Cyclophosphamide is frequently used for the treatment of severe lupus nephritis, but is very rarely associated with dilutional hyponatremia. Recently we experienced a case of water intoxication following low-dose intravenous cyclophosphamide. Five hours after one dose of intravenous pulse cyclophosphamide 750 mg, the patient developed nausea, vomiting, and general weakness. Serum sodium concentration revealed 114 mEq/L and her hyponatremia was initially treated with hypertonic saline infusion. Then her serum sodium concentration rapidly recovered to normal with water restriction alone. During the course of intravenous pulse cyclophosphamide therapy, one must be aware of the possibility of significant water retention.
Cyclophosphamide* ; Humans ; Hyponatremia ; Lupus Nephritis ; Nausea ; Sodium ; Vomiting ; Water Intoxication*

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common disease leading to hyponatremia, and it is characterized by an inappropriately elevated serum ADH level relative to serum osmolality. This syndrome may occur in a variety of clinical settings including malignancies. However, it is rarely observed in association with prostate cancer. Moreover, its pathogenesis and clinical characteristics have not been completely understood. We report a case of SIADH associated with prostate cancer in a 64-year-old male patient with a literature review.
Humans ; Hyponatremia ; Inappropriate ADH Syndrome* ; Male ; Middle Aged ; Osmolar Concentration ; Prostate* ; Prostatic Neoplasms*

Metabolic acidosis has been considered as one of the reverse epidemiologic factors for the morbidity and mortality in maintenance hemodialysis patients (MHP). Expectedly, in the recent large scale epidemiologic study (The Dialysis Outcome Practice Pattern Study, DOPPS), a mild to moderate degree of predialysis metabolic acidosis has shown better nutritional status and lower relative risk for mortality and hospitalization in MHP. Similarly, another recent study of the largest sample size of MHP of more than 55,000 revealed the lowest unadjusted mortality with mild to moderate degree of predialysis HCO3 levels (17 to 23 mEq/L). However, it was reversed after case-mix and multivariate adjustment, including the malnutrition-inflammation complex syndrome, so that predialysis HCO3 levels of more than 22 mEq/L had a lower death risk. On view of this up-to-date on-going controversy about the optimal acid-base status for MHP, this paper will review the historical and break-through data about the pros and cons of metabolic acidosis published in the clinical human studies of MHP, a special subgroup of chronic kidney disease patients. Based on these results, if possible, we would like to suggest the best practice guideline, particularly, for the optimal predialysis HCO3 level, dialysate HCO3 concentration, and dietary protein intake.
Acidosis* ; Dialysis ; Dietary Proteins ; Epidemiologic Factors ; Hospitalization ; Humans ; Mortality ; Nutritional Status ; Practice Guidelines as Topic ; Renal Dialysis* ; Renal Insufficiency, Chronic ; Sample Size

Hypokalemia is a common clinical problem. The kidney is responsible for long term potassium homoeostasis, as well as the serum potassium concentration. The main nephron site where K secretion is regulated is the cortical collecting duct, mainly via the effects of aldosterone. Aldosterone interacts with the mineralocorticoid receptor to increase sodium reabsorption and potassium secretion; the removal of cationic sodium makes the lumen relatively electronegative, thereby promoting passive potassium secretion from the tubular cell into the lumen through apical potassium channels. As a result, any condition that decreases the activity of renal potassium channels results in hyperkalemia (for example, amiloride intake or aldosterone deficiency) whereas their increased activity results in hypokalemia (for example, primary aldosteronism or Liddle's syndrome). The cause of hypokalemia can usually be determined from the history. If there is no apparent cause, the initial step is to see if hypokalemia is in associated with systemic hypertension or not. In the former group hypokalaemia is associated with a high mineralocorticoid effect or hyperactive sodium channel as in Liddle's syndrome. In hypertensive hypokalemic patients, measurement of the renin, aldosterone, and cortisol concentrations would be of help in differential diagnosis.
Aldosterone ; Amiloride ; Diagnosis, Differential ; Humans ; Hydrocortisone ; Hyperaldosteronism ; Hyperkalemia ; Hypertension ; Hypokalemia ; Kidney ; Mineralocorticoids ; Nephrons ; Potassium ; Potassium Channels ; Receptors, Mineralocorticoid ; Renin ; Sodium ; Sodium Channels

