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BACKGROUND Optimal estimated glomerular filtration rate (eGFR) to start maintenance dialysis is controversial. Observational studies have reported that initiation of dialysis at high eGFRs is associated with worse postdialysis survival. METHODS We retrospectively investigated 1,038 incident dialysis patients who started maintenance dialysis during 2010-2015. Patients were assessed for comorbidities and adverse events during the transitional period of dialysis initiation. Patients were classified as planned dialysis (PD) vs. unplanned dialysis (UD) according to indications for dialysis initiation. RESULTS UD group comprised 352 patients (33.9%). Mean eGFR at dialysis initiation was higher in UD patients than PD patients (7.9 ± 5.1 vs. 5.9 ± 3.4 mL/min/1.73 m2, p < 0.001). Mean Davies comorbidity index in the UD group was higher (vs. PD group, 1.3 ± 1.0 vs. 0.9 ± 1.0, p < 0.001). Patients with more comorbidities experienced more ischemic heart disease (hazard ratio [HR], 4.36; 95% confidence interval [CI], 1.71-11.14) in the medium-risk group and HR of 8.84 (95% CI, 3.06-25.55) in the high-risk group (vs. low-risk group, p < 0.001)) during the predialysis period. High-risk group had increased postdialysis mortality (HR, 2.48; 95% CI, 1.46-4.20; p = 0.001). Adjusted HR of mortality was higher in the medium-risk group of UD patients (HR, 1.72; 95% CI, 1.16-2.56; p = 0.007). CONCLUSION Patients with more comorbidities were at increased risk of predialysis ischemic heart disease and postdialysis mortality. UD patients in the medium-risk population had increased risk of postdialysis mortality. Dialysis start should be individualized by considering comorbidities.

Multiple endocrine neoplasia type 1 (MEN 1) is an autosomal dominant disorder characterized by two or more tumors of the parathyroid gland, duodenum-pancreas, and anterior pituitary. Membranous nephropathy is the most common manifestation of paraneoplastic glomerulopathy. However, minimal change disease in patients with MEN 1 has yet to be reported. Here, we report a case of minimal change disease in a 59-year-old man with MEN 1, along with a review of the relevant literature.

Background: Patients undergoing hemodialysis are susceptible to sarcopenia. As intracellular reservoirs of water, skeletal muscles are important contributors to intradialytic hypotension. This study was designed to determine the role of skeletal muscle mass in intradialytic hypotension. Methods: In a cross-sectional study, the body composition of 177 patients was measured immediately after hemodialysis using bioelectrical impedance analysis. The parameters measured were skeletal muscle mass, intracellular and extracellular water contents, total body water, and cell-membrane functionality (in phase angle at 50 kHz). Data from laboratory tests, chest radiography, measurements of handgrip strength and mid-arm circumference, and questionnaires were collected. The main outcome was intradialytic hypotension, defined as more than two episodes of hypotension (systolic blood pressure of

저자들은 다른 증상 없이 지속적인 현미경적 미세혈뇨만 관찰되어 시행한 신장 전산화단층촬영에서 발견된 뒤 호두까기 증후군 증례를 문헌고찰과 함께 보고하는 바이다. 대부분 증례의 경우 복통이나 단백뇨 또는 육안적 혈뇨 등 다양한 증상을 동반하고 있었지만 이 증례는 증상 없이 우연히 발견되었다는 점이 주목할 만하다고 생각된다. 이러한 특징으로 인하여 아직까지 명확한 진단 기준, 발생 기전, 예후 및 치료에 대하여 밝혀지지 않은 것이 많아 추후 지속적인 연구 및 추적 관찰이 필요하다.

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.

Additional file 1. Clinical outcomes and TBS according to medication use (PPI or warfarin).

Introduction 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. Methods 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. Findings 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. Discussion 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.

