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To evaluate the efficacy and safety of CKD-11101 (biosimilar darbepoetin-alfa, Chong Kun Dang Pharm.) compared with NESP® in treatment of anaemia in patients with chronic kidney disease not on dialysis.NCT03431623.In this multi-centre, randomized, double-blind study, patients were treated with CKD-11101 and NESP. The efficacy evaluation period (EEP) was 24 weeks, during which patients were treated every 2 weeks. All patients who completed the EEP were treated with CKD-11101 every 2 weeks for the first 4 weeks and every 4 weeks for the safety evaluation period (SEP), which was from 24 weeks to 52 weeks. The primary efficacy endpoint was the change in mean haemoglobin (Hb) level from baseline to end of EEP and mean dose needed to achieve the target Hb.The mean Hb level was increased in both groups during the EEP (both p 0.001). The difference in mean Hb level change between the two groups was 0.01 g/dL (95% CI = -0.213-0.242), indicating that CKD-11101 was equivalent to NESP. The difference in mean administration dose between groups was -1.40 mcg (95% CI = -6.859-4.059) included in the equivalent range. The incidence of AEs and ADRs was not different between the two groups, and the frequency of ADRs was favourable in both groups (1.2% in CKD-11101 vs 7.7% in the NESP to CKD-11101 conversion group).CKD-11101 has an equivalent therapeutic effect as NESP in chronic kidney disease patients with renal anaemia. CKD-11101 can be safely used for long-term treatment and in patients converted from NESP.

Chronic kidney disease–mineral bone disorder (CKD-MBD) is the most common complication in CKD patients. Although there is a consensus on treatment guidelines for CKD-MBD, it remains uncertain whether these treatment recommendations reflect actual practice. Therefore, the aim of this study was to investigate the CKD-MBD medication trend in real-world practice. This was a retrospective and observational study using a 12-year period database transformed into a common data model from three tertiary university hospitals. Study populations were subjects initially diagnosed as CKD. The date of diagnosis was designated as the index date. New patients were categorized year to year from 2008 to 2019 with a fixed observation period of 365 days to check the prescription of CKD-MBD medications including calcium-containing phosphate binder, noncalcium-containing phosphate binder, aluminium hydroxide, vitamin D receptor activator (VDRA), and cinacalcet. The numbers of CKD patients in the three hospitals were 7555, 2424, and 5351, respectively. The proportion for patients with CKD-MBD medication prescription decreased yearly regardless of hospital and CKD stage ( p for trend < 0.05). The use of aluminium hydroxide disappeared steadily while the use of VDRA increased annually in all settings. Despite these changes in prescription patterns, the mean value for CKD-MBD-related serologic markers was almost within target range. The proportion of the population within the target value was not significantly changed. Irrespective of hospital and CKD stage, similar trends of prescription for CKD-MBD medications were observed in real-world practice. Further research with a distributed network study may be helpful to understand medication trends in CKD-MBD treatment.

