Plasma calcium concentration is maintained within a narrow range (8.5-10.5 mg/dL) by the coordinated action of parathyroid hormone (PTH), 1,25(OH)2D3, calcitonin, and ionized calcium (iCa2+) itself. The kidney plays a key role in this process by the fine regulation of calcium excretion. More than 95% of filtered calcium is reabsorbed along the renal tubules. In the proximal tubules, 60% of filtered calcium is reabsorbed by passive mechanisms. In the thick ascending limb, 15% of calcium is reabsorbed by paracellular diffusion through paracellin-1 (claudin-16). The calcium sensing receptor (CaSR) in the basolateral membrane of the thick ascending limb senses the change in iCa2+ and inhibits calcium reabsorption independent to PTH and 1,25(OH)2D3. The fine regulation of calcium excretion occurs in the distal convoluted tubules and connecting tubules despite the fact that only 10-15% of filtered calcium is reabsorbed there. Transient receptor potential vanilloid 5 (TRPV5) and 6 (TRPV6) in the apical membrane act as the main portal of entry, calbindin-D28K delivers Ca2+ in the cytoplasm, and then Na2+/Ca2+ exchanger (NCX1) and plasma membrane Ca2+-ATPase in the basolateral membrane serve as an exit. In the cortical collecting duct, TRPV6 is expressed, but the role might be negligible. In addition to PTH and 1,25(OH)2D3, acid-base disturbance, diuretics, and estrogen affect on these calcium channels. Recently, klotho and fibroblast growth factor 23 (FGF23) are suggested as new players in the calcium metabolism. Klotho is exclusively expressed in the kidney and co-localized with TRPV5, NCX1, and calbindin-D28K. Klotho increases calcium reabsorption through trafficking of TRPV5 to the plasma membrane, and also converts FGF receptor to the specific FGF23 receptor. FGF23:klotho complex bound to FGF receptor inhibits 1alpha- hydroxylase of vitamin D, and contributes to calcium reabsorption and phosphate excretion in the kidney.
Calcitonin ; Calcium ; Calcium Channels ; Calcium-Binding Protein, Vitamin D-Dependent ; Cell Membrane ; Cytoplasm ; Diffusion ; Diuretics ; Estrogens ; Extremities ; Fibroblast Growth Factors ; Homeostasis ; Kidney ; Membranes ; Parathyroid Hormone ; Plasma ; Receptors, Calcium-Sensing ; Receptors, Fibroblast Growth Factor ; TRPV Cation Channels ; Vitamin D

Diuretic drugs are the most commonly used agents to control edema or volume overload. However, the clinical use of diuretics is not confined to edema control. Recently, diuretics have been revisited for the management of various diseases, including hypertension and congestive heart failure. Diuretics are classified mainly by their sites of action in the renal tubules, and have unique characteristics and adverse effects according to their mechanisms of action. To use diuretics adequately, it is very important to understand their characteristics.
Diuretics ; Edema ; Heart Failure ; Hypertension

Hypematremia is a rare but important medical condition and is associated with mortality rate of 40 to 70%. However, little has been known about its prognostic factors or treatment guidlines. To evaluate the prognostic factors and the outcome following treatment, we reviewed 22 available medical records among twenty five hypernatremic patients (0.2%) in 12841 admissions at medical ward from January to December 1995. We defined hypernatremia as serum sodium concentration more than or equal to 150 mEq/L. Of these patients, two had hypematrernia at admission and the remaining patients became hypernatremic during admission. Mean peak serum sodium concentration was 158 (150-178) mEq/L and mean total body water deficit was 11.4 (6.7-21.3)%. Factors correlated with the development of hypernatremia were diverse and multiple, and the most frequent factor was diminished access to water. Mortality rate was 59%, but mortality was not correlated with age, correction rate of hyper-natremia, primary route of fluid loss, and the severity of hypernatremia or total body water deficit. Mortality rate was higher in patients whose serum sodium concentrations were below 130 mEq/L at admission (P<0.05). In our study, development of hypernatremia from initial hyponatremic state was significantly associated with poor outcome, and age, rapidity of correction, route of fluid loss, and the severity of hypernatremia or total body water deficit were not.
Body Water ; Humans ; Hypernatremia* ; Medical Records ; Mortality ; Sodium ; Water

