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1.  Urinary Sodium Excretion Has Positive Correlation with Activation of Urinary Renin Angiotensin System and Reactive Oxygen Species in Hypertensive Chronic Kidney Disease 
Journal of Korean Medical Science  2014;29(Suppl 2):S123-S130.
It is not well described the pathophysiology of renal injuries caused by a high salt intake in humans. The authors analyzed the relationship between the 24-hr urine sodium-to-creatinine ratio (24HUna/cr) and renal injury parameters such as urine angiotensinogen (uAGT/cr), monocyte chemoattractant peptide-1 (uMCP1/cr), and malondialdehyde-to-creatinine ratio (uMDA/cr) by using the data derived from 226 hypertensive chronic kidney disease patients. At baseline, the 24HUna/cr group or levels had a positive correlation with uAGT/cr and uMDA/cr adjusted for related factors (P<0.001 for each analysis). When we estimated uAGT/cr in the 24HUna/cr groups by ANCOVA, the uAGT/cr in patients with ≥200 mEq/g cr was higher than in patients with <100 mEq/g cr (708 [95% CI, 448-967] vs. 334 [95% CI, 184-483] pg/mg cr, P=0.014). Similarly, uMDA/cr was estimated as 0.17 (95% CI, 0.14-0.21) pM/mg cr in patients with <100 mEq/g cr and 0.27 (95% CI, 0.20-0.33) pM/mg cr in patients with ≥200 mEq/g cr (P=0.016). During the 16-week follow-up period, an increase in urinary sodium excretion predicted an increase in urinary angiotensinogen excretion. In conclusion, high salt intake increases renal renin-angiotensin-system (RAS) activation, primarily, and directly or indirectly affects the production of reactive oxygen species through renal RAS activation.
doi:10.3346/jkms.2014.29.S2.S123
PMCID: PMC4194282  PMID: 25317016
Chronic Renal Insufficiency; Sodium Chloride; Renin; Angiotensinogen
2.  Effect of Dialysis Initiation Timing on Clinical Outcomes: A Propensity-Matched Analysis of a Prospective Cohort Study in Korea 
PLoS ONE  2014;9(8):e105532.
Background
Controversy persists regarding the appropriate initiation timing of renal replacement therapy for patients with end-stage renal disease. We evaluated the effect of dialysis initiation timing on clinical outcomes. Initiation times were classified according to glomerular filtration rate (GFR).
Methods
We enrolled a total of 1691 adult patients who started dialysis between August 2008 and March 2013 in a multi-center, prospective cohort study at the Clinical Research Center for End Stage Renal Disease in the Republic of Korea. The patients were classified into the early-start group or the late-start group according to the mean estimated GFR value, which was 7.37 ml/min/1.73 m2. The primary outcome was patient survival, and the secondary outcomes were hospitalization, cardiovascular events, vascular access complications, change of dialysis modality, and peritonitis. The two groups were compared before and after matching with propensity scores.
Results
Before propensity score matching, the early-start group had a poor survival rate (P<0.001). Hospitalization, cardiovascular events, vascular access complications, changes in dialysis modality, and peritonitis were not different between the groups. A total of 854 patients (427 in each group) were selected by propensity score matching. After matching, neither patient survival nor any of the other outcomes differed between groups.
Conclusions
There was no clinical benefit after adjustment by propensity scores comparing early versus late initiation of dialysis.
doi:10.1371/journal.pone.0105532
PMCID: PMC4138196  PMID: 25137235
3.  Circulating TNF Receptors Are Significant Prognostic Biomarkers for Idiopathic Membranous Nephropathy 
PLoS ONE  2014;9(8):e104354.
