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Trace elements are cofactors in various enzymes in the antioxidant defense and cell homeostasis required in the tissue during inflammation. In acute kidney injury induced by lipopolysaccharide (LPS), renal cells are affected by cytotoxicity. Renal evacuation and gastrointestinal absorption rates are important in regulating plasma levels of trace elements. Simvastatin is a widely used anti-lipidemic drug with known anti-inflammatory effects. This study aimed to examine the effect of simvastatin on trace elements and electrolyte levels in kidney tissue in rats with LPS-induced sepsis. Adult male Wistar albino rats were divided into four groups: control, LPS (20 mg/kg, i.p., single dose), simvastatin (20 mg/kg, o.p., 5 days), and LPS + Simvastatin (LPS + Sim). Sodium, potassium, calcium, magnesium, selenium, zinc, copper, and histological structural changes were examined in kidney tissue samples 4 h after LPS execution. The inductively coupled plasma optical emission spectroscopy technique (ICP-OES) was used to determine the tissue trace element levels. In rats with sepsis-induced LPS, selenium, calcium, sodium, and magnesium levels significantly decreased while copper, potassium, and zinc levels significantly increased compared to other experimental groups. In sepsis treated with the simvastatin (LPS + Simvastatin) group, trace elements and electrolyte levels are like the control groups, apart from selenium levels. Selenium levels were significantly decreased in the LPS + Simvastatin group compared to the controls. As a result of examining the kidney tissues under a light microscope, simvastatin improved tissue damage caused by LPS-induced acute kidney injury. LPS-induced renal injury and simvastatin caused significant changes in the oxidant/antioxidant system. In septic rats, simvastatin was shown to balance some trace element levels, and it may improve damage in the kidney tissue., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Carbonic anhydrase (CAII) binds to the electrogenic basolateral Na + -[Formula: see text] cotransporter (NBCe1) and facilitates [Formula: see text] reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with the ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats treated with ACTZ to NH 4 Cl loading for up to 2 wk. The results indicated that ACTZ-treated rats exhibited a sustained metabolic acidosis for up to 2 wk, whereas in NH 4 Cl-loaded rats, metabolic acidosis was corrected within 2 wk of treatment. [Formula: see text] excretion increased by 10-fold in NH 4 Cl-loaded rats but only slightly (1.7-fold) in ACTZ-treated rats during the first week despite a similar degree of acidosis. Immunoblot experiments showed that the protein abundance of glutaminase (4-fold), glutamate dehydrogenase (6-fold), and SN1 (8-fold) increased significantly in NH 4 Cl-loaded rats but remained unchanged in ACTZ-treated rats. Na + /H + exchanger 3 and NBCe1 proteins were upregulated in response to NH 4 Cl loading but not ACTZ treatment and were rather sharply downregulated after 2 wk of ACTZ treatment. ACTZ causes renal [Formula: see text] wasting and induces metabolic acidosis but inhibits the upregulation of glutamine transporter and ammoniagenic enzymes and thus suppresses ammonia synthesis and secretion in the proximal tubule, which prevented the correction of acidosis. This effect is likely mediated through the inhibition of the CA-NBCe1 metabolon complex, which results in cell alkalinization. During chronic ACTZ treatment, the downregulation of both NBCe1 and Na + /H + exchanger 3, along with the inhibition of ammoniagenesis and [Formula: see text] generation, contributes to the maintenance of metabolic acidosis.

Purpose: To analyse the changes in renal function and serum electrolytes in the early post-operative period ofpercutaneous nephrolithotomy (PCNL)., Materials and Methods: A total of 110 patients with normal renal function, who underwent PCNL in our institutewere evaluated prospectively. Haemoglobin percentage, packed cell volume, blood urea nitrogen, serum creatinineand serum electrolytes, namely sodium, potassium, chloride and ionized calcium were measured on the day beforesurgery and after 72 hours of the procedure. Renal function was assessed by Cockcroft-Gault formula and estimatedglomerular filtration rate was calculated by modification of diet in renal disease formula., Results: Serum creatinine increased significantly from a mean value of 0.89 ± 0.199 mg/dL to 0.96 ± 0.252 mg/dL(P = 0.0002) and both creatinine clearance and estimated glomerular filtration rate experienced a significant fall -from a median value (interquartile ranges) of 82.99 (72.37 to 96.88) mL/min to 75.38 (63.89 to 94.05) mL/min incase of creatinine clearance (P = 0.0004) and from a mean value of 95.18 ± 19.87 mL/min/1.73 m2 to 89.30 ± 23.14mL/min/1.73 m2 in case of estimated glomerular filtration rate (P = 0.003). Furthermore, there were significantdrops in both haemoglobin percentage and packed cell volume. There were no significant alterations in serum electrolytes- sodium and potassium (mmol/L) [Median (IQR)] changed from a pre-operative figure of 137.5 (134.0 to140.0) and 3.85 (3.60 to 4.10) to a post-operative value of 138 (135.0 to 140.0) and 3.85 (3.50 to 4.10) respectively., Conclusion: Even though there is no significant variation in serum electrolytes, PCNL causes significant reductionin renal function in the early post-operative period.

Background: Ischemia-reperfusion (I-R) leads to acute kidney injury (AKI). The present study investigated the effects of nitroglycerine (NG) on improving renal dysfunctions caused by I-R in rats., Methodology: Twenty-four rats were equally divided into four groups: (1) the control group, (2) the sham group, (3) the I-R group, and (4) NG-treated groups.NG (50 μg/kg) was injected intraperitoneally after induction of IR. I-R was induced through clamping of the bilateral renal artery and vein of both kidneys for 20 min followed by 24 h of reperfusion., Results: NG significantly increased the creatinine clearance levels and renal blood flow rate (which was reduced by I-R). NG also significantly improved serum electrolytes (sodium and potassium) that were disordered by I-R. In addition, NG significantly offset impaired antioxidant defense mechanism and inhibited lipid peroxidation., Conclusions: The results show NG has a protective effect on renal tissue against AKI caused by I-R. These protective effects mediated through antioxidant activity and decrease of lipid peroxidation., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (© Georg Thieme Verlag KG Stuttgart · New York.)

Fanconi's Syndrome (FS) is a disorder characterized by impaired renal proximal tubule function. FS is associated with a vast defect in the renal reabsorption of several chemicals. Inherited and/or acquired conditions seem to be connected with FS. Several xenobiotics including many pharmaceuticals are capable of inducing FS and nephrotoxicity. Although the pathological state of FS is well described, the exact underlying etiology and cellular mechanism(s) of xenobiotics-induced nephrotoxicity, serum electrolytes imbalance, and FS are not elucidated. Constant and high dependence of the renal reabsorption process to energy (ATP) makes mitochondrial dysfunction as a pivotal mechanism which could be involved in the pathogenesis of FS. The current review focuses on the footprints of mitochondrial impairment in the etiology of xenobiotics-induced FS. Moreover, the importance of mitochondria protecting agents and their preventive/therapeutic capability against FS is highlighted. The information collected in this review may provide significant clues to new therapeutic interventions aimed at minimizing xenobiotics-induced renal injury, serum electrolytes imbalance, and FS., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Complication of perinatal asphyxia is a major cause of neonatal mortality & morbidity in developing countries. This comparative cross sectional study was conducted in Mymensingh Medical College Hospital, Mymensingh, Bangladesh from May 2012 to September 2012 to determine electrolytes & renal function status in perinatal asphyxia & their impact on outcome. Thirty term normal birth weight babies with perinatal asphyxia in neonatal ward were included as a case group and thirty term normal birth weight neonates of same gestational age, without perinatal asphyxia in the department of Gynae & Obs were enrolled as a control group. Necessary information was collected by clinical examination; investigation and close follow up according to predetermined plan. There was no significant different in sex distribution, number of Antenatal care (ANC), number of gravidum of mother and mode of delivery between two groups. Among perinatal Asphyxia group most common risk factor was prolonged labor. Electrolyte abnormalities were documented (16) 53.3% cases. Among 16 electrolyte abnormalities isolated hyponatremia was found in 6(37.5%) cases, hyponatremia with hyperkalaemia 1(6.25%) case, hyponatremia with hypokalaemia in 1(6.25%) case, isolated hypokalaemia in 3(18.75%) cases and isolated hyperkalaemia in 5(31.25%) cases. None case had hypernatremia. On the other hand in control group Hypokalaemia was 3(10%) cases Hyperkalaemia 1(33.33%) case and none had Hyponatraemia. Among total cases 6 (20%) had renal impairment. Serum creatinine level was higher in case group. Twenty percent (20%) case initial value >1.5mg/dl, 20% 1.2-1.5mg/dl and17% had 0.3-0.8mg/dl. On the other hand in control group 83 % had 0.3-0.8 mg/dl & none hade above 1.1 mg/dl. Among case group 8 were died (27%). There was no death in control group. Among 8 neonatal death cases 3(37.5%) had normal electrolytes, isolated hyponatraemia were in 2(25%) cases, hyponatraemia with Hyperkalaemia in 1(6.25%) case and Isolated Hyperkalaemia in 2(25%) cases. Among those death 3(37.5%) had renal impairment. Case fatality was significantly associated with renal failure 50%, isolated Hyponatraemia 33.33%, Isolated hyperkalaemia 40%, Hyperkalaemia with Hyponatremia 100%. Hospital stay was also prolonged among alive case with abnormal electrolytes. So, we can conclude that electrolyte & renal impairments are significantly associated with morbidity & mortality of perinatal Asphyxia.

