Search

Psychotropic drugs may be associated with hyponatremia, but an understanding of how they induce water retention in the kidney remains elusive. Previous studies have postulated that they may increase vasopressin production in the hypothalamus without supporting evidence. In this study, we investigated the possibility of drug-induced nephrogenic syndrome of inappropriate antidiuresis using haloperidol, sertraline, and carbamazepine. Haloperidol, sertraline, or carbamazepine were treated in inner medullary collecting duct (IMCD) suspensions and primary cultured IMCD cells prepared from male Sprague-Dawley rats. The responses of intracellular cAMP production, aquaporin-2 (AQP2) protein expression and localization, vasopressin-2 receptor (V2R) and AQP2 mRNA, and cAMP-responsive element-binding protein (CREB) were tested with and without tolvaptan and the protein kinase A (PKA) inhibitors H89 and Rp-cAMPS. In IMCD suspensions, cAMP production was increased by haloperidol, sertraline, or carbamazepine and was relieved by tolvaptan cotreatment. In primary cultured IMCD cells, haloperidol, sertraline, or carbamazepine treatment increased total AQP2 and decreased phosphorylated Ser

Background/Aims: We investigated the distribution of serum uric acid (SUA) lev els and estimated the prevalence of hyperuricemia and hypouricemia in the Kore an population. Methods: This cross-sectional study used data from the Korean Genome and Epi demiology Study and included 172,970 participants (58,981 men and 113,989 wom en) aged 40 to 79 years. Hypouricemia and hyperuricemia were defined as SUA level ≤ 2.0 mg/dL and > 7 mg/dL, respectively. The prevalence of hyperuricemia and hypouricemia was evaluated by age and sex. Results: The mean SUA levels were significantly higher in men than in women (5.71 ± 1.27 mg/dL vs. 4.21 ± 0.96 mg/dL, p < 0.001). The mean SUA levels and prevalence of hyperuricemia increased with age in women but not in men. The overall preva lence of hyperuricemia and that in men and women was 50.82, 133.25, and 8.17 per 1,000 persons, respectively; the overall prevalence of hypouricemia and that in men and women was 4.16, 1.10, and 5.75 per 1,000 persons, respectively. The prev alence of hypouricemia in men was similar across all age groups; however, that in women was the highest in the age group of 40 to 49 years and the lowest in the age group of 50 to 59 years. Conclusions: The distribution of SUA levels and prevalence of hyperuricemia and hypouricemia differed according to age and sex. Age and sex should be considered in studies on uric acid-related diseases.

PURPOSE Oral adsorbents delay disease progression and improve uremic symptoms in patients with chronic kidney disease (CKD). DW-7202 is a newly developed oral adsorbent with high adsorptive selectivity for uremic toxins. We evaluated patient preference for and adherence to DW-7202 versus AST-120 therapy and compared treatment efficacy and safety in patients with pre-dialysis CKD. MATERIALS AND METHODS A seven-center, randomized, open-label, two-way crossover, active-controlled, phase IV clinical trial was conducted. Patients with stable CKD were randomly assigned to receive DW-7202 (capsule type) or AST-120 (granule type) for 12 weeks. The groups then switched to the other adsorbent and took it for the next 12 weeks. Patient preference was the primary outcome. Secondary outcomes included changes in estimated glomerular filtration rate (eGFR) and serum creatinine, cystatin C, and indoxyl sulfate (IS) levels. RESULTS Significantly more patients preferred DW-7202 than AST-120 (p

Objectives. The aim of this study was to evaluate the effectiveness of subtotal parathyroidectomy for patients with renal hyperparathyroidism.Methods. We studied 25 patients with renal hyperparathyroidism who underwent subtotal parathyroidectomy from October 2002 to October 2017. We analyzed serum intact parathyroid hormone (iPTH), calcium, and inorganic phosphorus levels before and at multiple time points following surgery, and evaluated the surgical outcomes and complications.Results. Of the 25 patients, 13 (52%) were male and 12 (48%) were female, and the mean age was 53.4±9.3 years. The mean duration of dialysis before parathyroidectomy was 156.8±79.5 months. Mean preoperative serum iPTH and calcium levels were 1,199.0±571.3 pg/mL and 10.5±1.0 mg/dL, respectively. At 6 months postoperatively, the mean iPTH and calcium levels decreased to 49.2±47.6 pg/mL (PP

Background: We hypothesized that tight junction (TJ) proteins may have a role in paracellular transport of solute and water in peritoneal dialysis (PD) patients. Previous studies on TJ proteins in PD patients have used only cultured human peritoneal mesothelial cells (HPMCs). This study was undertaken to test whether TJ proteins are directly identified from PD effluent and whether their expressions are associated with functional parameters of PD. Methods: Dialysis effluents were collected from 40 patients undergoing PD, after the peritoneal equilibration test (PET). Different molecular sizes of Amicon Ultra-15 Centrifugal Filter Units were used to concentrate and purify proteins in PD effluents, and immunoblot analyses for occludin, ZO-1, and claudins were carried out to test for their existence and relationships with peritoneal clearance or results of the PET. Results: Immunoblotting from PD effluents revealed discrete bands of occludin (∼65 kDa), ZO-1 (∼215 kDa), claudin-1 (∼22 kDa), and claudin-15 (∼22 kDa) in all 40 patients. The peritoneal creatinine clearance inversely correlated with the protein expression of claudin-1 (r= −0.369, p= .019), and the dialysate-to-plasma creatinine ratio at 4 h PET correlated with occludin (r = 0.396, p= .011) and inversely correlated with claudin-15 (r= −0.393, p= .012). Conclusion: In PD patients, expression of peritoneal TJ proteins can be estimated from the dialysis effluent and may be used as novel peritoneal biomarkers.

Impaired pressure natriuresis (PN) underlies salt-sensitive hypertension, and renal inflammation and hypoxia-inducible factor-1 (HIF-1) have been implicated in the modulation of systemic hypertension. Although sodium–glucose cotransporter-2 (SGLT2) inhibitors were reported to lower blood pressure (BP) in type 2 diabetes mellitus, whether they have a role in nondiabetic hypertensive kidney diseases is unclear. The present study was undertaken to investigate whether nondiabetic salt-sensitive hypertension and accompanying renal inflammation are ameliorated by SGLT2 inhibition. Male Sprague-Dawley rats were randomly divided into three groups: sham controls (SCs), uninephrectomized controls (UCs), and empagliflozin-treated rats (ETs). All rats were fed a rodent diet with 8% NaCl throughout the study period. Empagliflozin was orally administered for 3 weeks after uninephrectomy. Systolic blood pressure was recorded weekly, and kidneys were harvested for immunoblotting, immunohistochemistry, and quantitative PCR analysis at the end of the animal experiment. Systolic BP was significantly decreased in ETs that were orally given empagliflozin for 3 weeks after uninephrectomy. Although ETs did not show any increase in weekly measured urine sodium, the right-shifted PN relationship in UCs was improved by empagliflozin treatment. The expression of HIF-1α was increased in the renal outer medulla of ETs. Consistent with this, HIF prolyl-hydroxylase-2 protein and mRNA were decreased in ETs. The abundance of CD3 and ED-1 immunostaining in UCs was reduced by empagliflozin treatment. The increased IL-1ß, gp91phox, and NOX4 mRNA levels in UCs were also reversed. Empagliflozin restored impaired PN in nondiabetic hypertensive kidney disease in association with increased renal medullary expression of HIF-1α and amelioration of renal inflammation.