Idiopathic membranous nephropathy (iMN) is a common cause of nephrotic syndrome in adults. A biomarker to accurately indicate the severity of iMN and predict long-term prognosis is insufficient. Here, we evaluated the clinical significance of circulating tumor necrosis factor receptors (cTNFRs) as prognostic biomarkers of iMN with nephrotic syndrome. A total of 113 patients with biopsy-proven iMN and 43 healthy volunteers were enrolled in this study. Ninety patients with iMN had nephrotic range proteinuria. Levels of cTNFRs were measured by using serum samples collected at the time of initial diagnosis. Levels of cTNFRs were higher in the patients with nephrotic syndrome than in those with subnephrotic range proteinuria or in the healthy volunteers (P for trend <0.001). Estimated glomerular filtration rate and proteinuria tended to worsen as the cTNFRs levels increased. Having a cTNFR1 level within the highest tertile was a significant risk factor for renal progression after adjustment, in comparison with the other tertiles (hazard ratio [HR], 3.39; 95% confidence interval [95% CI], 1.48–7.78; P = 0.004). The cTNFR2 level within the highest tertile also significantly increased the risk of renal progression (HR, 3.29; 95% CI, 1.43–7.54; P = 0.005). Renal tubular TNFRs expression was associated with cTNFRs level. However, the cTNFRs levels were not associated with autoantibody against phospholipase A2 receptor reactivity/levels or treatment response. This study demonstrated that cTNFRs levels at the time of initial diagnosis could predict renal progression in patients with iMN.
doi:10.1371/journal.pone.0104354
PMCID: PMC4123977  PMID: 25098821
4.  Non-linear association of serum 25-hydroxyvitamin D with urinary albumin excretion rate in normoalbuminuric subjects 
BMC Nephrology  2014;15:97.
Background
Vitamin D deficiencies and increases in urinary albumin excretion (UAE) are both important and potentially related health problems; however, the nature of their relationship has not been established in normoalbuminuric subjects.
Methods
We obtained data from 14,594 normoalbuminuric Korean adults who underwent voluntary health screenings. We used a generalized additive model to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and urinary-albumin creatinine ratio (UACR) levels. We conducted multivariate logistic regression for high-normal UAE (UACR, 10–29 mg/g), according to various categories of vitamin D status.
Results
The generalized additive model confirmed a non-linear relationship between serum 25(OH)D and UACR levels, and the threshold concentration of 25(OH)D was 8.0 ng/mL after multivariate adjustment. Comparing subjects who fell into the lowest category of serum 25(OH)D levels with subjects who were in the reference range (the highest category), we observed that the multivariate adjusted odds ratio (OR) for high-normal UAE was significantly increased, regardless of the criteria used to categorize vitamin D levels: OR of the 1st quartile over the 4th quartile, 1.20 (95% CI, 1.04-1.39); OR of the 1.0-4.9th percentile over the 50-100th percentile, 1.56 (95% CI, 1.25-1.93); and OR of vitamin D deficiency group over vitamin D sufficiency group, 1.28 (95% CI, 1.08-1.52).
Conclusions
We demonstrated that there was an inverse relationship between serum 25(OH)D less than 8.0 ng/mL and UACR in normoalbuminuric subjects, suggesting that severe vitamin D deficiency could cause an increase in UAE in subjects with normoalbuminuria.
doi:10.1186/1471-2369-15-97
PMCID: PMC4079922  PMID: 24957097
Epidemiology; Low-grade albuminuria; Threshold; Vitamin D deficiency
5.  Long-term prognosis of clinically early IgA nephropathy is not always favorable 
BMC Nephrology  2014;15:94.
Background
The long-term prognosis of clinically early IgA nephropathy (IgAN) patients remains to be clarified. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival.
Methods
We included patients with biopsy-proven IgAN who had estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2, normal blood pressure, and proteinuria <0.5 g/day at the time of biopsy. The primary outcome was progression to end-stage renal disease (ESRD). The secondary outcome was a 50% increase in serum creatinine level or an increase in proteinuria to >1 g/day.
Results
The analysis included 153 patients who met the inclusion criteria. At diagnosis, their median systolic blood pressure was 120 (110–130) mmHg, eGFR was 85.9 (74.9–100.1) mL/min/1.73 m2, and proteinuria was 0.25 (0.13–0.38) g/day. Of these, 4 patients died and 6 reached ESRD. The 30-year renal survival rate was 85.5%. Three patients had increased serum creatinine levels and 11 developed proteinuria. Remission was observed in 35 (22.9%) patients. A moderate or severe degree of interstitial fibrosis (adjusted odd ratio [OR] 5.93, 95% confidence interval [CI] 1.44–24.45, P = 0.014) and hypoalbuminemia (adjusted OR 6.18, 95% CI 1.20–31.79, P = 0.029) were independent predictors of the secondary outcome.