Objective: This study evaluated the effect of cysteine-stabilized peptide fraction (CSPF) of Morinda lucida leaf on selected kidney function indices in mice., Methods: Sixty mice were assigned into six groups. Group A served as the control while groups B, C, D, E and F received 31.25, 61.5, 125, 250, and 500 mg/kg body weight of CSPF respectively for 7 or 28 days., Results: Administration of CSPF for 7 and 28 days caused no significant (p>0.05) alteration in kidney-body weight ratio, plasma concentrations of the selected electrolytes, urea and creatinine at all doses compared to controls. However, plasma uric acid concentration was significantly increased (p<0.05) after administration of CSPF for 7 days at doses of 125 and 500 mg/kg body weight while it was significantly reduced (p<0.05) after administration for 28 days at doses higher than 31.25 mg/Kg body weight compared to controls. The activities of Ca 2+ , Mg 2+ -ATPase and Na + , K + -ATPases in the kidney and the histology of the kidney remained unaltered (p>0.05) throughout the experimental period compared to controls., Conclusion: CSPF may adversely affect uric acid metabolism after prolonged administration.

The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp- Pkd1 -/- ) mice manifesting a precystic phenotype. Serum and urinary electrolyte determinations indicated that iKsp- Pkd1 -/- mice display reduced serum levels of magnesium (Mg 2+ ), calcium (Ca 2+ ), sodium (Na + ), and phosphate (P i ) compared with control ( Pkd1 +/+ ) mice and renal Mg 2+ , Ca 2+ , and P i wasting. In agreement with these electrolyte disturbances, downregulation of key genes for electrolyte reabsorption in the thick ascending limb of Henle's loop (TA;, Cldn16, Kcnj1, and Slc12a1), distal convoluted tubule (DCT; Trpm6 and Slc12a3) and connecting tubule (CNT; Calb1, Slc8a1, and Atp2b4) was observed in kidneys of iKsp- Pkd1 -/- mice compared with controls. Similarly, decreased renal gene expression of markers for TAL ( Umod) and DCT ( Pvalb) was observed in iKsp- Pkd1 -/- mice. Conversely, mRNA expression levels in kidney of genes encoding solute and water transporters in the proximal tubule ( Abcg2 and Slc34a1) and collecting duct ( Aqp2, Scnn1a, and Scnn1b) remained comparable between control and iKsp- Pkd1 -/- mice, although a water reabsorption defect was observed in iKsp- Pkd1 -/- mice. In conclusion, our data indicate that PC1 is involved in renal Mg 2+ , Ca 2+ , and water handling and its dysfunction, resulting in a systemic electrolyte imbalance characterized by low serum electrolyte concentrations.

Objectives: Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity., Methods: Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i.p.]) for 3 days. Groups 3, 4, and 5 received cisplatin for 3 days and thereafter l-carnitine (50 mg/kg/day), vitamin C (100 mg/kg/day), or their combination, respectively, for 28 days. At the end of the study, a biochemical study was carried out in which nephrotoxicity markers, electrolytes, hematological indices, oxidative stress biomarkers, and renal histopathological alterations were evaluated., Results: CIS-treated rats developed significant polyuria, increase in the plasma levels of creatinine, urea, and inorganic phosphate (P i ), alteration in hematological parameters, and decrease in plasma levels of Na + , Cl - , K + , Ca 2+ , and Mg 2+ . Measurements of 24-hour urine output demonstrated markedly decreased creatinine and urea and increased Na + , Cl - , K + , Ca 2+ , and Mg 2+ levels in the CIS-treated group, whereas P i levels were not changed. It also caused significantly decreased catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) levels in the rats' kidneys. Histopathological scores revealed renal tubular damage in CIS-treated rats. However, l-carnitine, vitamin C, or their combination significantly attenuated the alterations caused by CIS in the plasma and kidneys of the rats., Conclusion: l-Carnitine and vitamin C administration ameliorated CIS-induced nephrotoxicity due to their antioxidant and anti-inflammatory effects.

Aminoglycosides are the commonly used antibiotics against Gram negative bacteria. Their clinical applications are limited due to nephrotoxic side effects. Therefore, the current study was undertaken in an attempt to increase the use of these drugs without causing nephrotoxicity by exploring the nephroprotective effects of a medicinal plant with high flavonoid contents and strong antioxidant properties, namely Valeriana wallichii. A daily dose of 200mg/kg of the extract derived from V. wallichii was employed for a period of three weeks. The results obtained revealed that co-therapy of extract with gentamicin protected some changes in renal functions; however, failed to provide a complete protection as assessed by biochemical, physiological and histological parameters. It can be concluded from the current findings that V. wallichii failed to deliver protective effects against gentamicin induced renal damage in spite of strong flavonoid contents and antioxidant properties.

The handling of electrolytes by the kidney is essential for homeostasis. However, the heritability of these processes, the first step in gene discovery, is poorly known. To help clarify this, we estimated the heritability of serum concentration, urinary excretion, renal clearance, and fractional excretion of sodium, potassium, magnesium, calcium, phosphate, and chloride in a population-based study. Nuclear families were randomly selected from the general population in Lausanne, Geneva, and Bern, Switzerland, and urine collected over 24-hour periods. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including sex, age, body mass index, and study center as covariates in the model. The 1128 participants, from 273 families, had a mean age of 47 years, body mass index of 25.0 kg/m 2 , and an estimated glomerular filtration rate (CKD-EPI) of 98 mL/min/1.73 m 2 . The heritability of serum concentration was highest for calcium, 37% and lowest for sodium, 13%. The heritability of 24-hour urine clearances, excretions, and fractional excretions ranged from 15%, 10%, and 16%, respectively, for potassium to 45%, 44%, and 51%, respectively, for calcium. All probability values were significant. The heritability for phosphate-related phenotypes was lower than that for calcium. Thus, the serum and urine concentrations as well as urinary excretion and renal handling of electrolytes are heritable in the general adult population. The phenotypic variance attributable to additive genetic factors was variable and was higher for calcium. These results pave the way for identifying genetic variants involved in electrolyte homeostasis in the general population., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background/aim: Cisplatin is an anticancer drug that can induce nephrotoxicity. Its toxicity is associated with dyslipidemia and disturbed electrolyte balance. In the present study we investigated the changes in serum lipid profile and electrolyte levels and their contents in kidney and liver tissues of rabbits treated with cisplatin., Materials and Methods: Twenty-eight adult male New Zealand White rabbits were used in the experiment. Animals of groups C, P1, and P2 were injected with saline, cisplatin (4.0 mg/kg bw), and cisplatin (6.5 mg/kg bw), respectively, and killed 3 days after the injections. Animals of group R were given cisplatin (6.5 mg/kg bw) and killed after 7 days. All animals were killed after an overnight fast., Results: The P2 animals showed reductions in their body weights, significant (P < 0.001) increases in serum creatinine and urea levels, and significant (P < 0.001) drops in cortical alkaline phosphatase activity and necrotic kidney histology. The treatments had no effect on liver function. Moreover, the P2 animals showed increased serum cholesterol, TAG, and elevated LDL-cholesterol, with significant accumulations of the kidney cholesterol and TAG, but no change in serum phospholipid and depleted hepatic cholesterol. Moreover, the P2 animals had depressed serum levels of potassium, calcium, and magnesium, and reduced renal cortical calcium and magnesium contents and depressed liver calcium but not magnesium. However, the P1 animals had no significant alterations in their lipid or electrolyte levels. Most of the perturbed parameters returned to normal levels in the recovery group., Conclusion: Cisplatin nephrotoxicity in rabbits is accompanied by reductions in body weight, secondary dyslipidemia, and reduced serum potassium, calcium, and magnesium with depleted renal cortical magnesium and calcium and accumulated cortical lipids.

