Search

IntroductionTacrolimus (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.MethodsIn 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 TAC-C0, 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 TAC-C0 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.ResultsThe 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.DiscussionHigh 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.

Oxidative stress is one of the principal causes of hypoxia-induced kidney injury. The ceria nanoparticle (CNP) is known to exhibit free radical scavenger and catalytic activities. When zirconia is attached to CNPs (CZNPs), the ceria atom tends to remain in a Ce3+ form and its efficacy as a free radical scavenger thus increases. We determined the effectiveness of CNP and CZNP antioxidant activities against hypoxia-induced acute kidney injury (AKI) and observed that these nanoparticles suppress the apoptosis of hypoxic HK-2 cells by restoring autophagy flux and alleviating mitochondrial damage. In vivo experiments revealed that CZNPs effectively attenuate hypoxia-induced AKI by preserving renal structures and glomerulus function. These nanoparticles can successfully diffuse into HK-2 cells and effectively counteract reactive oxygen species (ROS) to block hypoxia-induced AKI. This suggests that these particles represent a novel approach to controlling this condition.

BACKGROUND Hypernatremia is associated with poor outcomes in critically ill patients, and an accurate assessment of water volume is important to determine appropriate fluid hydration. Bioelectrical impedance analysis (BIA) is a new, noninvasive, and relatively easy method for measuring hydration status. This study aimed to investigate whether bioelectrical impedance measurements of body water could reduce the frequency of blood sampling for fluid replacement in patients with hypernatremia. MATERIAL AND METHODS Fifty-one hospitalized patients were studied with hypernatremia, defined as a serum sodium ≥150 mmol/L determined by laboratory testing. Laboratory and BIA measurements were compared, and water deficiency was calculated with a conventional formula (sodium-corrected Watson formula) and measured by BIA. RESULTS The value of the absolute fluid overload (AFO) equivalent to the overhydration (OH) value, determined using BIA, did not accurately represent water deficit in patients with hypernatremia (r=0.137, P=0.347). Although the total body water (TBW) measured by BIA showed a significant correlation with that determined by the conventional formula (r=0.861, P

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.

Backgound: This study evaluated whether the hydration status affected health-related quality of life (HRQOL) during 12 months in peritoneal dialysis (PD) patients. Methods: The hydration status and the HRQOL were examined at baseline and after 12 months using a bioimpedance spectroscopy and Kidney Disease Quality of Life-Short Form, respectively in PD patients. Four hundred eighty-one patients were included and divided according to the baseline overhydration (OH) value; normohydration group (NH group, -2L≤ OH ≤+2L, n=266) and overhydration group (OH group, OH >+2L, n=215). Baseline HRQOL scores were compared between the two groups. The subjects were re-stratified into quartiles according to the OH difference (OH value at baseline - OH value at 12 months

Background Amyloidosis is a very rare disease that is difficult to diagnose because of the unspecific early clinical manifestations of the disease. Accurate and early diagnosis is extremely important because the effect of treatment is dependent on the extent of disease progression. Sicca syndrome and nail dystrophy are very rare symptoms of amyloidosis. We report here a case of sicca syndrome and nail dystrophy with renal dysfunction in a 52-year-old Korean woman who was diagnosed as having systemic amyloidosis. Case presentation We present the case of a 52-year-old Korean woman complaining of dry mouth and nail dystrophy for 4 months as an initial symptom. A slit lamp examination revealed superficial keratoconjunctival erosion in both eyes. A laboratory test showed anemia, azotemia, and proteinuria. Urine protein electrophoresis showed increased gamma globulin excretion. Serum free light chain of kappa and lambda were increased. Histopathological studies of biopsy specimens of minor salivary glands and kidney revealed deposits of amyloid fibrils. A bone marrow aspiration biopsy showed hypercellular marrow with 5% plasma cells. She was diagnosed as having primary systemic amyloidosis then started on chemotherapy. Conclusion Such atypical mucocutaneous manifestations of amyloidosis can serve as important early diagnostic signs with less invasive biopsy confirmation in patients with systemic amyloidosis.