Treatment of hypertension improves cardiovascular, renal, and cerebrovascular outcomes. However, the benefit of treatment may be different according to the patients’ characteristics. Additionally, the target blood pressure or initial drug choice should be customized according to the special conditions of the hypertensive patients. In this part III, we reviewed previous data and presented recommendations for some special populations such as diabetes mellitus, chronic kidney disease, elderly people, and cardio-cerebrovascular disease.

Background Thus far, human leukocyte antigen (HLA)-B∗58:01 has been recognized as the most important risk factor for allopurinol induced severe cutaneous adverse reactions (SCARs). Objective To determine the usefulness of prospective screening for the HLA-B∗58:01 allele to identify Korean individuals at risk for SCARs induced by allopurinol treatment. Methods We prospectively enrolled 542 patients with chronic renal insufficiency (CRI) from 10 hospitals nationwide and performed DNA genotyping to determine whether they carried the HLA-B∗58:01 allele. Of these, 503 HLA-B∗58:01-negative patients (92.8% of total) were treated with allopurinol, and 39 HLA-B∗58:01-positive patients (7.2%) were treated with febuxostat, an alternative drug. The patients then were followed up biweekly for 90 days using a telephone survey to monitor symptoms of adverse drug reactions, including SCARs. As a control, we used the historical incidence rate of allopurinol-induced SCARs in 4002 patients with CRI from the same hospitals who were enrolled retrospectively. Results Nineteen patients in the prospective cohort developed mild and transient adverse reactions but none showed allopurinol-induced SCARs. By contrast, we identified 38 patients with allopurinol-induced SCARs (0.95%) in the historical control. The difference in the incidence of allopurinol-induced SCARs between the prospective cohort and historical control was statistically significant (0% vs 0.95%, respectively; P = .029). Conclusions The present study demonstrated the clinical usefulness of the HLA-B∗58:01 screening test before allopurinol administration to prevent allopurinol-induced SCARs in patients with CRI.

Urate is produced in the liver by the degradation of purines from the diet and nucleotide turnover and excreted by the kidney and gut. The kidney is the major route of urate removal and has a pivotal role in the regulation of urate homeostasis. Approximately 10% of the glomerular filtered urate is excreted in the urine, and the remainder is reabsorbed by the proximal tubule. However, the transport of urate in the proximal tubule is bidirectional: reabsorption and secretion. Thus, an increase in reabsorption or a decrease in secretion may induce hyperuricemia. In contrast, a decrease in reabsorption or an increase in secretion may result in hyperuricosuria. In the proximal tubule, urate reabsorption is mainly mediated by apical URAT1 (SLC22A12) and basolateral GLUT9 (SLC2A9) transporter. OAT4 (SLC22A11) also acts in urate reabsorption in the apical membrane, and its polymorphism is associated with the risk of hyperuricemia. Renal hypouricemia is caused by SLC22A12 or SLC2A9 loss-of-function mutations, and it may be complicated by exercise-induced acute kidney injury. URAT1 and GLUT9 are also drug targets for uricosuric agents. Sodium-glucose cotransporter inhibitors may induce hyperuricosuria by inhibiting GLUT9b located in the apical plasma membrane. Urate secretion is mediated by basolateral OAT1 (SLC22A6) and OAT3 (SLC22A8) and apical ATP-binding cassette super-family G member 2 (ABCG2), NPT1 (SLC17A1), and NPT4 (SLC17A3) transporter in the proximal tubule. NPT1 and NPT4 may be key players in renal urate secretion in humans, and deletion of SLC22A6 and SLC22A8 in mice leads to decreased urate excretion. Dysfunctional variants of ABCG2 inhibit urate secretion from the gut and kidney and may cause gout. In summary, the net result of urate transport in the proximal tubule is determined by the dominance of transporters between reabsorption (URAT1, OAT4, and GLUT9) and secretion (ABCG2, NPT1, NPT4, OAT1, and OAT3).

New drugs were recently developed to treat hyperglycemia in patients with type 2 diabetes mellitus (T2D). However, metformin remains the first-line anti-diabetic agent because of its cost-effectiveness. It has pleiotropic action that produces cardiovascular benefits, and it can be useful in diabetic nephropathy, although metformin-associated lactic acidosis is a hindrance to its use in patients with kidney failure. New anti-diabetic agents, including glucagon-like peptide-1 receptor (GLP-1R) agonists, dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium-glucose transporter-2 (SGLT-2) inhibitors, also produce cardiovascular or renal benefits in T2D patients. Their glucose-independent beneficial actions can lead to cardiorenal protection via hemodynamic stabilization and inflammatory modulation. Systemic hypertension is relieved by natriuresis and improved vascular dysfunction. Enhanced tubuloglomerular feedback can be restored by SGLT-2 inhibition, reducing glomerular hypertension. Patients with non-diabetic kidney disease might also benefit from those drugs because hypertension, proteinuria, oxidative stress, and inflammation are common factors in the progression of kidney disease, irrespective of the presence of diabetes. In various animal models of non-diabetic kidney disease, metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors were favorable to kidney morphology and function. They strikingly attenuated biomarkers of oxidative stress and inflammatory responses in diseased kidneys. However, whether those animal results translate to patients with non-diabetic kidney disease has yet to be evaluated. Considering the paucity of new agents to treat kidney disease and the minimal adverse effects of metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors, these anti-diabetic agents could be used in patients with non-diabetic kidney disease. This paper provides a rationale for clinical trials that apply metformin, GLP-1R agonists, DPP-4 inhibitors, and SGLT-2 inhibitors to non-diabetic kidney disease.

Background:Regular monitoring of vascular access in patients on maintenance hemodialysis is important to detect early vascular access complications. We compared vascular access blood flow determined by blood temperature monitor and Doppler ultrasonography to evaluate the usefulness of blood temperature monitor.Methods:In total, 70 patients on maintenance hemodialysis were enrolled from three dialysis centers. Vascular access blood flow was measured thrice at 6-month intervals using Doppler ultrasonography to determine arterial inflow (Q-DUa), venous outflow (Q-DUv), and flow between punctures (Q-DUb) using BTM® (Q-BTM). Twister® was placed between the hemodialysis needle and blood lines, allowing simple reversal of flow without stopping the hemodialysis pump.Results:In total, 203 measurements were recorded, with median values (interquartile range) for Q-BTM, Q-DUa, Q-DUv, and Q-DUb of 1139.0 (868.0–1588.0) mL/min, 960.3 (658.7–1380.4) mL/min, 946.0 (552.0–1515.0) mL/min, and 1067.7 (544.8–1635.0) mL/min, respectively. For all measurements, the mean intraclass correlation coefficients were 0.52 (95% confidence interval, 0.36–0.64) for Q-DUa; 0.37 (95% confidence interval, 0.15–0.53) for Q-DUv; and 0.45 (95% confidence interval, 0.26–0.59) for Q-DUb. Analysis of a receiver operating characteristics curve yielded a cut-off of 627 mL/min for Q-BTM to predict stenosis.Conclusion:In patients on maintenance hemodialysis, blood flow measured by blood temperature monitor moderately correlated with Doppler blood flow. It was more related to arterial inflow than venous outflow or flow between punctures. The blood temperature monitor method was not inferior to Doppler ultrasonography. Therefore, blood temperature monitor could be recommended for routine vascular access monitoring because it can be done quickly without interrupting dialysis.