Background In the general population, the trabecular bone score (TBS) represents the bone microarchitecture and predicts fracture risk independent of bone mineral density (BMD). A few studies reported that TBS is significantly reduced in dialysis patients. Chronic kidney disease-mineral and bone disorder (CKD-MBD) are accompanied by increased fracture risk, cardiovascular morbidity, and mortality. We investigated whether TBS is associated with comorbidity related to CKD-MBD or frailty in hemodialysis patients. Methods In this prospective observational study, TBS was obtained using the TBS iNsight software program (Med-Imaps) with BMD dual energy x-ray absorptiometry (DXA) images (L1–L4) from prevalent hemodialysis patients. A Tilburg frailty indicator was used to evaluate frailty, and hand grip strength and bio-impedance (InBody) were measured. A patient-generated subjective global assessment (PG-SGA) was used for nutritional assessment. The history of cardiovascular events (CVE) and demographic, clinical, laboratory, and biomarker data were collated. We then followed up patients for the occurrence of CKD-MBD related complications. Results We enrolled 57 patients in total. The mean age was 56.8 ± 15.9 years (50.9% female). Prevalence of Diabetes mellitus (DM) was 40.4% and CVE was 36.8%. Mean TBS was 1.44 ± 0.10. TBS significantly reduced in the CVE group (1.38 ± 0.08 vs. 1.48 ± 0.10, p ß = − 0.030; p = 0.001) and CVE (ß = − 0.055; p = 0.024) were significant predictors of TBS. During the follow up period after TBS measurements (about 20 months), four deaths, seven incident fractures, and six new onset CVE were recorded. Lower TBS was associated with mortality (p = 0.049) or new onset fracture (p = 0.007, by log-rank test). Conclusion Lower TBS was independently associated with increased age and CVE prevalence in hemodialysis patients. Mortality and fracture incidence were significantly higher in patients with lower TBS values. These findings suggest that TBS may indicate a phenotype of frailty and also a CKD-MBD phenotype reciprocal to CVE.

Background/aims It has been shown that circulating tumor necrosis factor α (TNF-α) is elevated in end stage renal disease patients; however, the relationship between TNF-α and the development of infection in these patients is unknown. In this study, we investigated the association of plasma TNF-α and interleukin 6 (IL-6) with infection in peritoneal dialysis (PD) patients. We also evaluated the association of their plasma levels with the production by peripheral blood mononuclear cells (PBMC), and with various clinical parameters. Methods We enrolled 32 patients on maintenance PD and 10 healthy controls. Plasma and PBMC were isolated from blood. PBMC were stimulated with lipopolysaccharide in vitro. Results Mean follow-up duration was 775 days. Six patients developed organ infections (five pneumonia and one liver abscess), and six patients developed PD peritonitis and eight developed exit site infection. Plasma TNF-α and IL-6 levels were significantly elevated in organ infections but not in peritonitis or in exit site infection. Plasma TNF-α was the only significant risk factor for organ infections and pneumonia in multivariate regression analysis. Patients with high plasma TNF-α levels showed a significantly greater cumulative hazard rate for organ infections compared to those with low TNF-α levels. Plasma TNF-α levels correlated with TNF-α production by PBMC and showed an inverse association with Kt/V. Conclusions This is the first study showing that plasma TNF-α is a significant risk factor for infection in PD patients.

Malnutrition is prevalent in hemodialysis (HD) patients, and the risk of mortality is strongly correlated with malnutrition. Current methods of nutritional evaluation are mostly subjective, time-consuming, and cumbersome. Creatinine index (CI) and geriatric nutritional risk index (GNRI) are very simple and objective methods to assess the nutritional status of HD patients. The present study compares the performance of CI and GNRI as nutritional risk assessment tools.Eighty-eight patients with end-stage renal disease on HD were recruited from a single tertiary center. A clinical dietitian carried out individual interviews of all patients and made nutritional diagnosis. Demographic and clinical data were also used to derive GNRI and CI over 4 months.Thirty-eight out of 88 patients (44%) were diagnosed with normal nutritional status. Twenty-two patients (25%) were diagnosed with severe malnutrition and 27 (31%) had moderate malnutrition. Compared with patients with severe malnutrition, the normal group and those with moderate malnutrition showed significantly higher levels of body mass index and GNRI. Even though GNRI was associated with CI, protein intake, uric acid, and normalized protein nitrogen were not significantly correlated with GNRI, whereas the markers were highly associated with CI (P = 0.000). GNRI enable the identification of the severe malnutrition group but not the normal and moderate-malnutrition groups. However, based on CI, the normal group was distinguished while those with severe and moderate malnutrition were not.Either CI or GNRI was a valid tool for longitudinal observation of nutritional status of patients on chronic HD and facilitated the screening of cases with malnutrition. Compared with GNRI, CI ranked higher in performance for the assessment and monitoring of nutritional status in HD patients.