Hypoxia is an important cause of acute kidney injury (AKI) in various conditions because kidneys are one of the most susceptible organs to hypoxia. In this study, we investigated whether nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidase 4 (Nox4) plays a role in hypoxia induced AKI in a cellular and animal model. Expression of Nox4 in cultured human renal proximal tubular epithelial cells (HK-2) was significantly increased by hypoxic stimulation. TGF-β1 was endogenously secreted by hypoxic HK-2 cells. SB4315432 (a TGF-β1 receptor I inhibitor) significantly inhibited Nox4 expression in HK-2 cells through the Smad-dependent cell signaling pathway. Silencing of Nox4 using Nox4 siRNA and pharmacologic inhibition with GKT137831 (a specific Nox1/4 inhibitor) reduced the production of ROS and attenuated the apoptotic pathway. In addition, knockdown of Nox4 increased cell survival in hypoxic HK-2 cells and pretreatment with GKT137831 reproduce these results. This study demonstrates that hypoxia induces HK-2 cell apoptosis through a signaling pathway involving TGF-β1 via Smad pathway induction of Nox4-dependent ROS generation. In an ischemia/reperfusion rat model, pretreatment of GKT137831 attenuated ischemia/reperfusion induced acute kidney injury as indicated by preserved kidney function, attenuated renal structural damage and reduced apoptotic cells. Therapies targeting Nox4 may be effective against hypoxia-induced AKI.

Although erythropoietin (EPO)-related pure red-cell aplasia (PRCA) is a rare disorder, attention still needs to be paid because underline mechanism of EPO immunogenicity is various and controversial. Among several assay systems for screening of anti-EPO binding antibodies (Abs), we adopted and setup the bridging ELISA using streptavidin-coated plate. To test their neutralizing activities, cell-based neutralizing (NT) bioassay was setup. When we analyzed serum samples by using these two assays, we found two positive results in the two samples. In the sample 1, 411.9 ng/ml of anti-EPO Abs were found and neutralizing activity of 36.2% at 1:5 serum dilution was detected. In the sample 2, 40.5 ng/ml of anti-EPO Abs were found and neutralizing activity of 96.7% was detected. Our results indicate that the higher anti-EPO antibody (Ab) level in a serum does not always lead to the stronger neutralizing activity. This report gives crucial consideration to the needs of establishing clear criteria to link various assay parameters with the onset of PRCA and its progression.

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.

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 enrollment 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.

Background In recent years, laboratory and clinical research has suggested the need for peritoneal dialysis fluids (PDFs) that are more biocompatible than the conventional PDFs commonly used today. Bioincompatibility of PDF has been attributed to low pH, lactate, glucose, glucose degradation products (GDPs), and osmolality. PDFs with neutral pH and low GDPs are now available commercially. In vitro and early clinical studies suggest that these solutions are indeed more biocompatible but, as of now, there is no evidence that their use improves patient outcome. Methods Using a dedicated database of over 2000 patients treated with PD in Korea, we were able to conduct a retrospective observational study comparing outcomes for incident continuous ambulatory PD patients treated with a standard, conventional, heat-sterilized PDF to the outcomes for patients treated with a novel, low GDP, neutral-pH PDF prepared in a dual-compartment, double-bag PD system (Balance; Fresenius Medical Care, St. Wendel, Germany). In an intention-to-treat analysis, patient and technique survival, peritonitis-free survival, and peritonitis rates were compared in 611 patients treated with Balance for up to 30 months and 551 patients with a standard PDF (stay·safe; Fresenius Medical Care) treated in the same era and with equivalent follow-up. Results The patients were well matched for most relevant characteristics except older age distribution for the patients treated with the standard PDF. Patients treated with Balance had significantly superior survival compared to those treated with the standard PDF (74% vs 62% at 28 months, p = 0.0032). In a multivariate Cox regression model including age, diabetes, and gender, the survival advantage persisted (relative risk of death for Balance 0.75, 95% confidence interval 0.56 – 0.99, p = 0.0465). Modality technique survival was similar in Kaplan–Meier analysis for both PDFs. No differences were detected in peritonitis-free survival or in peritonitis rates between the two solutions. Conclusion This study, for the first time, suggests that treatment with a novel biocompatible PDF with low GDP concentration and neutral pH confers a significant survival advantage. The exact mechanisms for such a survival advantage cannot be determined from this study. The usual criticisms of observational studies apply and the results reported here strongly warrant the undertaking of appropriately designed, randomized, controlled clinical trials.