본 증례는 cGVHD가 있는 환자에서 발생하는 신부전증과는 다르게 acute GVHD로 면역억제제를 투여하고 있는 도중 다른 증상 없이 신증후군 수준의 단백뇨가 발생되어 신조직 검사 후 막성 신장병이 진단되었고, 이후 효과적으로 치료된 결과를 문헌고찰과 함께 보고하는 바이다. 이를 통해 allo-PBSCT 시행한 뒤 증상 없이 단백뇨가 발생한 환자에게는 cGVHD로 유발되는 사구체 질환을 감별 진단에 두고 검사 및 치료를 고려하여야 하겠다.

Background Plasmapheresis has become an essential element of kidney transplantation (KT). In the present study, we report clinical outcomes of filtration plasmapheresis using continuous renal replacement therapy machines with a single filter for the first time in Korea. Methods We retrospectively analyzed six patients who underwent filtration plasmapheresis for KT in our center; plasmapheresis was performed using the Plasmaflex (Baxter®) with a TPE 2000 filter set (Baxter®) in our hemodialysis unit. Five percent albumin was used as the replacement fluid, and intravenous immunoglobulin G was administered after each plasmapheresis session. The target preoperative ABO isoagglutinin titer was less than 1:8. Results Filtration plasmapheresis was performed in four patients for ABO-incompatible KT, one for antibody-mediated rejection after KT, and the last one for positive T cell crossmatch. Altogether, 46 sessions of plasmapheresis were performed. ABO isoagglutinin titers successfully declined to or below the target level in all patients, and all patients successfully received KT with no significant antibody titer rebound. Acute antibody-mediated rejection and positive T cell crossmatch were well treated with filtration plasmapheresis, and no patient required fresh frozen plasma infusion for coagulopathy. There were one episode of hypotension and three of hypocalcemia. No patients experienced bleeding, infection, or allergic reaction. Conclusion Filtration plasmapheresis was effective and safe. Although our result is from a single center, our protocol appears to be promising.

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.

Author(s): Lim, Eunsoo; Hyun, Sunah; Lee, Jae Myeong; Kim, Seirhan; Lee, Min-Jeong; Lee, Sun-Mi; Oh, Ye-Sung; Park, Inwhee; Shin, Gyu-Tae; Kim, Heungsoo; Morisky, Donald E; Jeong, Jong Cheol | Abstract: Background:For phosphate control, patient education is essential due to the limited clearance of phosphate by dialysis. However, well-designed randomized controlled trials about dietary and phosphate binder education have been scarce. Methods:We enrolled maintenance hemodialysis patients and randomized them into an education group (n = 48) or a control group (n = 22). We assessed the patients' drug compliance and their knowledge about the phosphate binder using a questionnaire. Results:The primary goal was to increase the number of patients who reached a calcium-phosphorus product of lower than 55. In the education group, 36 (75.0%) patients achieved the primary goal, as compared with 16 (72.7%) in the control group (P = 0.430). The education increased the proportion of patients who properly took the phosphate binder (22.9% vs. 3.5%, P = 0.087), but not to statistical significance. Education did not affect the amount of dietary phosphate intake per body weight (education vs. control: -1.18 ± 3.54 vs. -0.88 ± 2.04 mg/kg, P = 0.851). However, the dietary phosphate-to-protein ratio tended to be lower in the education group (-0.64 ± 2.04 vs. 0.65 ± 3.55, P = 0.193). The education on phosphate restriction affected neither the Patient-Generated Subjective Global Assessment score (0.17 ± 4.58 vs. -0.86 ± 3.86, P = 0.363) nor the level of dietary protein intake (-0.03 ± 0.33 vs. -0.09 ± 0.18, P = 0.569). Conclusion:Education did not affect the calcium-phosphate product. Education on the proper timing of phosphate binder intake and the dietary phosphate-to-protein ratio showed marginal efficacy.

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.