Conclusions
This study showed that the prognosis of early IgAN was not always favorable, even resulting in progression to ESRD in some cases. Hypoalbuminemia and interstitial fibrosis should also be considered important prognostic factors in clinically early IgAN patients.
doi:10.1186/1471-2369-15-94
PMCID: PMC4070337  PMID: 24946688
IgA nephropathy; Interstitial fibrosis; Progression of renal failure
6.  Early Nephrology Referral Reduces the Economic Costs among Patients Who Start Renal Replacement Therapy: A Prospective Cohort Study in Korea 
PLoS ONE  2014;9(6):e99460.
Background
The nature of cost-saving effects of early referral to a nephrologist in patients with chronic kidney disease (CKD) is not fully evaluated. We evaluated the health care costs before and after dialysis according to the referral time.
Methods
A total of 879 patients who were newly diagnosed as having end-stage renal disease from August 2008 to June 2011 were prospectively enrolled. The early referral (ER) group was defined as patients who were referred to a nephrologist more than a year before dialysis and had visited a nephrology clinic 2 or more times. Patients whose referral time was less than a year were considered the late referral (LR) group. Information about medical costs was acquired from the claim data of the Korea Health Insurance Review and Assessment Service.
Results
The total medical costs during the first 12 months after the initiation of dialysis were not different between the 526 ER patients and the 353 LR patients. However, the costs of the ER patients during the first month were significantly lower than those of the LR patients (ER vs. LR: 3029±2219 vs. 3438±2821 US dollars [USD], P = 0.025). The total 12-month health care costs before the initiation of dialysis were significantly lower in the ER group (ER vs. LR: 6206±5873 vs. 8610±7820 USD, P<0.001). In the multivariate analysis, ER significantly lowered the health care costs during the 12 months before (2534.0±436.2 USD, P<0.001) and the first month (428.5±172.3 USD, P = 0.013) after the initiation of dialysis.
Conclusions
The ER of patients with CKD to a nephrologist is associated with decreased medical costs during the pretreatment period of renal replacement therapy and the early period of dialysis initiation.
doi:10.1371/journal.pone.0099460
PMCID: PMC4057219  PMID: 24927081
7.  Serum Bilirubin Affects Graft Outcomes through UDP-Glucuronosyltransferase Sequence Variation in Kidney Transplantation 
PLoS ONE  2014;9(4):e93633.
Background
Oxidative stress is a major mediator of adverse outcome after kidney transplantation. Bilirubin is produced by heme oxygenase-1 (HO-1), catalyzed by UDP-glucuronosyltransferase (UGT1A1), and has potential as an antioxidant. In this study, we investigated the effects of HO-1 and UGT1A1 sequence variations on kidney allograft outcomes.
Methods
Clinical data were collected from 429 Korean recipients who underwent kidney transplantation from 1990–2008. Genotyping for UGT1A1*28 and HO-1 (A−413T) was performed. Acute rejection and graft survival were monitored as end-points.
Results
Serum levels of total bilirubin were significantly increased after transplantation (0.41±0.19 mg/dL to 0.80±0.33 mg/dL, P<0.001). Post-transplant 1-year bilirubin level was higher in 6/7 or 7/7 carriers compared with 6/6 homozygotes in terms of the UGT1A1*28 polymorphism (6/6 vs. 6/7 vs. 7/7: 0.71±0.27 vs. 1.06±0.36 vs. 1.10±0.45 mg/dL, P<0.001). According to an additive model of genotype analysis, the 7-allele genotype had a protective effect on the development of acute rejection compared with the 6-allele (odds ratio 0.43, 95% CI 0.25–0.73, P for trend = 0.006). Multivariate Cox regression analysis revealed that individuals carrying the 7-allele had a decreased risk of graft loss, by a factor of 0.36 (95% CI 0.15–0.85, P = 0.019). The HO-1 (A−413T) polymorphism had no effect on serum bilirubin levels or graft outcomes.
Conclusions
The UGT1A1*28 polymorphism is associated with changes in serum bilirubin and with graft outcome after kidney transplantation.
doi:10.1371/journal.pone.0093633
PMCID: PMC3972238  PMID: 24690955
8.  Dose selection method for pharmacokinetic study in hemodialysis patients using a subpharmacological dose: oseltamivir as a model drug 
BMC Nephrology  2014;15:46.