Background: Urinary concentration impairment is a major feature of cyclosporine nephrotoxicity. Methods: We explored two possible mechanisms that may underlie cyclosporine-induced polyuria; water, and/or osmotic diuresis. Cyclosporine was subcutaneously injected to normal salt-fed Sprague-Dawley rats at a daily dose of 25mg/kg for 2 weeks (Experiment I) and 7.5mg/kg for 6 weeks (Experiment II). Results: In Experiment I, cyclosporine treatment caused an increase in urine volume (2.7±0.5 vs. 10.3±1.13mL/d/100 g BW, p

Background: We investigated the associations between mineral metabolism parameters and mortality to identify optimal targets in Korean hemodialysis patients. Methods: Among hemodialysis patients registered in the end-stage renal disease registry of the Korean Society of Nephrology between March 2012 and June 2017, those with serum calcium, phosphorus, and intact parathyroid hormone (iPTH) measured at enrollment were included. Association of serum levels of calcium, phosphorus, and iPTH with all-cause mortality was analyzed. Results: Among 21,433 enrolled patients, 3,135 (14.6%) died during 24.8 ± 14.5 months of follow-up. After multivariable adjustment, patients in the first quintile of corrected calcium were associated with lower mortality (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.71-0.99; P = 0.003), while those in the fifth quintile were associated with higher mortality (HR, 1.39; 95% CI, 1.20-1.61; P⟨ 0.001) compared with those in the third quintile. For phosphorus, only the lowest quintile was significantly associated with increased mortality (HR, 1.24; 95% CI, 1.08-1.43; P = 0.003). The lowest (HR, 1.18; 95% CI, 1.02-1.36; P = 0.026) and highest quintiles of iPTH (HR, 1.24; 95% CI, 1.05-1.46; P = 0.013) were associated with increased mortality. For target counts achieved according to the Kidney Disease Outcomes Quality Initiative guideline, patients who did not achieve any mineral parameter targets hadhigher mortality than those who achieved all three targets (HR, 1.37; 95% CI, 1.12-1.67; P = 0.003). Conclusion: In Korean hemodialysis patients, high serum calcium, low phosphorus, and high and low iPTH levels were associated with increased all-cause mortality.

Background/Aims: Dipeptidyl peptidase-4 (DPP4) inhibitors are known to have a protective effect on diabetic kidney disease, possibly via reduction of oxidative stress and inflammation in the kidney. However, whether these potential mechanisms play a role in non-diabetic proteinuric kidney diseases is not clear. Methods: Two different animal experiments were carried out using sitagliptin and linagliptin for DPP4 inhibition. In each experiment, male Sprague-Dawley rats were uninephrectomized and randomly divided into vehicle-treated and doxorubicin-treated rats, with or without DPP4 inhibition. Administration of a DPP4 inhibitor was performed daily by oral gavage over six weeks. Results: A single intravenous injection of doxorubicin resulted in hypertension and remarkable proteinuria. Linagliptin, but not sitagliptin, lowered systolic blood pressure in rats with doxorubicin nephropathy. By contrast, sitagliptin ameliorated tubulointerstitial injury, inflammatory cell infiltration, and interstitial fibrosis in rat kidneys with doxorubicin nephropathy. Quantitative polymerase chain reaction analysis revealed that mRNA expression of NLRP3, caspase-1, ASC, and IL-1β was remarkably increased in rat kidneys with doxorubicin nephropathy, and that this upregulation of the major components of the NLRP3 inflammasome was effectively suppressed by treatment with either sitagliptin or linagliptin. Additionally, upregulation of IL-6 was reversed by linagliptin, but not by sitagliptin. On the other hand, sitagliptin, but not linagliptin, reversed the increase in mRNA expression of gp91phox, p47phox, and p67phox in rat kidneys with doxorubicin nephropathy. Conclusion: NLRP3 inflammasome activation was shown in our rat model of doxorubicin nephropathy. DPP4 inhibitors can suppress the activity of NLRP3, with or without relieving NADPH oxidase 2-related oxidative stress.

Anemia, complicating the course of chronic kidney disease, is a significant parameter, whether interpreted as subjective impairment or an objective prognostic marker. Renal anemia is predominantly due to relative erythropoietin (EPO) deficiency. EPO inhibits apoptosis of erythrocyte precursors. Studies using EPO substitution have shown that increasing hemoglobin (Hb) levels up to 10–11 g/dL is associated with clinical improvement. However, it has not been unequivocally proven that further intensification of erythropoiesis stimulating agent (ESA) therapy actually leads to a comprehensive benefit for the patient, especially as ESAs are potentially associated with increased cerebro-cardiovascular events. Recently, new developments offer interesting options not only via stimulating erythropoeisis but also by employing additional mechanisms. The inhibition of activin, a member of the transforming growth factor superfamily, has the potential to correct anemia by stimulating liberation of mature erythrocyte forms and also to mitigate disturbed mineral and bone metabolism as well. Hypoxia-inducible factor prolyl hydroxylase inhibitors also show pleiotropic effects, which are at the focus of present research and have the potential of reducing mortality. However, conventional ESAs offer an extensive body of safety evidence, against which the newer substances should be measured. Carbamylated EPO is devoid of Hb augmenting effects whilst exerting promising tissue protective properties. Additionally, the role of hepcidin antagonists is discussed. An innovative new hemodialysis blood tube system, reducing blood contact with air, conveys a totally different and innocuous option to improve renal anemia by reducing mechanical hemolysis.

Diabetes mellitus has been suspected to increase mortality in acute pyelonephritis (APN) patients and the goal of this study is to verify this suspicion with a large data set based on almost the entire population of South Korea. A nationwide cohort study was conducted using a South Korean Health Insurance Review and Assessment Service claim database. We collected demographic and clinical information including comorbidities of patients with APN as the primary discharge diagnosis during 2010–2014. Then we compared the in-hospital mortality and recurrence of APN across the diabetes and non-diabetes groups. Among 845,656 APN patients, 12.4% had diabetes mellitus. The median age was 65 in the diabetes group, which was much higher than 47 in the non-diabetes group; the female proportion was 91–92% in both groups. The in-hospital mortality rate was higher in the diabetes group (2.6/1000 events in the diabetes group vs. 0.3/1000 in the non-diabetes group, P

The standardized techniques of blood pressure (BP) measurement in the clinic are emphasized and it is recommended to replace the mercury sphygmomanometer by a non-mercury sphygmomanometer. Out-of-office BP measurement using home BP monitoring (HBPM) or ambulatory BP monitoring (ABPM) and even automated office BP (AOBP) are recommended to correctly measure the patient’s genuine BP. Hypertension (HTN) treatment should be individualized based on cardiovascular (CV) risk and the level of BP. Based on the recent clinical study data proving benefits of intensive BP lowering in the high risk patients, the revised guideline recommends the more intensive BP lowering in high risk patients including the elderly population. Lifestyle modifications, mostly low salt diet and weight reduction, are strongly recommended in the population with elevated BP and prehypertension and all hypertensive patients. In patients with BP higher than 160/100 mmHg or more than 20/10 mmHg above the target BP, two drugs can be prescribed in combination to maximize the antihypertensive effect and to achieve rapid BP control. Especially, single pill combination drugs have multiple benefits, including maximizing reduction of BP, minimizing adverse effects, increasing adherence, and preventing cardiovascular disease (CVD) and target organ damage.