The approach to acid-base chemistry in medicine includes several methods. Currently, the two most popular procedures are derived from Stewart's studies and from the bicarbonate/BE-based classical formulation. Another method, unfortunately little known, follows the Kildeberg theory applied to acid-base titration. By using the data produced by Dana Atchley in 1933, regarding electrolytes and blood gas analysis applied to diabetes, we compared the three aforementioned methods, in order to highlight their strengths and their weaknesses. The results obtained, by reprocessing the data of Atchley, have shown that Kildeberg's approach, unlike the other two methods, is consistent, rational and complete for describing the organ-physiological behavior of the hydrogen ion turnover in human organism. In contrast, the data obtained using the Stewart approach and the bicarbonate-based classical formulation are misleading and fail to specify which organs or systems are involved in causing or maintaining the diabetic acidosis. Stewart's approach, despite being considered 'quantitative', does not propose in any way the concept of 'an amount of acid' and becomes even more confusing, because it is not clear how to distinguish between 'strong' and 'weak' ions. As for Stewart's approach, the classical method makes no distinction between hydrogen ions managed by the intermediate metabolism and hydroxyl ions handled by the kidney, but, at least, it is based on the concept of titration (base-excess) and indirectly defines the concept of 'an amount of acid'. In conclusion, only Kildeberg's approach offers a complete understanding of the causes and remedies against any type of acid-base disturbance.

Objective: The Dahl salt-sensitive rat is a well-established model of salt-sensitive hypertension. The goal of this study was to assess the expression and activity of renal sodium channels and transporters in the renin-deficient salt-sensitive rat., Methods: Renin knockout (Ren(-/-)) rats created on the salt-sensitive rat background were used to investigate the role of renin in the regulation of ion transport in salt-sensitive hypertension. Western blotting and patch-clamp analyses were utilized to assess the expression level and activity of Na(+) transporters., Results: It has been described previously that Ren(-/-) rats exhibit severe kidney underdevelopment, polyuria, and lower body weight and blood pressure compared to their wild-type littermates. Here we found that renin deficiency led to decreased expression of sodium-hydrogen antiporter (NHE3), the Na(+)/H(+) exchanger involved in Na(+) absorption in the proximal tubules, but did not affect the expression of Na-K-Cl cotransporter (NKCC2), the main transporter in the loop of Henle. In the distal nephron, the expression of sodium chloride cotransporter (NCC) was lower in Ren(-/-) rats. Single-channel patch clamp analysis detected decreased ENaC activity in Ren(-/-) rats which was mediated via changes in the channel open probability., Conclusion: These data illustrate that renin deficiency leads to significant dysregulation of ion transporters., (© The Author(s) 2016.)

Ginseng preparations contain high concentrations of germanium (Ge), which was reported to contribute to diuretic resistance or renal failure. However, Ge content in ginseng and the influence on renal functions remain unclear. Forty rats were randomly divided into control group, low, moderate, and high Ge ginseng-treated group and observed for 25 days. Daily urine, renal functions, and serum and urine electrolytics were measured. Ge retention in the organs and renal histological changes were also evaluated. Ge content ranged from 0.007 to 0.450 µg/g in various ginseng samples. Four groups showed no difference in the daily urine output, glomerular filtration rate, urinary electrolytes excretions, 24 h-urine protein, as well as plasma and urine urea nitrogen, creatinine, osmotic pressure, and pH values. Ge did not cause any renal pathological effects in this study. No Na and water retention was detected in the ginseng-treated groups. Ge retention in various organs was found highest in spleen, followed by the kidney, liver, lung, stomach, heart, and pancreas. The total Ge contents in various ginsengs were low, and ginseng treatment did not affect renal functions or cause renal histological changes., (© 2015 by the Society for Experimental Biology and Medicine.)

Background and Objective: The fact that mineralocorticoid receptor antagonists reduce structural and functional alterations induced by cyclosporine A (CsA) indicates that aldosterone plays a key role in chronic CsA nephrotoxicity. We and other researchers have reported local renal aldosterone synthesis. To investigate local renal aldosterone's role in chronic CsA nephrotoxicity, we evaluated the effect of eplerenone (Epl) on renal structural damage and renal dysfunction in adrenalectomized (ADX) rats, and assessed whether the therapeutic benefit was associated with reduction of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), plasminogen activator inhibitor type 1 (PAI-1) and collagen I (COL-I) expression., Methods: Male Sprague-Dawley rats fed a normal-sodium diet were divided in four groups: sham-ADX, ADX, CsA, or Epl. Rats in the ADX, CsA and Epl groups were adrenalectomized first. Aldosterone, sodium and potassium levels in serum and urine were measured on the second day. Two weeks later, vehicle (sham-ADX and ADX group), CsA (25mg/kg/d), or CsA and Epl (100 mg/ kg/d) combination was administrated, respectively. After six weeks, urinary protein, creatinine clearance (Ccr), tubulointerstitial fibrosis (TIF), aldosterone level in kidney, and renal aldosterone synthase CYP11B2, COL-I, TGF-β1, CTGF and PAI-1 gene expression levels were determined., Results: On the second day after surgery, adrenalectomized rats showed undetectable aldosterone with natriuresis, hyponatremia, decreased urinary potassium excretion and hyperpotassemia. CsA reduced Ccr, induced urinary proteins and up-regulated COL-I, TGF-β1, CTGF and PAI-1 gene expression with a significant development of TIF. Eplerenone administration prevented TIF and COL-I, TGF-β1 and PAI-1 up-regulation but did not improve renal function., Conclusion: Our results suggest local renal aldosterone is an important mediator of renal injury induced by CsA., (© The Author(s) 2014.)

The kidney plays an important physiological function, maintaining the osmoregulation and electrolyte balance of Nile tilapia (Oreochromis niloticus). Selenium and α-tocopherol (α-toc) are potent antioxidants, which improve the aquaculture health. In this study, we tested the potential ability of selenium and α-toc to alleviate the oxidative stress in the kidney induced by lead toxicity. Two hundred and twenty-five O. niloticus were divided into five groups. The control group received a basal diet. Lead nephrotoxicity was induced by daily application of 73.40 mg lead acetate/liter water for up to 10 weeks. Selenium and α-tocopherol were given 1 week before lead intoxication. Selenium was administered as sodium selenite, 4 mg/kg dry diet. Alpha-tocopherol acetate was administered as α-toc, 200 mg/kg dry diet. The last group received a mixture of selenium and α-toc in diet. Fish treated with selenium and/or α-toc (groups III-V) showed an amelioration of the adverse effects of lead toxicity and significant improvement in serum electrolytes (calcium, inorganic phosphate, and magnesium) and creatinine level compared with the positive control group (P ≤ 0.05). Treated groups showed significant decrease in superoxide dismutase (SOD) and reduced glutathione (GSH) activity with significant increase in malondialdehyde (MDA; P ≤ 0.05). It could be concluded that selenium and α-toc have a potential antioxidant effect and have the ability to improve the kidney function after lead intoxication of O. niloticus.

