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1.  Effect of Peritoneal Dialysis Modality on the 1-Year Rate of Decline of Residual Renal Function 
Yonsei Medical Journal  2013;55(1):141-148.
The effect of different peritoneal dialysis (PD) modalities on the decline in residual renal function (RRF) is unclear due to inconsistencies among studies. In particular, the effect of automated peritoneal dialysis (APD) modalities [continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD)] on RRF has not been examined in a large cohort.
Materials and Methods
We conducted a single-center retrospective study to investigate the association between PD modalities and decline in RRF in 142 incident PD patients [34 on CCPD, 36 on NIPD, and 72 on continuous ambulatory peritoneal dialysis (CAPD)]. RRF was measured within 2 months from PD start and at 1 year after PD initiation.
The RRF at 1 year after PD initiation was 1.98±2.20 mL/min/1.73 m2 in CCPD patients and 3.63±3.67 mL/min/1.73 m2 in NIPD patients, which were moderately lower than 4.23±3.51 mL/min/1.73 m2 in CAPD patients (p=0.064). Moreover, there was no significant difference in the 1-year rate of decline of RRF between CCPD and NIPD patients, although APD patients had a faster 1-year RRF decline rate than CAPD patients (CCPD and NIPD vs. CAPD: -45.68 and -36.69 vs. 1.17%/year, p=0.045). APD was associated with a more rapid decline in RRF in patients with end-stage renal disease undergoing PD, although multivariate analysis attenuated the significance of this finding (β=-31.50; 95% CI, -63.61 to 0.62; p=0.052).
Our results suggest that CAPD might be more helpful than APD for preserving RRF during the first year of dialysis therapy, although there was no significant difference in the 1-year rate of decline of RRF between the two APD modalities.
PMCID: PMC3874913  PMID: 24339299
Continuous ambulatory peritoneal dialysis; end-stage kidney disease; glomerular filtration rate; peritoneal dialysis
2.  Rapid Decrease of Intact Parathyroid Hormone Could Be a Predictor of Better Response to Cinacalcet in Hemodialysis Patients 
Yonsei Medical Journal  2013;54(2):453-463.
Cinacalcet is effective for treating refractory secondary hyperparathyroidism (SHPT), but little is known about the response rates and clinical factors influencing the response.
Materials and Methods
A prospective, single-arm, multi-center study was performed for 24 weeks. Cinacalcet was administered to patients with intact parathyroid hormone (iPTH) level greater than 300 pg/mL. Cinacalcet was started at a dose of 25 mg daily and titrated until 100 mg to achieve a serum iPTH level <300 pg/mL (primary end point). Early response to cinacalcet was defined as a decrease of iPTH more than 50% within one month.
Fifty-seven patients were examined. Based on the magnitude of iPTH decrease, patients were divided into responder (n=47, 82.5%) and non-responder (n=10, 17.5%) groups. Among the responders, 38 achieved the primary end point, whereas 9 patients showed a reduction in serum iPTH of 30% or more, but did not reach the primary end point. Compared to non-responders, responders were significantly older (p=0.026), female (p=0.041), and diabetics (p<0.001). Additionally, early response was observed more frequently in the responders (30/47, 63.8%), of whom the majority (27/30, 90.0%) achieved the primary end point. Multivariate analysis showed that lower baseline iPTH levels [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], the presence of diabetes (OR 46.45, CI 1.92-1125.6) and early response (OR 21.54, CI 2.94-157.7) were significant clinical factors affecting achievement of iPTH target.
Cinacalcet was effective in most hemodialysis patients with refractory SHPT. The presence of an early response was closely associated with the achievement of target levels of iPTH.
PMCID: PMC3575968  PMID: 23364981
Cinacalcet; end-stage renal disease; hemodialysis; parathyroid hormone; secondary hyperparathyroidism
3.  Removal of Kidney Stones by Extracorporeal Shock Wave Lithotripsy Is Associated with Delayed Progression of Chronic Kidney Disease 
Yonsei Medical Journal  2012;53(4):708-714.
This study aimed to elucidate whether stone removal by extracorporeal shock wave lithotripsy (ESWL) is associated with delayed chronic kidney disease (CKD) progression.
Materials and Methods
We conducted a retrospective analysis of 131 nephrolithiasis patients with stage 3 and 4 CKD. We collected baseline clinical and laboratory data, kidney stone characteristics, and history of receiving ESWL. We classified study patients into two groups according to whether they underwent ESWL or not (Non-ESWL group vs. ESWL group). We initially compared annual estimated glomerular filtration rate (eGFR) changes of Non-ESWL group with those of ESWL group before undergoing ESWL. In the next step, we sought to compare annual eGFR changes in the same patients before and after ESWL. Finally, we compared annual eGFR changes between success and failure groups among patients undergoing ESWL.
The mean age of the patients was 62 years and 72.5% were male. The mean observation period was 3.2 years. Non-ESWL group and ESWL group before undergoing ESWL showed similar annual eGFR changes (-1.75±6.5 vs. -1.63±7.2 mL/min/1.73 m2/year, p=0.425). However, eGFR declined slower after undergoing ESWL than before ESWL (annual eGFR changes, -0.29±6.1 vs. -1.63±7.2 mL/min/1.73 m2/year, p<0.05). In addition, among patients in ESWL group, eGFR declined faster in the failure group than in the success group (annual eGFR change, -1.01±4.7 vs. -0.05±5.2 mL/min/1.73 m2/year, p<0.05).
Our results suggest that stone removal by ESWL is associated with delayed deterioration of renal function in CKD patients with nephrolithiasis.