BACKGROUND: Oxytocin is a nonapeptide hormone secreted from posterior pituitary gland and has a very similar structure to vasopressin. The aquaporin-2 (AQP2) water channel is predominantly expressed in the kidney and plays a key role in regulation of water permeability of mammalian collecting duct, exerted by both short-term and long-term vasopressin action. We speculated that oxytocin may be involved in some part of vasopressin-independent urinary concentrating mechanism by regulating AQP2 trafficking in the kidney. METHODS: This study was undertaken to investigate whether and how the acute stimulation of oxytocin induces changes in AQP2 localization in the kidney. Immunohistochemistry and semiquantitative immunoblotting of AQP2 were carried out from Sprague-Dawley rat kidneys after a single intraperitoneal injection of oxytocin with or without pretreatment of a vasopressin-2 receptor (V2R) antagonist. RESULTS: Urinary cAMP excretion was increased by oxytocin administration. Immuno- histochemistry of inner medullary collecting duct (IMCD) revealed that AQP2 was shifted from diffuse cytoplasmic localization in controls to the apical and basolateral membrane domains in oxytocin-treated rats. This pattern of AQP2 redistribution was noted in connecting tubule, cortical collecting duct and outer medullary collecting duct as in IMCD, although the tendency to basolateral localization was somewhat less. Semiquantitative immunoblotting of membrane fractions of whole kidney homogenates was also used to assess redistribution of AQP2. The band density ratio of the plasma membrane-rich fraction over cytoplasmic vesicle-rich fraction was higher in oxytocin-treated rats than in controls (3.64+/-0.60 vs. 1.09+/-0.14, P<0.05). Regarding the receptor pathway of oxytocin action in the kidney, we found that pretreatment with a V2R antagonist (OPC-31260) blocked redistribution of AQP2 which was induced by oxytocin. CONCLUSION: In conclusion, oxytocin induces a V2R-mediated redistribution of AQP2-containing cytoplasmic vesicles to both apical and basolateral plasma membrane domains in rat kidney. Oxytocin may be one of the factors that accounts for vasopressin-independent AQP2 targeting in the kidney.
Animals ; Aquaporin 2* ; Aquaporins ; Cell Membrane ; Cytoplasm ; Cytoplasmic Vesicles ; Immunoblotting ; Immunohistochemistry ; Injections, Intraperitoneal ; Kidney* ; Membranes ; Oxytocin* ; Permeability ; Pituitary Gland, Posterior ; Plasma ; Rats ; Rats, Sprague-Dawley ; Vasopressins ; Water

Enterococcus is a normal flora of the gastrointestinal or genitourinary tract. With the increased use of vancomycin and third generation cephalosporins, vancomycin-resistant enterococci (VRE) have become one of the major nosocomial pathogens in USA and Europe since 1986. In Korea, patients with VRE infection or colonization were increasingly reported recently and VRE may become a serious nosocomial pathogen in the near future. So we report a case of vancomycin-resistant E. faecium peritonitis in a patient on continuous ambulatory peritoneal dialysis.
Cephalosporins ; Colon ; Enterococcus ; Europe ; Humans ; Korea ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritonitis* ; Vancomycin

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. Long Evans Tokushima (LETO) rats were used as controls. Renal sodium transporter regulation was investigated by semiquantitative immunoblotting and immunohistochemistry of the kidneys of 40-week-old animals. The mean serum glucose level in OLETF rats was increased to 235+/-25 mg/dL at 25 weeks, and the hyperglycemia continued up to the end of 40 weeks. Urine protein/ creatinine ratios were 10 times higher in OLETF rats than in LETO rats. At 40th week, the abundance of the epithelial sodium channel (ENaC) beta-subunit was increased in OLETF rats, but the abundance of the ENaC gamma-subunit was decreased. No significant differences were observed in the ENaC alpha-subunit or other major sodium transporters. Immunohistochemistry for the ENaC beta-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC gamma-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC beta-subunit upregulation and ENaC gamma-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance.
Animals ; Blood Glucose/analysis ; Diabetes Mellitus, Type 2/*metabolism ; *Disease Models, Animal ; Epithelial Sodium Channel/*analysis ; Hypertension/complications ; Immunoblotting ; Immunohistochemistry ; Kidney/*metabolism ; Male ; Rats ; Sodium/*metabolism ; Sodium-Hydrogen Antiporter/genetics ; Sodium-Potassium-Chloride Symporters/genetics