Background Donor and recipient age in kidney transplantation are known to affect graft and patient survival. To address the question of whether the age difference between donor and recipient impacts on graft survival and death-censored graft survival after transplantation, we examined the impact of age matching (less than 10-year age difference) on the survivals after living donor kidney transplantation. Methods Two hundred one cases of the primary living donor kidney transplantation were performed and were divided into two groups, age-matched (n = 123) versus age-discrepant (n = 78). Variables included in this study were age, gender, body weight, height, kidney disease, type and duration of dialysis before transplantation, degree of human leukocyte antigen mismatch, ischemic time, graft weight, episode of rejection, type of immunosuppression, recipient serum creatinine after transplantation, and causes of patient death and graft loss. Results We observed the disparities of graft survival (P = .008) and death-censored graft survival (P = .003) between the groups. One-, 3-, and 5-year death-censored graft survival was 100%, 100%, and 97% in the age-matched group, respectively; and 97%, 90%, and 88% in the age-discrepant group, respectively. By Cox regression multivariate analysis, the variable of age-matching was an independent predictor for both graft survival (s = 1.325, P = .017) and death-censored graft survival (s = 2.217, P = .021). Conclusion During living donor and recipient matching, age difference between donor and recipient should be minimized.

Introduction The use of new selective immunosuppressants as well as the emergence of new antimicrobial resistances raise the use of prophylactic antibiotics as a matter of controversy. The purpose of this study was to retrospectively analyze the clinical significance of prophylactic antibiotics in kidney transplantation. Methods This retrospective study included 174 renal allograft recipients who were divided into two groups: group A including patients who received perioperative prophylactic antibiotics and group B, who did not receive them. We analyzed who the incidence of infectious complications as well as the causative micro-organisms and their antimicrobial resistance within 1 month after kidney transplantation. Results Overall bacterial infections were observed during the first postoperative month in 13 cases (7.4%): 6 (3.4%) surgical site 4 (2.3%) urinary tract, 2 (1.1%) bacteremic, and 1 (0.6%) central catheter infections. There was no respiratory infection. The incidence of bacterial infection was not significantly different between the two groups. The major micro-organisms isolated after kidney transplantation, were Staphylococcus aureus and Escherichia coli; both of which had already shown multidrug resistance at the initial time of infection. Conclusion Not only did use of prophylactic antibiotics have little impact to prevent bacterial infections after kidney transplantation, but also it may induce antimicrobial resistance against the antibiotics used for prophylaxis. Moreover, the increased antibiotic resistance prior to kidney transplantation hampers the effectiveness of prophylactic antimicrobial agents. Guidelines for perioperative antibiotic prophylaxis should be therefore revised.

Many studies have explored the participation of cytokines and their genes in renal allograft rejection by using biopsy tissues. To screen for rejection, a biopsy is too invasive to perform without a clinical clue. Therefore, we studied the expression of cytokines that contribute to the early phase of allograft rejection by analyzing mRNA transcripts in sequential blood samples of peripheral blood mononuclear cells (PBMCs) 120 of 6 among patients transplanted before diagnosis of rejection. for comparison with 6 control recipients. The relative expression amount of cytokine genes encoding interleukin (IL) 2, IL-4, IL-10, IL-15, and interferon-γ were assessed using real-time reverse-transcription polymerase chain reactions. IL-2, IL-4, and IL-15 mRNA expressions in clinically stable prerejection phase of the rejection group were significantly higher than those of the control group. In the prerejection samples, the expression of mRNA encoding IL-10 negatively correlated with the expressions of IL-2, IL-4, and IL-15 mRNAs, which were not different from the positive correlations in the postoperative samples from the control group. The expression patterns of IL-2, IL-4, IL-10, and IL-15 genes in PBMCs after transplantation may help to identify acute rejection episodes before clinical deterioration to monitor the efficacy of immunosuppressive treatment.