PMCID: PMC3381494  PMID: 22665335
Nephrolithiasis; chronic kidney disease; extracorporeal shock wave lithotripsy (ESWL); glomerular filtration rate (GFR)
4.  High Peritoneal Transport Status is Not an Independent Risk Factor for High Mortality in Patients Treated with Automated Peritoneal Dialysis 
Journal of Korean Medical Science  2010;25(9):1313-1317.
We undertook this study to elucidate whether baseline peritoneal membrane transport characteristics are associated with high mortality in incident automated peritoneal dialysis (APD) patients. This retrospective study includes 117 patients who started APD at Yonsei University Health System from 1996 to 2008 and had a PET within 3 months of APD initiation. High transporters were significantly older and had a higher incidence of cardiovascular disease. Patient survival for years 1, 3, and 5 were 85%, 64%, and 35% for high transporter and 94%, 81%, and 68% for non-high transporter group (P<0.01). Multivariate analysis revealed that age, diabetes, cardiovascular disease, serum albumin level, and residual renal function were independently associated with high mortality in APD patients. In contrast, high transport status was not a significant predictor for mortality in this population when the other covariates were included. Even though high transport was significantly associated with mortality in the univariate analysis, its role seemed to be influenced by other comorbid conditions. These findings suggest that the proper management of these comorbid conditions, as well as appropriate ultrafiltration by use of APD and/or icodextrin, must be considered as protective strategies to improve survival in peritoneal dialysis patients with high transport.
PMCID: PMC2923779  PMID: 20808674
Automated Peritoneal Dialysis; High Transport; Peritoneal Equilibration Test; Mortality
5.  Correlates of the Severity of Coronary Atherosclerosis in Long-term Kidney Transplant Patients 
Journal of Korean Medical Science  2010;25(5):706-711.
Coronary artery disease remains the leading cause of early death and graft loss in renal transplant patients. The aim of this study was to identify clinical and echocardiographic parameters independently associated with the angiographically-determined severity of coronary atherosclerosis in long-term kidney transplant patients. Fifty-two kidney transplant recipients who underwent elective coronary angiography were reviewed retrospectively. Angiographic severity was evaluated using the modified Gensini index (MGI). The mean age at coronary angiography was 52.5±7.9 yr with a mean prior transplant duration of 118.1±58.8 months. Pearson correlation analysis demonstrated a positive correlation of MGI with transplant duration before coronary angiography and chronic allograft nephropathy, whereas an inverse correlation was demonstrated with ejection fraction and statin use. On subsequent multivariate linear regression analysis, transplant duration before coronary angiography, statin use, and ejection fraction were independently associated with the severity of coronary atherosclerosis in long-term kidney transplant patients. In summary, our study demonstrates that statin use, ejection fraction, and transplant duration before coronary angiography are independent parameters associated with the severity of coronary atherosclerosis in long-term kidney transplant patients. Further investigation is required to reduce the atherosclerotic burden in kidney transplant patients.
PMCID: PMC2858828  PMID: 20436705
Coronary Artery Disease; Coronary Angiography; Kidney Transplantation
6.  Cancer in Patients on Chronic Dialysis in Korea 
Journal of Korean Medical Science  2009;24(Suppl 1):S95-S101.
The study of cancer in patients treated with dialysis in Korea has not been reported. The aim of this study was to investigate the incidence and mortality of cancer among patients on dialysis in Korea. The study subjects were 106 cancer patients (2.3%) out of 4,562 end-stage renal disease (ESRD) patients maintained on hemodialysis (HD) or peritoneal dialysis (PD) at Yonsei University Health System from 1996 to 2005. We excluded patients in whom the diagnosis of cancer preceded dialysis or those who received renal allograft or started dialysis after renal allograft. Seventy-three (69%) of our subjects were male and 33 (31%) were female. The mean age at the time of cancer diagnosis was 57.9±11.7 yr. The mean time from the start of dialysis to the diagnosis of cancer was 75.2±63.9 months. The most common cancer site was gastrointestinal tract (GIT) (51%) followed by urinary tract (20%), lung (8%), and thyroid (7%). Sixty nine percent of the total mortality was due to cancer. The mean time from diagnosis to death was 2.9±2.5 yr. In ESRD patients with cancer, there were no significant differences in mortality rates by dialysis modality. In ESRD patients, the most common cancer was GIT cancer followed by urinary tract cancer. Therefore, careful surveillance of these cancers in ESRD patients is highly recommended.
PMCID: PMC2633193  PMID: 19194570
Neoplasms; Kidney Failure, Chronic; Gastrointestinal tract; Urinary Tract
7.  Modified Peritoneal Dialysis Catheter Insertion: Comparison with a Conventional Method 
Yonsei Medical Journal  2015;56(4):981-986.
The conventional trocar and cannula method in peritoneal dialysis (PD) catheter insertion has its limitation in clinical setting. The aim of this study was to compare a modified method for percutaneous PD catheter insertion with the conventional method, and demonstrate advantages of the modified method.
Materials and Methods
Patients at a single center who had percutaneous PD catheters inserted by nephrologists from January 2006 until September 2012, using either a modified method (group M) or the conventional trocar and cannula method (group C), were retrospectively analyzed, in terms of baseline characteristics, complications experienced up to 3 months after the procedure, and the suitability of the procedure for patients.