Background
Dose selection is an important step in pharmacokinetic (PK) studies of hemodialysis patients. We propose a simulation-based dose-selection method for PK studies of hemodialysis patients using a subpharmacological dose of oseltamivir as a model drug.
Methods
The concentrations of oseltamivir and its active metabolite, oseltamivir carboxylate (OC), were measured by liquid chromatography-tandem mass spectrometry. To determine a low oseltamivir dose exhibiting PK linearity, a pilot low dose determination investigation (n = 4) was performed using a single administration dose-escalation study. After the dose was determined, a low dose study (n = 10) was performed, and the optimal dose required to reach the hypothetical target OC exposure (area under the concentration-time curve [AUC] of 60,000 ng · hr/mL) was simulated using a nonparametric superposition method. Finally, observed PKs at the optimal dose were compared to the simulated PKs to verify PK predictability.
Results
In the pilot low dose determination study, 2.5 mg of oseltamivir was determined to be the low dose. Subsequently, we performed a single-dose PK study with the low oseltamivir dose in an additional group of 10 hemodialysis patients. The predicted AUClast of OC following continuous oseltamivir doses was simulated, and 35 mg of oseltamivir corresponded to the hypothetical target AUClast of OC. The observed PK profiles of OC at a 35-mg oseltamivir dose and the simulated data based on the low dose study were in close alignment.
Conclusion
The results indicate that the proposed method provides a rational approach to determine the proper PK dose in hemodialysis patients.
doi:10.1186/1471-2369-15-46
PMCID: PMC3995549  PMID: 24636040
Hemodialysis; Pharmacokinetics; Drug; Dosage
9.  Effect of beraprost sodium on arterial stiffness in patients with type 2 diabetic nephropathy 
Trials  2013;14:275.
Background
Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD). Cardiovascular (CV) complications are the most common cause of death among ESRD patients. Beraprost sodium (BPS) is a prostacyclin analog with vasodilatory and antiplatelet effects.
Methods
This is a multicenter prospective, randomized, double-blind, placebo-controlled trial to determine whether treatment with BPS improves arterial stiffness in patients with type 2 diabetic nephropathy. A total of 102 participants with type 2 diabetic nephropathy will be screened, enrolled, and randomly assigned to receive either 80 μg BPS or placebo daily for 12 weeks. The primary outcome is the change in brachial-ankle pulse wave velocity between baseline and after 12 weeks of medication use. The secondary outcomes will include changes in the ankle-brachial index, the urine albumin to creatinine ratio, the estimated glomerular filtration rate, lipid profiles, and blood pressure from baseline to after treatment.
Discussion
This clinical trial is the first to investigate the effects of BPS on changes in CV biomarkers, albuminuria, renal function, and lipid profiles in patients with diabetic nephropathy.
Trial registration
ClinicalTrials.gov number NCT01796418
doi:10.1186/1745-6215-14-275
PMCID: PMC3765998  PMID: 24066672
Beraprost sodium; Arterial stiffness; Diabetic nephropathy; Cardiovascular; Pulse wave velocity
10.  Non-Linear Relationship between Serum 25-Hydroxyvitamin D and Hemoglobin in Korean Females: The Korean National Health and Nutrition Examination Survey 2010–2011 
PLoS ONE  2013;8(8):e72605.
Background
Anemia and vitamin D deficiency are both important health issues; however, the nature of the association between vitamin D and either hemoglobin or anemia remains unresolved in the general population.
Methods
Data on 11,206 adults were obtained from the fifth Korean National Health and Nutritional Examination Survey. A generalized additive model was used to examine the threshold level for relationship between serum 25-hydroxyvitamin D [25(OH)D] and hemoglobin levels. A multivariate logistic regression for anemia was conducted according to 25(OH)D quintiles. All analyses were stratified according to sex and menstrual status.
Results
The generalized additive model confirmed a threshold 25(OH)D level of 26.4 ng/mL (male, 27.4 ng/mL; premenopausal females, 11.8 ng/mL; postmenopausal females, 13.4 ng/mL). The threshold level affected the pattern of association between 25(OH)D and anemia risk: the odds ratio of the 1st quintile but not the 2nd, 3rd, and 4th quintiles were significantly different from the 5th quintile in both premenopausal and postmenopausal females, however there was no obvious trend in males.