The Korean Society of Hypertension guideline defines hypertension as systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg, where the effectiveness of pharmacological treatment has been established. It is confirmed that higher blood pressure levels are associated with increased risk of cardiovascular disease and mortality also in the Korean population. About one third of Korean adults aged 30 years or older are estimated to have hypertension, and the prevalence of hypertension gradually increases as the age increases. The awareness, treatment, and control rates of hypertension are generally improving in Korea, but more efforts are required to increase awareness and treatment among younger patients with hypertension and to improve lifestyle modification compliance at all ages. More studies are required to determine the magnitude and impact of white coat hypertension and masked hypertension in the Korean population.

Background: Cicletanine is an antihypertensive agent with vasorelaxant and diuretic properties. It has been widely used in European countries; however, cicletanine-associated electrolyte disturbances have yet to be defined. We investigated cicletanine-induced hyponatremia and hypokalemia in kidney transplant patients. Methods: Data from a total of 68 kidney transplant recipients who were treated for hypertension with cicletanine were retrospectively analyzed. Cicletanine-induced hyponatremia and hypokalemia were defined as serum sodium

Background/Aims: Either protein-to-creatinine ratio (PCR) or albumin-to-creatinine ratio (ACR) can be adopted for estimation of proteinuria in patients with chronic kidney disease (CKD). Estimated protein excretion rate (ePER) and estimated albumin excretion rate (eAER) may be superior to ACR and PCR. Reports show that urine albumin-to-protein ratio (APR) may be useful in detecting tubular proteinuria, but should be compared with urine protein electrophoresis (PEP). Methods: Both 24-h urine and spot urine were collected from 77 stable CKD patients for measurement of albumin, protein, and creatinine, and PEP. Based on MDRD and CKD-EPI equations, ePERMDRD, ePERCKD-EPI, eAERMDRD and eAERCKD-EPI were calculated to estimate daily proteinuria and albuminuria. Glomerular CKD was defined by clinical and/or pathological evidence. Results: ACR correlated significantly with PCR. However, microalbuminuria was present in patients without pathologic proteinuria. Twenty-four-hour urine albumin correlated better with eAERMDRD and eAERCKD-EPI than ACR, and 24-h urine protein correlated better with ePERMDRD and ePERCKD-EPI than PCR. APR significantly but not well correlated with the albumin fraction in urine PEP. The albumin fraction obtained from urine PEP was significantly higher in patients with glomerulopathy than those with non-glomerular CKD, whereas there were no differences in APR between groups. In contrast with APR, the albumin fraction in urine PEP was independently associated with glomerular CKD. Conclusions: Both PCR and ACR are useful in evaluation of proteinuria. In quantifying daily proteinuria and albuminuria, ePER and eAER are superior to PCR and ACR, respectively. Compared with APR, urine PEP is more useful in diagnosing glomerular proteinuria.

Because it is associated with mortality, hyponatremia is an important feature of pulmonary arterial hypertension. Its mechanisms remain unclear, although right heart failure resulting from pulmonary arterial hypertension may lead to systemic congestion and arterial underfilling. However, most patients with pulmonary arterial hypertension are clinically euvolemic and have no peripheral edema. Unlike patients with underlying heart disease, neurohumoral activation is not demonstrated in hyponatremic patients with pulmonary arterial hypertension, who show features of congestive heart failure only at later stages in their disease. Here, a case vignette is introduced, and the pathophysiology of hyponatremia in pulmonary arterial hypertension will be discussed. Syndrome of inappropriate antidiuresis (SIAD) appears to underlie hyponatremia in the initial phase of pulmonary arterial hypertension. The mechanisms by which various lung diseases can lead to SIAD remain an enigma.

Background: Puromycin aminonucleoside (PA) can induce nephrotic syndrome in rats, and proteinuria is an important mediator of tubulointerstitial injury in glomerulopathy. We assumed that glomerular proteinuria may affect tubular function, such as urinary concentration, and investigated whether a urinary concentration defect is associated with proteinuria in puromycin aminonucleoside nephrosis (PAN). We also investigated the defect response to enalapril. Methods: Glomerular proteinuria was induced by a single intraperitoneal injection of PA (150mg/kg BW) in male Sprague-Dawley rats. In a half of these rats, enalapril (35mg/kg BW) was administered daily in a food mixture for two weeks. After the animal experiment, kidneys were harvested for immunoblot analysis and histopathologic examination. Results: Compared with the control group, PA-treated rats had severe proteinuria, polyuria, and a lower urine osmolality. PA treatment induced remarkable tubulointerstitial injury and significant reductions in protein abundances of aquaporin-1 and Na-K-2Cl co-transporter type 2 (NKCC2). Proteinuria significantly correlated with osteopontin expression in the kidney and inversely correlated with renal expression of aquaporin-1, aquaporin-2, and NKCC2. The degree of tubulointerstitial injury significantly correlated with proteinuria, urine output, and osteopontin expression and inversely correlated with urine osmolality and renal expression of aquaporin-1, aquaporin-2, and NKCC2. No significant differences in parameters were found between PA-treated rats with and without enalapril. Conclusion: In PAN, glomerular proteinuria was associated with tubulointerstitial injury and water diuresis. Downregulation of aquaporin-1 and NKCC2 can impair countercurrent multiplication and cause a urinary concentration defect in PAN.

Voriconazole, a triazole antifungal agent used to treat serious fungal infections, has a pharmacokinetic characteristic of undergoing hepatic metabolism by the cytochrome P450 system. Few cases of hyperkalemia have been reported, which presented only when the serum voriconazole level was exceptionally elevated by drug-drug interactions. Additionally, azole antifungals may interfere with the biosynthesis of adrenal steroids and therefore can predispose patients to aldosterone deficiency. However, it is unclear whether voriconazole itself can induce hypoaldosteronism or hyperkalemia. Here, we report a case of voriconazole-induced hyperkalemia in a patient administered concurrent medications to treat comorbidities. Voriconazole was orally administered for pulmonary aspergillosis, and three episodes of severe hyperkalemia recurred, which improved with emergency treatment. In the first episode, renin-angiotensin-aldosterone system inhibitors were associated. We found that dronedarone might have increased the voriconazole level in the second episode. At that time, severe hypercalcemia was concurrent, which improved with acute hemodialysis and eliminating dronedarone. Finally, severe hyperkalemia recurred without concurrent medications known to interact with voriconazole. Upon switching from voriconazole to itraconazole, the hyperkalemia was resolved. Drug level monitoring is necessary when voriconazole is used. Genetic susceptibility, such as through CYP2C19 polymorphism, may be investigated for patients with adverse reactions to voriconazole.

