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1.  Urinary adiponectin and albuminuria in non-diabetic hypertensive patients: an analysis of the ESPECIAL trial 
BMC Nephrology  2015;16:123.
Although adiponectin levels have been reported to be correlated with albuminuria, this issue remains unresolved in non-diabetic hypertensive subjects, particularly when urinary adiponectin is considered.
Urinary adiponectin levels were examined using an enzyme-linked immunosorbent assay in 229 participants. who used olmesartan as a hypertensive agent. Their albuminuria levels were measured for 16 weeks after randomization and initiation of conventional or intensive diet education. Linear or logistic regression models were applied, as appropriate, to explore the relationship with albuminuria itself or its response after the intervention.
Urinary adiponectin levels were positively related to baseline albuminuria level (r = 0.529). After adjusting for several covariates, the adiponectin level was associated with the albuminuria level (β = 0.446). Among the 159 subjects with baseline macroalbuminuria, the risk of consistent macroalbuminuria (> 300 mg/day) at 16 weeks was higher in the 3rd tertile of adiponectin than in the 1st tertile (odds ratio = 6.9), despite diet education. In contrast, among all subjects, the frequency of the normoalbuminuria achievement (< 30 mg/day) at 16 weeks was higher in the 1st tertile than in the 3rd tertile (odds ratio = 13.0).
Urinary adiponectin may be a useful biomarker for albuminuria or its response after treatment in non-diabetic hypertensive patients.
Electronic supplementary material
The online version of this article (doi:10.1186/s12882-015-0124-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4522110  PMID: 26232133
Adiponectin; Albuminuria; Biomarker; Kidney; Urine
2.  The Decrement of Hemoglobin Concentration with Angiotensin II Receptor Blocker Treatment Is Correlated with the Reduction of Albuminuria in Non-Diabetic Hypertensive Patients: Post-Hoc Analysis of ESPECIAL Trial 
PLoS ONE  2015;10(6):e0128632.
Blockade of the renin-angiotensin-aldosterone system exhibits a renoprotective effect; however, blockade of this system may also decrease hemoglobin (Hb) and erythropoietin (EPO) levels. We evaluated the correlation between reduced albuminuria and decreased hemoglobin concentrations after treatment with an angiotensin II receptor blocker (ARB). Two hundred forty-five non-diabetic hypertensive participants with established albuminuria and relatively preserved renal function were treated with an ARB (40 mg/day olmesartan) for eight weeks. Subsequent changes in various clinical parameters, including Hb, EPO, and albuminuria, were analyzed following treatment. After the 8-week treatment with an ARB, Hb and EPO levels significantly decreased. Patients with a greater decrease in Hb exhibited a greater reduction in 24-hour urinary albumin excretion compared with patients with less of a decrease or no decrease in Hb, whereas no associations with a decline in renal function and EPO levels were noted. Multivariate logistic regression analysis demonstrated a correlation between the reduction of urine albumin excretion and the decrease in Hb levels (after natural logarithm transformation, adjusted odds ratio 1.76, 95% confidence interval 1.21-2.56, P = 0.003). Linear regression analysis also supported this positive correlation (Pearson correlation analysis; R = 0.24, P < 0.001). Decreased Hb concentrations following ARB treatment were positively correlated with reduced albuminuria in non-diabetic hypertensive patients, regardless of decreased blood pressure and EPO levels or renal function decline.
PMCID: PMC4476682  PMID: 26098847
3.  Outcomes of Predialysis Nephrology Care in Elderly Patients Beginning to Undergo Dialysis 
PLoS ONE  2015;10(6):e0128715.
The proportion of elderly patients beginning to undergo dialysis is increasing globally. Whether early referral (ER) of elderly patients is associated with favorable outcomes remains under debate. We investigated the influence of referral timing on the mortality of elderly patients.
We retrospectively assessed mortality in 820 patients aged ≥70 years with end-stage renal disease (ESRD) who initiated hemodialysis at a tertiary university hospital between 2000 and 2010. Mortality data was obtained from the time of dialysis initiation until December 2010. We assigned patients to one of two groups according to the time of their first encounters with nephrologists: ER (≥ 3 months) and late referral (LR; < 3 months).