High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice (n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K(+) and decreased plasma Na(+) with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na(+)-K(+)-2Cl(-) cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption., (Copyright © 2015 the American Physiological Society.)

The paracellular pathway through the tight junction provides an important route for transepithelial chloride reabsorption in the kidney, which regulates extracellular salt content and blood pressure. Defects in paracellular chloride reabsorption may in theory cause deregulation of blood pressure. However, there is no evidence to prove this theory or to demonstrate the in vivo role of the paracellular pathway in renal chloride handling. Here, using a tissue-specific KO approach, we have revealed a chloride transport pathway in the kidney that requires the tight junction molecule claudin-4. The collecting duct-specific claudin-4 KO animals developed hypotension, hypochloremia, and metabolic alkalosis due to profound renal wasting of chloride. The claudin-4-mediated chloride conductance can be regulated endogenously by a protease-channel-activating protease 1 (cap1). Mechanistically, cap1 regulates claudin-4 intercellular interaction and membrane stability. A putative cap1 cleavage site has been identified in the second extracellular loop of claudin-4, mutation of which abolished its regulation by cap1. The cap1 effects on paracellular chloride permeation can be extended to other proteases such as trypsin, suggesting a general mechanism may also exist for proteases to regulate the tight junction permeabilities. Together, we have discovered a theory that paracellular chloride permeability is physiologically regulated and essential to renal salt homeostasis and blood pressure control.

Intrauterine environments are related to fetal renal development and postnatal health. Influence of salty diets during pregnancy on renal functions and renin-angiotensin system (RAS) was determined in the ovine fetuses and offspring. Pregnant ewes were fed high-salt diet (HSD) or normal-salt diet (NSD) for 2 months during middle-to-late gestation. Fetal renal functions, plasma hormones, and mRNA and protein expressions of the key elements of renal RAS were measured in the fetuses and offspring. Fetal renal excretion of sodium was increased while urine volume decreased in the HSD group. Fetal blood urea nitrogen was increased, while kidney weight:body weight ratio decreased in the HSD group. The altered ratio was also observed in the offspring aged 15 and 90 days. Maternal and fetal plasma antidiuretic hormone was elevated without changes in plasma renin activity and Ang I levels, while plasma Ang II was decreased. The key elements of local renal RAS, including angiotensinogen, angiotensin converting enzyme (ACE), ACE2, AT1, and AT2 receptor expression in both mRNA and protein, except renin, were altered following maternal high salt intake. The results suggest that high intake of salt during pregnancy affected fetal renal development associated with an altered expression of the renal key elements of RAS, some alterations of fetal origins remained after birth as possible risks in developing renal or cardiovascular diseases.

The effects of diclofenac sodium, diclofenac potassium, alminoprofen and aspirin on serum electrolytes (serum Na(+) and K(+)), urea and creatinine were compared in rabbits in acute and chronic phases of treatment. The data suggested that all the four drugs markedly increased the serum electrolytes, urea and creatinine levels in both post-treatment phases. In conclusion, present study does not present any advantage of diclofenac sodium over diclofenac potassium at electrolyte levels on short and long term treatment. Nevertheless, current data support the evidence of renal function impairment by all the four drug therapies used in the present study, which is generally caused by NSAIDS.

Background: The ex vivo porcine liver perfused model isolates the organ from extrinsic regulatory mechanisms, facilitating an improved understanding of the organ physiology and reaction to various conditions. We have assessed the influence of the addition of a porcine kidney to the circuit., Methods: Eight livers were harvested and perfused for 6 hours. In 5 additional experiments a kidney also was connected in parallel. Hourly arterial blood gases were collected to analyze glucose, acid base, and renal parameters. The primary end point was an evaluation of the influence of the kidney on glucose, pH, and electrolyte levels., Results: In the combined porcine liver-kidney circuit all the parameters significantly improved compared with the liver circuit alone. This was particularly evident for glucose values because normoglycemia was reached by the end of the perfusion, and for pH and electrolyte values that were maintained at initial levels., Conclusions: The addition of a porcine kidney to the perfusion circuit improves the biochemical milieu. This might produce more consistent and reliable results, particularly during studies requiring a steady-state environment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

It is well known that uremia causes an increase in the serum anion gap (AG); however, whether changes in the AG occur earlier in the course of chronic kidney disease is not known. Here we investigated whether different measures of the AG, as a marker of kidney function, are associated with mortality. To do this, we analyzed the available laboratory data of 11,957 adults in the National Health and Nutrition Examination Survey 1999-2004 to calculate AG using the traditional method, or one that was albumin-adjusted, as well as a full AG reflecting other electrolytes. A significant elevation in the traditional AG was seen only with an estimated glomerular filtration rate (eGFR) <45 ml/min per 1.73 m(2), whereas increases in the albumin-adjusted and full AG were found with eGFRs <60 or 90 ml/min per 1.73 m(2), respectively. Higher levels of each AG were associated with an increased risk of all-cause mortality after adjustment for age, gender, race/ethnicity, and eGFR. After adjustment for additional covariates including body mass index and comorbidities, higher levels of the albumin-adjusted and full AG were associated with mortality (relative hazard for the highest compared with the lowest quartile were 1.62 and 1.64, respectively). Thus, higher levels of AG are present in individuals with less advanced kidney disease than previously recognized, and are associated with increased risk of mortality. Further study is needed to identify the unmeasured anions and to determine their physiological significance.

Background: The aim of this study was to assess renal morbidity, associated with the use of low flow anaesthesia (LFA), in cancer patients previously treated with nephrotoxic chemotherapeutic agents., Methods: Seventy-five patients, aged 30-70 years, scheduled for elective surgery, were randomly allocated to three groups: Group A included those patients who had received nephrotoxic chemotherapeutic agents (cisplatin, carboplatin, methotrexate or cyclophosphamide) within 90 days before surgery, and who were anaesthetised with low flow (0.8(-1) L min(-1)) air-oxygen-sevoflurane (1-3 MAC) anaesthesia; Group B included similar patients who received high flow (6 L min-1) anaesthesia. Non-cancer patients receiving low flow anaesthesia served as controls. Blood was sampled for serum creatinine, BUN, cistatin C, and electrolytes (Na(+), K(+), Cl(-), Ca(2+), P(3+), Mg(2+)) before anaesthesia, and one, three and five days after., Results: There were no statistically significant differences between the groups., Conclusions: The use of low flow sevoflurane anaesthesia is not associated with an increased risk of nephrotoxicity in those previously exposed to nephrotoxic chemotherapeutic agents.

Molecular regulation of tight junctions in osmoregulatory epithelia of euryhaline fishes must be extensive during ontogeny and acclimation to salinity changes. In this study, five tight junction proteins were examined in Atlantic salmon (Salmo salar): tight junction associated tricellulin, occludin and claudin-3 isoforms (a, b, c). A survey of tissue distribution in freshwater (FW) salmon showed that tricellulin expression was highest in the intestine. Occludin was detected in tissues with importance for epithelial transport and the order of expression was gill>intestine>kidney. The three claudin-3 isoforms were expressed at highest level in kidney tissue. Transfer of juvenile FW salmon to seawater (SW) elevated intestinal tricellulin and occludin mRNA, and these transcripts were also elevated at the time of best SW-tolerance during the course of smoltification. In the kidney, expression of tricellulin and claudin-3 isoforms was elevated after SW-transfer and tricellulin, occludin, claudin-3a and -3b increased in March before the peak smolt stage. In the gill, none of the examined tight junction proteins were impacted by SW-transfer. The data suggest that expression of tricellulin and occludin is dynamically involved in reorganization of intestinal epithelium and possibly changed paracellular permeability during SW-acclimation. The increased renal tricellulin and claudin-3 expression in SW suggests a role in remodeling of the kidney during SW-acclimation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: There are scarce data on estimating the time of completing kidney maturation in very-low-birth-weight (VLBW) infants. The aim of this study was to determine whether different aspects of kidney function differ between VLBW infants and normal babies at 18 to 30 months postconceptional age., Materials and Methods: This study was carried on 23 VLBW infants and 21 normal-birth-weight infants at 18 to 30 months corrected postconceptional age, who were born between June 2007 and June 2008 at Alzahra Hospital and Shahid Beheshti Hospital, in Isfahan, Iran. Very low birth weight was defined as a birth weight between 1000 g and 1500 g, while gestational age is less than 32 weeks. In both groups, children with a history of sepsis, asphyxia, intubation, hypoxic ischemic encephalopathy, and pyelonephritis were excluded., Results: The mean of systolic, diastolic, and mean arterial blood pressure were not significantly different between the two groups. Urine calcium-creatinine ratio, fraction excretion of magnesium, and renal threshold for phosphate were significantly higher in the VLBW children compared with the control group. Glomerular filtration rate was higher in the control group than in the VLBW group., Conclusions: Our results demonstrated that in VLBW children at the corrected age of 24 ± 6 months, some aspects of tubular and glomerular functions are still impaired. Longer longitudinal cohort studies on VLBW are required to determine the time of completing kidney function maturation in these children.