Background The aim of this multicenter study was to evaluate the safety and efficacy of tolvaptan (TLV) in Korean patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Methods Of 51 enrolled patients with SIADH, 39 patients (16 female patients, aged 70.8 ± 11.3 years) were included in an intention to treat analysis. All patients received 15 mg/day as the initial dose, and the dose was then increased up to 60 mg/day (as needed) until day 4. Results Serum sodium increased significantly from baseline during the first 24 hours (126.8 ± 4.3 vs. 133.7 ± 3.8 mmol/L, P < 0.001), rose gradually between days 1 and 4 (133.7 ± 3.8 vs. 135.6 ± 3.6 mmol/L, P < 0.05), and then plateaued until day 11 (136.7 ± 4.5 mmol/L). The correlation between the change in serum sodium for the first 24 hours and initial serum sodium concentration was significant (r = −0.602, P < 0.001). In severe hyponatremia (< 125 mmol/L), the change was significantly higher (11.1 ± 4.8 mmol/L) than in moderate (6.4 ± 2.5 mmol/L, P < 0.05) or mild hyponatremia (4.3 ± 3.3 mmol/L, P < 0.01). In addition, logistic regression analysis showed that body weight (odds ratio [OR], 0.858; 95% confidence interval [CI], 0.775–0.976; P = 0.020) and body mass index (BMI) (OR, 0.692; 95% CI, 0.500–0.956; P = 0.026) were associated with rapid correction. No serious adverse events were reported, but in 13% of patients hyponatremia was overcorrected. Conclusion TLV is effective in correcting hyponatremia and well-tolerated in Korean patients with SIADH. However, those with low body weight, low BMI or severe hyponatremia, could be vulnerable to overcorrection with the initial dose of 15 mg TLV., Graphical Abstract

Hyperuricemia following kidney transplantation (KT) may contribute to a decline in allograft renal function, but be affected by KT-related confounding factors. Some studies have even suggested that a reduction in serum uric acid (UA) is associated with poor patient outcomes. Thus, we retrospectively analyzed the impact of serum UA on allograft outcomes in 281 KT recipients. KT recipients were divided into five groups according to serum UA level (mg/dL): Group I (n = 46), ≤ 5; Group II (n = 62), > 5 and ≤ 6; Group III (n = 70), > 6 and ≤ 7; Group IV (n = 53), > 7 and ≤ 8; Group V (n = 50), > 8. Regression analysis showed that serum UA level was significantly associated with future allograft function. In a Kaplan-Meier analysis, the dialysis-free survival of Group II recipients was better than that of the other groups (Group I, 140 ± 5 months; Group II, 208 ± 7 months; Group III, 148 ± 4 months; Group IV, 185 ± 12 months; Group V, 164 ± 11 months; P = 0.0164). In Cox proportional hazard models adjusting for estimated glomerular filtration rate, the relative risk of allograft loss still tended to be elevated in Group I (HR=3.417, 95% CI 1.138-10.258) and Group V (HR=2.793, 95% CI 1.108-7.041), using Group II as the reference. Our results suggest that there is a J-shaped association between serum UA levels and allograft outcomes in living donor KT recipients.

Hypoalbuminemia is associated with poor outcomes in kidney transplantation (KT). However, what level is optimal in serum albumin is not clear for the long-term prognosis. To determine whether the long-term outcomes are different even between the normal ranges of serum albumin after KT, we analyzed data from 404 renal allograft recipients whose 1-year post-transplant serum albumin levels were within the normal limits (3.5-5.5 g/dL). During a follow-up of 122 ± 56 months, 97 graft losses, 20 patient deaths, and 50 cardiovascular (CV) events occurred. Based on 1-year serum albumin levels, the patients were divided into high normal (≥4.6 g/dL, n = 209) and low normal (

For Korean dialysis patients, chronic kidney disease–mineral bone disorder is a serious burden because of cardiovascular calcification and mortality. However, recent epidemiologic data have demonstrated that many patients undergoing maintenance hemodialysis are out of the target ranges of serum calcium, phosphorus, and intact parathyroid hormone. Thus, we felt the necessity for the development of practical recommendations to treat abnormal serum phosphorus, calcium, and iPTH in dialysis patients. In this paper, we briefly comment on the measurement of serum calcium, phosphorus, iPTH, dialysate calcium concentration, dietary phosphorus restriction, use of phosphate binders, and medical and surgical options to correct secondary hyperparathyroidism. In particular, for the optimal management of secondary hyperparathyroidism, we suggest a simplified medication adjustment according to certain ranges of serum phosphorus and calcium. Large-scale, well-designed clinical studies are required to support our strategies to control chronic kidney disease–mineral bone disorder in this country. Based on such data, our practice guidelines could be established and better long-term outcomes should be anticipated in our dialysis patients.

Tolvaptan is useful for correcting dilutional hyponatraemia because of its aquaretic effect. On the other hand, there is a distinct lack of data regarding tolvaptan-induced natriuresis, although previous studies have demonstrated improvement of congestive symptoms and signs in heart failure patients following tolvaptan treatment. Here, we report the case of a 47-year-old man diagnosed with minimal change nephrotic syndrome and whose refractory oedema was immediately controlled by tolvaptan before steroid response was induced. With tolvaptan treatment, patient urine output increased dramatically to approximately 5.5 L/day and body weight decreased by 9 kg over 5 days. Interestingly, urine sodium concentration, fractional excretion of sodium and urine osmolality all increased in response to tolvaptan administration. However, serum sodium concentration was maintained within the normal range, and mild azotaemia was corrected. Tolvaptan was discontinued after 11 days when heavy proteinuria and generalized oedema had been resolved. We discuss the potential mechanisms by which V2 receptor antagonists may stimulate natriuresis in the kidney. In conclusion, tolvaptan may be useful as an adjunctive treatment for oedematous disorders.

Background: Desmopressin is used for treating nocturnal polyuria, but hyponatremia is an associated concern in the elderly due to impaired urinary dilution. This study was undertaken to characterize hyponatremia occurring in adults using desmopressin for nocturnal polyuria. Methods: Data from 172 patients who were prescribed desmopressin for nocturnal polyuria at a urology clinic from September 2010 through February 2013 were retrospectively analyzed. Demographic and laboratory parameters were investigated to examine the risk factors for desmopressin-associated hyponatremia. Results: The average follow-up serum sodium measured 21 ± 22 days after using desmopressin was 138 ± 5 mmol/l. Hyponatremia (Conclusion: Hyponatremia is not infrequently associated with desmopressin use. Those with advanced age (≥65 years) and lower hemoglobin are at risk of desmopressin-associated hyponatremia and need to be carefully monitored.