BackgroundGrowth Arrest and DNA Damage 45γ (GADD45γ) is a member of the DNA damage-inducible gene family which responds to environmental stresses. Apoptosis is a critical mode of renal tubular cell death in nephrotoxin-induced acute kidney injury. In this study, we investigated the role of GADD45γ in renal tubular cell apoptosis induced by nephrotoxic drugs.MethodsPrimary human renal tubular epithelial (HRE) cells were used in this study. To derive stable cell lines in which GADD45γ expression was silenced, HRE cells were transduced with a plasmid encoding GADD45γ-specific shRNA. The recombinant adenovirus containing the GADD45γ gene was synthesized to overexpress GADD45γ protein. Cell death was induced by cisplatin and cyclosporine A (CsA). To prevent apoptotic cell death, pan-caspase inhibitor ZVAD-FMK was used. To prevent non-apoptotic cell death, necrostatin-1 and ferrostatin-1 were used. The degree of apoptosis and necrosis of cultured cells were evaluated by flow cytometry.ResultsExpression of the GADD45γ gene was significantly upregulated in response to treatment with CsA and cisplatin. Apoptosis and necrosis induced by these drugs were significantly reduced by silencing of GADD45γ, and significantly augmented by the overexpression of GADD45γ. The activation of caspase-3 and caspase-7 as well as caspase-9 induced by cisplatin or CsA was reduced by silencing of GADD45γ, and was augmented by the overexpression of GADD45γ, indicating that caspase activation is dependent on the expression of GADD45γ. ZVAD-FMK significantly inhibited apoptosis induced by cisplatin or CsA, indicating a role of caspases in mediating apoptotic cell death. ZVAD-FMK was effective to prevent necrosis as well, indicating that the observed necrosis was a secondary event following apoptosis at least in part.ConclusionsTo our knowledge, this is the first study to show that GADD45γ is required for the caspase-dependent apoptosis of renal tubular cells induced by nephrotoxic drugs.

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: Although it has been a popular practice to use preventative antibiotics for the kidney recipients, it could increase the cost, encourage the growth of resistant micro-organism and have adverse effects. There has been no reported concrete evidence about the benefits and risks of using peri-operative prophylactic antibiotics for an immunosuppressed population. Therefore, we retrospectively evaluated the differences in the incidences of bacterial infection and adverse events after transplant surgery according to using peri-operative prophylactic antibiotics. Methods: We reviewed retrospectively 106 cases of renal transplantations (cadaver donor: 42 cases, living donor: 64 cases) that were performed at Ajou University Hospital, Korea from January, 2006 to December, 2008. We divided the cases into two groups: Group A (n=41; 38.7%) included the patients who did not receive prophylactic antibiotics and Group B (n= 65; 61.3%) included the patients who did receive prophylactic antibiotics. We analyzed the infectious complications that occurred within 1 month after renal transplantation. Results: In Group A, most patients (62 cases, 95.3%) used a 1 generation cephalosporin. The incidence of wound infection after kidney transplant for the 65 patients who received prophylactic antibiotics was 1.5%, compared to 2.5% for the 41 patients who did not receive prophylactic antibiotics. Conclusions: This retrospective study could not demonstrate a statistically significant difference in the rates of infectious complications between the two groups, although renal transplantation is considered to be a clean-contaminated surgery. But in order to obtain a definite conclusion, we need a bigger cohort in a prospective study.

Results: The mean age of the patients was 43.0±12.0 (7∼75) and the study included 364 males (56.0%) and 286 females (44.0%). The average follow up period after renal transplantation was 49.5±53.4 (1∼307) months. There were 366 (56.3%) living related cases, 145 (22.3%) living non-related cases and 139 (21.4%) deceased donor cases. Cyclosporine was the most common calcineurin inhibitor (CNI) used in combination therapy with MPS (476 cases, 73.2%) followed by tacrolimus (169 cases, 26.0%). The mean daily dose of MPS was 909.7±336.3 (180∼1,620)mg and the mean daily dose per kg was 15.3±5.9 (2.65∼32.73)mg/kg. The daily dose showed significant positive correlation with patient body weight but the daily dose per kg showed negative correlation. The daily dose of MPS was significantly higher in the combination therapy with cyclosporine than that with tacrolimus. The daily dose and the dose per kg decreased with increment of recipient age and post-transplant period. Conclusions: Our study concluded that MPS dosages correlated with the combined type of CNI, post-transplant period and age.