Atherosclerosis is a chronic progressive inflammatory disorder and the leading cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell-derived cytokines, such as inteferon (IFN)-gamma, interleukin (IL)-17 and IL-4, during the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice, to understand the role of immune responses in different stages of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat, western-type diet (WD: 21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6 wild-type control mice fed a standard chow diet. Atherosclerotic lesions appeared in the aortic sinus of ApoE(-/-) mice 4 weeks after WD and the lesions progressed and occupied >50% of the total sinus area 16 weeks after WD. Aortic IL-17 mRNA and protein expression started to increase in ApoE(-/-) mice after 4 weeks on the WD and peaked at around 8-12 weeks on the WD. In terms of systemic expression of T-cell-derived cytokines, IL-17 production from splenocytes after anti-CD3/CD28 stimuli increased from 4 weeks on the WD, peaked at 12 weeks and returned to control levels at 16 weeks. The production of IFN-gamma and IL-4 (Th1 and Th2 cytokines, respectively) from splenocytes was delayed compared with IL-17. Taken together, the present data indicate that Th17 cell response may be involved at an early stage in the development of atherosclerosis.
Animals ; Aorta/metabolism/*pathology ; Apolipoproteins E/*genetics ; Atherosclerosis/etiology/*genetics/immunology/*pathology ; Diet, High-Fat/adverse effects ; Gene Deletion ; Interferon-gamma/genetics ; Interleukin-17/*genetics/immunology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes/immunology/metabolism/pathology ; Up-Regulation

Atherosclerosis is a chronic progressive inflammatory disorder and the leading cause of cardiovascular mortality. Here we assessed the dynamic changes of T-cell-derived cytokines, such as inteferon (IFN)-gamma, interleukin (IL)-17 and IL-4, during the progression of atherosclerosis in apolipoprotein E-null (ApoE(-/-)) mice, to understand the role of immune responses in different stages of atherosclerosis. Male ApoE(-/-) mice were fed a high-fat, western-type diet (WD: 21% lipid, 1.5% cholesterol) after 5 weeks of age and were compared with C57BL/6 wild-type control mice fed a standard chow diet. Atherosclerotic lesions appeared in the aortic sinus of ApoE(-/-) mice 4 weeks after WD and the lesions progressed and occupied >50% of the total sinus area 16 weeks after WD. Aortic IL-17 mRNA and protein expression started to increase in ApoE(-/-) mice after 4 weeks on the WD and peaked at around 8-12 weeks on the WD. In terms of systemic expression of T-cell-derived cytokines, IL-17 production from splenocytes after anti-CD3/CD28 stimuli increased from 4 weeks on the WD, peaked at 12 weeks and returned to control levels at 16 weeks. The production of IFN-gamma and IL-4 (Th1 and Th2 cytokines, respectively) from splenocytes was delayed compared with IL-17. Taken together, the present data indicate that Th17 cell response may be involved at an early stage in the development of atherosclerosis.
Animals ; Aorta/metabolism/*pathology ; Apolipoproteins E/*genetics ; Atherosclerosis/etiology/*genetics/immunology/*pathology ; Diet, High-Fat/adverse effects ; Gene Deletion ; Interferon-gamma/genetics ; Interleukin-17/*genetics/immunology ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; T-Lymphocytes/immunology/metabolism/pathology ; Up-Regulation