During a mean follow-up period of 25.1 months, the ER group showed a 24% reduced risk of long-term mortality relative to the LR group (HR = 0.760, P = 0.009). Rate of reduction in 90-day mortality for ER patients was 58% (HR = 0.422, P=0.012). However, the statistical significance of the difference in mortality rates between ER and LR group was not observed across age groups after 90 days. Old age, LR, central venous catheter, high white blood cell count and corrected Ca level, and lower levels of albumin, creatinine, hemoglobin, and sodium were significantly associated with increased risk of mortality.
Timely referral was also associated with reduced mortality in elderly ESRD patients who initiated hemodialysis. In particular, the initial 90-day mortality reduction in ER patients contributed to mortality differences during the follow-up period.
PMCID: PMC4451015  PMID: 26030256
4.  Cutaneous vasculitis and renal involvement in Mycoplasma pneumoniae infection 
PMCID: PMC4438296  PMID: 25995672
Skin; Glomerulonephritis; Mycoplasma infections
5.  A Higher Salt Intake Leads to a Lower Rate of Adequate Blood Pressure Control 
Journal of Korean Medical Science  2014;29(Suppl 2):S103-S108.
The relationship between salt intake and adequate blood pressure control is not well investigated in Korea populations, especially in patients with cardiovascular disease. This cross-sectional study enrolled 19,083 subjects who participated in the Korea National Health and Nutrition Examination Survey conducted from 2009-2011. The amount of salt intake was estimated using the Tanaka equations based on spot urine samples. Comparing patients with and without cardiovascular disease, systolic blood pressure (129.1±18.1 mmHg vs. 120.0±18.1 mmHg, P<0.001) and the amount of urinary sodium excretion (149.4±37.5 mM/day vs. 144.1±36.2 mM/day, P<0.001) were higher in patients with cardiovascular diseases. Among patients with cardiovascular disease, the high blood pressure group showed an increased amount of urinary sodium excretion compared to the normal blood pressure group (155.5±38.2 vs. 146.6±36.9 mM/day, P<0.001). The odds ratio (OR) of high blood pressure was higher (OR, 1.825; 95% CI, 1.187-2.807; P-for-trend 0.003, highest quartile of urinary sodium excretion vs. lowest quartile) in patients with cardiovascular disease. A higher amount of urinary sodium excretion was associated with a lower rate of adequate blood pressure control in Korean population, especially with cardiovascular disease.
Graphical Abstract
PMCID: PMC4194279  PMID: 25317013
Blood Pressure; Cardiovascular Diseases; KNHANES; Sodium
6.  Estimated 24-Hour Urine Sodium Excretion Is Correlated with Blood Pressure in Korean Population: 2009-2011 Korean National Health and Nutritional Examination Survey 
Journal of Korean Medical Science  2014;29(Suppl 2):S109-S116.
No large-scale studies have investigated the association between salt intake and hypertension in Korean population. To investigate the relationship of blood pressure to salt consumption, we analyzed data from 19,476 participants in the 2009-2011 Korean National Health and Nutritional Examination Survey (KNHANES). Urinary sodium excretion over 24-hr (24HUNa) was estimated from spot urine tests using Tanaka's equation. The study subjects were stratified into hypertensive and normotensive groups. Hypertensive participants (n=6,552, 33.6%) had higher estimated 24HUNa, 150.4±38.8 mEq/day, than normotensive participants, 140.5±34.6 mEq/day (P<0.001). The association between 24HUNa and blood pressure outcomes was not affected by adjustment for other risk factors for hypertension (odds ratio 0.001; 95% confidence interval 0.001-0.003; P<0.001). Increases in 24HUNa of 100 mEq/day were associated with a 6.1±0.3/2.9±0.2 mmHg increase in systolic/diastolic blood pressure in all participants. This effect was stronger in hypertensive participants (increase of 8.1±0.5/3.4±0.3 mmHg per 100 mEq/day) and smaller in normotensive participants (2.9±0.3/1.3±0.2 mmHg). These results support recommendations for low salt intake in Korean population to prevent and control adverse blood pressure levels.
