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1.  Change in Body Compositions of Asian Recipients after Kidney Transplantation 
Journal of Korean Medical Science  2012;27(10):1182-1187.
Kidney transplantation and accompanying medical conditions may result in changes in body composition. Such changes have been evaluated in Caucasian recipients, but not in Asian recipients. Herein, we conducted a study on Asian recipients because Asians have a different body composition from Caucasians. A total of 50 Asian recipients was enrolled as a prospective cohort. Using bioelectrical impedance analysis, body composition (muscle and fat mass) was assessed after 2 weeks (baseline), and at 1, 3, 6, 9, and 12 months following kidney transplantation. To find predictors related to changes, the data were analyzed by multivariate analysis using forward selection. All of the patients had good graft function during the study period. Patients gained approximately 3 kg within 1 yr of kidney transplantation. The proportion of muscle mass significantly decreased (Ptrend = 0.001) and the proportion of fat mass significantly increased over time (Ptrend = 0.002). The multivariate results revealed that male recipients, deceased donor type, and low protein intake were associated with an increase in fat mass and a decrease in muscle mass. The results from this study may help to investigate differences in body composition changes between races, as well as the factors related to these changes.
PMCID: PMC3468754  PMID: 23091315
Asian; Body Composition; Fat; Kidney Transplantation; Muscle
2.  Induction of Donor-Specific Tolerance: Is This Achievable? 
PMCID: PMC3295979  PMID: 22403511
Donor-specific tolerance; Antigen-presenting cells; Intercellular adhesion molecule 1
3.  Renal adverse effects of sunitinib and its clinical significance: a single-center experience in Korea 
Sunitinib is an oral multitargeted tyrosine kinase inhibitor used mainly for the treatment of metastatic renal cell carcinoma. The renal adverse effects (RAEs) of sunitinib have not been investigated. The aim of this study was to determine the incidence and risk factors of RAEs (proteinuria [PU] and renal insufficiency [RI]) and to investigate the relationship between PU and antitumor efficacy.
We performed a retrospective review of medical records of patients who had received sunitinib for more than 3 months.
One hundred and fifty-five patients (mean age, 58.7 ± 12.6 years) were enrolled, and the mean baseline creatinine level was 1.24 mg/dL. PU developed in 15 of 111 patients, and preexisting PU was aggravated in six of 111 patients. Only one patient developed typical nephrotic syndrome. Following discontinuation of sunitinib, PU was improved in 12 of 17 patients but persisted in five of 17 patients. RI occurred in 12 of 155 patients, and the maximum creatinine level was 3.31 mg/dL. RI improved in two of 12 patients but persisted in 10 of 12 patients. Risk factors for PU were hypertension, dyslipidemia, and chronic kidney disease. Older age was a risk factor for RI. The median progression-free survival was significantly better for patients who showed PU.
The incidence of RAEs associated with sunitinib was lower than those of previous reports. The severity of RAEs was mild to moderate, and partially reversible after cessation of sunitinib. We suggest that blood pressure, urinalysis, and renal function in patients receiving sunitinib should be monitored closely.
PMCID: PMC3932394  PMID: 24574832
Acute kidney injury; Proteinuria; Sunitinib
4.  Survival Advantage of Peritoneal Dialysis Relative to Hemodialysis in the Early Period of Incident Dialysis Patients: A Nationwide Prospective Propensity-Matched Study in Korea 
PLoS ONE  2013;8(12):e84257.
The impact of dialysis modality on survival is still somewhat controversial. Given possible differences in patients’ characteristics and the cause and rate of death in different countries, the issue needs to be evaluated in Korean cohorts.
A nationwide prospective observational cohort study (NCT00931970) was performed to compare survival between peritoneal dialysis (PD) and hemodialysis (HD). A total of 1,060 end-stage renal disease patients in Korea who began dialysis between September 1, 2008 and June 30, 2011 were followed through December 31, 2011.
The patients (PD, 30.6%; HD, 69.4%) were followed up for 16.3±7.9 months. PD patients were significantly younger, less likely to be diabetic, with lower body mass index, and larger urinary volume than HD patients. Infection was the most common cause of death. Multivariate Cox regression with the entire cohort revealed that PD tended to be associated with a lower risk of death compared to HD [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.36–1.08]. In propensity score matched pairs (n = 278 in each modality), cumulative survival probabilities for PD and HD patients were 96.9% and 94.1% at 12 months (P = 0.152) and 94.3% and 87.6% at 24 months (P = 0.022), respectively. Patients on PD had a 51% lower risk of death compared to those on HD (HR 0.49, 95% CI 0.25–0.97).