Alcohol can cause rhabdomyolysis by either direct toxicity or associated metabolic abnormality such as hypophosphatemia and hypokalemia. It can also predispose to or cause trauma, seizures, or coma- induced ischemic pressure necrosis. In order to investigate the clinical features of acute renal failure caused by alcohol induced rhabdomyolysis, we reviewed the medical records of the 12 patients. All patients had been drinking much amounts of alcohol for several years. All patients showed elevation of muscle enzyme such as creatine phosphokinase, lactic dehydrogenase, aspartate transaminase and blood urea nitrogen and serum creatinine. Predisposing factors of rhabdomyolysis were ischemic compression due to unconsciousness and dehydration(2 cases), and hypophosphatemia and dehydration(1 case), seizure and dehydration(1 case), and only severe dehydration(3 cases). Initial symptoms were painful swelling at lesion site(5 cases), abdominal pain(2 cases), general ache(2 cases), leg pain without swelling(1 case), dyspnea(1case), and lethargy(1 case). Seven patients developed delirium tremens during recovery stage. Eight patients showed oliguric acute renal failure and 8 patients were treated with hemodialysis. Complications were disseminated intravascular coagulation(DIC)(3 cases), compartment syndrome(2 cases), capillary leak syndrome and DIC(1 case). One of 12 patients died of disseminated intravascular coagulation and other patients showed complete recovery of renal function.
Acidosis* ; Acute Kidney Injury ; Alcohol Withdrawal Delirium ; Aspartate Aminotransferases ; Blood Urea Nitrogen ; Capillary Leak Syndrome ; Causality ; Creatine Kinase ; Creatinine ; Disseminated Intravascular Coagulation ; Drinking ; Humans ; Hypokalemia ; Hypophosphatemia ; Leg ; Medical Records ; Necrosis ; Oxidoreductases ; Renal Dialysis ; Rhabdomyolysis ; Seizures ; Unconsciousness

BACKGROUND: Sodium retention occurs in some patients taking NSAIDs (nonsteroidal anti-inflammatory drugs). Although the renal effects of NSAIDs are predominantly mediated through the inhibition of prostaglandins synthesized by cyclooxygenase-2 (COX-2), the mechanisms of sodium retention are not clear at the sodium transporter levels in the kidney. Previous studies have shown that compensatory upregulation of COX-2 is induced in renal medulla by high salt intake and that NSAID-induced sodium retention may be transitory. METHODS: To investigate whether renal sodium transporter abundances are altered by NSAID administration and whether renal sodium transporter abundances are affected by high salt intake or chronic NSAID administration, we performed an acute study treated with a single injection of diclofenac and another chronic study treated with 7 days' administration of DFU, a selective COX-2 inhibitor, using semiquantitative immunobotting from rat kidneys. Male Sprague-Dawley rats were divided into three groups in each study: controls, NSAID treatment, and high-salt intake plus NSAID treatment. The control diet contained sodium 1 mmol/200 g BW/day, and the high-salt diet 10 mmol/200 g BW/day. RESULTS: The acute study using diclofenac (100 mg/kg BW) increased the abundances of NKCC2 (by 73%) and ENaC-alpha (by 60%) in cortex and of NKCC2 (by 165%) and ENaC-alpha (by 91%) in outer medulla, in association with a significant decrease in urinary sodium excretion. The increased ENaC-alpha abundance was reversed by addition of high salt intake in both cortex and outer medulla. The chronic study using DFU (40 mg/kg/d for 7 days) showed no significant changes in distal renal sodium transporters except a decreased abundance of Na-K- ATPase alpha1-subunit (by 24%) in outer medulla. The addition of high salt intake decreased the abundances of ENaC-alpha (by 35%) and ENaC-beta (by 47 %) in outer medulla. CONCLUSION: The abundances of thick ascending limb NKCC2 and collecting duct ENaC are altered in response to NSAID administration. It is suggested that NKCC2 & ENaC are contributory to NSAID- induced sodium retention and also have a compensatory role in high salt intake and chronic NSAID administration.
Adenosine Triphosphatases ; Animals ; Anti-Inflammatory Agents, Non-Steroidal ; Cyclooxygenase 2 ; Diclofenac ; Diet ; Extremities ; Humans ; Kidney ; Male ; Prostaglandins ; Rats ; Rats, Sprague-Dawley ; Sodium* ; Up-Regulation