Graphical Abstract
PMCID: PMC4194280  PMID: 25317014
Hypertension; Blood Pressure; Sodium
7.  Analysis of Correlation between 24-Hour Urinary Sodium and the Degree of Blood Pressure Control in Patients with Chronic Kidney Disease and Non-Chronic Kidney Disease 
Journal of Korean Medical Science  2014;29(Suppl 2):S117-S122.
We investigated the association between 24-hr urinary sodium (24UNA) and adequacy of blood pressure (BP) control in patients with chronic kidney disease (CKD) and nonCKD. All data were collected retrospectively by accessing the electrical medical records in patients with 24-hr urine collection and serum creatinine. Enrolled 400 subjects were subgrouped by the amount of 24UNA, or CKD stage. The appropriate BP was defined as BP < 130/80 mmHg for subjects with proteinuria, and BP < 140/90 mmHg for subjects without proteinuria. The mean level of 24UNA was 166±76 mEq/day. The 24UNA group was an independently related factor to diastolic BP as a continuous variable. The rate of appropriate BP control in patients with proteinuria was highest in 24UNA <100 mEq/L (P=0.012). The odds to fail achievement of BP target in subjects with 24UNA≥90 mEq/day was 2.441 (1.249-4.772, P=0.009) higher than that of 24UNA <90 mEq/day among participants with proteinuria. There was difference in the amount of 24UNA between CKD and non-CKD except each stage of CKD group. In conclusion, salt intake estimated by 24-hr urine sodium excretion is a risk factor to achieve appropriate BP control.
Graphical Abstract
PMCID: PMC4194281  PMID: 25317015
Salt; Hypertension; Blood pressure; Renal insufficiency
8.  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.
PMCID: PMC4194282  PMID: 25317016
Chronic Renal Insufficiency; Sodium Chloride; Renin; Angiotensinogen
9.  Estimated Amount of 24-Hour Urine Sodium Excretion Is Positively Correlated with Stomach and Breast Cancer Prevalence in Korea 
Journal of Korean Medical Science  2014;29(Suppl 2):S131-S138.
Stomach cancer is one of the most common cancers in Korea. The aim of this study was to identify the association between the prevalence of cancer, particularly stomach cancer, and the amount of 24-hr urine sodium excretion estimated from spot urine specimens. The study included 19,083 subjects who took part in the Korean National Health and Nutritional Examination Survey between 2009 and 2011. The total amount of urine sodium excreted in a 24-hr period was estimated by using two equations based on the values for spot urine sodium and creatinine. In subjects who had an estimated 24-hr urine sodium excretion of more than two standard deviations above the mean (group 2), the prevalence of stomach cancer was higher than in subjects with lower 24-hr sodium excretion (group 1). By using the Tanaka equation to estimate it, the prevalence of stomach cancer was 0.6% (114/18,331) in group 1, whereas it was 1.6% (9/568) in group 2 (P=0.006). By using the Korean equation, the prevalence was 0.6% (115/18,392) in group 1, and 1.6% in group 2 (8/507) (P=0.010). By using the Tanaka equation, breast cancer in women is more prevalent in group 2 (1.9%, 6/324) than group 1 (0.8%, 78/9,985, P=0.039). Higher salt intake, as defined by the estimated amount of 24-hr urine sodium excretion, is positively correlated with a higher prevalence of stomach or breast cancer in the Korean population.
Graphical Abstract
PMCID: PMC4194283  PMID: 25317017
24-Hour Urine Sodium; Spot Urine Sodium; Cancer
Journal of Korean Medical Science  2014;29(Suppl 2):S86.
PMCID: PMC4194288
11.  Estimation of Daily Salt Intake through a 24-Hour Urine Collection in Pohang, Korea 
Journal of Korean Medical Science  2014;29(Suppl 2):S87-S90.