BACKGROUND:Calcium polystyrene sulfonate (CPS) has long been used to treat hyperkalemia in patients with chronic kidney disease (CKD). However, its efficacy and safety profile have not been systematically explored. We investigated the long-term efficacy of oral CPS for treating mild hyperkalemia on an outpatient basis. METHODS:We performed a retrospective analysis of ambulatory CKD patients who were prescribed CPS for > 1 week because of elevated serum potassium levels > 5.0 mmol/L. Patients were divided into four groups according to the length of time that they took a fixed dosage of CPS (Group 1, < 3 months; Group 2, 3-6 months; Group 3, 6-12 months; and Group 4, > 1 year). Response was defined as a decrease in the serum potassium level (> 0.3 mmol/L) after treatment with CPS. RESULTS:We enrolled a total of 247 adult patients with a basal eGFR level of 30 ± 15 mL/min/1.73 m2. All patients took small doses of CPS (8.0 ± 3.6 g/d), and serum potassium decreased in a dose-dependent fashion. Serum potassium of all patients decreased significantly from 5.8 ± 0.3 mmol/L to 4.9 ± 0.7 mmol/L with CPS treatment (P < 0.001). The response rates were 79.9%, 71.4%, 66.7%, and 86.8% in Groups 1, 2, 3, and 4, respectively. No serious adverse effects were reported during CPS administration, though constipation was noted in 19 patients (8%). CONCLUSION:Small doses of oral CPS are effective and safe for controlling mild hyperkalemia in CKD patients over a long period of time.

Reserve capacity of donated kidney may be an important determinant of allograft survival in kidney transplantation (KT). Here, we investigate change in estimated glomerular filtration rate of donor kidney (ΔeGFR(Donor)) over 30 days after KT as a predictor of the allograft function. A total of 222 recipients were divided into two groups according to ΔeGFR(Donor) as follows: Group I (n = 110), ΔeGFR(Donor) ≥ -25%; Group II (n = 112), ΔeGFR(Donor)

Hyperkalemia is frequently complicated in patients with advanced chronic kidney disease (CKD) because kidney is the major route of potassium excretion. Urinary potassium excretion is reduced according to the decline in glomerular filtration rate, and the risk of hyperkalemia is increased in patients with high potassium intake, advanced age, diabetes mellitus, congestive heart failure, and medications such as renin-angiotensin-aldosterone system(RAAS) blockades. On the other hand, the benefits of RAAS blockades and a high-potassium diet should be considered in CKD patients. To overcome these contradictory treatment strategies, potassium binders have emerged as new options to enhance fecal potassium excretion. In different regions of the world, four types of potassium binders are preferentially used. Whereas sodium polystyrene sulfonate (SPS) exchanges sodium for potassium, calcium polystyrene sulfonate (CPS) has the advantage of avoiding hypervolemia because it exchanges calcium for potassium. SPS was first introduced in the 1950s and used for a long time in western countries, and CPS is currently prescribed in Asia including South Korea. In contrast with the paucity of clinical studies using SPS or CPS, the recent randomized, controlled trials reported that two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), effectively and safely reduce serum potassium levels in CKD patients taking RAAS blockades. Our experiences showed that the long-term administration of a small dose of CPS was also effective and safe in treatment of chronic hyperkalemia. Further comparative trials among patiromer, ZS-9, and CPS are required to provide guides to cost-effective management of hyperkalemia in CKD patients.

To improve the long-term outcome of kidney transplantation (KT), it is important to identify and take active steps to reduce the number or severity of novel risk factors. We investigated whether changes in estimated glomerular filtration rate over the first year after KT (ΔeGFR12-3) was associated with long-term renal allograft function and survival.Four hundred twenty-eight allograft recipients transplanted between 1990 and 2001 underwent ΔeGFR12-3 calculation using the equation: ΔeGFR12-3 = ([eGFR at 12 months post-KT - eGFR at 3 months post-KT]/[eGFR at 3 months post-KT]) × 100%. Recipients were divided into 3 groups according to their ΔeGFR12-3: group I (n = 150), ΔeGFR12-3 ≥ 10%; group II (n = 151), 10ΔeGFR12-3 ≥ -10%; and group III (n = 127), ΔeGFR12-3-10%. Multiple linear regression analysis was used to adjust for confounding variables that may affect long-term renal allograft function, and Kaplan-Meier analysis, to compare allograft survival.At a mean follow-up of 120 ± 58 months, we observed 112 renal allograft losses. The ΔeGFR over 10 years post-KT (ΔeGFR120-3) was significantly associated with the serum uric acid levels at 3 months post-transplantation and ΔeGFR12-3. Group III showed poor renal allograft survival; group I, 194 ± 8 months; group II, 197 ± 7 month and; group III, 163 ± 4 months; (log-rank test, P.05). A Cox proportional hazard model revealed ΔeGFR12-3 to be independently associated with future renal allograft loss (hazard ratio, 0.981; 95% confidence interval, 0.974-0.992).Our results suggested that ΔeGFR12-3 may be an independent predictor of kidney allograft survival. Routine application of eGFR is strongly recommended to identify patients at risk for chronic allograft dysfunction.

Acute postinfectious glomeruonephritis (APIGN) is an immune complex-mediated form of glomerulonephritis that follows non-renal infection, often caused by Streptococci. It mostly affects children after an upper respiratory tract infection or impetigo. The typical histological pattern of APIGN includes: diffuse endocapillary proliferative and exudative glomerulonephritis (GN) on light microscopy (LM), coarsely granular deposition of IgG and C3 in a predominantly capillary wall distribution on immunofluorescence (IF), and characteristic subepithelial hump-shaped deposits on electron microscopy (EM). Over recent decades, the spectrum of the disease has been changed. Not only Streptococci but also other bacterial, viral, and parasitic organisms have been implicated in the pathogenesis of postinfectious glomerulonephritis (PIGN).1-3 Extensive use of renal biopsy has demonstrated the presence of atypical histological features of PIGN. Recently, there have been several reports of PIGN with IgA-dominant immune complex deposition, mostly related to staphylococcal infection, especially in patients with underlying diabetic nephropathy.4-19 IgA-dominant PIGN is characterized by diffuse endocapillary proliferative GN on LM, intense deposits of IgA as the dominant or co-dominant immunoglobulin on IF, along with mesangial and subepithelial electron dense deposits on EM.9 However, there have been additional reports of IgA-dominant PIGN that lacked typical features such as diffuse endocapillary hypercellularity, subepithelial deposits, underlying diabetes mellitus and history of infection.11,12,15,17-19 Therefore, to avoid potential ambiguity, the clinicopathological features of IgA-dominant PIGN need to be investigated. Here we present seven cases of APIGN which showed IgA-dominant deposition on renal biopsy. Clinical features and renal pathologic findings were analyzed and discussed with a review of the literature.