Conclusions
This population-based study demonstrated a non-linear relationship with a threshold effect between serum 25(OH)D and hemoglobin levels in females. Further interventional studies are warranted to determine whether the appropriate level of hemoglobin can be achieved by the correction of vitamin D deficiency.
doi:10.1371/journal.pone.0072605
PMCID: PMC3755993  PMID: 24015265
11.  Severe hyperkalemia requiring hospitalization: predictors of mortality 
Critical Care  2012;16(6):R225.
Introduction
Severe hyperkalemia, with potassium (K+) levels ≥ 6.5 mEq/L, is a potentially life-threatening electrolyte imbalance. For prompt and effective treatment, it is important to know its risk factors, clinical manifestations, and predictors of mortality.
Methods
An observational cohort study was performed at 2 medical centers. A total of 923 consecutive Korean patients were analyzed. All were 19 years of age or older and were hospitalized with severe hyperkalemia between August 2007 and July 2010; the diagnosis of severe hyperkalemia was made either at the time of admission to the hospital or during the period of hospitalization. Demographic and baseline clinical characteristics at the time of hyperkalemia diagnosis were assessed, and clinical outcomes such as in-hospital mortality were reviewed, using the institutions' electronic medical record systems.
Results
Chronic kidney disease (CKD) was the most common underlying medical condition, and the most common precipitating factor of hyperkalemia was metabolic acidosis. Emergent admission was indicated in 68.6% of patients, 36.7% had electrocardiogram findings typical of hyperkalemia, 24.5% had multi-organ failure (MOF) at the time of hyperkalemia diagnosis, and 20.3% were diagnosed with severe hyperkalemia at the time of cardiac arrest. The in-hospital mortality rate was 30.7%; the rate was strongly correlated with the difference between serum K+ levels at admission and at their highest point, and with severe medical conditions such as malignancy, infection, and bleeding. Furthermore, a higher in-hospital mortality rate was significantly associated with the presence of cardiac arrest and/or MOF at the time of diagnosis, emergent admission, and intensive care unit treatment during hospitalization. More importantly, acute kidney injury (AKI) in patients with normal baseline renal function was a strong predictor of mortality, compared with AKI superimposed on CKD.
Conclusions
Severe hyperkalemia occurs in various medical conditions; the precipitating factors are similarly diverse. The mortality rate is especially high in patients with severe underlying disease, coexisting medical conditions, and those with normal baseline renal function.
doi:10.1186/cc11872
PMCID: PMC3672605  PMID: 23171442
12.  Soluble Epoxide Hydrolase Activity Determines the Severity of Ischemia-Reperfusion Injury in Kidney 
PLoS ONE  2012;7(5):e37075.
Soluble epoxide hydrolase (sEH) in endothelial cells determines the plasma concentrations of epoxyeicosatrienoic acids (EETs), which may act as vasoactive agents to control vascular tone. We hypothesized that the regulation of sEH activity may have a therapeutic value in preventing acute kidney injury by controlling the concentration of EETs. In this study, we therefore induced ischemia-reperfusion injury (IRI) in C57BL/6 mice and controlled sEH activity by intraperitoneal administration of the sEH inhibitor 12-(3-adamantan-1-ylureido)-dodecanoic acid (AUDA). The deterioration of kidney function induced by IRI was partially moderated and prevented by AUDA treatment. In addition, AUDA treatment significantly attenuated tubular necrosis induced by IRI. Ischemic injury induced the down-regulation of sEH, and AUDA administration had no effect on the expression pattern of sEH induced by IRI. In vivo sEH activity was assessed by measuring the substrate epoxyoctadecenoic acid (EpOME) and its metabolite dihydroxyoctadec-12-enoic acid (DHOME). Ischemic injury had no effects on the plasma concentrations of EpOME and DHOME, but inhibition of sEH by AUDA significantly increased plasma EpOME and the EpOME/DHOME ratio. The protective effect of the sEH inhibitor was achieved by suppression of proinflammatory cytokines and up-regulation of regulatory cytokines. AUDA treatment prevented the intrarenal infiltration of inflammatory cells, but promoted endothelial cell migration and neovascularization. The results of this study suggest that treatment with sEH inhibitors can reduce acute kidney injury.
doi:10.1371/journal.pone.0037075
PMCID: PMC3349654  PMID: 22590647
13.  The association of moderate renal dysfunction with impaired preference-based health-related quality of life: 3rd Korean national health and nutritional examination survey 
BMC Nephrology  2012;13:19.
