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

The aim of this cross-over study was to investigate whether albumin infusion before furosemide administration could potentiate the diuretic action of furosemide. Seven patients with nephrotic syndrome were given the following infusions in random order on two separate days: 1) a sham solution followed by 160 mg of furosemide, 2) 100 ml of 20% human albumin followed by 160 mg of furosemide. Urine and serum furosemide concentrations were measured by high-performance liquid chromatography. The increment of urine volume was greater in albumin preinfusion than in furosemide alone. However, the increments of sodium and chloride excretions between furosemide alone and albumin preinfusion were not different. No significant differences in the pharmacokinetic parameters between the two treatments were observed: area under the concentration-time curve (AUC: 12.7+/-2.2 vs 15.1+/-4.4 g/ml hr), total plasma clearance (253+/-41 vs 256+/-54 ml/min), volume of distribution (341+/-34 vs 494+/-153 ml/kg), elimination half life (4.0+/-1.1 vs 4.6+/-0.8 hr), and urine furosemide excretion of the administered amount (16.5+/-7.3 vs 7.5+/-1.6%). In conclusion, these data show that albumin preinfusion potentiated diuresis, but not natriuresis, of furosemide without any change in the pharmacokinetics of the agent in patients with nephrotic syndrome.
Adolescence ; Adult ; Aged ; Albumins/*pharmacology ; Cross-Over Studies ; Diuretics/*pharmacology ; Drug Synergism ; Female ; Furosemide/*pharmacology ; Human ; Male ; Middle Age ; Nephrotic Syndrome/*drug therapy/metabolism ; Serum Albumin/analysis

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

Recently the results of alpha-interferon treatement in hepatitis B virus associated glomerulonephritis showed a reduction of proteinuria and a loss of HBeAg in some treated patients. But, alpha- interferon therapy was mainly tried in membranous nephropathy of children. So, we treated 13 adults patients with recombinant alpha-interferon who were diagnosed as HBV associated membranous nephropathy(2) and membranoproliferative GN(11) at Seoul National unversity hospital. All of them had nephrotic range proteinuria and HBe antigenemia for more than 6 months, normal serum creatinine level and had no other systemic disease. Three million units of recombinant alpha-interferon was given six times a week for 16 weeks intramuscularly and the therapeutic effect was analyzed during treatment periods, especially in terms of changes in urine protein excretion and serum HBeAg. And we compared them with 14 control patients who had received conservative therapy only. As a results, at the end of interferon therapy, serum HBeAg disappeared in 4 of 13 treated patients, and serum HBsAg disappeared in 1 of 4. At the end of therapy, proteinuria diminished to non-nephrotuc range in 6 of 13 treated patients and decrement of proteinuria was accompanied with disappearance of serum HBeAg in 3 patients. And proteinuria diminished in 5 of 11 MPGN patients and serum HBeAg disappread in 3 of them. But in 14 controls there were no significant changes in 24 hour urine protein excretion and serum HBeAg. During interferon therapy, mild febrile reaction was developed in 8 patients, anemia in 3 patients, and cytopenia in 7 patients, but most of these adverse effects resolved spontaneously after discontinuation of interferon therapy. During follow up periods over 1 years, proteinuria relapsed to nephrotic range in 3 of 6 patients and serum HBeAg reappreared in 2 of them. In conclusion, the alpha-interferon at the dose induced a clearance of HBeAg and the decrement of the proteinuria in some adult MN and MPGN patients. And these results suggested the possibilities that HBeAg might be involved in the pathogenesis of HBV associated MPGN and alpha-interferon might be effective in some HBV associated MPGN.
Adult ; Anemia ; Child ; Creatinine ; Follow-Up Studies ; Glomerulonephritis ; Glomerulonephritis, Membranoproliferative ; Glomerulonephritis, Membranous ; Hepatitis B e Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Interferon-alpha ; Interferons ; Nephrotic Syndrome ; Proteinuria ; Seoul

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

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

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