Group M included 82 subjects, while group C included 66 cases. The overall early complication rate in group M (1.2%) was significantly lower than that in group C (19.7%) (p<0.001). The catheter revision rate during timeframe for early complications was significantly lower in group M (0%) than in group C (6.1%) (p=0.024). When comparing Procedure time (1 h 3 min±16 min vs. 1 h 36 min±19 min, p<0.01), immediate post-procedural pain (2.43±1.80 vs. 3.14±2.07, p<0.05), and post-procedure days until ambulation (3.95±1.13 days vs. 6.17±1.34 days, p<0.01), group M was significantly lower than group C. There was no significant difference in total hospitalization period (14.71±7.05 days vs. 13.86±3.7 days).
Our modified PD catheter insertion method shows its advantages in early complication rate, early complications revision rate, and the patients' conveniences.
PMCID: PMC4479866  PMID: 26069120
Continuous ambulatory peritoneal dialysis; peritoneal catheter insertion; nephrologists; modified method; trocar and cannula method; complication rate
8.  Hyponatremia Predicts New-Onset Cardiovascular Events in Peritoneal Dialysis Patients 
PLoS ONE  2015;10(6):e0129480.
Background and Aim
Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients on peritoneal dialysis (PD). Hyponatremia was recently shown to be a modifiable factor that is strongly associated with increased mortality in PD patients. However, the clinical impact of hyponatremia on CV outcomes in these patients is unclear.
To determine whether a low serum sodium level predicts the development of CV disease, we carried out a prospective observational study of 441 incident patients who started PD between January 2000 and December 2005. Time-averaged serum sodium (TA-Na) levels were determined to investigate the ability of hyponatremia to predict newly developed CV events in these patients.
During a mean follow-up of 43.2 months, 106 (24.0%) patients developed new CV events. The cumulative incidence of new-onset CV events after the initiation of PD was significantly higher in patients with TA-Na levels ≤ 138 mEq/L than in those with a TA-Na > 138 mEq/L. After adjustment for multiple potentially confounding covariates, an increase in TA-Na level was found to be associated with a significantly lower risk of CV events (subdistribution hazard ratio per 1 mEq/L increase, 0.90; 95% confidence interval, 0.83–0.96; p = 0.003). Patients with a TA-Na ≤ 138 mEq/L had a 2.31-fold higher risk of suffering a CV event.
These results provide evidence of a clear association between low serum sodium and new-onset CV events after dialysis initiation in PD patients. Whether the correction of hyponatremia for this indication provides additional protection for the development of CV disease in these patients remains to be addressed in interventional studies.
PMCID: PMC4460085  PMID: 26053619
9.  The Effect of Specialized Continuous Renal Replacement Therapy Team in Acute Kidney Injury Patients Treatment 
Yonsei Medical Journal  2015;56(3):658-665.
Continuous renal replacement therapy (CRRT) has been established for critically ill acute kidney injury (AKI) patients. In addition, some centers consist of a specialized CRRT team (SCT) with physicians and nurses. To our best knowledge, however, ona a few studies have yet been carried out on the superiority of SCT management.
Materials and Methods
A total of 551 patients, who received CRRT between January 2008 and March 2009, were divided into two groups based on the controller of CRRT. The impact of the CRRT management on 28-day mortality was compared between two groups by Kaplan-Meier curve and Cox analysis.
During the study period, the number of filters used, down-time per day, and intensive care unit length of day were significantly higher in non-SCT group than in SCT group (6.2 hrs vs. 5.0 hrs, p=0.042; 5.0 hrs vs. 3.8 hrs, p<0.001; 27.5 days vs. 21.1 days, p=0.027, respectively), while net ultrafiltration rate was significantly lower in non-SCT group than SCT group (28.0 mL/kg/hr vs. 29.5 mL/kg/hr, p=0.043, respectively). In addition, 28-day mortality rate was significantly lower in SCT group than with non-SCT group (p=0.031). Moreover, Cox regression analysis showed that 28-day mortality rate was significantly lower in SCT control group, even after adjusting for age, gender, severity scores, biomarkers, risk, injury, failure, loss, and end-stage renal disease, and contributing factors (hazard ratio 0.91, p=0.046).
A well-trained CRRT team could be beneficial for mortality improvement of AKI patients requiring CRRT.
PMCID: PMC4397434  PMID: 25837170
SCT management; acute kidney injury; continuous renal replacement therapy; 28-day mortality
10.  Hyponatremia as a Predictor of Mortality in Peritoneal Dialysis Patients 
PLoS ONE  2014;9(10):e111373.
Background and Aim
Hyponatremia is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, few studies have addressed this issue in peritoneal dialysis (PD) patients.
This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum sodium (TA-Na) levels, we aimed to investigate whether hyponatremia can predict mortality in these patients.
Among the baseline parameters, serum sodium level was positively associated with serum albumin (β = 0.145; p = 0.003) and residual renal function (RRF) (β = 0.130; p = 0.018) and inversely associated with PD ultrafiltration (β = −0.114; p = 0.024) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. All-cause death occurred in 81 (55.9%) patients in the lowest tertile compared to 37 (25.0%) and 31 (20.9%) patients in the middle and highest tertiles, respectively. After adjusting for multiple potentially confounding covariates, increased TA-Na level was associated with a significantly decreased risk of all-cause (HR per 1 mEq/L increase, 0.79; 95% CI, 0.73–0.86; p<0.001) and infection-related (HR per 1 mEq/L increase, 0.77; 95% CI, 0.70–0.85; p<0.001) deaths.
This study showed that hyponatremia is an independent predictor of mortality in PD patients. Nevertheless, whether correcting hyponatremia improves patient survival is unknown. Future interventional studies should address this question more appropriately.