Contrast-induced acute kidney injury (CIAKI) is a leading cause of acute kidney injury following radiographic procedures. Intrarenal oxidative stress plays a critical role in CIAKI. Nicotinamide adenine dinucleotide 3-phosphate (NADPH) oxidases (Noxs) are important sources of reactive oxygen species (ROS). Among the various types of Noxs, Nox4 is expressed predominantly in the kidney in rodents. Here, we evaluated the role of Nox4 and benefit of Nox4 inhibition on CIAKI using in vivo and in vitro models. HK-2 cells were treated with iohexol, with or without Nox4 knockdown, or the most specific Nox1/4 inhibitor (GKT137831). Effects of Nox4 inhibition on CIAKI mice were examined. Expression of Nox4 in HK-2 cells was significantly increased following iohexol exposure. Silencing of Nox4 rescued the production of ROS, downregulated pro-inflammatory markers (particularly phospho-p38) implicated in CIAKI, and reduced Bax and caspase 3/7 activity, which resulted in increased cellular survival in iohexol-treated HK-2 cells. Pretreatment with GKT137831 replicated these effects by decreasing levels of phospho-p38. In a CIAKI mouse model, even though the improvement of plasma blood urea nitrogen was unclear, pretreatment with GKT137831 resulted in preserved structure, reduced expression of 8-hydroxy-2’-deoxyguanosine (8OHdG) and kidney injury molecule-1 (KIM-1), and reduced number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling)-positive cells. These results suggest Nox4 as a key source of reactive oxygen species responsible for CIAKI and provide a novel potential option for prevention of CIAKI.

Background/aims Gastroesophageal reflux disease (GERD) is a common upper gastrointestinal disorder in patients with chronic kidney disease (CKD). However, little is known about the prevalence of GERD in dialysis patients. The aim of the present study was to investigate the difference in the prevalence of GERD in peritoneal dialysis and hemodialysis patients. Methods From July 2010 to August 2011, peritoneal dialysis patients (n=30) and hemodialysis patients (n=38) were enrolled. The prevalences of GERD were assessed at a single center with endoscopic findings and interviews using a questionnaire. Also, risk factors of GERD were evaluated. Results The prevalences of GERD in peritoneal dialysis and hemodialysis patients were 33.3% and 39.5% (p=0.748), respectively. The prevalences of erosive reflux esophagitis (ERD) in peritoneal dialysis and hemodialysis patients were 16.7% and 23.7% (p=0.477), respectively. The prevalences of nonerosive reflux disease (NERD) in peritoneal dialysis and hemodialysis patients were 16.7% and 13.2% (p=0.685), respectively. The prevalences of GERD, ERD and NERD were higher than those of the general population. The risk factor for GERD was age in hemodialysis patients. Conclusions The prevalence of GERD in dialysis patients was higher than that in the general population. However, there was no significant difference between peritoneal dialysis and hemodialysis patients.

Henoch-Schönlein purpura (HSP) is a vasculitis involving small vessels of skin, joints, gastrointestinal (GI) tract, and kidneys. The patients typically show palpable purpura with one or more characteristic manifestations including abdominal pain, hematuria or arthritis. HSP shows gastrointestinal symptoms in 50~85% of patients, and in 14~40% of patients GI symptoms precede purpuric rash which makes the diagnosis of HSP difficult. We present a case of Henoch-Schonlein purpura with GI bleeding, septic shock by ileal microperforation, small bowel obstruction as a result of ileal stricture and psoas muscle abscess.

Background/Aims: The aim of this study was to evaluate the peritonitis-causing bacteria detected in peritoneal fluid using a blood culture bottle in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Methods: One-hundred and eleven dialysates from 43 patients suspected of peritonitis related to CAPD were retrospectively evaluated between May 2000 and February 2008. In all cases, 5 to 10 mL of dialysate was inoculated into a pair of BacT/Alert blood culture bottles, and 50 mL of centrifuged dialysate was simultaneously inoculated into a solid culture media for conventional culture. The results were compared to those of the conventional culture method. Isolated microorganisms were compared between the two methods. Results: The blood culture method was positive in 78.6% (88 / 112) of dialysate specimens and the conventional culture method in 50% (56 / 112, p < 0.001). Conclusions: The blood culture method using the BacT/Alert system is useful for culturing dialysates and improves the positive culture rate in patients with suspected peritonitis compared to the conventional culture method. (Korean J Intern Med 2010;25:82-85)

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.