The objective of this study was to investigate the effects of chronic inhibition of nitric oxide synthase (NOS) on cyclooxygenase-2 (COX-2) expression in the macula densa (MD) of swine, as well as the effects on expression of related proteins. Adult female Yucatan swine were given either tap water (control, n = 6) or water with N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg/liter, n = 5) for a minimum of 30 days. Duplicate samples of kidney were fixed or snap frozen. There was a significant (P = .0082) upregulation of COX-2 mRNA expression in the MD of L-NAME, as well as an apparent increase in COX-2 protein. Plasma renin activity also increased with L-NAME treatment (control, 0.34 ± 0.08 ng/ml; L-NAME, 1.26 ± 0.03 ng/ml; P = .00000003). There were no differences between groups in expression of either inducible NOS or renin protein or in serum electrolyte concentrations. In conclusion, with chronic inhibition of NOS, COX-2 in MD is upregulated, perhaps to compensate for loss of nitric oxide. Increases in COX-2 products may counteract renal arteriolar constriction and sustain renin release.

Renal injury in early life may lead to hypertension and renal disease in adulthood. In this prospective study, we estimated renal glomerular and tubular function and kidney length (KL) during the first 2 years of life of preterm infants with nephrocalcinosis (NC) associated with prematurity. The study cohort comprised 107 preterm children, 63 with NC and 44 control subjects without NC who were matched for gender, gestational age and birth weight. Kidney function was estimated based on measurements of serum creatinine (Scr), estimated glomerular filtration rate (eGFR), fractional excretion (FE) of sodium (Na), potassium (K), phosphate (P), magnesium (Mg) and uric acid (UA) and on the ratios of urinary Ca, oxalate (UOx) and citrate (UCit) to urinary creatinine (UCa/Ucr, UOx/Ucr and UCit/Ucr, respectively) calculated from morning urine collections. KL was measured by ultrasonography. Measurements were made at 40 weeks postmenstrual age and at 3, 6, 12 and 24 months of age. At 3 and 6 months, the NC group had higher UCa/Ucr, FEK and FEUA than the control group; at 12 months, only the UCa/Ucr and FEUA was still higher. The UCa/UCit ratio was higher in the NC group. Scr and eGFR did not differ between the groups at any time point. The NC group had a shorter KL up to 12 months of life (left kidney) or 24 months (right kidney). Based on these results, we conclude that NC in the preterm infants enrolled in our study was associated with impaired renal tubular function and a shorter KL in the first year of life.

Objective: Prenatal glucocorticoid excess programs hypertension in adulthood. The underlying mechanisms are unknown. Here, we tested whether hypertension in this model is due to increased renal mineralocorticoid activity., Methods: Pregnant rats were injected daily with the synthetic glucocorticoid dexamethasone (DEX) or vehicle during the last week of pregnancy. Blood pressure, electrolytes and target gene expression were measured in the offspring., Results: Adult DEX-treated offspring were hypertensive (SBP, 140.1 ± 2.4 vs. 128.6 ± 3.2 mmHg; P = 0.009), hypokalemic (4.5 ± 0.2 vs. 5.1 ± 0.2 mmol/l; P = 0.03) and had suppressed plasma renin concentration (23.6 ± 4.8 vs. 43.8 ± 5.9 ng/ml; P = 0.017). DEX programming had similar effects in younger rats (age 2 months), but only when fed a high-salt diet. Although these data are consistent with excess mineralocorticoid activity, plasma aldosterone levels were unaffected and daily urinary aldosterone values were decreased (136.1 ± 27.0 vs. 303.6 ± 47.0 ng/kg; P = 0.008). Accordingly, we assessed renal factors that might influence mineralocorticoid responsiveness. Renal expression of mineralocorticoid receptor and glucocorticoid receptor mRNAs was unaltered, as was 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which regenerates active glucocorticoids. However, renal mRNA for 11β-HSD2, which catalyses inactivation of glucocorticoids in the distal nephron and thus protects mineralocorticoids from glucocorticoids, was decreased by 45% in both new born and adult rats (P < 0.01). The functional significance of this reduction was confirmed by measurements of renal 11β-HSD activity and by demonstrating that the mineralocorticoid properties of cortisol were enhanced in DEX-programmed rats. Additionally, the difference in blood pressure between DEX and control groups was abolished upon administration of spironolactone, a mineralocorticoid receptor antagonist., Conclusion: The blood pressure phenotype of DEX-programmed rats may in part be explained by a life-long reduction in renal 11β-HSD2 activity. Salt-sensitive hypertension could be programmed by prenatal stress.

Objective: To study the pharmacological effects of compound Centella asiatica enema on chronic renal failure (CRF) rats., Methods: Rats were divided into control group, CRF model group, Niaoduqing positive control group, compound Centella asiatica enema high, middle and low three groups kidney coefficient, electrolyte levels, hematocrit (HCT), red blood cell counts (RBC), hemoglobin (HGB) content were observed after 30 days's treatment., Results: Compared with the model group, the level of the electrolyte, HCT, RBC, HGB of rats in compound Centella asiatica enema high-doses group and the Niaoduqing group were significantly improved., Conclusion: High-doses of compound Centella asiatica enema has significant therapeutic effect on CRF rats.

The endothelin receptor antagonist avosentan may cause fluid overload at doses of 25 and 50 mg, but the actual mechanisms of this effect are unclear. We conducted a placebo-controlled study in 23 healthy subjects to assess the renal effects of avosentan and the dose dependency of these effects. Oral avosentan was administered once daily for 8 days at doses of 0.5, 1.5, 5, and 50 mg. The drug induced a dose-dependent median increase in body weight, most pronounced at 50 mg (0.8 kg on day 8). Avosentan did not affect renal hemodynamics or plasma electrolytes. A dose-dependent median reduction in the fractional renal excretion of sodium was found (up to 8.7% at avosentan 50 mg); this reduction was paralleled by a dose-related increase in proximal sodium reabsorption. It is suggested that avosentan dose-dependently induces sodium retention by the kidney, mainly through proximal tubular effects. The potential clinical benefits of avosentan should therefore be investigated at doses of