PMCID: PMC4213027  PMID: 25354265
11.  Ability of Nafamostat Mesilate to Prolong Filter Patency during Continuous Renal Replacement Therapy in Patients at High Risk of Bleeding: A Randomized Controlled Study 
PLoS ONE  2014;9(10):e108737.
Continuous renal replacement therapy (CRRT) is considered as an effective modality for renal replacement therapy in hemodynamically unstable patients within intensive care units (ICUs). However, the role of heparin anticoagulation, which is used to maintain circuit patency, is equivocal due to the risk of bleeding and morbidity. Among various alternative anticoagulants, nafamostat mesilate has been shown to be an effective anticoagulant in patients prone to bleeding. Hence, we conducted a prospective, randomized controlled study investigating the effect of nafamostat mesilate on mortality, CRRT filter life span and adverse events in patients with bleeding tendency. Seventy-three Patients were randomized into either the futhan or no-anticoagulation group. Thirty-six subjects in the futhan group received nafamostat mesilate, while thirty seven subjects in the no-anticoagulation group received no anticoagulants. Baseline characteristics and appropriate laboratory tests were taken from each group. The mortality between the two groups was not significantly different. Nevertheless, between the futhan group and the no-anticoagulation group, the overall number of filters used during CRRT (2.71±2.12 vs. 4.50±3.25; p = 0.042) and the number of filters changed due to clots per 24 hours (1.15±0.81 vs. 1.74±1.62; p = 0.040) were significantly different. When filter life span was subdivided into below and over 12 hours, the number of filters functioning over 12 hours was significantly higher in the futhan group than in the no-anticoagulation group (p = 0.037, odds ratio 1.84). There were no significant differences in transfusion, mortality, or survival between the two groups, and no adverse events related to nafamostat mesilate were noted. Hence, nafamostat mesilate may be used as an effective and safe anticoagulant, without increasing the risk of major bleeding complications, in patients prone to bleeding.
Trial Registration NCT01761994
PMCID: PMC4193755  PMID: 25302581
12.  Optimal Proteinuria Target for Renoprotection in Patients with IgA Nephropathy 
PLoS ONE  2014;9(7):e101935.
Proteinuria is a target for renoprotection in kidney diseases. However, optimal level of proteinuria reduction in IgA nephropathy (IgAN) is unknown.
We conducted a retrospective observational study in 500 patients with biopsy-proven IgAN. Time-averaged proteinuria (TA-P) was calculated as the mean of every 6 month period of measurements of spot urine protein-to-creatinine ratio. The study endpoints were a 50% decline in estimated glomerular filtration rate (eGFR), onset of end-stage renal disease (ESRD), and slope of eGFR.
During a median follow-up duration of 65 (12–154) months, a 50% decline in eGFR occurred in 1 (0.8%) patient with TA-P of <0.3 g/g compared to 6 (2.7%) patients with TA-P of 0.3–0.99 g/g (hazard ratio, 2.82; P = 0.35). Risk of reaching a 50% decline in eGFR markedly increased in patients with TA-P of 1.0–2.99 g/g (P = 0.002) and those with TA-P≥3.0 g/g (P<0.001). ESRD did not occur in patients with TA-P<1.0 g/g compared to 26 (20.0%) and 8 (57.1%) patients with TA-P of 1.0–2.99 and ≥3.0 g/g, respectively. Kidney function of these two groups deteriorated faster than those with TA-P<1.0 g/g (P<0.001). However, patients with TA-P of 0.3–0.99 g/g had a greater decline of eGFR than patients with TA-P<0.3 g/g (−0.41±1.68 vs. −0.73±2.82 ml/min/1.73 m2/year, P = 0.03).
In this study, patients with TA-P<1.0 g/g show favorable outcomes. However, given the faster eGFR decline in patients with TA-P of 0.3–0.99 g/g than in patients with TA-P<0.3 g/g, the ultimate optimal goal of proteinuria reduction can be lowered in the management of IgAN.
PMCID: PMC4086982  PMID: 25003873
13.  KNOW-CKD (KoreaN cohort study for Outcome in patients With Chronic Kidney Disease): design and methods 
BMC Nephrology  2014;15:80.
The progression and complications of chronic kidney disease should differ depending on the cause (C), glomerular filtration rate category (G), and albuminuria (A). The KNOW-CKD (KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease), which is a prospective cohort study, enrolls subjects with chronic kidney disease stages 1 to 5 (predialysis).
Nine nephrology centers in major university hospitals throughout Korea will enroll approximately 2,450 adults with chronic kidney disease over a 5-year period from 2011 to 2015. The participating individuals will be monitored for approximately 10 years until death or until end-stage renal disease occurs. The subjects will be classified into subgroups based on the following specific causes of chronic kidney disease: glomerulonephritis, diabetic nephropathy, hypertensive nephropathy, polycystic kidney disease, and others. The eligible subjects will be evaluated at baseline for socio-demographic information, detailed personal/family history, office BP, quality of life, and health behaviors. After enrollment in the study, thorough assessments, including laboratory tests, cardiac evaluation and radiologic imaging, will be performed according to the standardized protocol. The biospecimen samples will be collected regularly. A renal event is defined by >50% decrease in estimated GFR (eGFR) from the baseline values, doubling of serum creatinine, or end-stage renal disease. The primary composite outcome consists of renal events, cardiovascular events, and death. As of September 2013, 1,470 adult chronic kidney disease subjects were enrolled in the study, including 543 subjects with glomerulonephritis, 317 with diabetic nephropathy, 294 with hypertensive nephropathy and 249 with polycystic kidney disease.
