The aging suppressor gene Klotho encodes a single-pass transmembrane protein. Klotho-deficient mice exhibit variety of aging-like phenotypes, many which are similar to those observed in fibroblast growth factor-23 (FGF23)-deficient mice. To test the possibility that and FGF23 may function common signal transduction pathway(s), we investigated whether is involved FGF signaling. Here show protein directly binds multiple receptors (FGFRs). Klotho-FGFR complex with higher affinity than FGFR or...

Klotho has profound effects on phosphate metabolism, but the mechanisms of how affects homeostasis is unknown. We detected in proximal tubule cell, brush border, and urinary lumen, where resides. Increasing kidney urine chronically by transgenic overexpression or acutely intravenous infusion caused hypophosphatemia, phosphaturia from decreased reabsorption, activity protein principal renal transporter NaPi-2a. The phosphaturic effect was present FGF23-null mice, indicating a direct action...

Dexamethasone is frequently administered to the developing fetus accelerate pulmonary development. The purpose of present study was determine if prenatal dexamethasone programmed a progressive increase in blood pressure and renal injury rats. Pregnant rats were given either vehicle or 2 daily intraperitoneal injections (0.2 mg/kg body weight) on gestational days 11 12, 13 14, 15 16, 17 18, 19 20. Offspring 16 gestation had 20% reduction glomerular number compared with control at 6 9 months...

The clinical and biochemical effects of continuous ambulatory peritoneal dialysis in 20 children hemodialysis 16 were compared over a 2 1/2-year period. Statistically significant differences between the treatment groups included higher hematocrit, serum carbon dioxide cholesterol levels, large intake calories protein, lower systolic blood pressure rates transfusion patients receiving dialysis. These had more complications than hemodialysis, but hospitalization two similar. cost was +19,600...

Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in the pathogenesis of several hypophosphatemic disorders. FGF23 causes hypophosphatemia by decreasing expression sodium phosphate cotransporters (NaPi-2a and NaPi-2c) serum 1,25(OH)(2)Vitamin D(3) levels. We previously showed that FGFR1 predominant receptor for actions renal NaPi-2a 2c while receptors regulating levels remained elusive. To determine FGFRs levels, we studied FGFR3(-/-)FGFR4(-/-) mice as these have...

Renal ischaemia for one hour in two groups of Gunn rats, with and the other without bile-duct ligation, produced comparable reversible renal tubular lesions both groups. Since rats have an unconjugated hyperbilirubinaemia, which is unaffected by it seems likely that high levels bilirubin glucuronide are responsible sensitizing tubules to ischaemia, possibly depressing cell respiration.

The epithelial Na+ channel (ENaC) is essential for homeostasis, and dysregulation of this underlies many forms hypertension. Recent studies suggest that mTOR regulates phosphorylation activation serum/glucocorticoid regulated kinase 1 (SGK1), which known to inhibit ENaC internalization degradation; however, it not clear whether contributes the regulation renal tubule ion transport. Here, we evaluated effect selective inhibitors on kidney K+ transport in WT Sgk1–/– mice, as well isolated...

The proximal convoluted tubule (PCT) reabsorbs most of the filtered bicarbonate. Proton secretion is believed to be mediated predominantly by an apical membrane Na+/H+ exchanger (NHE). Several NHE isoforms have been cloned, but only NHE3 and NHE2 are known present on PCT. Here we examined PCT sodium-dependent proton wild-type (NHE3+/+/NHE2+/+), NHE3–/–, NHE2–/–, double-knockout NHE3–/–/NHE2–/– mice determine their relative contribution luminal secretion. NHE2–/– had comparable rates...

To examine the efficacy and complications of albumin diuretic therapy in treatment edema due to nephrotic syndrome.The clinical biochemical effects 35 courses diuretics administered 21 children with syndrome were retrospectively examined. Treatment consisted intravenous infusion 25% furosemide. A second was addition furosemide during 10 courses. There an average 5 infusions per hospitalization.Albumin resulted a 1.2 +/- 0.2% (SEM) body weight loss infusion. The administration two did not...