Insulin and insulin-like growth factor (IGF1) participate in the regulation of renal electrolyte excretion. Insulin- and IGF1-dependent signaling includes phosphatidylinositide-3 (PI3)-kinase, phosphoinositide-dependent kinase PDK1 as well as protein kinase B (PKB) and serum and glucocorticoid inducible kinase (SGK) isoforms, which in turn phosphorylate and thus inhibit glycogen synthase kinase GSK3alpha,beta. Replacement of the serines in the PKB/SGK consensus sequences by alanine (gsk3 ( KI )) confers resistance of GSK3 to PKB/SGK. To explore the role of PKB/SGK-dependent inhibition of GSK3 in the regulation of water/electrolyte metabolism, mice carrying the PKB/SGK resistant mutant (gsk3 ( KI )) were compared to their wild-type littermates (gsk3 ( WT ) ). Body weight was similar in gsk3 ( KI ) and gsk3 ( WT ) mice. Plasma aldosterone at 10 A.M: . and corticosterone concentrations at 5 P.M: . were significantly lower, but 24-h urinary aldosterone was significantly higher, and corticosterone excretion tended to be higher in gsk3 ( KI ) than in gsk3 ( WT ) mice. Food and water intake, fecal excretion, glomerular filtration rate, urinary flow rate, urine osmolarity, as well as urinary Na+, K+, urea excretion were significantly larger, and plasma Na+, urea, but not K+ concentration, were significantly lower in gsk3 ( KI ) than in gsk3 ( WT ) mice. Body temperature was significantly higher in gsk3 ( KI ) than in gsk3 ( WT ) mice. When allowed to choose between tap water and saline, gsk3 ( WT ) mice drank more saline, whereas gsk3 ( KI ) mice drank similar large volumes of tap water and saline. During high-salt diet, urinary vasopressin excretion increased to significantly higher levels in gsk3 ( KI ) than in gsk3 ( WT ) mice. After water deprivation, body weight decreased faster in gsk3 ( KI ) than in gsk3 ( WT ) mice. Blood pressure, however, was significantly higher in gsk3 ( KI ) than in gsk3 ( WT ) mice. The observations disclose a role of PKB/SGK-dependent GSK3 activity in the regulation of steroid hormone release, renal water and electrolyte excretion and blood pressure control.

Avian kidneys have loopless and looped nephrons; a countercurrent multiplier mechanism operates in the latter by NaCl recycling. We identified an aquaporin-2 (AQP2) homolog in apical/subapical regions of cortical and medullary collecting duct (CD) cells in kidneys of Japanese quail (q), Coturnix japonica. We investigated whether undernutrition during the embryonic/maturation period retards kidney and AQP2 development in quail and programs impaired volume regulation in adults. Protocols included 1) time course and 2) effects of 5-10% egg white withdrawal (EwW) or 48-h post-hatch food deprivation (FD) on nephron growth and qAQP2 mRNA expression, and 3) effects of EwW and FD on qAQP2 mRNA responses to 72-h water deprivation in adults. In metanephric kidneys, qAQP2 mRNA is expressed in medullary CDs at embryonic day 10; distribution and intensity increase during maturation. The number and size of glomeruli continue to increase after birth, whereas nephrogenic zones decrease. In EwW embryos, qAQP2 mRNA expression is initially delayed, then restored; birth weight and hatching rate are lower than in controls. Adults from EwW embryos and FD chicks have fewer (P < 0.01) glomeruli. Water deprivation reduces body weight more in EwW birds than in controls. The results suggest that qAQP2 evolved in metanephric kidneys and that undernutrition may retard nephrogenesis, leading to impaired adult water homeostasis.

Cutaneous leishmaniasis has been recognized as a major public health problem in several countries. Pentavalent antimonies, meglumine antimoniate and sodium stibogluconate, have been considered as standard treatment for leishmaniasis. Side effects have been reported to be increased hepatic enzyme levels and electrocardiographic abnormalities. We performed this study to evaluate the influence of meglumine antimoniate on some liver, kidney, and pancreas function tests. Eighty patients fulfilled the study criteria. Forty-one (51.3%) patients were female and the mean age of the patients was 30.4 +/- 15.7 years. Blood samples were taken to evaluate liver, kidney, and pancreas function tests before and after treatment with intramuscular injections of MA at a dose of 20 mg Sb(+5)/kg/day for 15 days. Mean serum levels of blood urea nitrogen, creatinine, sodium, total and direct bilirubin, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase significantly increased after treatment, although most of them were within normal ranges. There were no significant differences in serum levels of potassium, amylase, lipase, and gamma-glutamyl transpeptidase before and after treatment. In conclusion it can be stated that one course of treatment with 20 mg Sb(+5)/kg/day MA for 15 days does not significantly alter the liver, kidney and pancreas function tests in patients with cutaneous Leishmaniasis.

Cadmium fluoride (CdF) is commonly used as an insulator for ulta high speed mass telecommunications equipment, and there is a considerable risk that industrial workers will inhale CdF particles. Despite the possibility that acute exposure can cause harmful systemic effects, there are no studies to date that address the health consequences of acute CdF exposure. This study therefore aimed to determine the acute lethal dose of CdF and its effects on various target organs, including the liver and kidney. We also determined the effect of CdF on serum electrolytes and acid-base balance. The effective lethal dose was determined and dose-response study was conducted after intravenous administration of CdF in rats. The 24 h LD(50) of CdF was determined to be 3.29 mg/kg. The dose-response study used doses of 1.34, 2.67, 4.01 mg/kg CdF. Saline or sodium fluoride solution were used for controles. Severe hepatocellular injury was induced at doses greater than 2.67 mg/kg, as demonstrated by AST and ALT activities greater than 1,500 IU/l in rats injected with a dose of 4.01 mg/kg. Acute renal failure was induced at doses greater than 2.67 mg/kg. Decreased serum Ca, increased serum K and metabolic acidosis were induced at a dose of 4.01 mg/kg. Decreased serum Ca was caused by exposure to ionized F. CdF has the strongest lethal and hepatic toxicity among all Cd containing compounds.

Objective: To study the effect of extracellular matrix of xenogenic femoral fascia in repair of renal trauma., Methods: Twelve adult dogs were used and randomly assigned to 6 groups, and the animals were sacrificed separately in 1 and 2 weeks 1,2,4 and 8 months after renal repair operations. The examinations of blood and urine routine, blood urea nitrogen and creatinine, electrolyte and serum renin were performed before and after operations at various times. The creatinine clearances of affected and contralateral normal kidneys were evaluated before death and the local areas of renal repair were studied by light and electron microscopy., Results: Bleeding was stopped completely after the entire patch was sutured, and only mild adhesions to around tissues were found in various times after operations. As time passed, the repair patch was replaced by smooth neocapsule like normal renal capsule., Conclusion: Extracellular matrix of xenogenic femoral fascia might be an ideal tissue engineering material for renal repair.

Serum- and glucocorticoid-inducible kinase (SGK1) is transcriptionally upregulated by mineralocorticoids and activated by insulin. The kinase stimulates the renal epithelial Na(+) channel and may thus participate in blood pressure regulation. Hyperinsulinemia is triggered by dietary fructose, which sensitizes blood pressure for salt intake. The role of SGK1 in hypertensive effects of combined fructose and high-salt intake was thus explored in SGK1 knockout mice (sgk1(-/-)) and their wild-type littermates (sgk1(+/+)). Renal SGK1 transcript levels of sgk1(+/+) mice were significantly elevated after fructose diet. Under control diet, fluid intake, urinary flow rate, urinary Na(+), K(+), and Cl(-) excretion, and blood pressure were similar in sgk1(-/-) and sgk1(+/+) mice. Addition of 10% fructose to drinking water increased fluid intake and urinary flow rate in both genotypes, and did not significantly alter urinary Na(+), K(+), and Cl(-) output in either genotype. Additional high NaCl diet (4% NaCl) did not significantly alter fluid intake and urine volume but markedly increased urinary output of Na(+) and Cl(-), approaching values significantly (P < 0.05) larger in sgk1(-/-) than in sgk1(+/+) mice (Na(+): 2,572 +/- 462 vs. 1,428 +/- 236; Cl(-): 2,364 +/- 388 vs. 1,379 +/- 225 micromol/24 h). Blood pressure was similar in sgk1(+/+) and sgk1(-/-) mice at control diet or fructose alone but increased only in sgk1(+/+) mice (115 +/- 1 vs. 103 +/- 0.7 mmHg, P < 0.05) after combined fructose and high-salt intake. Acute intravenous insulin infusion (during glucose clamp) caused antinatriuresis in sgk1(+/+) mice, an effect significantly blunted in sgk1(-/-) mice. The observations reveal a pivotal role of SGK1 in insulin-mediated sodium retention and the salt-sensitizing hypertensive effect of high fructose intake.