As the first large-scale chronic kidney disease cohort study to be established and maintained longitudinally for up to 10 years, the KNOW-CKD will help to clarify the natural course, complication profiles, and risk factors of Asian populations with chronic kidney disease.
Trial registration
No. NCT01630486 at
PMCID: PMC4050398  PMID: 24884708
KNOW-CKD; Chronic kidney disease; Cohort; Etiology; Progression; Complication; Natural course
14.  Clinical features and outcomes of focal segmental glomerulosclerosis pathologic variants in Korean adult patients 
BMC Nephrology  2014;15:52.
Many studies have shown that clinical characteristics and outcomes differ depending on pathologic variants of focal segmental glomerulosclerosis (FSGS). However, these are not well defined in Asian populations.
This retrospective study evaluated clinical features and outcomes of pathologic FSGS variants in 111 adult patients between January 2004 and December 2012. Primary outcome was the composite of doubling of baseline serum creatinine concentrations (D-SCr) or onset of end-stage renal disease (ESRD). Secondary outcome included complete (CR) or partial remission (PR).
There were 70 (63.1%), 20 (18.0%), 17 (15.3%), 3 (2.7%), and 1 (0.9%) patients with not-otherwise specified (NOS), tip, perihilar, cellular, and collapsing variants, respectively. At presentation, nephrotic-range proteinuria occurred more commonly in tip lesion than in other variants. The overall 5-year renal survival rate was 76.8%. During a median follow-up of 34.5 months, only 1 (5.0%) patient with a tip lesion reached the composite end point compared to 2 (11.8%) and 12 (17.1%) patients in perihilar and NOS variants, but this difference was not statistically significant in an adjusted Cox model. However, tip lesion was associated with a significantly increased probability of achieving CR (P = 0.044).
Similar to other populations, Korean adult patients with FSGS have distinct clinical features with the exception of a rare frequency of cellular and collapsing variants. Although pathologic variants were not associated with overall outcome, the tip variant exhibited favorable outcome in terms of achieving remission. Further studies are required to delineate long-term outcome and response to treatment of the pathologic variants.
PMCID: PMC4230406  PMID: 24666814
Focal segmental glomerulosclerosis; Pathology; Outcome
15.  Comparison of Two Creatinine-Based Equations for Predicting Decline in Renal Function in Type 2 Diabetic Patients with Nephropathy in a Korean Population 
Aim. To compare two creatinine-based estimated glomerular filtration rate (eGFR) equations, the chronic kidney disease epidemiology collaboration (CKD-EPI) and the modification of diet in renal disease (MDRD), for predicting the risk of CKD progression in type 2 diabetic patients with nephropathy. Methods. A total of 707 type 2 diabetic patients with 24 hr urinary albumin excretion of more than 30 mg/day were retrospectively recruited and traced until doubling of baseline serum creatinine (SCr) levels was noted. Results. During the follow-up period (median, 2.4 years), the CKD-EPI equation reclassified 10.9% of all MDRD-estimated subjects: 9.1% to an earlier stage of CKD and 1.8% to a later stage of CKD. Overall, the prevalence of CKD (eGFR < 60 mL/min/1.73 m2) was lowered from 54% to 51.6% by applying the CKD-EPI equation. On Cox-regression analysis, both equations exhibited significant associations with an increased risk for doubling of SCr. However, only the CKD-EPI equation maintained a significant hazard ratio for doubling of SCr in earlier-stage CKD (eGFR ≥ 45 mL/min/1.73 m2), when compared to stage 1 CKD (eGFR ≥ 90 mL/min/1.73 m2). Conclusion. In regard to CKD progression, these results suggest that the CKD-EPI equation might more accurately stratify earlier-stage CKD among type 2 diabetic patients with nephropathy than the MDRD study equation.
PMCID: PMC3884626  PMID: 24454370
16.  A Low Serum Bicarbonate Concentration as a Risk Factor for Mortality in Peritoneal Dialysis Patients 
PLoS ONE  2013;8(12):e82912.
Background and Aim
Metabolic acidosis is common in patients with chronic kidney disease and is associated with increased mortality in hemodialysis patients. However, this relationship has not yet been determined in peritoneal dialysis (PD) patients.
This prospective observational study included a total of 441 incident patients who started PD between January 2000 and December 2005. Using time-averaged serum bicarbonate (TA-Bic) levels, we aimed to investigate whether a low serum bicarbonate concentration can predict mortality in these patients.
Among the baseline parameters, serum bicarbonate level was positively associated with hemoglobin level and residual glomerular filtration rate (GFR), while it was negatively associated with albumin, C-reactive protein (CRP) levels, peritoneal Kt/V urea, and normalized protein catabolic rate (nPCR) in a multivariable linear regression analysis. During a median follow-up of 34.8 months, 149 deaths were recorded. After adjustment for age, diabetes, coronary artery disease, serum albumin, ferritin, CRP, residual GFR, peritoneal Kt/V urea, nPCR, and percentage of lean body mass, TA-Bic level was associated with a significantly decreased risk of mortality (HR per 1 mEq/L increase, 0.83; 95% CI, 0.76-0.91; p < 0.001). In addition, compared to patients with a TA-Bic level of 24-26 mEq/L, those with a TA-Bic level < 22 and between 22-24 mEq/L conferred a 13.10- and 2.13-fold increased risk of death, respectively.