There is an established relationship between a high salt diet and public health problems, especially hypertension and cardiovascular disease. We estimated daily salt intake in a group of adults and assessed its association with related variables in Pohang, Korea. We conducted a cross-sectional survey in 2013 with 242 adults. Urine was collected for 24 hr to estimate daily salt intake, and questionnaires about salt preference were administered. The mean daily salt intake was 9.9±4.6 g. There was no difference in salt intake between high systolic blood pressure (SBP) participants and normal SBP participants (10.5±4.7 g/d vs. 9.6±4.3 g/d, P=0.339), but high diastolic blood pressure (DBP) participants reported more salt intake than normal DBP participants (10.4±4.9 g/d vs. 9.7±4.1 g/d, P=0.049). Salt intake and body mass index demonstrated a positive correlation (P=0.001). A preference for Korean soup or stew was associated with high salt intake (P=0.038). Dietary salt intake in Korean adults is still higher than the recommendation from the World Health Organization. More efforts should be made to reduce the salt consumption of Korean adults.
PMCID: PMC4194289  PMID: 25317022
Salt Intake; 24-hr Urine Collection; Hypertension; Public Health
12.  Not Salt Taste Perception but Self-Reported Salt Eating Habit Predicts Actual Salt Intake 
Journal of Korean Medical Science  2014;29(Suppl 2):S91-S96.
Excessive dietary salt intake is related to cardiovascular morbidity and mortality. Although dietary salt restriction is essential, it is difficult to achieve because of salt palatability. However, the association between salt perception or salt eating habit and actual salt intake remains uncertain. In this study, we recruited 74 healthy young individuals. We investigated their salt-eating habits by questionnaire and salt taste threshold through a rating scale that used serial dilution of a sodium chloride solution. Predicted 24-hr urinary salt excretions using Kawasaki's and Tanaka's equations estimated dietary salt intake. Participants' mean age was 35 yr, and 59.5% were male. Salt sense threshold did not show any relationship with actual salt intake and a salt-eating habit. However, those eating "salty" foods showed higher blood pressure (P for trend=0.048) and higher body mass index (BMI; P for trend=0.043). Moreover, a salty eating habit was a significant predictor for actual salt intake (regression coefficient [β] for Kawasaki's equation 1.35, 95% confidence interval [CI] 10-2.69, P=0.048; β for Tanaka's equation 0.66, 95% CI 0.01-1.31, P=0.047). In conclusion, a self-reported salt-eating habit, not salt taste threshold predicts actual salt intake.
Graphical Abstract
PMCID: PMC4194290  PMID: 25317023
Salt-Eating Habit; Salt Taste Threshold; Salt Intake
13.  Estimating 24-Hour Urine Sodium Level with Spot Urine Sodium and Creatinine 
Journal of Korean Medical Science  2014;29(Suppl 2):S97-S102.
The 24-hr urine sodium excretion level was estimated based on the spot urine sodium, and the efficacy of the formula was validated to determine the status of low salt intake <100 mEq Na/day. The 24-hr urine samples were collected from 400 patients. The 24-hr urine creatinine level was estimated with the use of three formulas: a newly derived Korean equation (E24UCR_K), and Tanaka (E24UCR_T) and Cockcroft-Gault (E24UCR_CG) equations. The correlation coefficients between the estimated and measured 24-hr urine creatinine for these three equations were 0.863, 0.846, and 0.896, respectively (All P<0.001). After estimating the 24-hr urine sodium levels, the correlation coefficients between the estimated and measured 24-hr urine sodium levels were 0.466, 0.490, and 0.516, respectively (All P<0.001). The sensitivity of three formulas to estimate the measured 24-hr urine sodium≥100 mEq/day using the estimated amount≥100 mEq/day was 84.3%, 87.6%, and 84.8%, respectively. In conclusion, the three equations used to estimate the 24-hr urine sodium content were useful to determine the status of low salt intake.
Graphical Abstract
PMCID: PMC4194291  PMID: 25317024
24-hr Urine Sodium; Spot Urine Sodium; Spot Urine Creatinine
14.  Relationship between Changes in Body Fat and a Decline of Renal Function in the Elderly 
PLoS ONE  2014;9(1):e84052.
