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Introduction: Tacrolimus (TAC) has been widely used as an immunosuppressant after kidney transplantation (KT); however, the combined effects of intra-patient variability (IPV) and inter-patient variability of TAC-trough level (C0) in blood remain controversial. This study aimed to determine the combined impact of TAC-IPV and TAC inter-patient variability on allograft outcomes of KT. Methods: In total, 1,080 immunologically low-risk patients who were not sensitized to donor human leukocyte antigen (HLA) were enrolled. TAC-IPV was calculated using the time-weighted coefficient variation (TWCV) of TACC0, and values > 30% were classified as high IPV. Concentration-to-dose ratio (CDR) was used for calculating TAC inter-patient variability, and CDR < 1.05 ng*mg/mL was classified as rapid metabolizers (RM). TWCV was calculated based on TAC-C0 up to 1 year after KT, and CDR was calculated based on TACC0 up to 3 months after KT. Patients were classified into four groups according to TWCV and CDR: low IPV/non-rapid metabolizer (NRM), high IPV/NRM, low IPV/RM, and high IPV/RM. Subgroup analysis was performed for pre-transplant panel reactive antibody (PRA)-positive and -negative patients (presence or absence of non-donor-specific HLA-antibodies). Allograft outcomes, including deathcensored graft loss (DCGL) and biopsy-proven allograft rejection (BPAR), were compared. Results: The incidences of DCGL, BPAR, and overall graft loss were the highest in the high-IPV/RM group. In addition, a high IPV/RM was identified as an independent risk factor for DCGL. The hazard ratio of high IPV/RM for DCGL and the incidence of active antibody-mediated rejection were considerably increased in the PRA-positive subgroup. Discussion: High IPV combined with RM (inter-patient variability) was closely related to adverse allograft outcomes, and hence, more attention must be given to pre-transplant PRA-positive patients. [ABSTRACT FROM AUTHOR]

Background: Colistin (polymyxin E) is an important constituent of the polymyxin class of cationic polypeptide antibiotics. Intrarenal oxidative stress can contribute to colistin-induced nephrotoxicity. Nicotinamide adenine dinucleotide 3-phosphate oxidases (Noxs) are important sources of reactive oxygen species. Among the various types of Noxs, Nox4 is predominantly expressed in the kidney. Objectives: We investigated the role of Nox4 and benefit of Nox4 inhibition in colistin-induced acute kidney injury using in vivo and in vitro models. Methods: Human proximal tubular epithelial (HK-2) cells were treated with colistin with or without NOX4 knockdown, or GKT137831 (most specific Nox1/4 inhibitor). Effects of Nox4 inhibition on colistin-induced acute kidney injury model in Sprague-Dawley rats were examined. Results: Nox4 expression in HK-2 cells significantly increased following colistin exposure. SB4315432 (transforming growth factor-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells. Knockdown of NOX4 transcription reduced reactive oxygen species production, lowered the levels of pro-inflammatory markers (notably mitogen-activated protein kinases) implicated in colistin-induced nephrotoxicity and attenuated apoptosis by altering Bax and caspase 3/7 activity. Pretreatment with GKT137831 replicated these effects mediated by downregulation of mitogen-activated protein kinase activities. In a rat colistin-induced acute kidney injury model, administration of GKT137831 resulted in attenuated colistin-induced acute kidney injury as indicated by attenuated impairment of glomerulus function, preserved renal structures, reduced expression of 8-hydroxyguanosine and fewer apoptotic cells. Conclusions: Collectively, these findings identify Nox4 as a key source of reactive oxygen species responsible for kidney injury in colistin-induced nephrotoxicity and highlight a novel potential way to treat drug-related nephrotoxicity. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy is the most frequent cause of end-stage renal disease worldwide. Dialysis patients with diabetes mellitus (DM) have more complications and shorter survival duration than non-DM dialysis patients, requiring more clinical attention and difficult management. The registry committee of the Korean Society of Nephrology has collected data about dialysis therapy in Korea through an on-line registry program and analyzed the characteristics of patients. A survey of dialysis patients in 2016 showed that 50.2% of new dialysis patients had DM nephropathy as the cause of end-stage renal disease. The proportion of patients receiving hemodialysis (HD) for more than 5 years was 38% in DM patients and 51% in non-DM patients. The mean pulse pressure in DM HD patients was 71.5 mmHg, compared with 62.6 mmHg in non-DM patients. The proportion of DM patients with native vessel arteriovenous fistula as vascular access for HD was lower than that of non-DM patients (73% vs. 78%). Mean serum creatinine of DM and non-DM dialysis patients was 8.4 mg/dL and 9.5 mg/dL respectively. As vascular access of the DM HD patients was poor, the dialysis adequacy of DM patients was slightly lower than that of non- DM patients. The 5-year survival rate for DM HD patients was 53.9%, which was much lower than that of chronic glomerulonephritis patients (78.2%). The proportion of patients with a full-time job was 17% for DM patients and 28% for non-DM patients. [ABSTRACT FROM AUTHOR]