PD exhibits superior survival to HD in the early period of dialysis, even after adjusting for differences in the patients’ characteristics between the two modalities. Notably, the most common cause of death was infection in this Korean cohort.
PMCID: PMC3875495  PMID: 24386357
5.  An Antagonist IL-15/Fc Protein Prevents Costimulation Blockade-Resistant Rejection1 
IL-15 is a powerful T cell growth factor (TCGF) with particular importance for the maintenance of CD8+ T cells. Because costimulation blockade does not result in universal tolerance, we hypothesized that “escape” from costimulation blockade might represent a CD8+ and IL-15/IL-15R+-dependent process. For this analysis, we have used an IL-15 mutant/Fcγ2a protein, a potentially cytolytic protein that is also a high-affinity receptor site specific antagonist for the IL-15Rα receptor protein, as a therapeutic agent. The IL-15-related fusion protein was used as monotherapy or in combination with CTLA4/Fc in murine islet allograft models. As monotherapies, CTLA4/Fc and an IL-15 mutant/Fcγ2a were comparably effective in a semiallogeneic model system, and combined treatment with IL-15 mutant/Fcγ2a plus CTLA4/Fc produced universal permanent engraftment. In a fully MHC-mismatched strain combination known to be refractory to costimulation blockade treatment, combined treatment with both fusion proteins proved to be highly effective; >70% of recipients were tolerized. The analysis revealed that the IL-15 mutant/Fc treatment confers partial protection from both CD4+ and CD8+ T cell graft infiltration. In rejections occurring despite CTLA4/Fc treatment, concomitant treatment with the IL-15 mutant/Fcγ2a protein blocked a CD8+ T cell-dominated rejection processes. This protection was linked to a blunted proliferative response of alloreactive T cells as well silencing of CTL-related gene expression events. Hence, we have demonstrated that targeting the IL-15/IL-15R pathway represents a new and potent strategy to prevent costimulation blockade-resistant CD8+ T cell-driven rejection.
PMCID: PMC3806296  PMID: 11544341
6.  Targeting the IL-15 Receptor with an Antagonist IL-15 Mutant/Fcγ2a Protein Blocks Delayed-Type Hypersensitivity1 
Owing to shared receptor components, the biologic activities of IL-15 are similar to those of IL-2. However, the patterns of tissue expression of IL-2/IL-2Rα and IL-15/IL-15Rα differ. The development of agents targeting the receptor and signaling elements of IL-15 may provide a new perspective for treatment of diseases associated with expression of IL-15/IL-15R. We designed, genetically constructed, and expressed a receptor site-specific IL-15 antagonist by mutating glutamine residues within the C terminus of IL-15 to aspartic acid and genetically linked this mutant IL-15 to murine Fcγ2a. These mutant IL-15 proteins specifically bind to the IL-15R, competitively inhibit IL-15-triggered cell proliferation, and do not activate the STAT-signaling pathway. Because the receptor site-specific antagonist IL-15 mutant/Fcγ2a fusion proteins had a prolonged t½ in vivo and the potential for destruction of IL-15R+ leukocytes, we examined the immunosuppressive activity of this agent. An IL-15 mutant/Fcγ2a fusion protein markedly attenuated Ag-specific delayed-type hypersensitivity responses and decreased leukocyte infiltration within the delayed-type hypersensitivity sites. These findings suggest that 1) IL-15/IL-15R+ cells are crucial to these T cell-dependent immune responses, and 2) treatment with IL-15 mutant/Fcγ2a protein may ameliorate T cell-dependent immune/inflammatory diseases.
PMCID: PMC3806316  PMID: 9637483
7.  Evaluation of Nutrient Intake in Early Post Kidney Transplant Recipients 
Clinical Nutrition Research  2013;2(1):1-11.