Obesity is a risk factor for chronic kidney disease, and its prevalence among the elderly is increasing. We investigated the effects of changes in body fat percentage (BFP) on the longitudinal changes in the estimated glomerular filtration rate (eGFR) in the elderly. This prospective cohort study included 390 participants aged >65 years who underwent bioelectrical impedance analysis at baseline and follow-up as a part of the Korean Longitudinal Study on Health and Aging. After a median follow-up period of 5.3 years, BFP was significantly higher than that at the start point (P<0.05). Participants who had the largest increase in BFP had the highest BMI and waist circumference (WC) (P<0.001). The highest tertile had the highest white blood cell count and erythrocyte sedimentation rate, incidence of rapid progression, and decline in eGFR >25% (P≤0.017, P = 0.025, P = 0.005, respectively). The lowest tertile had the lowest triglyceride and highest high-density lipoprotein levels (P<0.05). The adjusted decline rate in eGFR was correlated with a change in BFP (P = 0.039), but not with that in BMI or WC. The highest tertile had a 4.875-fold increase in the risk for rapid progression to a decline in eGFR (95% CI: 1.366–17.397) and a 4.931-fold decrease in the risk to a decline in eGFR>25% (95% CI: 1.617–15.037), when compared with the lowest tertile. In subgroup analysis, the incidence of renal outcomes was significantly increased according to the increase in BFP in patients with lower eGFR (P≤0.010). A change in BFP may be associated with inflammation and dyslipidemia development, and longitudinal changes in body fat are related to a decrease in eGFR in the elderly.
PMCID: PMC3894176  PMID: 24454716
15.  Correction of Anemia with Continuous Erythropoietin Receptor Activator in Korean Patients on Long-Term Hemodialysis 
Continuous erythropoietin receptor activator (CERA) is an erythropoietin with a long-half life. This study investigated the efficacy of CERA for correcting anemia in Korean patients on dialysis. Patients (≥18 yr) who were not receiving any ESAs for more than 8 weeks were randomly assigned to either intravenous CERA once every 2 weeks (n=39) or epoetin beta thrice-weekly (n=41) during a 24-week correction phase. Hemoglobin (Hb) response was defined as increase of Hb by at least 1 g/dL and Hb≥11 g/dL without red blood cell (RBC) transfusion. Median dialysis duration was 1.7 (0.3-20.8) and 1.6 (0.4-13.8) yr in CERA and epoetin beta group, respectively. Hemoglobin response rate of CERA was 79.5% (95% confidence interval [CI], 63.5-90.7). As the lower limit of 95% CI was higher than pre-specified 60% response rate, it can be concluded that CERA corrected anemia (P<0.05). Hb response rate of epoetin beta was 87.8% (95% CI, 73.8-95.9) (P=0.37). Median time to response was 12 weeks in CERA and 10.3 weeks in epoetin beta (P=0.03). It is suggested that once every 2 weeks administration of CERA is effective for correcting anemia in Korean patients on long-term hemodialysis with longer time-to-response than thrice weekly epoetin beta. ( registry No. NCT00546481)
PMCID: PMC3890480  PMID: 24431909
Anemia Correction; Continuous Erythropoietin Receptor Activator; Kidney Failure, Chronic; Renal Dialysis
16.  Tacrolimus Decreases Albuminuria in Patients with IgA Nephropathy and Normal Blood Pressure: A Double-Blind Randomized Controlled Trial of Efficacy of Tacrolimus on IgA Nephropathy 
PLoS ONE  2013;8(8):e71545.
Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is not applicable due to low blood pressure.
Trial design
A double blinded randomized trial.
The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR).
The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (–52.0±26.4 vs –17.3±29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were –60.2±28.2%, –62.2±33.9%, –48.5±29.8%, and –55.5±24.0%, and, in the control group, –6.8±32.2%, –2.5±35.9%, –12.7±34.2%, and –21.9±30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) ≥50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable.
Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure anti-hypertensive medication.