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.

Effects of suppressing intrarenal angiotensinogen on renal transforming growth factor-β1 expression in acute ureteral obstruction. Background Angiotensin II (Ang II) mediates the up-regulation of fibrogenic factors such as transforming growth factor-β1 (TGF-β1) in chronic renal diseases. In addition, it has been proposed that the intrarenal renin-angiotensin system (RAS) is as important as the systemic RAS in kidney disease progression. Methods We suppressed angiotensinogen (AGT) gene expression in the kidney by transferring recombinant adenoviral vectors carrying a transgene expressing AGT antisense mRNA, and determined the effect of the local inhibition of the RAS on TGF-β1 synthesis in the kidneys of rats with unilateral ureteral obstruction (UUO). Immediately after UUO, recombinant adenovirus vectors were injected intraparenchymally into the cortex of obstructed kidneys. Results β-galactosidase (β-gal)–stained kidney sections revealed the efficient transduction of the recombinant adenoviral vectors into tubular epithelial cells. Kidney cortex injected with AGT antisense showed significantly lower native AGT mRNA and protein expressions than control UUO kidneys at 24 hours and 5 days post-UUO. TGF-β1 was significantly up-regulated in the renal cortex 24 hours and 5 days post-UUO, whereas AGT antisense–injected UUO rats showed significantly reduced TGF-β1 expression compared to control UUO rats. Both fibronectin and collagen type I expressions were increased 24 hours and 5 days post-UUO, and these augmentations were considerably reduced by AGT antisense RNA treatment. Conclusion This study demonstrates that the suppression of intrarenal RAS prevents the formation of renal cortical TGF-β1, and of related fibrogenic factors, in early UUO.

An antibody phage library obtained from peripheral blood lymphocytes of a systemic lupus erythematosus (SLE) patient was used to isolate four monoclonal autoantibodies against histones H2A and H2B. Analysis of the variable region sequences revealed that the anti-histone monoclonal antibodies were not clonally related; they used V H genes from three different V H gene families (V H 3, V H 4, and V H 5) and distant members of the Vκ group (L25, L6, A27, and O8) in conjunction with different D and J gene segments. These observations suggest that certain gene families or segments are not critical in producing anti-histone autoantibodies in SLE. Most of the utilized V H and Vκ sequences were highly mutated and the complementarity-determining regions (CDRs) varied greatly in length. The V H region of the antibody SLEhis18 had an isoelectric point of 6.1, and 29% of the mutations were changes to acidic amino acid residues. The second CDR (CDR2) of SLEhis18 V H contained one basic and three acidic residues. Acidic residues were observed in the CDR3 regions of V H , but not V L , in all isolated clones; this is unusual, as most autoantibodies are comprised predominantly of non-acidic residues. This is the first report of a systematic sequence analysis of human anti-histone monoclonal antibodies. Our results suggest that certain V genes are not important for autoreactive specificity to histones in SLE; instead, other mechanisms such as an existence of acidic residues and somatic mutations in CDRs are required for specific binding to histones, which might play a role as a stimulatory autoantigen for the activation of autoantibody-producing B-cells and the selection of high affinity antibody.

Mushroom-related poisoning can cause acute kidney injury. Here we report a case of acute kidney injury after ingestion of Amanita punctata, which is considered an edible mushroom. Gastrointestinal symptoms occurred within 24 hours from the mushroom intake and were followed by an asymptomatic period, acute kidney injury, and elevation of liver and pancreatic enzymes. Kidney function recovered with supportive care. Nephrotoxic mushroom poisoning should be considered as a cause of acute kidney injury.

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.

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.