The purpose of our study was to evaluate the dietary intake of kidney transplant recipients (KTRs) and assess oral intake related nutrition problems. Fifty patients who had undergone kidney transplantation were included: 24 males, 26 females. The mean age was 46.8 ± 11.2 years, height was 161.3 ± 8.3 cm, and body weight was 60.5 ± 8.7 kg. We conducted nutrition education based on the diet guideline for KTRs (energy 32 kcal/kg of ideal body weight [IBW], protein 1.3 g/kg of IBW) and neutropenic diet guideline before discharge. Dietary intake of the patients at 1 month after transplantation was investigated by 3-day food records. Body weight and laboratory values for nutritional status and graft function were also collected. Body weight was significantly decreased from admission to discharge. Body weight from discharge to 1 month and 3 months after transplantation was increased but was not significant. Biochemical measurements were generally improved but the number of patients with hypophosphatemia increased. The daily dietary intake of energy and protein was adequate (33.1 kcal/kg, 1.5 g/kg, respectively). However, the dietary intake of calcium, folate, and vitamin C did not meet the Korean Recommended Nutrient Intake of vitamins and minerals (86.8%, 62.4%, and 88.0%, respectively). Patients with low intake of calcium, folate, and vitamin C presented low intake in milk and dairy products, vegetables, and fruits, and these foods were related to restricted food items in neutropenic diet. More attention should be paid on improving quality of diet, and reconsideration of present neutropenic diet guideline is necessary. These results can be used to establish evidence-based medical nutrition therapy guideline for KTRs.
PMCID: PMC3572820  PMID: 23429928
Kidney transplant recipients; Oral intake; Medical nutrition therapy guideline
8.  Chronic allograft injury by subclinical borderline change: evidence from serial protocol biopsies in kidney transplantation 
This study investigated the impact of subclinical borderline changes on the development of chronic allograft injury in patients using a modern immunosuppression protocol.
Seventy patients with stable renal allograft function and who underwent protocol biopsies at implantation, 10 days and 1 year after transplantation were included and classified based on biopsy findings at day 10. The no rejection (NR) group included 33 patients with no acute rejection. The treatment (Tx) group included 21 patients with borderline changes following steroid pulse therapy, and the nontreatment (NTx) group included 16 patients with borderline changes nontreated.
The Banff Chronicity Score (BChS) and modified BChS (MBChS) were not different among the three groups at implantation (P = 0.48) or on day 10 (P = 0.96). Surprisingly, the NTx group had more prominent chronic scores at the 1-year biopsy, including BChS (3.07 ± 1.33, P = 0.005) and MBChS (3.14 ± 1.41, P = 0.008) than those in the Tx and NR group, and deterioration of BChS was more noticeable in the NTx group (P = 0.037), although renal function was stable (P = 0.66). No difference in chronic injury scores was observed between the Tx and NR groups at the 1-year biopsy.
Subclinical borderline changes can be a risk factor for chronic allograft injury and should be considered for antirejection therapy.
PMCID: PMC3514476  PMID: 23230552
Borderline change; Chronic allograft injury; Kidney transplantation; Protocol kidney biopsy; Steroid pulse therapy
9.  Severe hyperkalemia requiring hospitalization: predictors of mortality 
Critical Care  2012;16(6):R225.
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.
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.
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.
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.
PMCID: PMC3672605  PMID: 23171442
10.  Recurrent Thrombotic Events after Catastrophic Antiphopholipid Syndrome 
PMCID: PMC3372811  PMID: 22707899
Antiphospholipid syndrome; Thrombosis; Anticoagulants
11.  Clinical Relevance of Pretransplant HLA Class II Donor-specific Antibodies in Renal Transplantation Patients with Negative T-cell Cytotoxicity Crossmatches 
Annals of Laboratory Medicine  2012;32(2):139-144.
We evaluated the clinical relevance of pretransplant donor-specific HLA antibodies (DSA) in renal transplantation patients who had negative T-cell cytotoxicity crossmatches.
From 328 consecutive renal transplant recipients, we selected 28 patients who had positive pretransplant (historical or at the time of transplantation) flow cytometry crossmatches, but negative T-cell cytotoxicity crossmatches at the time of transplantation. The presence of DSA and its level at the time of transplantation were retrospectively tested using Luminex single antigen assays.