Background: Growth arrest and DNA damage-45γ (GADD-45γ) is induced in response to environmental stresses and functions in the regulation of cell cycles. Previous findings by our group suggested that GADD45γ contributed to renal tubular cell damage through induction of inflammatory and fibrogenic molecules. We examined the effects of urinary GADD45γ expression on the decline in renal function with IgA nephropathy in the present study. Methods: Patients (n = 62) were followed for a total of 710.3 ± 287.5 days. The rate of renal function decline was assessed by the slopes of inverse serum creatinine and estimated glomerular filtration rate (GFR) plotted against time. Renal survival was calculated by Kaplan-Meier analysis and the primary endpoint was an increase in serum creatinine levels by 50% or more. Results: Kidney function declined more rapidly in the GADD45γ-positive group compared to the GADD45γ-negative group. Kidney survival estimates at the end of the study period were 82.9% in the GADD45γ-positive group and 100% in the negative group (p = 0.03). This difference remained significant in the group with GFR values 2 when adjusted to stratification factors. Conclusion: The results suggest that urinary GADD45γ expression is associated with progression of renal disease.

Progressive nephropathies are characterized by the enhanced accumulation of extracellular matrix in the kidney. Overproduction of transforming growth factor-beta (TGF-beta) was shown to result in pathological tissue fibrosis through the accumulation of extracellular matrix proteins. It has been proposed that angiotensin II stimulates TGF-beta production. Despite accumulating data supporting the effects of angiotensin-converting enzyme (ACE) inhibitors on the attenuation of TGF-beta in vitro and in rats, such studies in humans are lacking. The present study sought to determine the effects of ACE inhibitors on TGF-beta1 in patients with glomerulonephritis. Using competitive polymerase chain reaction and the sandwich enzyme-linked immunosorbent assay, TGF-beta1 messenger RNA (mRNA) abundance and TGF-beta1 protein levels were measured. Patients with immunoglobulin A nephropathy administered ACE inhibitors showed significantly lower renal TGF-beta1 gene expression than patients not administered these medications (mean ratios of TGF-beta1/beta-actin, 4.27 +/- 0.62 [SEM] versus 14.81 +/- 3.87; P < 0.05), whereas no difference was noted between patients administered ACE inhibitors and healthy controls (4.27 +/- 0.62 versus 2.78 +/- 0.71). ACE inhibitor therapy did not affect TGF-beta1 mRNA expression in freshly isolated mononuclear cells. Urine and serum TGF-beta1 protein levels were not affected by the administration of ACE inhibitors. However, possibly a longer duration of treatment would decrease TGF-beta1 levels in urine or blood. In conclusion, we observed a significant reduction in TGF-beta1 expression in the kidney by ACE inhibitors, and this suggests that the effects of ACE inhibitors observed in animals can be extrapolated to patients with chronic renal disease.

Summary What is known and objective Angiotensin receptor blockers (ARBs) are medications commonly used for treating conditions such as hypertension. However, ARBs are frequently associated with hyperkalemia, a potentially critical adverse event, in high-risk patients. Although both the liver and the kidney are major elimination routes of ARBs, the relationship between hepatorenal function and ARB-related hyperkalemia has not yet been investigated. The purpose of this study was to evaluate the risk of hyperkalemia, in terms of various hepatorenal functions, for hospitalized patients newly initiated on ARB treatment. Methods We evaluated ARB-related hyperkalemia in a cohort of 5530 hospitalized patients, who had not previously used ARBs, between 12 April 2004 and 31 May 2012. Hepatorenal function was assessed by the Model for End-stage Liver Disease (MELD) score. Hyperkalemia risk was assessed by hepatorenal function, risks were categorized into the four MELD scoring groups, and the groups were compared with one another. Results and discussion The MELD score was significantly different between the hyperkalemic and non-hyperkalemic groups (independent t-test, P