Background/Aims: Subclinical hypovolemia may contribute to allograft dysfunction in long-term kidney transplant (KT) patients. In order to predict responsiveness to saline hydration, indices for tubular transport were investigated. Methods: Fifty-four clinically euvolemic long-term KT patients with recently aggravated azotemia were given intravenous hydration as follows: 0.9% saline 5 ml/kg over 1 h, followed by 0.9% saline 1 ml/kg/h over 12 h and 1 liter of 0.45% saline over the next 24 h. Serum and urine data were collected and analyzed to assess responses. Results: In all patients, saline hydration relieved azotemia, as shown by blood urea nitrogen (46.9 ± 17.2 vs. 39.3 ± 15.4 mg/dl; p < 0.01) and serum creatinine levels (2.9 ± 1.1 vs. 2.5 ± 1.1 mg/dl; p < 0.01) on day 0 versus day 2. In 38 patients, serum creatinine did not increase in the following month (70% responders). Compared with the nonresponders, the responders had a higher urine-to-plasma creatinine ratio and lower fractional excretion of sodium, uric acid and urea at admission. Multivariate logistic regression analysis revealed that responsiveness to saline hydration was independently associated with lower fractional excretion of uric acid. Conclusion: Subclinical hypovolemia should be considered in long-term KT patients with azotemia of unexplainable causes. Fractional excretion of uric acid may predict responsiveness to saline hydration.

BACKGROUND/AIMS: Although high-flux (HF) dialyzers with enhanced membrane permeability are widely used in current hemodialysis (HD) practice, urea kinetic modeling is still being applied to indicate the adequacy of both low-flux (LF) and HF HD. In comparison with urea (molecular weight, 60 Da) and beta(2)-microglobulin (beta(2)MG, 12 kDa), cystatin C (CyC, 13 kDa) is a larger molecule that has attractive features as a marker for assessing solute clearance. We postulated that CyC might be an alternative for indicating the clearance of middle molecules (MMs), especially with HF HD. METHODS: Eighty-nine patients were divided into LF and HF groups. Using single pool urea kinetic modeling, the urea reduction ratio (URR) and equilibrated Kt/V(urea) (eKt/V(urea)) were calculated. The serum CyC concentrations were measured using particle-enhanced immunonephelometry. As indices of the middle molecular clearance, the reduction ratios of beta(2)MG and CyC were calculated. RESULTS: The beta(2)MG reduction ratio (beta(2)MGRR) and CyC reduction ratio (CyCRR) were higher in the HF group compared to the LF group. However, the URR and eKt/Vurea did not differ between the two groups. The CyCRR was significantly correlated with the eKt/V(urea) and beta(2)MGRR (r = 0.47 and 0.69, respectively, both p < 0.0001). CONCLUSIONS: Compared to the LF dialyzer, the HF dialyzer removed CyC and beta(2)MG more efficiently. Unlike the beta(2)MGRR, the CyCRR was correlated with the eKt/V(urea) and beta(2)MGRR. This study suggests a role for the CyCRR as an alternative indicator of the removal of MMs.

Renal Fanconi syndrome (RFS) is caused by generalized proximal tubular dysfunction and can be divided into hereditary and acquired form. Adult-onset RFS is usually associated with drug toxicity or systemic disorders, and modern molecular genetics may explain the etiology of previous idiopathic cases of RFS. Here, we report the case of a 52-year-old woman with RFS whose etiology could not be identified. She presented with features of phosphaturia, renal glucosuria, aminoaciduria, tubular proteinuria, and proximal renal tubular acidosis. Her family history was unremarkable, and previous medications were nonspecific. Her bone mineral density was compatible with osteoporosis, serum intact parathyroid hormone level was mildly elevated, and 25(OH) vitamin D level was insufficient. Her blood urea nitrogen and serum creatinine levels were 8.4 and 1.19 mg/dL, respectively (estimated glomerular filtration rate, 53 mL/min/1.73 m2). Percutaneous renal biopsy was performed but revealed no specific renal pathology, including mitochondrial morphology. No mutation was detected in EHHADH gene. We propose the possibility of involvement of other genes or molecules in this case of adult RFS.

BACKGROUND Cyclophosphamide is an alkylating agent and was traditionally known to potentiate the renal action of vasopressin. Although low-dose intravenous pulse cyclophosphamide therapy is being used extensively in the treatment of malignant and rheumatological diseases, there have been only a few case reports of cyclophosphamide-induced hyponatraemia. METHODS Clinical data were retrospectively analysed from 84 patients (42 lupus nephritis; 42 non-Hodgkin's lymphoma; a total of 112 treatment episodes) admitted for intravenous pulse cyclophosphamide (500-750 mg/m(2)) therapy. In all patients, half-isotonic saline was used for prophylactic hydration. Cyclophosphamide-induced hyponatraemia was defined as serum sodium concentration

Background Obesity has been strongly associated with the development and aggravation of hypertension and chronic kidney disease. To date, the systemic renin-angiotensin system (RAS) has been known to involve in obesity-induced tissue damage and hypertension. However, the intrarenal mechanism whereby obesity induces and aggravates hypertension and renal disease remains poorly understood. Therefore, we investigated the role of intrarenal RAS and oxidative stress in diet-induced hypertension and renal inflammation in spontaneously hypertensive rats (SHR) fed a high-fat diet. Methods Male SHR and Wistar-Kyoto rats (WKY) were divided into eight groups: normal-fat diet-fed WKY (WKY-NF), high-fat diet-fed WKY (WKY-HF), high-fat diet-fed tempol-treated WKY (WKY-HF/T), high-fat diet-fed candesartan-treated WKY (WKY-HF/C), normal-fat diet-fed SHR (SHR-NF), high-fat diet-fed SHR (SHR-HF), high-fat diet-fed tempol-treated SHR (SHR-HF/T) and high-fat diet-fed candesartan-treated SHR (SHR-HF/C). After 12 weeks of treatment, haemodynamic measurements and histological assessment of the kidney were performed. Results At the end of week 12, the high-fat fed SHR gained more body weight, their systolic blood pressure was further elevated and glucose intolerance induced. There was no significant difference in the insulin resistance index, serum lipid profile, plasma renin activity and serum aldosterone levels according to diet. However, the high-fat diet resulted in increases in immunohistochemical stains of renin and angiotensin II in the kidney. The real-time PCR also demonstrated significant increases in mRNA levels of renin, angiotensinogen and angiotensin-converting enzyme in the kidney, reflecting enhanced activation of the intrarenal RAS, which findings were also shown by Western blot analysis for renin and angiotensin II type 1 receptor. The expression of ED-1, osteopontin and TGF-beta1 in the renal cortex were prominently enhanced in the SHR-HF group with the increased intrarenal lipid concentrations and oxidative stress. Administration of tempol or candesartan in the high-fat diet-induced SHR inhibited the elevation of the systolic blood pressure, intrarenal lipid concentrations, oxidative stress and the degree of renal inflammation to the levels of, or more than, the SHR-NF with no differences in the body weight and periepididymal fat weight, compared to those in the SHR-HF group without such treatment. Conclusions Our study suggests that a high-fat diet induces fatty kidneys, aggravation of blood pressure and renal inflammation in the SHR. Blockade of oxidative stress by tempol or of RAS by candesartan ameliorates the increase in blood pressure and renal inflammation and improves intrarenal lipid accumulation. Therefore, antioxidants or angiotensin receptor blockers can prevent diet-induced hypertension and renal inflammation in hypertensive rats.