Urea accumulation in the renal inner medulla plays a key role in the maintenance of maximal urinary concentrating ability. Urea transport in the kidney is mediated by transporter proteins that include renal urea transporter (UT-A) and erythrocyte urea transporter (UT-B). UT-A1 and UT-A2 are produced from the same gene. There is an active tonicity-responsive enhancer (TonE) in the promoter of UT-A1, and the UT-A1 promoter is stimulated by hypertonicity via tonicity-responsive enhancer binding protein (TonEBP). The downregulation of UT-A2 raises the possibility that TonEBP also regulates its promoter. There is some evidence that TonEBP regulates expression of UT-A in vivo; (1) during the renal development of the urinary concentrating ability, expression of TonEBP precedes that of UT-A1; (2) in transgenic mice expressing a dominant negative form of TonEBP, expression of UT-A1 and UT-A2 is severely impaired; (3) in treatment with cyclosporine A, TonEBP was significantly downregulated after 28 days. This downregulation involves mRNA levels of UT-A2; (4) in hypokalemic animals, downregulation of TonEBP contributed to the down regulation of UT-A in the inner medulla. These data support that TonEBP directly contributes to the urinary concentration and renal urea recycling by the regulation of urea transporters.
Animals ; Carrier Proteins* ; Cyclosporine ; Down-Regulation ; Erythrocytes ; Kidney ; Mice ; Mice, Transgenic ; Recycling ; RNA, Messenger ; Urea*

Acute renal failure is mainly caused by ischemia/reperfusion (I/R) injury or nephrotoxic drugs, in which reactive oxygen species (ROS) may play an important role. Therefore, antioxidants are expected to decrease the vulnerability of renal injury associated with oxidative challenges. alpha-Lipoic acid (alpha-LA), potent antioxidant, could act as ROS scavengers, iron chelators and enzyme modulators. In rats with acute renal injury, dysregulation of aquaporin (AQP) water channels and sodium transporters has been noted. I/R injury or cisplatin induced marked down-regulation of AQP1, AQP2 and AQP3 water channels, and type-3 Na-H exchanger, Na,K-ATPase, and Na-K-2Cl cotransporters, in association with impairment of urinary concentration and tubular sodium reabsorption. Treatment with alpha-LA prevented the dysregulation of AQP channels and sodium transporters, along with improved urinary concentrating capability and renal sodium reabsorption.
Acute Kidney Injury* ; Animals ; Antioxidants ; Aquaporins ; Chelating Agents ; Cisplatin ; Down-Regulation ; Iron ; Rats* ; Reactive Oxygen Species ; Reperfusion Injury ; Sodium ; Thioctic Acid

Vasopressin, angiotensin II (AngII), and aldosterone are essential hormones in the regulation of body fluid homeostatsis. We examined the effects of AngII or aldosterone on the regulation of body water balance. We demonstrated that 1) short-term treatment with AngII in the primary cultured inner medullary collecting duct cells played a role in the regulation of AQP2 targeting to the plasma membrane through AT1 receptor activation. This potentiated the effects of dDAVP on cAMP accumulation, AQP2 phosphorylation, and AQP2 plasma membrane targeting; 2) pharmacological blockade of the AngII AT1 receptor in rats co-treated with dDAVP and dietary NaCl-restriction (to induce high plasma endogenous AngII) resulted in an increase in urine production, a decrease in urine osmolality, and blunted the dDAVP-induced upregulation of AQP2; 3) long-term aldosterone infusion in normal rats or in rats with diabetes insipidus was associated with polyuria and decreased urine concentration, accompanied by decreased apical but increased basolateral AQP2 labeling intensity in the connecting tubule and cortical collecting duct; and 4) in contrast to the effects of dDAVP and AngII, short-term aldosterone treatment does not alter the intracellular distribution of AQP2. In conclusion, angiotensin II, and aldosterone could play a role in the regulation of renal water reabsorption by changing intracellular AQP2 targeting and/or AQP2 abundance, in addition to the vasopressin.
Aldosterone* ; Angiotensin II* ; Angiotensins* ; Animals ; Aquaporin 2 ; Body Fluids ; Body Water ; Cell Membrane ; Deamino Arginine Vasopressin ; Diabetes Insipidus ; Osmolar Concentration ; Phosphorylation ; Plasma ; Polyuria ; Rats ; Up-Regulation ; Vasopressins ; Water-Electrolyte Balance

