of end stage renal disease in patients with IgA nephropathy.

Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea.

Effects of thiazide on the expression of TRPV5, calbindin-D28K, and sodium transporters in hypercalciuric rats.

TRPV5 is believed to play an important role in the regulation of urinary calcium excretion. We assessed the effects of hydrochlorothiazide (HCTZ) on the expression of TRPV5, calbindin-D(28K), and several sodium transporters in hypercalciuric rats. Sprague-Dawley rats were divided into 4 groups; control, HCTZ, high salt, and high salt with HCTZ group in experiment 1; control, HCTZ, high calcium (Ca), and high Ca with HCTZ group in experiment 2.

Effects of interleukin-6 T15A single nucleotide polymorphism on baseline peritoneal solute transport rate in incident peritoneal dialysis patients.

Objective: To study the genetic effects of various inflammatory cytokines on peritoneal solute transport rate (PSTR) in incident Korean peritoneal dialysis (PD) patients.

Design: Case-control association study.

Methods: 132 patients with baseline peritoneal equilibration test within 1-3 months after starting PD were enrolled.

Altered renal sodium transporter expression in an animal model of type 2 diabetes mellitus.

Hemodynamic factors play an important role in the development and/or progression of diabetic nephropathy. We hypothesized that renal sodium transporter dysregulation might contribute to the hemodynamic alterations in diabetic nephropathy. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as an animal model for type 2 diabetes.

Electrolyte and Acid-base disturbances associated with non-steroidal anti-inflammatory drugs.

Inhibition of renal prostaglandin synthesis by non-steroidal anti-inflammatory drugs (NSAIDs) causes various electrolyte and acid-base disturbances including sodium retention (edema, hypertension), hyponatremia, hyperkalemia, and decreased renal function. Decreased sodium excretion can result in weight gain, peripheral edema, attenuation of the effects of antihypertensive agents, and rarely aggravation of congestive heart failure. Although rare, NSAIDs can cause hyponatremia by reducing renal free water clearance.

Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data.

Background: The relationship between SLC12A3 mutations and actual sodium-chloride (Na-Cl) cotransporter (NCC) expression in patients with Gitelman syndrome (GS) was rarely evaluated. Detection of urinary thiazide-sensitive NCC was not tried in patients with GS.

Study Design: Case series.

MCP-1 and RANTES polymorphisms in Korean diabetic end-stage renal disease.

Macrophage infiltration has been observed in the renal biopsy specimens of diabetic nephropathy (DN), and hyperglycemic state stimulates the renal expression of RANTES (regulated upon activation, normal T-cell expressed and secreted) and MCP- 1 (monocyte chemoattractant protein-1). Upregulation of RANTES and MCP-1 with infiltrating macrophages may play a crucial role in the development and progression of DN. Genetic polymorphisms of RANTES and its receptors were reported to be independent risk factors for DN.

Chronic furosemide or hydrochlorothiazide administration increases H+-ATPase B1 subunit abundance in rat kidney.

Furosemide administration stimulates distal acidification. This has been attributed to the increased lumen-negative voltage in the distal nephron, but the aspect of regulatory mechanisms of H(+)-ATPase has not been clear. The purpose of this study is to investigate whether chronic administration of diuretics alters the expression of H(+)-ATPase and whether electrogenic Na(+) reabsorption is involved in this process.

Two cases of pure red-cell aplasia due to anti-erythropoietin antibodies.

We report on two Korean patients who developed pure red-cell aplasia (PRCA) due to anti-erythropoietin (EPO) antibodies. The first patient became refractory to EPO treatment after a good response for an initial 26 months. Anti-EPO antibodies were detected by enzyme linked immunosorbent assay (ELISA) and by radioimmunoprecipitation (RIPA), and these were found to inhibit erythroid colony formation by in vitro bioassay.

Antidiuretic effect of hydrochlorothiazide in lithium-induced nephrogenic diabetes insipidus is associated with upregulation of aquaporin-2, Na-Cl co-transporter, and epithelial sodium channel.