This study showed that a low serum bicarbonate concentration is an independent risk factor for mortality in PD patients. This relationship between low bicarbonate levels and adverse outcome could be related to enhanced inflammation and a more rapid loss of RRF associated with metabolic acidosis. Large randomized clinical trials to correct acidosis are warranted to confirm our findings.
PMCID: PMC3861444  PMID: 24349396
17.  Renal Histologic Parameters Influencing Postoperative Renal Function in Renal Cell Carcinoma Patients 
Korean Journal of Pathology  2013;47(6):557-562.
Pre-existing non-neoplastic renal diseases or lesions may influence patient renal function after tumor removal. However, its description is often neglected or omitted in pathologic reports. To determine the incidence and clinical significance of non-neoplastic lesions, we retrospectively examined renal tissues obtained during 85 radical nephrectomies for renal cell carcinoma.
One paraffin-embedded tissue block from each case containing a sufficient amount of non-tumorous renal parenchyma was cut and processed with hematoxylin and eosin and periodic acid-Schiff methods. Non-neoplastic lesions of each histological compartment were semi-quantitatively and quantitatively evaluated.
Among the various histologic lesions found, tubular atrophy, arterial intimal thickening, and glomerulosclerosis were the most common (94.1%, 91.8%, and 88.2%, respectively). Glomerulosclerosis correlated with estimated glomerular filtration rate at the time of surgery, as well as at 1- and 5-years post-surgery (p=.0071), but tubulointerstitial fibrosis or arterial fibrous intimal thickening did not. Post-hoc analysis revealed that glomerulosclerosis of more than 20% predicted post-operative renal function. However, its significance disappeared when gender and age were considered.
In conclusion, non-neoplastic lesions, especially with regard to glomerulosclerosis percentage, should be described in pathology reports to provide additional information on renal function decline.
PMCID: PMC3887158  PMID: 24421849
Nephrectomy; Carcinoma, renal cell; Glomerular filtration rate; Histology
18.  A case of Tsutsugamushi disease presenting with nephrotic syndrome 
Nephrotic syndrome associated with Tsutsugamushi disease has not been previously reported. We are describing a case of Tsutsugamuchi disease presenting with nephrotic syndrome. A 72-year-old woman presented with fever and generalized edema. Laboratory studies revealed a leukocytosis, hypoalbuminemia, and hypercholesterolemia. Her urine protein excretion was 5.4 g/day. The anti-Tsutsugamushi antibody test was strongly positive (1:2,560). A renal biopsy was performed, and pathologic findings revealed membranous glomerulonephritis. The patient's clinical symptoms improved markedly after treatment with doxycycline.
PMCID: PMC3847001  PMID: 24307851
Nephrotic syndrome; Scrub typhus; Glomerulonephritis; Membranous
19.  Sagittal Abdominal Diameter Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Incident Peritoneal Dialysis Patients 
PLoS ONE  2013;8(10):e77082.
Backgrounds and Aims
Visceral fat has a crucial role in the development and progression of cardiovascular disease, the major cause of death in end-stage renal disease (ESRD). Although sagittal abdominal diameter (SAD), as an index of visceral fat, significantly correlated with mortality in the general population, the impact of SAD on clinical outcomes has never been explored in ESRD patients. Therefore, we sought to elucidate the prognostic value of SAD in incident peritoneal dialysis (PD) patients.
We prospectively determined SAD by lateral abdominal X-ray at PD initiation, and evaluated the association of SAD with all-cause and cardiovascular mortality in 418 incident PD patients.
The mean SAD was 24.5±4.3 cm, and during a mean follow-up of 39.4 months, 97 patients (23.2%) died, and 49.4% of them died due to cardiovascular disease. SAD was a significant independent predictor of all-cause [3rd versus 1st tertile, HR (hazard ratio): 3.333, 95% CI (confidence interval): 1.514–7.388, P = 0.01; per 1 cm increase, HR: 1.071, 95% CI: 1.005–1.141, P = 0.03] and cardiovascular mortality (3rd versus 1st tertile, HR: 8.021, 95% CI: 1.994–32.273, P = 0.01; per 1 cm increase, HR: 1.106, 95% CI: 1.007–1.214, P = 0.03). Multivariate fractional polynomial analysis also showed that all-cause and cardiovascular mortality risk increased steadily with higher SAD values. In addition, SAD provided higher predictive value for all-cause (AUC: 0.691 vs. 0.547, P<0.001) and cardiovascular mortality (AUC: 0.644 vs. 0.483, P<0.001) than body mass index (BMI). Subgroup analysis revealed higher SAD (≥24.2 cm) was significantly associated with all-cause mortality in men, women, younger patients (<65 years), and patients with lower BMI (<22.3 kg/m2).
SAD determined by lateral abdominal X-ray at PD initiation was a significant independent predictor of all-cause and cardiovascular mortality in incident PD patients. Estimating visceral fat by SAD could be useful to stratify mortality risk in these patients.
PMCID: PMC3805560  PMID: 24167560
20.  Diastolic dysfunction is associated with an increased risk of contrast-induced nephropathy: a retrospective cohort study 
BMC Nephrology  2013;14:146.
Contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute kidney injury, and it is associated with poor long-term clinical outcomes. Although systolic heart failure is a well-known risk factor for CIN, no studies have yet evaluated the association between diastolic dysfunction and CIN.
We conducted a retrospective study of 735 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) and had an echocardiography performed within one month of the procedure at our institute, between January 2009 and December 2010. CIN was defined as an increase of ≥ 0.5 mg/dL or ≥ 25% in serum creatinine level during the 72 hours following PTCA.