DSA was present in 16 (57.1%) of 28 patients. Biopsy-proven acute rejection (9 patients) occurred more frequently in patients with DSA than in those without DSA (56.3% vs. 0.0%; P=0.003). The positivity rate of class II DSA was significantly higher in patients with antibody-mediated rejection (AMR) than in those without AMR (100% vs. 21.7%; P=0.003). However, the positivity rate of class I DSA was not different between the two groups (40% vs. 40.9%). Among patients with class II DSA, those with AMR tended to have higher antibody levels (median fluorescence intensity, MFI) than those without AMR (16,359 vs. 5,910; P=0.056). A cut-off MFI value of 4,487 for class II DSA predicted the occurrence of AMR with good sensitivity and specificity (100% and 87.0%).
In patients with negative T-cell cytotoxicity crossmatches, the presence of class II DSA and its level at the time of transplantation were associated with the occurrence of AMR. Pretransplant DSA measurement with Luminex single antigen assay would be useful in renal transplantation.
PMCID: PMC3289779  PMID: 22389881
Donor-specific HLA antibodies; Renal transplantation; Antibody-mediated rejection
12.  Epithelial transglutaminase 2 is needed for T cell interleukin-17 production and subsequent pulmonary inflammation and fibrosis in bleomycin-treated mice 
The Journal of Experimental Medicine  2011;208(8):1707-1719.
Inhibition of transglutaminase 2 reduces bleomycin-induced epithelial cell release of interleukin 6 in vitro and pulmonary inflammation and fibrosis in vivo.
Pulmonary fibrosis is a potentially life-threatening disease that may be caused by overt or asymptomatic inflammatory responses. However, the precise mechanisms by which tissue injury is translated into inflammation and consequent fibrosis remain to be established. Here, we show that in a lung injury model, bleomycin induced the secretion of IL-6 by epithelial cells in a transglutaminase 2 (TG2)–dependent manner. This response represents a key step in the differentiation of IL-17–producing T cells and subsequent inflammatory amplification in the lung. The essential role of epithelial cells, but not inflammatory cells, TG2 was confirmed in bone marrow chimeras; chimeras made in TG2-deficient recipients showed reduced inflammation and fibrosis, compared with those in wild-type mice, regardless of the bone marrow cell phenotype. Epithelial TG2 thus appears to be a critical inducer of inflammation after noninfectious pulmonary injury. We further demonstrated that fibroblast-derived TG2, acting downstream of transforming growth factor-β, is also important in the effector phase of fibrogenesis. Therefore, TG2 represents an interesting potential target for therapeutic intervention.
PMCID: PMC3149214  PMID: 21746810
13.  Outcome of Early Initiation of Peritoneal Dialysis in Patients with End-Stage Renal Failure 
Journal of Korean Medical Science  2012;27(2):170-176.
Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone.
PMCID: PMC3271290  PMID: 22323864
Peritoneal Dialysis; End Stage Renal Failure; Dialysis Initiation; Propensity Score Match; Outcome; Survival
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.
PMCID: PMC3247777  PMID: 22219616
Peritoneal Dialysis; Depression; Health-Related Quality of Life; Residual Renal Function; Beck's Depression Inventory; KDQOL-SF
15.  Maturation-Resistant Dendritic Cells Ameliorate Experimental Autoimmune Uveoretinitis 
Immune Network  2011;11(6):399-405.
Endogenous uveitis is a chronic inflammatory eye disease of human, which frequently leads to blindness. Experimental autoimmune uveoretinitis (EAU) is an animal disease model of human endogenous uveitis and can be induced in susceptible animals by immunization with retinal antigens. EAU resembles the key immunological characteristics of human disease in that both are CD4+ T-cell mediated diseases. Dendritic cells (DCs) are specialized antigen-presenting cells that are uniquely capable of activating naïve T cells. Regulation of immune responses through modulation of DCs has thus been tried extensively. Recently our group reported that donor strain-derived immature DC pretreatment successfully controlled the adverse immune response during allogeneic transplantation.
EAU was induced by immunization with human interphotoreceptor retinoid-binding protein (IRBP) peptide1-20. Dendritic cells were differentiated from bone marrow in the presence of recombinant GM-CSF.
In this study, we used paraformaldehyde-fixed bone marrow-derived DCs to maintain them in an immature state. Pretreatment with fixed immature DCs, but not fixed mature DCs, ameliorated the disease progression of EAU by inhibiting uveitogenic CD4+ T cell activation and differentiation.