Prostaglandin E2may antagonize vasopressin-stimulated salt absorption in the thick ascending limb and water absorption in the collecting duct. Blockade of prostaglandin E2synthesis by nonsteroidal anti-inflammatory drugs (NSAIDs) enhances urinary concentration, and these agents have antidiuretic effects in patients with nephrogenic diabetes insipidus (NDI) of different etiologies. Because renal prostaglandins are derived largely from cyclooxygenase-2 (COX-2), we hypothesized that treatment of NDI with a COX-2 inhibitor may relieve polyuria through increased expression of Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and aquaporin-2 (AQP2) in the collecting duct. To test this hypothesis, semiquantitative immunoblotting and immunohistochemistry were carried out from the kidneys of lithium-induced NDI rats with and without COX-2 inhibition. After male Sprague-Dawley rats were fed an LiCl-containing rat diet for 3 wk, the rats were randomly divided into control and experimental groups. The COX-2 inhibitor DFU (40 mg·kg−1·day−1) was orally administered to the experimental rats for an additional week. Treatment with the COX-2 inhibitor significantly relieved polyuria and raised urine osmolality. Semiquantitative immunoblotting using whole-kidney homogenates revealed that COX-2 inhibition caused significant increases in the abundance of AQP2 and NKCC2. Immunohistochemistry for AQP2 and NKCC2 confirmed the effects of COX-2 inhibition in lithium-induced NDI rats. The upregulation of AQP2 and NKCC2 in response to the COX-2 inhibitor may underlie the therapeutic mechanisms by which NSAIDs enhance antidiuresis in patients with NDI.

Loop and thiazide diuretics are clinically useful to induce negative sodium balance. However, with chronic treatment, their effects tend to be blunted since the kidney adapts to diuretics. Molecular identification of the renal ion transporters has provided us with a new understanding of the mechanisms of intrarenal adaptation to diuretics at molecular levels. In the kidney, loop and thiazide diuretics are secreted from the proximal tubule via the organic anion transporter-1 (OAT1) and exert their diuretic action by binding to the Na-K-2Cl cotransporter type 2 (NKCC2) in the thick ascending limb and the Na-Cl cotransporter (NCC) in the distal convoluted tubule, respectively. Recent studies in animal models suggest that abundance of these ion transporters is affected by long-term diuretic administration. Downstream from the primary site of diuretic action, an increase in epithelial Na+ channel (ENaC) abundance is induced by chronic furosemide or hydrochlorothiazide treatment. This adaptation is consistent with previous reports showing cellular hypertrophy and increased Na+ absorption in distal tubular segments. The abundance of NKCC2 and NCC is increased by furosemide and hydrochlorothiazide, respectively. This compensatory upregulation suggests that either diuretic may activate the ion transporter within the primary site of action. In the proximal tubule, the abundance of OAT1 is increased by chronic treatment with furosemide or hydrochlorothiazide. This upregulation of OAT1 seems to be induced by substrate stimulation, lessening diuretic tolerance associated with long-term diuretic use.

Depression is the most common psychological complication and may increase mortality in chronic hemodialysis patients. Because depression could be associated with poor oral intake and activation of proinflammatory cytokines that could further increase mortality by malnutrition, we investigated the relation between depression and nutritional status in chronic hemodialysis patients.Sixty-two Korean patients completed the Beck Depression Inventory (BDI) questionnaire, and the diagnosis of depression was confirmed by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for major depressive disorder. Nutritional status was evaluated using serum albumin level, normalized protein catabolic rate, subjective global assessment (SGA), and anthropometric measurement.Mean BDI score was 22.7 +/- 11.4, and 35 patients (56.5%) had a BDI score greater than 21, which is the suggested cutoff score for the diagnosis of depression for the Korean population. Of 40 patients who had a score higher than 18 on the BDI, 34 patients met DSM-IV criteria for major depressive disorder. BDI score correlated negatively with a variety of nutritional parameters: serum albumin level (r = -0.47; P0.001), normalized protein catabolic rate (r = -0.32; P0.05), SGA (r = -0.47; P0.01), triceps skinfold thickness (r = -0.40; P0.05), midarm muscle circumference (r = -0.57; P0.01), and body mass index (r = -0.28; P0.05). Multiple regression analysis also identified BDI score as an independent determinant for all kinds of nutritional parameters.In patients on chronic hemodialysis therapy, depression is related closely to nutritional status and could be an independent risk factor for malnutrition.

Background: Acute renal failure (ARF) is not a rare occurrence in severe burns and is an important complication leading to an increase in mortality. The severity of the burn is largely determined by the burn size, and severe burns are likely to cause enough loss of extracellular fluid and albumin from plasma volume to produce shock and hypoalbuminemia. Hypothesis: We hypothesized that initial serum albumin level may be useful as an indicator of prognosis and severity of injury in burned patients. Methods: The clinical characteristics of 147 adult patients with second- and third-degree burns covering 30% or more of their body surface area were analyzed retrospectively. Logistic regression was used to estimate the relative risks of ARF and mortality associated with the larger burn size and the lower serum albumin level at admission. Results: Mean burned body surface was 60.0 ± 21.8% (range 30–100%). Twenty-eight (19.0%) out of 147 patients experienced ARF, defined as a serum creatinine ≧2 mg/dl, during the admission. The patients with ARF had larger burn size (79.5 ± 15.4 vs. 55.3 ± 20.5%, p < 0.0001) and lower serum albumin concentration at admission (1.92 ± 0.66 vs. 2.48 ± 0.82 g/dl, p < 0.0005) compared with those without ARF. All patients with ARF expired, whereas 29.4% (35/119) of the patients without ARF died. The burn size ≧65% was associated with a risk of ARF that was 9.9 times and with a risk of death that was 14.2 times as high as that for the burn size Conclusions: When major burns are complicated by ARF, the mortality rate increases significantly. Burn size is an independent predictor of ARF occurring in major burns. Initially depressed serum albumin level is associated with an increase in mortality in the major burn patients.

Paraquat poisoning is characterized by multiorgan failure and pulmonary fibrosis with respiratory failure. Multiorgan failure with circulatory collapse is a major cause of early death within 3 days of paraquat ingestion. Recent studies suggested that continuous venovenous hemofiltration (CVVH) had a role in the treatment of multiorgan failure by promoting hemodynamic stability. We therefore evaluated the effect of prophylactic CVVH in 80 patients with paraquat poisoning (August 1996 to February 1999). The amount ingested was 2.1 +/- 1.0 mouthfuls (as 20% concentrate). All patients were treated with hemoperfusion (HP; duration, 6.4 +/- 3.0 hours) within 24 hours of ingestion and then randomly assigned to the HP-alone or HP-CVVH group. Forty-four patients underwent HP only, and 36 patients underwent CVVH (duration, 57.4 +/- 31.3 hours; ultrafiltration volume, 40.2 +/- 4.8 L/d) after HP. Although time to death after ingestion was significantly longer in the HP-CVVH than HP group (5.0 +/- 5.0 versus 2.5 +/- 2.1 days; P < 0.05), there was no difference in mortality rates between the two groups (66.7% versus 63.6%; P = 0.82). In the HP group, early circulatory collapse was a major cause of death compared with the HP-CVVH group, in which late respiratory failure was a major cause of death. In conclusion, prophylactic CVVH after HP prevented early death caused by circulatory collapse and prolonged survival time. However, it could not prevent late death caused by respiratory failure and did not provide a survival benefit in acute paraquat poisoning.