Thiazides have been used in patients with nephrogenic diabetes insipidus (NDI) to decrease urine volume, but the mechanism by which it produces the paradoxic antidiuretic effect remains unclear. Previous studies have reported that downregulation of aquaporin-2 (AQP2) is important for the development of lithium-induced (Li-induced) polyuria and that hydrochlorothiazide (HCTZ) increases renal papillary osmolality and Na(+) concentration in Brattleboro rats. For elucidating the molecular basis of the antidiuretic action of HCTZ in diabetes insipidus, whether administration of HCTZ may affect the expression of AQP2 and major renal Na(+) transporters in Li-induced NDI rats was investigated, using semiquantitative immunoblotting and immunohistochemistry.

Recombinant uteroglobin prevents the experimental crescentic glomerulonephritis.

Background: Although uteroglobin is known to have an immunomodulatory property and prevents the deposition of immune-complexes on the glomeruli of mice, the therapeutic potential of uteroglobin is uncertain in glomerulonephritis. To test the hypothesis that uteroglobin can prevent glomerulonephritis, we have studied the effects of recombinant uteroglobin on the development of experimental crescentic glomerulonephritis that is induced by anti-glomerular basement membrane (anti-GBM) antibodies.

Methods And Results: Glomerulonephritis was induced by the intravenous injection of rabbit anti-GBM globulin antibodies into mice (C57BL/6), and renal injury was evaluated 7, 14, and 21 days afterward.

Antidiuretic action of oxytocin is associated with increased urinary excretion of aquaporin-2.

Background: The antidiuretic effect of oxytocin in humans is controversial. Urinary excretion of aquaporin-2 (AQP2) can be used as an index of the action of vasopressin on the kidney. We investigated whether exogenous oxytocin affects urinary concentration and urinary AQP2 excretion in human beings.

The urine-blood PCO gradient as a diagnostic index of H(+)-ATPase defect distal renal tubular acidosis.

Background: Urine pH during acidemia and urine PCO2 upon alkalization both may be useful to indicate H+ secretion from collecting ducts. The urine anion gap has been used to detect urinary NH4+ for differential diagnosis of hyperchloremic metabolic acidosis. We have previously demonstrated that the lack of normal H(+)-ATPase may underlie secretory defect distal renal tubular acidosis (dRTA).

Up-regulation of organic anion transporter 1 protein is induced by chronic furosemide or hydrochlorothiazide infusion in rat kidney.

Background: Thiazide and loop diuretics are secreted from the proximal tubule via the organic anion transport system to reach their principal sites of action. Recently, a multispecific organic anion transporter 1 (OAT1) was identified in rat kidney and was localized to the basolateral membrane of the S2 segment in the proximal tubule. We postulated that interactions between thiazide or loop diuretics and OAT1 may play a role in the adaptation to long-term diuretic use, and investigated whether OAT1 is regulated in vivo by chronic administration of diuretics at the protein level.

Oxytocin induces apical and basolateral redistribution of aquaporin-2 in rat kidney.

The aquaporin-2 (AQP2) water channel is mainly located in the apical plasma membrane of collecting duct epithelial cells, but there has been some evidence of a moderate amount of basolateral localization of AQP2 at least in the inner medullary collecting duct (IMCD). Previous in vitro microperfusion studies showed that oxytocin has an antidiuretic action, most likely mediated by the vasopressin V2 receptor (V2R) in rat IMCD. By using immunohistochemistry in kidneys from male Sprague-Dawley rats, we observed acute effects of oxytocin on AQP2 localization which were prevented by a V2R antagonist.

Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats.

Furosemide and hydrochlorothiazide (HCTZ) exert their diuretic actions by binding to apical Na(+) transporters, viz., the Na(+)-K(+)-2Cl(-) cotransporter in the thick ascending limb and the Na(+)-Cl(-) cotransporter in the distal convoluted tubule, respectively. We carried out semiquantitative immunoblotting and immunohistochemistry of rat kidneys to investigate whether chronic administration of furosemide or HCTZ is associated with compensatory changes in the abundance of Na(+) transporters downstream from the primary site of action.

Secretory-defect distal renal tubular acidosis is associated with transporter defect in H(+)-ATPase and anion exchanger-1.

Recent progress in molecular physiology has permitted us to understand pathophysiology of various channelopathies at a molecular level. The secretion of H(+) from alpha-intercalated cells is mediated by apical plasma membrane H(+)-ATPase and basolateral plasma membrane anion exchanger-1 (AE1). Studies have demonstrated the lack of H(+)-ATPase immunostaining in the intercalated cells in a few patients with distal renal tubular acidosis (dRTA).