Summary What is known and objective Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high-risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy. Methods We carried out a retrospective analysis to determine the onset time of hyperkalaemia (serum potassium >5·5 mm) among hospitalized patients newly starting ARB therapy between 2004 and 2012, in a tertiary teaching hospital. Predefined possible risk factors and concomitant medications were evaluated. Results and discussion During the 97-month study period, a total of 4267 hospitalized patients started ARBs as new drugs and 225 patients showed hyperkalaemia. A significantly increased risk of hyperkalaemia was detected among patients with a high baseline potassium [odds ratio (OR) 6·0] and those who took non-potassium-sparing diuretics (OR 2·2) or potassium supplements (OR 1·6). A high glomerular filtration rate (GFR) was associated with a lower risk of hyperkalaemia (OR 0·992). Fifty-two percentage of hyperkalaemic events occurred within the first week after initiation of ARB therapy. The highest frequency of hyperkalaemia occurred on the first day after initiation of ARBs. Hyperkalaemia occurred earlier in patients with a high baseline serum potassium level, reduced GFR, diabetes and in those without heart failure. What is new and conclusion Hyperkalaemia occurs most frequently at the beginning of ARB therapy in hospitalized patients. Monitoring of serum potassium and estimated GFR after initiation of ARBs should be started within a few days or not later than 1 week, especially in patients with risk factors.

Long-term effects of donor and recipient gender on the outcome of living donor kidney transplantation have been examined but the impact on early graft function is less certain. In this study, we analyzed age, gender, body weight, height, body surface area (BSA), and lean body weight (LBW) of both donors and recipients. Preoperatively we collected 24-hour urine samples to measure creatinine excretion from donor and postoperatively we determined when the recipient serum creatinine (Scr) reached baseline levels. Variables included were ischemic times, kidney graft weight, duration of dialysis, cause of end-stage renal disease (ESRD), degree of HLA match, and mismatch, types of immunosuppression (cyclosporine or FK506, dual or triple), and episodes of acute rejection. The variables were analyzed by independent sample t tests and chi-square statistics using SPSS. Values of P < .05 were considered significant. Male patients of both donors and recipients were significantly taller and heavier (higher BSA and LBW) than female. Urinary 24-hour creatinine excretion was greater in male patients whether donors or recipients. There were no statistical differences in graft weight or creatinine clearance based on the gender of the donor or recipient. The creatinine of male donors or recipients was higher than that of females. The other variables were not significantly different. In conclusion, the effect of donor or recipient gender on early graft function depends on the metabolic demands, which are higher in male recipients.

Infection or colonisation with vancomycin-resistant enterococci (VRE) is common in chronic haemodialysis (HD) patients. However, there is limited information on the duration of VRE colonisation or on the reliability of consecutive negative rectal cultures to determine the clearance of VRE in chronic HD patients. Chronic HD patients from whom VRE was isolated were examined retrospectively. Rectal cultures were collected more than three times, at least one week apart, between 1 June 2003 and 1 March 2010. The results of the sequential VRE cultures and patients' data were analysed. Among 812 patients from whom VRE was isolated, 89 were chronic HD patients and 92 had three consecutive negative cultures. It took 60.7 ± 183.9 and 111.4 ± 155.4 days to collect three consecutive negative cultures in the 83 non-chronic haemodialysis patients and nine chronic HD patients, respectively (P = 0.011). The independent risk factors for more than three negative sequential rectal cultures were glycopeptide usage [odds ratio (OR): 2.155; P = 0.003] and length of hospital stay (OR: 1.009; P = 0.001). After three consecutive negative rectal cultures, two of six chronic HD patients and 10 of 36 non-HD patients were culture positive again. In conclusion, a significant proportion of patients colonised with VRE cannot be detected by three-weekly rectal cultures, and the duration of VRE colonisation in chronic haemodialysis patients tends to be prolonged. These results may be contributing to the continued increase in the prevalence of VRE.