Application of iBMDC prepared according to the protocol of this study would provide an important treatment modality for the autoimmune diseases and transplantation rejection.
PMCID: PMC3275710  PMID: 22346781
Dendritic cells; Maturation; Experimental Autoimmune Uveoretinitis (EAU)
16.  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
17.  Improved Gastrointestinal Symptoms and Quality of Life after Conversion from Mycophenolate Mofetil to Enteric-Coated Mycophenolate Sodium in Renal Transplant Patients Receiving Tacrolimus 
Journal of Korean Medical Science  2010;25(12):1759-1765.
It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL.
PMCID: PMC2995230  PMID: 21165291
Mycophenolate mofetil; Enteric-coated mycophenolate sodium; Tacrolimus; Gastrointestinal Symptom; Quality of Life; Kidney Transplantation
18.  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.
PMCID: PMC2966999  PMID: 21060751
Coefficient; Glomerular Filtration Rate; Inulin Clearance; Modification of Diet in Renal Disease Study
19.  Improvement in Erythropoieis-stimulating Agent-induced Pure Red-cell Aplasia by Introduction of Darbepoetin-α When the Anti-erythropoietin Antibody Titer Declines Spontaneously 
Journal of Korean Medical Science  2010;25(11):1676-1679.
Anti-erythropoietin antibodies usually cross-react with all kinds of recombinant erythropoietins; therefore, erythropoiesis-stimulating agent (ESA)-induced pure red-cell aplasia (PRCA) is not rescued by different ESAs. Here, we present a case of ESA-induced PRCA in a 36-yr-old woman with chronic kidney disease, whose anemic condition improved following reintroduction of darbepoetin-α. The patient developed progressive, severe anemia after the use of erythropoietin-α. As the anemia did not improve after the administration of either other erythropoietin-α products or erythropoietin-β, all ESAs were discontinued. Oxymetholone therapy failed to improve the transfusion-dependent anemia and a rechallenge with ESAs continuously failed to obtain a sustained response. However, her anemia improved following reintroduction of darbepoetin-α at 3 yr after the initial diagnosis. Interestingly, anti-erythropoietin antibodies were still detectable, although their concentration was too low for titration. In conclusion, darbepoetin-α can improve ESA-induced PRCA when the anti-erythropoietin antibody titer declines and its neutralizing capacity is lost.
PMCID: PMC2967010  PMID: 21060762
Red-Cell Aplasia, Pure; Kidney Failure, Chronic; Erythropoietin, Recombinant; Darbepoetin-alfa
20.  Trends in Deceased Organ Donation and Utilization in Korea: 2000-2009 
Journal of Korean Medical Science  2010;25(8):1122-1127.
Continuous efforts have been made by the organ donation and transplantation community in Korea to increase organ donation by the deceased. The authors detailed trends of organ donation and utilization over the past 10 yr using data provided by the KONOS. The yearly number of deceased donors has grown gradually since 2003. The number and percentage of old donors (≥50 yr) and donors dying from intracranial hemorrhage has increased continuously. Therefore, the percentage of standard criteria donors (SCD) has been declining significantly, from 94% in 2000 to 79.2% in 2009. The number of organs transplanted per donor (OTPD) has also declined slightly since 2007, from 3.28 in 2007 to 2.95 in 2009. This decline may be attributable to increases in the number and percentage of extended criteria donors (ECD) and donors after cardiac death (DCD), since the OTPD was 2.25 for DCD, 2.5 for ECD, and 3.09 for SCD in 2009. In summary, the makeup of donors has changed significantly. There is an urgent need for establishment of an institutional framework including an independent organ procurement organization and for improvement for the National Transplant Act to increase deceased donor pool and to optimize management of ECD and DCD.
PMCID: PMC2908778  PMID: 20676320
Deceased Organ Donors; Expanded Criteria Donors; Donors after cardiac death; Tissue and Organ Procurement; Organ Utilization
21.  Quality of life and mortality from a nephrologist's view: a prospective observational study 
BMC Nephrology  2009;10:39.
Although health-related quality of life (HRQOL) is a potential independent predictor of mortality, nephrologists have shown little interest in HRQOL with respect to mortality in chronic kidney disease (CKD). The aim of this article is to evaluate the impact of HRQOL on mortality in the elderly, who are likely to develop or already have CKD.