BACKGROUND Transforming growth factor-beta1 (TGF-beta1) is an immunoregulatory and fibrogenic cytokine. In an earlier in vitro study, we demonstrated that cyclosporine (CsA) increases TGF-beta1 transcription rate in human T lymphocytes. Herein, we explored whether CsA augments the in vivo expression of TGF-beta1 in humans. METHODS The inherent difficulty in studying the in vivo effect of CsA in humans was circumvented by investigating stable end-stage renal disease patients who were preconditioned with CsA before their living donor renal transplantation. Sera and peripheral blood mononuclear cells were obtained from CsA-preconditioned patients and quantified for TGF-beta1 expression at the mRNA (by competitive polymerase chain reaction) and protein (sandwich enzyme-linked immunosorbent assay) levels. RESULTS Our studies demonstrated a significant increase in TGF-beta1 expression after CsA therapy. The stimulatory effect was unique to TGF-beta1, and CsA did not increase interleukin (IL)-10, IL-6, IL-2, or tumor necrosis factor-alpha expression. CONCLUSIONS Our first-time demonstration of a TGF-beta1-selective in vivo stimulatory effect of CsA in humans: (1) advances a TGF-beta1-centered hypothesis for the beneficial (immunosuppression) and detrimental (fibrosis, hypertension) effects of CsA use, and (2) broadens the mechanism of immunosuppressive action of CsA to include heightened expression of an endogenous immunosuppressive cytokine.

The functional capacity of each kidney of a healthy donor may change under the influence of genetic and environmental factors. An assumption that the donor kidneys show equal function is not always true. As part of the pre-nephrectomy evaluation of potential donors, radioisotope renal scintigraphy using technetium-99m diethylenetriaminepentaacetic acid (99mTcDTPA) was routinely included to evaluate renal functional asymmetry of undetermined etiology. The functional ratios of each kidney using 99mTcDTPA as well as serum creatinine (Scr) and creatinine clearance (Ccr) in a 24-hour urine were measured and calculated from a hundred donors. The left kidneys showed greater function (51.67%-53.35% under 95% confidence interval [CI]) and the average left versus right ratio was 52.5 versus 47.5. The average fraction of Ccr of left kidneys was 57.8 mL/min/1.73 m +/- 10.99 compared with right kidneys at 52.6 mL/min/1.73 m +/- 11.63. Seventy-three healthy volunteers donated their left kidneys, and 27, their right kidney. The average fraction of Ccr of the donated kidneys was 55.9 mL/min/1.73 m +/- 11.78 compared with that of the remnant kidneys (54.5 mL/min/1.73 m +/- 11.39). After kidney donation, the Scr of the donors increased from 0.85 mg/dL +/- 0.17 to 1.33 mg/dL +/- 0.27. The average postnephrectomy Ccr was 68.0 mL/min/1.73 m +/- 14.29. Even though the Ccr after kidney donation was higher than that of the remnant kidney estimated before the donation, one must pay attention to possible functional kidney asymmetry to select the nephrectomy site.

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.

This study investigated the link between growth arrest and DNA damage 45γ (GADD45γ) expression and tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) synthesis.We stimulated THP-1 monocyte cells using lipopolysaccharide (LPS). We knocked-down and over-expressed GADD45γ using lentiviral vectors harboring GADD45γ short hairpin RNA and GADD45γ open reading frame, respectively. To inhibit activation of c-Jun-terminal kinase (JNK), we used a specific inhibitor, SP600125.LPS stimulation of THP-1 cells resulted in increased expression of GADD45γ mRNA which reached its peak 2 h after stimulation and gradually diminished thereafter. TNF-α and IL-6 were up-regulated at both the mRNA and protein levels in activated THP-1 cells. Knock-down of GADD45γ reduced TNF-α protein production by up to 75 % and IL-6 protein by up to 60 %. In contrast, over-expression of GADD45γ increased TNF-α production by six-fold and IL-6 protein by 80-fold. There was a discrepancy between TNF-α mRNA and its protein level, whereas IL-6 mRNA and its protein level were correlated. Knock-down of GADD45γ decreased the JNK activity, suggesting that JNK may play the role of a downstream mediator for the pro-inflammatory effects of GADD45γ.We show evidence that GADD45γ may regulate TNF-α and IL-6 expression in activated THP-1 monocyte cells.

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.