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

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

Fungal peritonitis is one of the leading causes of patient dropout from continuous ambulatory peritoneal dialysis (CAPD) therapy. Although the most causative agents of peritonitis associated with CAPD are bacteria, fungi are implicated in up to 10% of cases. The most common organism of fungal peritonitis is Candida specises, but Trichosporon beigelii was reported as a rare causative agent of fungal peritonitis. We experienced a case of CAPD peritonitis by Trichosporon beigelii, which was treated with CAPD catheter removal, and antifungal agents with amphotericin B and fluconazole. Thus, we report our experience of CAPD peritonitis caused by Trichosporon beigelii and review of the literature.
Amphotericin B ; Antifungal Agents ; Bacteria ; Candida ; Catheters ; Fluconazole ; Fungi ; Humans ; Patient Dropouts ; Peritoneal Dialysis, Continuous Ambulatory* ; Peritonitis* ; Trichosporon*

BACKGROUND: The antidiuretic action of oxytocin in human has been controversial. To investigate whether oxytocin directly acts on water balance in human, we evaluated the parameters of urinary concentration in response to administration of oxytocin in ten healthy male volunteers. METHODS: Oxytocin was infused intravenously at a rate of 20 mU/hour for 2.5 hours and urine was collected during the last 2 hours of oxytocin infusion. Changes in urine volume, urine osmolality, excretions of urine electrolytes and free water clearance after the administrartion of oxytocin were compared with the baseline data. RESULTS: The changes in the levels of serum electrolytes and osmolality after the administration of oxytocin were not significant compared with the baseline data. The volume of 2 hours' urine were 446+/-75 mL and 289+/-53 mL in the basal state and after the administration of oxytocin, respectively. The urine osmolality was increased significantly by the infusion of oxytocin(427+/-63 mOsm/kg) compared with that in the basal state(223+/-25 mOsm/kg)(p < 0.05). The free water clearance was 110+/-51 mL/2 hours in the basal state and decreased significantly to -57+/-51 mL/2 hours(p < 0.05). CONCLUSION: We conclude that administration of oxytocin to normal men enhances urinary concentration, evidenced by increased urinary osmolality and decreased free water clearance. In human, oxytocin may play an important role in the regulation of renal water excretion as an antidiuretic hormone.
Electrolytes ; Humans ; Male ; Osmolar Concentration ; Oxytocin* ; Volunteers ; Water

Membranous nephropathy is one of the most common causes of the nephrotic syndrome in adults. Membranous nephropathy is known as a disease associated with many other disorders and the presumed etiology of the disease is a deposition of circulating immune complexes. But, it has rarely been reported in association with autoimmune thyroiditis. We report a case of membranous nephropathy associated with Graves' disease and review the literature regarding this disease entity.
Adult ; Antigen-Antibody Complex ; Glomerulonephritis ; Glomerulonephritis, Membranous* ; Graves Disease* ; Humans ; Immune Complex Diseases ; Nephrotic Syndrome ; Thyroiditis ; Thyroiditis, Autoimmune

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

Mineralocorticoids influences on acid-base homeostasis by the regulation of urine acidification. But its mechanism of acion is not well known in human. This study compared the acid-base status and the indices of urine acidification before and after mineralocorticoid administration in human, and analyzed the effect of mineralocorticoids on human acid-base homeostasis. We administered 9a-fludrocortisone in 6 chronic renal failure patients and 6 normal controls 0.5mg daily for 7 days. The results were as following: 1) After administration of 9a-fludrocortisone in patients group, serum aldosterone level changed from 120.2+/-71.0pg/mL to 44.8+/-32.2pg/mL(mean+/-SD, p< 0.05). Serum HCO- level was not changed. Urine ammonium excretion was incresed from 24.6+/-12.3 mmol/day to 43.7+/-19.0 (p<0.05), but there were no change in urine pH and urine anion gap, Serum potassium level decreased from 5.5+/-0.7mBq/L to 4.1+/-0.5mEq/L (p<0.05), and TTKG increased from 3.9 to 8.9(p<0.05). 2) After administration of 9a-fludrocortisone in control group, serum aldosterone level changed from 99.7+/-44.5pg/mL to 25.1+/-3 mL(p<0.05). Serum HCO- level was not changed. Urine ammonium excretion was incresed from 44.3+/-21.6mmoVday to 76.3+/-19.6(p<0.05), but there were no change in urine pH and urine anion gap. Serum potassium level decreased from 4.8+/-0.5mEq/L to 3.9+/-0.2mHq/L(p< 0.05), but there was no change in TTKG. 3) No patient or control showed any discomfort after 9-fludrocortisone administration, and there was no elevation in diastolic blood pressure, increase in body weight, electrolyte abnormality. In summary, after 9alpha-fludrocortisane administration, urinary ammonium excretion increased in both patients and control group, and this phenomenon occured with correction of hyperkalemia without urine pH change. This result implies urinary ammonium excretion increase by mineralocorticoid. In human increase in renal distal acidification by mineralocorticoid is due to increase in renal ammoniagenesis rather than stimulation on proton excretion.
Acid-Base Equilibrium ; Aldosterone ; Ammonium Compounds* ; Blood Pressure ; Body Weight ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Hyperkalemia ; Kidney Failure, Chronic ; Mineralocorticoids ; Potassium* ; Protons