Trial Registration NCT1224028
PMCID: PMC3747236  PMID: 23977072
17.  Small Increases in Plasma Sodium Are Associated with Higher Risk of Mortality in a Healthy Population 
Journal of Korean Medical Science  2013;28(7):1034-1040.
Elevated blood pressure (BP) is the most common cause of cardiovascular disease. Salt intake has a strong influence on BP, and plasma sodium (pNa) is increased with progressive increases in salt intake. However, the associations with pNa and BP had been reported inconsistently. We evaluated the association between pNa and BP, and estimated the risks of all-cause-mortality according to pNa levels. On the basis of data collected from health checkups during 1995-2009, 97,009 adult subjects were included. Positive correlations between pNa and systolic BP, diastolic BP, and pulse pressure (PP) were noted in participants with pNa ≥138 mM/L (P<0.001). In participants aged ≥50 yr, SBP, DBP, and PP were positively associated with pNa. In participants with metabolic syndrome components, the differences in SBP and DBP according to pNa were greater (P<0.001). A cumulative incidence of mortality was increased with increasing pNa in women aged ≥50 yr during the median 4.2-yr-follow-up (P<0.001). In women, unadjusted risks for mortality were increased according to sodium levels. After adjustment, pNa ≥145 mM/L was related to mortality. The positive correlation between pNa and BP is stronger in older subjects, women, and subjects with metabolic syndrome components. The incidence and adjusted risks of mortality increase with increasing pNa in women aged ≥50 yr.
PMCID: PMC3708074  PMID: 23853486
Age; Blood Pressure; Mortality; Plasma Sodium; Sex Characteristics
18.  Bilirubin attenuates the renal tubular injury by inhibition of oxidative stress and apoptosis 
BMC Nephrology  2013;14:105.
Bilirubin (BIL) has been recognized as an endogenous antioxidant that shows a protective effect for cardiorenal diseases. We investigated whether administration of BIL had a protective effect on cyclosporine (CsA)-induced nephropathy (CIN), and examined the effects of BIL on the oxidative stress and apoptosis.
BIL was pretreated intraperitoneally three times for a week (60 mg/kg), and CsA was injected for 4 weeks (15 mg/kg/day, subcutaneous). Proximal tubular epithelial (HK2) cells were pretreated with 0.1mg/ml of BIL for 24 hours, and then treated with 20 μM of CsA for another 24 hours.
CsA induced marked increases in urine kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) concentrations (P < 0.05). BIL reduced urine Kim-1 in CIN (P < 0.05), while urine NGAL exhibited a decreasing tendency. In CsA-treated rat kidneys, the protein expression of NOX4 and p22phox was reduced by BIL (P < 0.05). BIL ameliorated CsA-induced arteriolopathy, tubulointerstitial fibrosis, tubular injury, and the apoptosis examined by TUNEL assay (P < 0.01). In HK2 cells, BIL reduced intracellular reactive oxygen species in CsA-treated cells. CsA increased the protein expression of bax, cleaved caspase-9, caspase-3 and the activity of caspase-3; however, the anti-apoptotic bcl-2 protein was reduced. These changes were recovered by BIL (P < 0.05).
The direct administration of BIL protected against CsA-induced tubular injury via inhibition of oxidative stress and apoptosis.
PMCID: PMC3681641  PMID: 23683031
Apoptosis; Bilirubin; Cyclosporine; Oxidative stress; Renal injury
19.  Air pollution and hemorrhagic fever with renal syndrome in South Korea: an ecological correlation study 
BMC Public Health  2013;13:347.
The effects of air pollution on the respiratory and cardiovascular systems, and the resulting impacts on public health, have been widely studied. However, little is known about the effect of air pollution on the occurrence of hemorrhagic fever with renal syndrome (HFRS), a rodent-borne infectious disease. In this study, we evaluated the correlation between air pollution and HFRS incidence from 2001 to 2010, and estimated the significance of the correlation under the effect of climate variables.