CIN occurred in 64 patients (8.7%). Patients with CIN were older, had more comorbidities, and had an intra-aortic balloon pump (IABP) placed more frequently during PTCA than patients without CIN. They showed greater high-sensitivity C-reactive protein (hs-CRP) levels and lower estimated glomerular filtration rates (eGFR). Echocardiographic findings revealed lower ejection fraction and higher left atrial volume index and E/E’ in the CIN group compared with non-CIN group. When patients were classified into 3 groups according to the E/E’ values of 8 and 15, CIN occurred in 42 (21.6%) patients in the highest tertile compared with 20 (4.0%) in the middle and 2 (4.3%) in the lowest tertile (p < 0.001). In multivariate logistic regression analysis, E/E’ > 15 was identified as an independent risk factor for the development of CIN after adjustment for age, diabetes, dose of contrast media, IABP use, eGFR, hs-CRP, and echocardiographic parameters [odds ratio (OR) 2.579, 95% confidence interval (CI) 1.082-5.964, p = 0.035]. In addition, the area under the receiver operating characteristic curve of E/E’ was 0.751 (95% CI 0.684-0.819, p < 0.001), which was comparable to that of ejection fraction and left atrial volume index (0.739 and 0.656, respectively, p < 0.001).
This study demonstrated that, among echocardiographic variables, E/E' was an independent predictor of CIN. This in turn suggests that diastolic dysfunction may be a useful parameter in CIN risk stratification.
PMCID: PMC3717078  PMID: 23849485
Contrast-induced nephropathy; Diastolic dysfunction; E/E’
21.  Stepwise Treatment Using Corticosteroids Alone and in Combination with Cyclosporine in Korean Patients with Idiopathic Membranous Nephropathy 
Yonsei Medical Journal  2013;54(4):973-982.
We undertook an observational study to investigate the effects of immunosuppressive treatment on proteinuria and renal function in 179 Korean idiopathic membranous nephropathy patients with nephrotic syndrome.
Materials and Methods
The primary outcome was regarded as the first appearance of remission and the secondary outcomes as a decline in estimated glomerular filtration rate (eGFR) >50% or initiation of dialysis, and all-cause mortality. Seventy-two (40.2%) and 50 (27.9%) patients were treated with corticosteroids alone (C) and corticosteroids plus cyclosporine (C+C), respectively, whereas 57 (31.8%) did not receive immunosuppressants (NTx). Cyclosporine was added if there was no reduction in proteinuria of >50% from baseline by corticosteroids alone within 3 months.
There were no differences in baseline renal function and the amount of proteinuria among the three groups. Overall, complete remission (CR) was achieved in 88 (72.1%) patients by immunosuppressants. In a multivariate analysis adjusted for covariates associated with adverse renal outcome, the probability of reaching CR was significantly higher in the C [hazard ratio (HR), 4.09; p<0.001] and C+C groups (HR, 2.57; p=0.003) than in the NTx group. Kaplan-Meier analysis revealed that 5-year CR rates of C, C+C, and NTx groups were 88.5%, 86.2%, and 56.7% (p<0.001). Ten-year event-free rates for the secondary endpoints in these three groups were 91.7%, 79.9%, and 57.2% (p=0.01).
Immunosuppressive treatment was effective in inducing remission and preserving renal function in these patients. Therefore, stepwise treatment using corticosteroids alone and in combination with cyclosporine is warranted in these patients.
PMCID: PMC3663215  PMID: 23709434
Corticosteroids; cyclosporine; idiopathic membranous nephropathy; nephrotic syndrome; remission
22.  Reduced Residual Renal Function is Associated with Endothelial Dysfunction in Patients Receiving Peritoneal Dialysis 
♦ Background: Endothelial dysfunction, which contributes to atherosclerosis and arteriosclerosis, commonly accompanies end-stage renal disease (ESRD). However, little is known about the role of residual renal function (RRF) in endothelial protection in ESRD patients. This study aimed to investigate the relationship between endothelial function and RRF in patients undergoing peritoneal dialysis (PD).
♦ Methods: This was a cross-sectional study involving 72 prevalent PD patients. Demographic and clinical data were recorded and residual glomerular filtration rate (GFR), Kt/V urea, and serum concentrations of inflammatory markers were measured. Endothelial function was assessed by brachial artery endothelium-dependent vasodilation [flow-mediated dilation (FMD)] to reactive hyperemia following 5 minutes of forearm ischemia.
♦ Results: In patients with FMD% above the median value (FMD > 2.41%), residual GFR was significantly higher compared to that in patients with FMD% below the median [1.50 (0 – 9.64) vs 0.48 (0 – 3.89) mL/min/1.73 m2, P = 0.026]. Correlation analyses revealed that residual GFR (ρ = 0.381, P = 0.001) and total Kt/V urea (γ = 0.408, P < 0.001) were positively correlated with FMD%, whereas PD duration (γ = –0.351, P = 0.003), high-sensitivity C-reactive protein (ρ = –0.345, P = 0.003), pulse pressure (γ = –0.341, P = 0.003), and age (γ = –0.403, P < 0.001) were inversely correlated with FMD%. In contrast, there was no correlation between peritoneal Kt/V urea and FMD%. In multivariate linear regression analysis adjusted for these factors, residual GFR was found to be an independent determinant of FMD% (β = 0.317, P = 0.017).
♦ Conclusion: This study shows that RRF is independently associated with endothelial dysfunction in ESRD patients on PD, suggesting that RRF may contribute to endothelial protection in these patients.