This is the first reported case of Nocardia niigatensis infection in an adult kidney transplant recipient. A 57-year-old Asian woman presented with multiple cutaneous abscesses and rapidly growing fungating mass on the left pretibial area for 2 months. She received a cadaveric kidney transplant 4 years previously and was undergoing immunosuppression with prednisolone, cyclosporine and mycophenolate sodium. The microbiological diagnosis was established by isolation of Nocardia from the purulent material expressed from a granule. The strain was identified to the species level by 16S rRNA gene-targeted PCR. The closest match was with N. niigatensis. Antibiotic treatment (trimethotrim-sulfamethoxazole) was continued for 6 months and the skin lesions improved.

In living donor kidney transplantation, initial function of the donor kidneys is split into the remnant kidney and the recipient's implanted kidney. We addressed the questions whether the donor's remnant kidney function increases or decreases after donation and whether the donor's donated kidney is greater or less than that of the recipient's implanted kidney after transplantation. We measured and calculated the functional ratio of each kidney using technetium-99m diethylenetriaminepentaacetic acid (99mTcDTPA) as well as serum creatinine (Scr; mg/dL) and creatinine clearance (Ccr; mL/min/1.73 m2) using 24-hour urines from 100 donors. The Ccr was also calculated using the Cockcroft-Gault formula (Ccr-CG; mL/min/1.73 m2). Within 7 days postnephrectomy, we measured Scr, Ccr, and Ccr-CG of the remnant kidney. For recipients, the Scr, Ccr, and Ccr-CG of the implanted kidney with 24-hour urine were obtained within 7 days posttransplantation. The average Scr, Ccr, and Ccr-CG of the donors were 0.85 +/- 0.17 mg/dL, 110.4 +/- 20.8 mL/min/1.73 m2, and 82.8 +/- 17.3 mL/min/1.73 m2, respectively. After donation, the Ccr and Ccr-CG of remnant kidney increased from 54.5 +/- 11.4 and 40.8 +/- 9.3 mL/min/1.73 m2 to 68.0 +/- 14.3 and 53.6 +/- 11.6 mL/min/1.73 m2, respectively. The recipient Ccr and Ccr-CG of donated kidney also increased from 55.9 +/- 11.8 and 42.0 +/- 9.9 mL/min/1.73 m2 to 78.4 +/- 18.0 and 53.4 +/- 16.4 mL/min/1.73 m2, respectively. Kidney transplantation from a living donor should be encouraged with total functional benefit for both donors and recipients.

About 6% to 9% of cases of membranous nephropathy develop secondary to exposure to drugs. Fluconazole is a widely used antifungal agent that was never implicated in the development of membranous nephropathy. We report the case of a patient found to have membranous nephropathy secondary to fluconazole treatment. This patient had recurrent episodes of nephrotic syndrome caused by readministration of fluconazole. This is the first reported case of membranous nephropathy caused by fluconazole treatment and the first case report of the clinical course of recurrent membranous nephropathy caused by reexposure to this medication.

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

This study was to investigate clinical characteristics and any differential trends in survival among renal replacement therapy (hemodialysis [HD], peritoneal dialysis [PD], and kidney transplantation [KT]) in Korean end-stage renal disease (ESRD) population. We tried to analyze retrospectively the survival rate adjusted by risk factors and the relative risk stratified by key risk factors among 447 ESRD patients who began dialysis or had a kidney transplant at Ajou University Hospital from 1994 to 2004. In adjusted Cox survival curves, the KT patients had the best survival rate, and the HD patients had better survival than PD patients. The consistent trends in different subgroups stratified by age and diabetes were as following: 1) The risk of death for PD and HD was not proportional over time, 2) The relative risk of PD was similar or lower than that of HD for the first 12 months, but it became higher at later period. The significant predictors for mortality were age (over 55 yr), presence of diabetes, cerebrovascular accident at ESRD onset, and more than one time of hospitalization caused by malnutrition. Further large-scaled, multicenter-based comparative study is needed in Korean ESRD patients and more meticulous attention is required in high-risk patients.