We obtained data regarding HFRS, particulate matter smaller than 10 μm (PM10) as an index of air pollution, and climate variables including temperature, humidity, and precipitation from the national database of South Korea. Poisson regression models were established to predict the number of HFRS cases using air pollution and climate variables with different time lags. We then compared the ability of the climate model and the combined climate and air pollution model to predict the occurrence of HFRS.
The correlations between PM10 and HFRS were significant in univariate analyses, although the direction of the correlations changed according to the time lags. In multivariate analyses of adjusted climate variables, the effects of PM10 with time lags were different. However, PM10 without time lags was selected in the final model for predicting HFRS cases. The model that combined climate and PM10 data was a better predictor of HFRS cases than the model that used only climate data, for both the study period and the year 2011.
This is the first report to document an association between HFRS and PM10 level.
PMCID: PMC3641006  PMID: 23587219
Air pollution; Hantavirus; Hemorrhagic fever with renal syndrome; Particulate matter; Infection
20.  Mortality of IgA Nephropathy Patients: A Single Center Experience over 30 Years 
PLoS ONE  2012;7(12):e51225.
Research on the prognosis of IgA nephropathy (IgAN) has focused on renal survival, with little information being available on patient survival. Hence, this investigation aimed to explore long-term patient outcome in IgAN patients. Clinical and pathological characteristics at the time of renal biopsy were reviewed in 1,364 IgAN patients from 1979 to 2008. The outcomes were patient death and end stage renal disease (ESRD) progression. Overall, 71 deaths (5.3%) and 277 cases of ESRD (20.6%) occurred during 13,916 person-years. Ten-, 20-, and 30-year patient survival rates were 96.3%, 91.8%, and 82.7%, respectively. More than 50% patient deaths occurred without ESRD progression. Overall mortality was elevated by 43% from an age/sex-matched general population (GP) (standardized mortality ratio [SMR], 1.43; 95% confidence interval [CI], 1.04–1.92). Men had comparable mortality to GP (SMR, 1.22; 95% CI, 0.82–1.75), but, in women, the mortality rate was double (SMR, 2.17; 95% CI, 1.21–3.57). Patients with renal risk factors such as initial renal dysfunction (estimated glomerular filgration rate <60 ml/min per 1.73m2; SMR, 1.70; 95% CI, 1.13–2.46), systolic blood pressure ≥140 mmHg (SMR, 1.88; 95% CI, 1.19–2.82) or proteinuria ≥1 g/day (SMR, 1.66; 95% CI, 1.16–2.29) had an elevated mortality rate. Patients with preserved renal function, normotension, and proteinuria <1 g/day, however, had a similar mortality rate to GP. When risk stratification was performed by counting the number of major risk factors present at diagnosis, low-risk IgAN patients had a mortality rate equal to that of GP, whereas high-risk patients had a mortality rate higher than that of GP. This investigation demonstrated that overall mortality in IgAN patients was higher than that of GP. Women and patients with renal risk factors had a higher mortality than that of GP, Therefore, strategies optimized to alleviate major renal risk factors are warranted to reduce patient mortality.
PMCID: PMC3514188  PMID: 23226568
21.  Recurrent Thrombotic Events after Catastrophic Antiphopholipid Syndrome 
PMCID: PMC3372811  PMID: 22707899
Antiphospholipid syndrome; Thrombosis; Anticoagulants
22.  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.
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.
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.
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.
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.
PMCID: PMC3404912  PMID: 22530944
Chronic kidney disease; EuroQol-5D; Preference-based health utility
23.  Aspergillus-Associated Cerebral Aneurysm Successfully Treated by Endovascular and Surgical Intervention with Voriconazole in Lupus Nephritis Patient 
Journal of Korean Medical Science  2012;27(3):317-320.