PMCID: PMC3525403  PMID: 20864603
Endothelial dysfunction; residual renal function
23.  Progression of Aortic Arch Calcification Over 1 Year Is an Independent Predictor of Mortality in Incident Peritoneal Dialysis Patients 
PLoS ONE  2012;7(11):e48793.
Backgrounds and Aims
The presence and progression of vascular calcification have been demonstrated as important risk factors for mortality in dialysis patients. However, since the majority of subjects included in most previous studies were hemodialysis patients, limited information was available in peritoneal dialysis (PD) patients. Therefore, the aim of this study was to investigate the prevalence of aortic arch calcification (AoAC) and prognostic value of AoAC progression in PD patients.
We prospectively determined AoAC by chest X-ray at PD start and after 12 months, and evaluated the impact of AoAC progression on mortality in 415 incident PD patients.
Of 415 patients, 169 patients (40.7%) had AoAC at baseline with a mean of 18.1±11.2%. The presence of baseline AoAC was an independent predictor of all-cause [Hazard ratio (HR): 2.181, 95% confidence interval (CI): 1.336–3.561, P = 0.002] and cardiovascular mortality (HR: 3.582, 95% CI: 1.577–8.132, P = 0.002). Among 363 patients with follow-up chest X-rays at 12 months after PD start, the proportion of patients with AoAC progression was significantly higher in patients with baseline AoAC (64.2 vs. 5.3%, P<0.001). Moreover, all-cause and cardiovascular death rates were significantly higher in the progression groups than in the non-progression group (P<0.001). Multivariate Cox analysis revealed that AoAC progression was an independent predictor for all-cause (HR: 2.625, 95% CI: 1.150–5.991, P = 0.022) and cardiovascular mortality (HR: 4.008, 95% CI: 1.079–14.890, P = 0.038) in patients with AoAC at baseline.
The presence and progression of AoAC assessed by chest X-ray were independently associated with unfavorable outcomes in incident PD patients. Regular follow-up by chest X-ray could be a simple and useful method to stratify mortality risk in these patients.
PMCID: PMC3492238  PMID: 23144974
24.  A Novel Multiplex Real-Time PCR Assay for the Concurrent Detection of Hepatitis A, B and C Viruses in Patients with Acute Hepatitis 
PLoS ONE  2012;7(11):e49106.
A novel multiplex real-time PCR assay for concurrent detection of hepatitis viruses was evaluated for its clinical performance in screening patients with acute hepatitis. A total of 648 serum samples were collected from patients with acute symptoms of hepatitis. Concurrent detection of nucleic acids of HAV, HBV and HCV was performed using the Magicplex™ HepaTrio Real-time Detection test. Serum nucleic acid levels of HBV and HCV were also quantified by the Cobas® AmpliPrep/Cobas® TaqMan® (CAP/CTM) HBV and HCV tests. Patients’ medical records were also reviewed. Concordance rates between the results from the HepaTrio and the CAP/CTM tests for the detection of HBV and HCV were 94.9% (k = 0.88) and 99.2% (k = 0.98), respectively. The cycle threshold values with the HepaTrio test were also correlated well with the levels of HBV DNA (r = −0.9230) and HCV RNA (r = −0.8458). The sensitivity and specificity of the HepaTrio test were 93.8% and 98.2%, respectively, for detecting HBV infection, and 99.1% and 100.0%, respectively, for HCV infection. For the HepaTrio test, 21 (3.2%) cases were positive for both HBV and HCV. Among the positive cases, 6 (0.9%) were true coinfections. This test also detected 18 (2.8%) HAV positives. The HepaTrio test demonstrated good clinical performance and produced results that agreed well with those of the CAP/CTM assays, especially for the detection of HCV. This assay was also able to detect HAV RNA from anti-HAV IgM-positive individuals. Therefore, this new multiplex PCR assay could be useful for the concurrent detection of the three hepatitis viruses.
PMCID: PMC3493491  PMID: 23145085
25.  The impact of pretransplant 25-hydroxy vitamin D deficiency on subsequent graft function: An observational study 
BMC Nephrology  2012;13:22.
In addition to its canonical role in musculoskeletal health, several reports have demonstrated that serum vitamin D level may influence kidney function. However, the effect of pretransplant serum vitamin D level on subsequent graft function has not been explored. Therefore, this study was undertaken to examine the effect of serum vitamin D level at the time of kidney transplantation (KT) on subsequent graft function.
We analyzed 106 patients who underwent KT and for whom 25-hydroxy vitamin D (25-OHD) levels were measured during hospitalization prior to transplantation. We measured estimated glomerular filtration rates (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula at baseline and at six-month intervals up to 36 months after KT.
38.7% of the patients were diagnosed with 25-OHD deficiency defined as less than 10 ng/mL. Recipient gender (female vs. male, odds ratio [OR] 3.30, 95% CI 1.33-8.21, P = 0.010), serum albumin level (per 1 mg/dl increase, OR 0.35, 95% CI 0.13-0.98, P = 0.047), and predominant renal replacement therapy modality before KT (P < 0.001) were found to be independent pretransplant risk factors for 25-OHD deficiency by multivariate logistic regression analysis. Subsequent repeated measures analysis of covariance revealed that 25-OHD level had the only significant main effect on eGFR during the 36-month follow-up period [F (1, 88) = 12.07, P = 0.001].
Pretransplant 25-OHD deficiency was significantly associated with a lower post-transplant eGFR, suggesting that 25-OHD may play an important role in maintaining graft function after KT.
PMCID: PMC3393620  PMID: 22533967

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