Among 1,000 randomly sampled participants aged more than 65 years (sourced from the Korean Longitudinal Study on Health and Ageing), 944 subjects were evaluated for HRQOL. HRQOL was assessed using a 36-item Short-Form health survey (SF36). A cumulative survival rate was calculated according to tertiles of SF36 scores and classified by the presence of CKD (estimated GFR <60 ml/min/1.73 m2).
Among 944 subjects, 46.6% had CKD. CKD patients had lower total and physical component scores compared with subjects without CKD. The 3-year cumulative survival rate was 90.0% (non-CKD vs. CKD: 92.6% vs. 87.4%, P = 0.005 by log rank test). After adjusting for multiple variables, a reduced SF36 score (physical and mental components) was a strong predictor of all-cause mortality. Physical components were consistently able to predict mortality after CKD classification, but mental components were statistically significant only in the CKD group.
In addition to traditional risk factors of mortality, nephrologists should be aware of HRQOL as a predictor of mortality and should make efforts to improve HRQOL in CKD patients.
PMCID: PMC2787507  PMID: 19930696
22.  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.
PMCID: PMC2633200  PMID: 19194539
Korea; Kidney Failure, Chronic; Epidemiologic Studies
23.  Clinicopathologic Characteristics of IgA Nephropathy with Steroid-responsive Nephrotic Syndrome 
Journal of Korean Medical Science  2009;24(Suppl 1):S44-S49.
Nephrotic syndrome is an unusual manifestation of IgA Nephropathy (IgAN). Some cases respond to steroid treatment. Here we describe a case-series of IgAN patients with steroid-responsive nephrotic syndrome. Twelve patients with IgAN with steroid-responsive nephrotic syndrome were evaluated and followed up. All patients presented with generalized edema. Renal insufficiency was found in two patients. The renal biopsy of eight patients revealed wide foot process effacement in addition to the typical features of IgAN. They showed complete remission after steroid therapy. Seven relapses were reported in five patients; six of the relapsed cases responded to steroid therapy. Compared with steroid-non-responsive patients, the patients with steroid-responsive nephrotic syndrome had shorter symptom duration, more weight gain, more proteinuria, and lower histologic grade than did those that had steroid-non-responsive nephrotic syndrome at presentation. None of the responders progressed to end stage renal disease, whereas five (38%) non-responders required dialysis or renal transplantation. Patients with IgAN who have steroid-responsive nephrotic syndrome likely have both minimal change disease and IgAN. The clinical features of sudden onset of generalized edema, initial heavy proteinuria and initial severe hypoalbuminemia might help identify the subset of patients, especially in low grade IgAN.
PMCID: PMC2633194  PMID: 19194561
Glomerulonephritis, IGA; Nephrosis, Lipoid; Nephrotic Syndrome; Steroids
24.  Kidney Transplantation in Sensitized Recipients; A Single Center Experience 
Journal of Korean Medical Science  2009;24(Suppl 1):S143-S147.
A successful transplantation, across a positive crossmatch barrier, is one of the most persistent long-standing problems in the field of kidney transplant medicine. The aim of this study was to describe seven consecutive living renal transplantations in recipients with positive crossmatch for donors or positive for donor specific antibodies (DSAs). A preconditioning regimen including plasmapheresis and intravenous immunoglobulin was delivered three times a week until the crossmatch and/or DSAs became negative. Mycophenolate mofetil and tacrolimus were started two days before the plasmapheresis. The protocol was modified to include administration of anti-CD 20 antibody (rituximab, 375 mg/m2) from the patient number 3 through the patient number 7. All seven patients achieved negative conversion of the crossmatch or DSAs, and the kidney transplantations were successfully performed in all cases. Acute cellular rejection occurred in two patients, which were subclinical and controlled with high dose steroid treatment. Antibody-mediated rejection occurred in one patient, which was easily reversed with plasmapheresis. All recipients attained normal graft function during the 7-24 months of follow up. Our study suggests that sensitized patients can be transplanted successfully with desensitization pretreatment.
PMCID: PMC2633205  PMID: 19194544
Desensitization, Immunologic; Immunoglobulins, Intravenous; Kidney Transplantation; Plasmapheresis; Rituximab
25.  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.
PMCID: PMC2633177  PMID: 19194557
Bilirubin; Glomerulonephritis, IGA; Kidney Failure, Chronic

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