Background
Only a few large-scale studies have investigated the association between health-related quality of life (HRQOL) and renal function. Moreover, the HRQOL of patients with moderate renal dysfunction is frequently underestimated by healthcare providers. This study assessed the impact of renal function on preference-based HRQOL in Korean adult population.
Methods
We analyzed data for 5,555 adults from the 3rd Korean National Health and Nutritional Examination Survey 2005. The EuroQol-5D (EQ-5D) utility score was used to evaluate HRQOL. The study subjects were stratified into three groups based on their estimated glomerular filtration rates (eGFRs): ≥ 90.0, 60.0-89.9 and 30.0-59.9 mL/min/1.73 m2. Individuals with advanced renal dysfunction were excluded from the analysis.
Results
The proportions of participants who reported problems in each of the five EQ-5D dimensions increased significantly with decreasing eGFR. However, a significant decrease in the EQ-5D utility score was observed among participants with an eGFR of 30.0-59.9 mL/min/1.73 m2. Participants with an eGFR of 30.0-59.9 mL/min/1.73 m2 had an almost 1.5-fold higher risk of impaired health utility (the lowest quartile of EQ-5D utility score) compared with those participants with eGFRs ≥ 90.0 mL/min/1.73 m2, after adjustment for age, gender, health-related behaviors, socioeconomic and psychological variables, and other comorbidities. Among the five dimensions of the EQ-5D, an eGFR of 30.0-59.9 mL/min/1.73 m2 was an independent determinant of self-reported problems in the mobility and pain/discomfort dimensions.
Conclusions
Although age affects the association between renal dysfunction and the EQ-5D, moderate renal dysfunction seems to be an important determinant of impaired health utility in a general population and may affect the mobility and pain/discomfort dimensions of health utility.
doi:10.1186/1471-2369-13-19
PMCID: PMC3404912  PMID: 22530944
Chronic kidney disease; EuroQol-5D; Preference-based health utility
14.  Lower Residual Renal Function is a Risk Factor for Depression and Impaired Health-Related Quality of Life in Korean Peritoneal Dialysis Patients 
We retrospectively evaluated demographic and biochemical parameters associated with depression and health-related quality of life (HRQOL) in maintenance peritoneal dialysis (PD) patients. This study included 105 patients maintaining PD at Seoul National University Hospital. Data were collected from electronic medical record. Korean Beck's Depression Inventory and Korean version of Kidney Disease Quality of Life short form, version 1.3 were used to evaluate depression and HRQOL, respectively. Moderate to severe depression was found in 24.8% of patients. Patients with lower normalized protein equivalent of nitrogen appearance (nPNA) (< 1.2 g/kg/day), lower weekly renal Kt/Vurea (< 0.2), and lower serum albumin level (≤ 4.0 g/dL) were associated with depression (P < 0.05). Among them, lower weekly renal Kt/Vurea was the only independent risk factor associated with depression (OR = 3.1, P = 0.007). Depressed patients showed significantly lower scores in every dimension of HRQOL (P < 0.001). Lower weekly renal Kt/Vurea (β = 0.24, P = 0.005) and lower nPNA (β = 0.15, P = 0.03) were the independent risk factors associated with lower kidney dialysis component summary, whereas lower plasma hemoglobin level was the consistent risk factor for lower physical component summary (β = 0.22, P = 0.03) and mental component summary (β = 0.22, P = 0.01). Depression is a prevalent psychological problem in PD population. Residual renal function is the most important factor associated with depression and impaired HRQOL in PD patients.
doi:10.3346/jkms.2012.27.1.64
PMCID: PMC3247777  PMID: 22219616
Peritoneal Dialysis; Depression; Health-Related Quality of Life; Residual Renal Function; Beck's Depression Inventory; KDQOL-SF
15.  Ethnic Coefficients for Glomerular Filtration Rate Estimation by the Modification of Diet in Renal Disease Study Equations in the Korean Population 
Journal of Korean Medical Science  2010;25(11):1616-1625.