During the last five decades, long-term therapy with immunosuppressive agents such as pulse cyclophosphamide in conjunction with high-dose corticosteroids has enhanced both patient survival and renal survival in patients with diffuse proliferative lupus nephritis. Nevertheless, severe side effects such as infectious complications remain the main cause of morbidity and mortality. Central nervous system aspergillosis is uncommon but life-threatening in lupus patients. In this single-patient case study, carotid aneurysm with sphenoidal sinusitis was suspected when severe epistaxis occurred during cyclophosphamide pulse therapy. With anti-fungal therapy, a graft stent was successfully deployed to the aneurysm and specimens of sphenoidal mucosa showed typical hyphae, indicating aspergillosis. Three months after stopping voriconazole treatment, two cerebral aneurysms that were revealed on MR images were successfully removed by aneurysmal clipping. The patient remained alive at one-year follow-up with lupus nephritis in remission. The rarity and high mortality of aspergillus-related fungal aneurysms have led to most cases being recognized postmortem. However, such aneurysms must be diagnosed early to prevent fatal complications by performing appropriate management such as surgical procedure or endovascular intervention.
PMCID: PMC3286781  PMID: 22379345
Lupus Nephritis; Neuroaspergillosis; Intracranial Aneurysm; Voriconazole; Endovascular Procedure
24.  Anti-Proteinuric Effect of Sulodexide in Immunoglobulin A Nephropathy 
Yonsei Medical Journal  2011;52(4):588-594.
We conducted a multi-center randomized double-blind study to determine the effects of 6-month therapy with sulodexide on urinary protein excretion in patients with idiopathic Immunoglobulin A (IgA) nephropathy.
Materials and Methods
A total of seventy-seven patients participated in the study. They were randomly allocated to one of three groups: sulodexide 75 mg or 150 mg daily or the placebo for 6 months. The primary end point was the achievement, at 6 months, of at least 50% reduction in urine protein/creatinine ratio (UPCR) from the baseline value.
At 6 months, the primary end point was achieved by 12.5% of the patients assigned to the placebo, 4.0% of the patients assigned to sulodexide 75 mg daily and 21.4% of those assigned to 150 mg (p=0.308). Treatment with sulodexide 150 mg daily for 6 months significantly reduced log UPCR from 6.38±0.77 at baseline to 5.98±0.94 at 6 months (p=0.045), while treatment with sulodexide 75 mg daily and placebo did not.
A 6-month treatment with sulodexide did not achieve 50% reduction of urinary protein excretion in IgA nephropathy patients, but showed a tendency to increase the time-dependent anti-proteinuric effect. Therefore, long-term clinical trials on a larger scale are warranted to elucidate the hypothesis that sulodexide affords renal protection in IgA nephropathy patients.
PMCID: PMC3104455  PMID: 21623600
IgA nephropathy; sulodexide; proteinuria
25.  Effect of RAAS Inhibition on the Incidence of Cancer and Cancer Mortality in Patients with Glomerulonephritis 
Angiotensin II type 1 receptor blocker (ARB), which is frequently prescribed in patients with glomerulonephritis (GN), is suggested to increase the risk of cancer. We registered 3,288 patients with renal biopsy and analyzed the relationship between the use of renin-angiotensin-aldosterone system (RAAS) blockade and the incidence of cancer or cancer mortality. After renal biopsy, cancer developed in 33 patients with an incidence rate of 1.0% (95% of CI for incidence: 0.7%-1.3%). There was no difference in the cancer incidence among the groups according to the use of angiotensin-converting enzyme inhibitors (ACEI) or ARB: 1.2% in the None (23/1960), 0.7% in the ARB-only (5/748), 0.4% in the ACEI-only (1/247), and 1.2% in the ACEI-ARB (4/333) (P = 0.487) groups. The cancer mortality was 2.1%, 0.4%, 0.0%, and 0.3% in None, ACEI-only, ARB-only, and ACEI-ARB group, respectively (P < 0.001). The risk of cancer mortality in patients with ARB was only 0.124 (0.034-0.445) compared to that of non-users of ARB by Cox's hazard proportional analysis. In conclusion, prescription of ACEI or ARB in patients with GN does not increase cancer incidence and recipients of ARB show rather lower rates of all-cause mortality and cancer mortality.
PMCID: PMC3012851  PMID: 21218031
Glomerulonephritis; Neoplasms; Angiotensin II Type 1 Receptor Blockers

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