Chronic metabolic acidosis induces dramatic increases in net acid excretion that are predominantly due to increases in urinary ammonia excretion. The current study examines whether this increase is associated with changes in the expression of the renal ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). Chronic metabolic acidosis was induced in Sprague-Dawley rats by HCl ingestion for 1 wk; control animals were pair-fed. After 1 wk, metabolic acidosis had developed, and urinary ammonia excretion increased significantly. Rhcg protein expression was increased in both the outer medulla and the base of the inner medulla. Intercalated cells in the outer medullary collecting duct (OMCD) and in the inner medullary collecting duct (IMCD) in acid-loaded animals protruded into the tubule lumen and had a sharp, discrete band of apical Rhcg immunoreactivity, compared with a flatter cell profile and a broad band of apical immunolabel in control kidneys. In addition, basolateral Rhcg immunoreactivity was observed in both control and acidotic kidneys. Cortical Rhcg protein expression and immunoreactivity were not detectably altered. Rhcg mRNA expression was not significantly altered in the cortex, outer medulla, or inner medulla by chronic metabolic acidosis. Rhbg protein and mRNA expression were unchanged in the cortex, outer and inner medulla, and no changes in Rhbg immunolabel were evident in these regions. We conclude that chronic metabolic acidosis increases Rhcg protein expression in intercalated cells in the OMCD and in the IMCD, where it is likely to mediate an important role in the increased urinary ammonia excretion.

To explore the effects of decreased amounts or absence of aldosterone, we have disrupted the gene coding for aldosterone synthase (AS) in mice and investigated blood pressure and kidney function in AS+/+, AS+/-, and AS-/- mice. AS+/- mice have normal blood pressures and show no abnormalities in electrolytes or kidney gene expression, but they have significantly higher than normal urine volume and lower urine osmolality. In contrast, the AS-/- mice have low blood pressure, abnormal electrolyte homeostasis (increased plasma concentrations of K+, Ca2+, and Mg2+ and decreased concentrations of HCO3(-) and Cl- but no difference in the plasma Na+ level), and disturbances in water metabolism (higher urine output, decreased urine osmolality, and impaired urine concentrating and diluting ability). Absence of aldosterone in the AS-/- mice induced several compensatory changes: an increased food intake-to-body weight ratio, an elevated plasma concentration of glucocorticoids, and strong activation of the renin-angiotensin system. Parallel with the markedly increased synthesis and release of renin, the AS-/- mice showed increased expression of cyclooxygenase-2 (COX-2) in macula densa. On salt supplementation, plasma electrolyte concentrations and kidney renin and COX-2 levels became similar to those of wild-type mice, but the lower blood pressure of the AS-/- mice was not corrected. Thus absence of aldosterone in AS-/- mice results in impairment of Na+ reabsorption in the distal nephron, decreased blood pressure, and strong renin-angiotensin system activation. Our data show the substantial correction of these abnormalities, except the low blood pressure, by high dietary salt does not depend on aldosterone.

In recreational cyclists marathon cycling influences renal function only on a minimal scale. Respective information on extreme ultramarathon cycling in better trained athletes is not available. The objective was to evaluate the renal and haematological effects of ultraendurance cycling in the world's best ultramarathon cyclists. Creatinine (CR), urea, haemoglobin (Hb), haematocrit (Hct) and plasma volume (PV) were investigated in 16 male ultramarathon cyclists during the 1st Race Across the Alps in 2001 (distance: 525 km; cumulative altitude difference: 12,600 m). All renal functional parameters were normal pre-exercise. During the race serum CR, urea and uric acid rose significantly by 33, 97 % and 18 % (p <0.001 respectively) and nearly normalised again on the following day. The decline in calculated CR clearance was 25 %. There was a negative correlation (r=- 0.575, p=0.02) between the rise in serum CR and the athlete's training kilometers. The serum urea/CR ratio rose above 40 in 12 athletes (75 %). Mean fractional sodium excretion and fractional uric acid excretion fell below 0.5 % (p <0.001) and 7 %, indicating reduced renal perfusion. The deflection of the renal functional parameters was temporary and nearly gone after 24 hours of recovery. Hct declined during the race from 0.44 to 0.42, and continued falling on the next day (0.42 --> 0.40; p <0.001). The corresponding rises in calculated PV were + 8 % and + 22 %. The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale. The impact on the PV, however, is pronounced leading to marked haemodilution post-exercise. This very temporary "impairment of renal function" seems to be the physiological response to ultramarathon cycling and may be attenuated to some extent by preceding high-volume training.

The syndrome of inappropriate antidiuretic hormone (SIADH) is associated with water retention and hyponatremia. The kidney adapts via a transient natriuresis and persistent diuresis, i.e., vasopressin escape. Previously, we showed an increase in the whole kidney abundance of aldosterone-sensitive proteins, the alpha- and gamma (70-kDa-band)-subunits of the epithelial Na(+) channel (ENaC), and the thiazide-sensitive Na-Cl cotransporter (NCC) in our rat model of SIADH. Here we examine mean arterial pressure via radiotelemetry, aldosterone activity, and cortical vs. medullary ENaC subunit and 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD-2) protein abundances in escape. Eighteen male Sprague-Dawley rats (300 g) were sham operated (n = 6) or infused with desmopressin (dDAVP; n = 12, a V(2) receptor-selective analog of AVP). After 4 days, one-half of the rats receiving dDAVP were switched to a liquid diet, i.e., water loaded (WL) for 5-7 additional days. The WL rats had a sustained increase in urine volume and blood pressure (122 vs. 104 mmHg, P < 0.03, at 7 days). Urine and plasma aldosterone levels were increased in the WL group to 844 and 1,658% of the dDAVP group, respectively. NCC and alpha- and gamma-ENaC (70-kDa band) were increased significantly in the WL group (relative to dDAVP), only in the cortex. Beta- and gamma-ENaC (85-kDa band) were increased significantly by dDAVP in cortex and medulla relative to control. 11beta-HSD-2 was increased by dDAVP in the cortex and not significantly affected by water loading. These changes may serve to attenuate Na(+) losses and ameliorate hyponatremia in vasopressin escape.

A new maintenance fluid containing sodium acetate as the base component and electrolytes (Veen 3G, test preparation) for a maximum of 24 h was infused to 15 patients hospitalized for renal biopsies and requiring intravenous supplements of water, electrolytes and energy because oral or enteric ingestion was inadequate or impossible. A physical examination, blood chemistry tests and urinalysis were performed, and the global improvement rating was obtained by scoring the effects on a) maintenance of cardiovascular hemodynamics (systolic blood pressure), b) blood glucose control (blood glucose level), c) utilization of sugar (free fatty acids, total ketone bodies), d) maintenance of serum electrolytes, e) amount of sugar excreted in the urine and f) maintenance of urinary volume. The results were excellent or good in all of the 15 patients analyzed. The test agent was not the direct cause of any adverse events or abnormal changes in laboratory findings, and no safety-related problems were observed in any of the patients. These results indicated that the test preparation used in this study is a clinically useful and highly safe fluid agent.

Objectives: Nephropathy is a well-recognised complication of diabetes mellitus (DM). The aim of this study was to investigate the effect of DM on the density and distribution of nitric oxide (NO) synthase (NOS) in the rabbit kidney. Quantification of the NOS radioligand on slide-mounted sections was compared with the nitroblue tetrazolium reaction, where the intensity of the reaction varies with the nicotinamide adenine dinucleotide diaphorase (NADPH-d) activity of NOS., Materials and Methods: DM was induced with alloxan in six New Zealand White (NZW) rabbits. Plasma creatinine, urea and electrolytes were monitored at monthly intervals. The kidneys were removed following 6 months of DM. Transverse serial sections were cut and low-resolution autoradiography was performed using a radioligand for NOS ([(3)H]-NOARG). Histochemical localisation of NADPH-d activity was also performed. Densitometric analysis was performed on the autoradiographs and the results compared with those obtained from six age-matched control rabbits., Results: There was a significant (p < 0.01) rise in plasma creatinine levels in the diabetic rabbits, although the mean values remained within the reference range. There was a significant (p < 0.0001) down-regulation of NOS binding sites in both the cortex and medulla of the DM kidney when compared with the controls. A similar decrease in NADPH-d activity was seen in the diabetic renal cortex and medulla. In addition, NADPH-d activity also appeared to be reduced in the diabetic glomeruli when compared with controls., Conclusions: NOS binding sites and NADPH-d activity are significantly decreased in the DM renal cortex and medulla. These changes are associated with a mild deterioration in renal function and may be an early event that could subsequently play a role in the progression of DM nephropathy. Manipulating the NO pathway during the early stages of DM nephropathy may be beneficial.