Race and ethnicity are influential in estimating glomerular filtration rate (GFR). We aimed to find the Korean coefficients for the Modification of Diet in Renal Disease (MDRD) study equations and to obtain novel proper estimation equations. Reference GFR was measured by systemic inulin clearance. Serum creatinine (SCr) values were measured by the alkaline picrate Jaffé kinetic method, then, recalibrated to CX3 analyzer and to isotope dilution mass spectrometry (IDMS). The Korean coefficients for the 4 and 6 variable MDRD and IDMS MDRD study equations based on the SCr recalibrated to CX3 and to IDMS were 0.73989/0.74254 and 0.99096/0.9554, respectively. Coefficients for the 4 and 6 variable MDRD equations based on the SCr measured by Jaffé method were 1.09825 and 1.04334, respectively. The modified equations showed better performances than the original equations. The novel 4 variable equations for Korean based on the SCr measured and recalibrated to IDMS were 107.904×SCr-1.009×age-0.02 (×0.667, if woman) and 87.832×SCr-0.882×age0.01 (×0.653, if woman), respectively. Modified estimations of the MDRD and IDMS MDRD study equations with ethnic coefficients and the novel equations improve the performance of GFR estimation for the overall renal function.
doi:10.3346/jkms.2010.25.11.1616
PMCID: PMC2966999  PMID: 21060751
Coefficient; Glomerular Filtration Rate; Inulin Clearance; Modification of Diet in Renal Disease Study
16.  The Prevalence of Chronic Kidney Disease (CKD) and the Associated Factors to CKD in Urban Korea: A Population-based Cross-sectional Epidemiologic Study 
Journal of Korean Medical Science  2009;24(Suppl 1):S11-S21.
Chronic kidney disease (CKD) is a worldwide problem. This study was designed to survey the prevalence and risk factors for CKD in Korea. The 2,356 subjects were selected in proportion to age, gender, and city. Subjects 35 yr of age or older were selected from 7 cities. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) Study equation, with albuminuria defined as a urine albumin to creatinine ratio of 30 mg/g or more. The overall prevalence of CKD was 13.7%. The prevalences of CKD according to stage were 2.0% stage 1, 6.7% stage 2, 4.8% stage 3, 0.2% stage 4, and 0.0% stage 5. The prevalences of microalbuminuria and macroalbuminuria were 8.6% and 1.6%, respectively. The prevalence of eGFR less than 60 mL/min/1.73 m2 was 5.0%. Age, body mass index (BMI), hypertension, diabetes mellitus, systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting blood glucose were independent factors related to the presence of CKD. In conclusions, Korea, in which the prevalence of CKD is increasing, should prepare a policy for early detection and appropriate treatment of CKD. The present data will be helpful in taking those actions.
doi:10.3346/jkms.2009.24.S1.S11
PMCID: PMC2633200  PMID: 19194539
Korea; Kidney Failure, Chronic; Epidemiologic Studies
17.  The Mildly Elevated Serum Bilirubin Level is Negatively Associated with the Incidence of End Stage Renal Disease in Patients with IgA Nephropathy 
Journal of Korean Medical Science  2009;24(Suppl 1):S22-S29.
Oxidative stress plays various roles in the development and progression of IgA nephropathy, while bilirubin is known as a potent antioxidant. We therefore hypothesized that serum bilirubin would be associated with renal prognosis in IgA nephropathy. The study subjects comprised 1,458 adult patients with primary IgA nephropathy in Korea. We grouped patients according to the following quartile levels of bilirubin: <0.4 mg/dL (Q1), 0.4-0.5 mg/dL (Q2), 0.6-0.7 mg/dL (Q3), and >0.8 mg/dL (Q4). The outcome data were obtained from the Korean Registry of end-stage renal disease (ESRD). Eighty patients (5.5%) contracted ESRD during a mean follow-up period of 44.9 months. The ESRD incidences were 10.7% in Q1, 8.2% in Q2, 2.8% in Q3, and 2.8% in Q4 (p<0.001). The relative risk of ESRD compared to that in Q1 was 0.307 (95% confidence interval [CI], 0.126-0.751) in Q3 and 0.315 (95% CI, 0.130-0.765) in Q4. The differences of ESRD incidence were greater in subgroups of males and of patients aged 35 yr or more, with serum albumin 4.0 g/dL or more, with normotension, with eGFR 60 mL/min/1.73 m2 or more, and with proteinuria less then 3+ by dipstick test. In conclusion, higher bilirubin level was negatively associated with ESRD incidence in IgA nephropathy.