Gitelman syndrome is characterized by hypokalemia, metabolic alkalosis, hypocalciuria, and hypomagnesemia. The clinical course of Gitelman syndrome in pregnant women remains unclear, but it is thought to be benign. We report here the first Korean case of atypical eclampsia in a 31-year-old who was diagnosed with Gitelman syndrome incidentally during an antenatal screening test. The patient did well during pregnancy despite significant hypokalemia. At 33 weeks' gestation, the patient exhibited eclampsia, hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome, and renal insufficiency without significant hypertension or proteinuria. We explain this unusual clinical course through a review of the relevant literature. [ABSTRACT FROM AUTHOR]

Introduction: Thromboangiitis obliterans or Buerger's disease is a nonatherosclerotic, segmental, inflammatory vasculitis that is strongly associated with tobacco products and commonly affects the small- and medium-sized arteries of the upper and lower extremities. However, the disease can, rarely, involve large central or visceral arteries. We report here the case of end stage renal disease due to renal artery thrombosis caused by thromboangiitis obliterans. Case presentation: A 51-year-old Korean man who had previously required amputation of both great toes due to thromboangiitis obliterans presented with left flank pain and oliguria. Both his renal arteries were occluded on contrast-enhanced abdominal computed tomography and abdominal angiography. He also had abdominal angina. He had no risk factor of thromboembolism from cardiac origin, atherosclerosis except for tobacco abuse, collagen diseases or hypercoagulable disorders. Renal failure and mesenteric ischemia associated with thromboangiitis obliterans progression was diagnosed. Conclusions: Renal failure due to renal artery thrombosis and mesenteric ischemia represents an unusual manifestation of thromboangiitis obliterans. But once it occurs, it can be life-threatening. When we care for a patient with thromboangiitis obliterans, we should pay attention to this rare disease course, and encourage cessation of the smoking of tobacco products. [ABSTRACT FROM AUTHOR]

A range of infections including cytomegalovirus (CMV) infections are associated with IgA nephropathy. Several reports have suggested that the risk of Pneumocystis infections is lower in the presence of preceding immunomodulating infections, such as a CMV infection. We report a patient with Pneumocystisjiroveci pneumon (PJP) in CMV-associated IgA nephropathy, who was treated with trimethoprim sulfamethoxazole and gancyclovir. A 52 year old man suffered from fever, chill an dyspnea for 2 days. He has taken low dose immunosuppressants (prednisolone, cyclophosphamide) for 3 months due to IgA nephropathy. PJP was confirmed by Chest CT and P.jiroveci PCR was performed from a bronchoalveolar lavage. H CMV serology was CMV-lgM/IgG(-/+) and CMV PCR (+), and his urine CMV culture was positive. The patient recovered completely from pneumonia after administerin oral trimethoprim/sulfamethoxazole and intravenous ganciclovir, and his renal function and proteinuria improved. [ABSTRACT FROM AUTHOR]