To determine whether damage to the fetal kidneys plays a role in the formation of hydrops fetalis following a severe asphyxial episode, six chronically catheterised fetal sheep, at 0.6 gestation (90 days; term 150 days), were subjected to 30 min of complete umbilical cord occlusion. During the occlusion period, mean arterial pressure, heart rate and renal blood flow decreased (P < 0.001). There were falls in arterial pH and PO2 and a rise in PCO2 (P < 0.001). Urine flow rate decreased (P < 0.005), as did the excretion rates of sodium and osmoles (P < 0.05). However, by 60 min after release of occlusion, urine flow rate was similar to control values. By the end of day 1, most renal variables returned to normal. At post-mortem, 72 h after occlusion, all asphyxiated fetuses showed gross signs of hydrops. Body weight was higher (P < 0.05) due to fluid accumulation in the peritoneal (P < 0.001) and pleural cavities (P < 0.05) as well as subcutaneously (P < 0.05). Amniotic/allantoic fluid volume was increased (P < 0.05). Kidney histology was normal except for clusters of apoptotic cells in some proximal tubules. In conclusion, this severe asphyxial episode caused surprisingly little damage to the kidney and the changes in renal function were very transient. Thus renal damage was not important in the development of hydrops. Possibly, the midgestation fetal kidney has a limited capacity to increase urinary salt and water excretion in response to increased fluid delivery across the placenta.

The stress of strenuous long-term exercise may alter renal function. Whether this is also true for marathon cycling is unknown so far. The purpose of this study was to evaluate renal function following competitive marathon cycling. We investigated 38-male, well-trained recreational cyclists credibly not taking any kind of doping who participated in the Otztal Radmarathon. Blood and urine specimens were taken the day before, immediately after and one day after competition. Baseline renal functional parameters--normal before competition--increased significantly afterwards and remained elevated during 24 hours of recovery. The rises in serum creatinine, urea and uric acid were 20, 54 and 42 % (p < 0.001 respectively). The corresponding decline in estimated creatinine clearance was 18 %. In all athletes the serum urea/creatinine ratio rose above 40, fractional sodium excretion and fractional uric acid excretion fell below 0.4 % and 15 %, indicating reduced renal perfusion. The observed effects lasted for at least 24 h despite a stable fluid balance during the race and an expanding plasma volume (PV) in the recovery period. Levels of haematocrit remained unchanged immediately post-race but significantly declined from 0.44 to 0.41 on the following day (p < 0.001). The calculated rise in PV was + 10.8 %. Electrolyte homeostasis was preserved throughout the observation period. Post-exercise proteinuria was small and of the mixed glomerular-tubular type. There was neither evidence for exercise-induced haemolysis, nor for significant skeletal muscle damage. The finding obtained from well-hydrated recreational athletes reveals that the extraordinary strains of marathon cycling influence renal function only on a minimal scale. Though minor, the physiological effects were long-lasting. The results obtained suggest that a reduced renal perfusion is the mechanism responsible for the slight impairment of renal function following exhaustive marathon cycling.

To test the role of epithelial Na channels in the day-to-day regulation of renal Na excretion, rats were infused via osmotic minipumps with the Na channel blocker amiloride at rates that achieved drug concentrations of 2-5 microM in the lumen of the distal nephron. Daily Na excretion rates were unchanged, although amiloride-treated animals tended to excrete more Na in the afternoon and less in the late evening than controls. When the rats were given a low-Na diet, Na excretion rates were elevated in the amiloride-treated group within 4 h and remained higher than controls for at least 48 h. Adrenalectomized animals responded similarly to the low-Na diet. In contrast, rats infused with polythiazide at rates designed to inhibit NaCl transport in the distal tubule were able to conserve Na as well as did the controls. Injection of aldosterone (2 microg/100 g body wt) decreased Na excretion in control animals after a 1-h delay. This effect was largely abolished in amiloride-treated rats. On the basis of quantitative analysis of the results, we conclude that activation of amiloride-sensitive channels by mineralocorticoids accounts for 50-80% of the immediate natriuretic response of the kidney to a reduction in Na intake. Furthermore, the channels are necessary to achieve minimal rates of Na excretion during more chronic Na deprivation.

The purpose of the present study was to determine whether the training-induced hypervolaemic response seen in the horse is associated with aldosterone-mediated renal mechanisms affecting sodium conservation during the first days of training. Five healthy, Standardbred mares (weight 450-500 kg, age 4-8 years) that were unfit, but accustomed to running on the treadmill, were used to test the hypothesis that repeated submaximal exercise would alter plasma aldosterone (ALDO) concentration and renal excretion of electrolytes in horses within the first 3 days of training. The experiment consisted of a 2 week housing equilibration period followed by a 1 week control period and a 3 day exercise training period (30 min/day at 60% VO2max). During control, ALDO and renal fluid and electrolyte losses were measured for 24 h on 3 separate days. Renal function (urine volume [UV], 24 h excretion of Na+, K+ and Cl- [UNA+ V, UK+ V, UCl- V], clearance of Na+ [CNa+], K+ [CK+] and Cl- [CCl-], creatinine [CCr], osmotic substances [Cosm], and solute-free water [FWC], and the fractional excretion of Na+, K+ and Cl-) and ALDO were measured for an additional 3 consecutive days during the training period. There were no differences (P>0.05) in any variable during the control period. Plasma volume increased (+18.7%, P<0.05) after 3 days of training. During training, there were no significant changes in plasma osmolality, electrolyte concentrations or CCr. Training caused decreases (P<0.05) in UV (-30%), UNA+ V (-73%), UK+ V, (-55%) and UCl- V (-70%). Training also caused decreases (P<0.05) in Cosm (-30%), through decreases in CNa+ (-60%), CK+ (-60%), and CCl- (-66%). Interestingly, FWC increased (+30%, P<0.05), whereas, there were significant decreases in the fractional excretion of Na+ (-59%), K+ (-48%) and Cl- (-60%). Training caused substantial elevations in both pre-exercise (967%, P<0.05) and postexercise (+3013%, P<0.05) plasma ALDO concentrations suggesting an increase in both basal levels and the responsiveness to acute exercise. Together, these observations suggest that mechanisms affecting tubular conservation of electrolytes contribute to the early response to training. However, it is also concluded that renal mechanisms appear to be only part of the mechanism for conserving sodium and water intake as well as training-induced changes in gastrointestinal mechanisms affecting electrolyte and water balance.

Gitelman's syndrome is a variant of Bartter's syndrome characterized by hypocalciuria and hypomagnesemia. The administration of thiazide diuretics may induce a subnormal increase of urinary Na+ and Cl- excretion in patients with Gitelman's syndrome, consistent with the hypothesis that less Na+ and Cl- than normal is reabsorbed by the thiazide-inhibitable transporter in Gitelman's syndrome. Specific mutations of NaCl cotransporter, coupled with mutant NaCl cotransporter expression studies clearly demonstrated that many of the characteristics of individuals with Gitelman's syndrome are explained by lack of function of NaCl cotransporter. We recently diagnosed a patient with Gitelman's syndrome by performing the thiazide and furosemide tests, and it is suggested that the clearance studies by diuretic administration may be of diagnostic help in Gitelman's syndrome.