Glucocorticoids have important effects on renal function, including the modulation of acidification by major proximal tubular Na(+)/H(+) exchanger, NHE3. While chronic effect glucocorticoids is considered to be primarily at transcriptional level, with increases in NHE3 mRNA and protein expression driving increased transport activity, mechanisms which activate an acute setting not been investigated. Previous studies shown that a glucocorticoid-stimulated increase activity can occur before any...

Prenatal glucocorticoids are often administered to pregnant women accelerate pulmonary maturation. We have demonstrated that administration of dexamethasone during specific periods pregnancy in the rat causes hypertension offspring when they studied as adults. The purpose present study was determine whether due prenatal mediated by renal nerves. rats daily for 4 days between 15 and 18 gestation. Rats underwent bilateral denervation or sham operation at 6 wk age, blood pressure measured 8...

Epithelial ion transport is essential to renal homeostatic function, and it dysregulated in several diseases, such as hypertension. An understanding of the insect (Malpighian) tubule yields insights into conserved epithelial processes higher organisms also has implications for control infectious disease vectors. Here, we examine role Na + -K -2Cl − (NKCC) cotransporter Ncc69 Drosophila function. mutant tubules have decreased rates fluid secretion K flux, these phenotypes were rescued by...

The kidney has the highest abundance of cytochrome P-450 all extrahepatic organs. Within kidney, concentration is found in proximal tubule. Whether 20- or 19( S)-hydroxyeicosatetraenoic acid (HETE), major metabolites arachidonic tubule, affect transport this segment not been previously investigated. We examined direct effects and S)-HETE on volume absorption ( J v ) rabbit straight tubule (PST). Production 20-HETE by PST was demonstrated incubating microdissected tubules with [ 3...

The electrical nature of active NaCl transport and the significance a basolateral membrane chloride conductance were examined in isolated perfused rabbit proximal convoluted tubules (PCT). PCT with high solution that simulated late tubular fluid bathed an albumin serum control recovery periods. was by bathing where there no anion gradients. Volume reabsorption (Jv) during period 0.56 0.51 nl/mm X min, respectively, 0.45 min when bath. transepithelial potential difference (PD) periods...

Whole animal clearance studies and in vitro microperfusion were performed to examine the effect of atrial natriuretic factor (ANF) on rabbit proximal tubule. Infusion ANF into rabbits resulted an increase glomerular filtration rate a natriuresis diuresis. To determine whether has direct tubule account for part observed natriuresis, convoluted tubules (PCT) straight (PST) perfused vitro. Addition 10(-9) M ANF, concentration recently measured vivo during volume expansion, bathing solution PCT...

Several hormones induce phosphatidylinositol turnover in cell membranes and thus activate protein kinase C. Activation of C can, turn, have effects on epithelial transport. These experiments were designed to investigate the two activators C, phorbol 12-myristate,13-acetate (PMA) L-alpha-1,2-dioctanoylglycerol (L-alpha-1,2-DOG), inactive analogues, 4 alpha-phorbol 4-O-methyl 12-myristate,13-acetate, sodium, potassium, chloride, total CO2 transport rabbit cortical collecting tubule. Utilizing...

Inwardly rectifying potassium channels play essential roles in renal physiology across phyla. Barium-sensitive K(+) conductances are found on the basolateral membrane of a variety insect Malpighian (renal) tubules, including Drosophila melanogaster. We that barium decreases lumen-positive transepithelial potential difference isolated perfused tubules and fluid secretion flux. In those species which it has been studied, transcripts from multiple genes encoding inwardly expressed (Malpighian)...

Kidney disease is an important cause of morbidity and mortality in patients with sickle cell anemia (SCA). The factors that affect progression renal are unknown, especially children adolescents. Alterations blood pressure, including hypertension lack the normal nocturnal dip determinants diabetic nephropathy other diseases may play a role nephropathy. Our primary hypothesis was SCA who have microalbuminuria will demonstrate less dipping pressure compared to without microalbuminuria. We also...