doi:10.3346/jkms.2009.24.S1.S22
PMCID: PMC2633177  PMID: 19194557
Bilirubin; Glomerulonephritis, IGA; Kidney Failure, Chronic
18.  Restless Legs Syndrome in Patients on Hemodialysis: Symptom Severity and Risk Factors 
Background and Purpose
Restless legs syndrome (RLS) is a sleep disorder that frequently occurs in dialysis patients, which disturbs the sleep and reduces the quality of life. The aim of this study was to determine the risk factors for RLS in dialysis patients.
Methods
Patients who visited any of four outpatient dialysis clinics between September 2005 and May 2006 were included in this study. The diagnosis of RLS and the severity assessment were made using the criteria described by the International Restless Legs Syndrome Study Group. We collected basic demographic data, clinical information, and laboratory findings, and then analyzed their association with various aspects of RLS using univariate and multivariate analyses.
Results
RLS was present in 46 (28.0%) of 164 dialysis patients. We found no significant risk factor for inducing RLS. The predialysis serum blood urea nitrogen (BUN) level in the dialysis patients with RLS was significantly correlated with RLS symptom severity.
Conclusions
Predialysis BUN is related to RLS symptom severity. Further studies on the underlying mechanism are needed.
doi:10.3988/jcn.2008.4.4.153
PMCID: PMC2686851  PMID: 19513290
restless legs syndrome; hemodialysis; blood urea nitrogen
19.  Altered Renal Sodium Transporter Expression in an Animal Model of Type 2 Diabetes Mellitus 
Journal of Korean Medical Science  2007;22(6):1034-1041.
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) β-subunit was increased in OLETF rats, but the abundance of the ENaC γ-subunit was decreased. No significant differences were observed in the ENaC α-subunit or other major sodium transporters. Immunohistochemistry for the ENaC β-subunit showed increased immunoreactivity in OLETF rats, whereas the ENaC γ-subunit showed reduced immunoreactivity in these rats. In OLETF rats, ENaC β-subunit upregulation and ENaC γ-subunit downregulation after the development of diabetic nephropathy may reflect an abnormal sodium balance.
doi:10.3346/jkms.2007.22.6.1034
PMCID: PMC2694262  PMID: 18162719
Diabetic Nephropathies; Rats, Inbred OLETF; Sodium-Hydrogen Exchanger 3; Bumetanide Sensitive NaK2Cl Cotransporter; Thiazide Sensitive Nacl Cotransporter; Epithelial Sodium Channel
20.  Interleukin-10 Promoter Polymorphism is Associated with the Predisposition to the Development of IgA Nephropathy and Focal Segmental Glomerulosclerosis in Korea 
Journal of Korean Medical Science  2005;20(6):989-993.
The roles of interleukin-10 (IL-10) have been emphasized in several models of glomerulonephritis (GN). Three biallelic polymorphisms within the IL-10 promoter region, at positions -1,082, -819, and -592 from the transcription initiation site, were shown to affect the level of IL-10 production. To investigate the effect of IL-10 promoter polymorphisms on the predisposition to development of GN in Korea, IL-10 promoter polymorphisms were assayed by polymerase chain reaction followed by restriction fragment length polymorphism in 108 patients with IgA nephropathy (IgAN), 49 focal segmental glomerulosclerosis (FSGS), and 100 healthy controls. In comparison with the control, the frequency of -1,082*G alleles were lower in IgAN and the frequencies of -592*C and -819*C were lower in FSGS, respectively. As for the haplotype, GCC haplotype was less frequent among IgAN than the control and ATA haplotype was more frequent among FSGS than the control (p<0.05). The frequency of intermediate producer genotypes (GCC/ACC and GCC/ATA) were lower among IgAN or FSGS than the control. Our findings suggested that IL-10 promoter polymorphism predisposed to the development of IgAN and FSGS in Korean patients.
doi:10.3346/jkms.2005.20.6.989
PMCID: PMC2779332  PMID: 16361810
Glomerulonephritis, IGA; Glomerulosclerosis, Focal; Polymorphism, Single Nucleotide

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