Background: Various studies have indicated that malnutrition and chronic inflammation are strong predictors of morbidity and mortality in patients with chronic kidney disease (CKD). The purpose of this study was to investigate the relationship between pulmonary function, malnutrition and chronic inflammation in patients with CKD. Methods: One hundred and six consenting patients with CKD were enrolled in the study between 2005 and 2007. Pulmonary function was assessed by forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF), expressed as the normal percentage of predicted values (%FEV1, %FVC and %PEF, respectively). Nutritional status was evaluated by skeletal muscle index (SMI), subjective global nutritional assessment (SGA), lean body mass, body mass index and serum albumin. Inflammation was assessed by the serum measurement of high-sensitive C reactive protein (hsCRP) levels. Results: Malnutrition (defined as SMI ≥1) and inflammation (defined as hsCRP >2 mg/l) in ESRD patients had significant negative associations with percentage predicted values for pulmonary function tests except %PEF (SMI: %FEV1, p = 0.009, %FVC, p = 0.001; hsCRP: %FEV1, p = 0.025, %FVC, p = 0.022). Multivariate Cox analysis showed that the ejection fraction in echocardiography and SGA were associated with poor survival, but there was no association for %FEV1. Conclusions: Impaired pulmonary function was associated with malnutrition and inflammation in these dialysis patients. We were not able to determine a significant relationship between pulmonary function and mortality. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Novel, biocompatible peritoneal dialysis (PD) solutions have become available in recent years. In 2001, low glucose degradation products (GDP), neutral pH solutions became commercially available in Korea. To date, there are no reports regarding the large scale adoption of these solutions in clinical practice and regarding what, if any, impact these solutions have on patient outcomes.Methods. Using a database of almost 4000 patients treated by PD in Korea, we conducted a prospective, longitudinal observational study documenting the patterns of use of one novel low GDP solution (balance®, Fresenius Medical Care, St Wendel, Germany) in 1909 PD incident patients between 1 January 2002 and midyear 2005. Outcomes including patient and technique survival and peritonitis rates were analysed using univariate and multivariate analysis.Results. Prescription of low GDP solutions reached between 70 and 80% by the year 2003 and persisted at this level. Patients prescribed low GDP PD solution tended to be younger and were more likely to be treated in centres with larger enrolment in the database. Survival of diabetic patients treated with the new PD solution was identical to that of the non-diabetic patients treated with standard PD fluids (PDF) and treatment with low GDP PDF independently reduced the relative risk (RR) of death (RR = 0.613; CI 0.50–0.74; P < 0.00001) in a proportional hazards model which included age, diabetes and centre experience. In a univariate analysis, low GDP PD solution was associated with a longer technique survival (P = 0.049) but this effect was not significant in multivariate analysis. No significant differences in peritonitis-free interval or peritonitis rate could be attributed to the prescribed PDF.Conclusion. Prescription of low GDP, pH-neutral PD solutions has rapidly increased in Korea. This change has resulted in a significant improvement in patient and technique survival without any measurable change in peritonitis incidence or rate. Reasons for the improved patient survival cannot be determined from this analysis and require further study. [ABSTRACT FROM AUTHOR]

It is possible to observe improvement in the general state of patients receiving maintenance hemodialysis, including decreased joint symptoms, decreased pruritus, and better appetite, by using a high-efficiency, high-flux dialysis membrane. We aimed to determine the effects of the use of a high-flux dialysis membrane on improvement in the nutritional status of dialysis patients. Two months before the replacement with a high-efficiency, high-flux dialysis membrane and one, three, six, and twelve months after the replacement, the subjective global assessment (SGA), biochemical markers, and a Body Composition Analyzer was used to assess the nutritional status and determine hemodialysis adequacy, along with a biochemical test, in 25 stable patients (M: F=10:15, 54.5±12.7 (37∼80) yrs). Of all the patients, 3 got better results from SGA, 12 the same results, and 10 worse results, in the follow-up period. There was no significant increase or decrease after the replacement with a high-flux dialysis membrane in biochemical parameters and nutritional parameters. While there was also no improvement in body weight, fat mass, muscle mass, lean fat mass, visceral fat, or the degree of edema measured by the body composition analyzer after the replacement, basal metabolism was improved from 1179.2±143.5kcal before the replacement to 1264.8±145.4, 1241±138.3, and 1201.0±317.0 kcal one, three, twelve months after the replacement, respectively, on the average (p<0.001, p=0.001, p=0.023); thus, the improvement was greatest one month after the replacement and, then, decreased over time. In conclusion, the use of a high-efficiency, high-flux dialysis membrane generally failed to improve the nutritional status of patients receiving maintenance hemodialysis but increased the indirect index of basal metabolism alone at its early stage. [ABSTRACT FROM AUTHOR]