Due to their unique living conditions and dietary habits, the Koreans' renal function model may be different from that of the Western people. About 40 years ago, a researcher reported that two thirds of the urine osmolality in Koreans was contributed by NaCl, while less than 1/3 by urea. It is known that the Koreans' daily consumption of NaCl is higher while their protein intake is lower, compared to that of the Westerners. Now-a-days, the Korean's dietary habit is changing to a westernized life style. In this study, we investigated whether there were changes in urine composition and osmolality according to age. The subject of study were 215 Koreans (128 male, 142 female, age 7-68 years) living in the Chonbuk and Chonnam province in Korea. We performed routine physical examinations and analyses of the urine Na+, K+, Cl-, urea, NH3, creatinine, and osmolality on their 24 hour urine samples. In the case of the male, total body water, Na and Cl excretion, urine ammonia excretion were significantly changed between groups. In the case of the female, total body water and urine creatinine excretion were significantly changed between groups. We calculated the urine osmolar contribution of NaCl and urea. Our results showed that NaCl composed 63.6 % of total urine osmolality and Urea composed 36.4% of total urine osmolality. In conclusion, urine osmolar composition is similar to the 1960's, but further studies are required to elucidate the change of urine composition in this population for another 50 years.
Ammonia ; Body Water ; Creatinine ; Female ; Food Habits ; Humans ; Jeollabuk-do ; Jeollanam-do ; Korea ; Life Style ; Male ; Osmolar Concentration ; Physical Examination ; Social Conditions ; Urea

Metabolic acidosis is the most frequent acid-base disorder in critically ill patients and dialysis patients. This study is to compare the conventional approach with the physicochemical approach between the intensive care unit (ICU) and hemodialysis (HD) patients. Fifty-seven ICU patients and 33 HD patients were enrolled. All data sets included simultaneous measurements of arterial blood gas with base deficit (BD), serum electrolytes, albumin, lactate, and calculated anion gap observed (AGobs). Physiochemical analysis was used to calculate the albumin and lactate-corrected anion gap (AGcorr), the base deficit corrected for unmeasured anions (BDua), the strong ion difference apparent (SIDa), the strong ion difference effective (SIDe), and the strong ion gap (SIG). The SIDa (37.5+/-5.3 vs 33.9+/-9.0, p=0.045) and SIG (12.3+/-5.3 vs 8.6+/-8.8, p=0.043) was significantly higher in the HD group than the ICU group. SIG in the ICU group showed the highest correlation coefficient with AGobs, whereas SIG in the HD group with AGcorr. Concerning the contributions of the three main causes of metabolic acidosis, increased SIG was comparable between the ICU and HD group (n=48, 90.6% vs n=30, 93.8%), whereas hyperlactatemia (n=9, 17.0% vs n=0, 0%) and hyperchloremia (n=20, 35.1% vs n=2, 6.1%) was significantly increased in the ICU group compared with the HD group. Multiple underlying mechanisms are present in most of the ICU patients with metabolic acidosis compared with the HD patients. In conclusion, the physicochemical approach can elucidate the detailed mechanisms of metabolic acidosis in ICU and HD patients compared with conventional measures.
Acid-Base Equilibrium ; Acidosis* ; Anions ; Critical Illness ; Dataset ; Dialysis ; Electrolytes ; Humans ; Intensive Care Units ; Lactic Acid ; Renal Dialysis*

Ubiquitination is known to be important for endocytosis and lysosomal degradation of aquaporin-2 (AQP2). Ubiquitin (Ub) is covalently attached to the lysine residue of the substrate proteins and activation and attachment of Ub to a target protein is mediated by the action of three enzymes (i.e., E1, E2, and E3). In particular, E3 Ub-protein ligases are known to have substrate specificity. This minireview will discuss the ubiquitination of AQP2 and identification of potential E3 Ub-protein ligases for 1-deamino-8-D-arginine vasopressin (dDAVP)-dependent AQP2 regulation.
Aquaporin 2 ; Deamino Arginine Vasopressin ; Endocytosis ; Kidney ; Kidney Tubules, Collecting ; Ligases ; Lysine ; Proteins ; Substrate Specificity ; Ubiquitin ; Ubiquitination ; Vasopressins