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Drowned victims possibly obtain various pathogens from drowning sites. Using drowned renal donors to expand the donor pool still lacks consensus due to the potential risk of disease transmission. This retrospective study enrolled 38 drowned donor renal recipients in a large clinical center from August 2012 to February 2021. A 1:2 matched cohort was generated with donor demographics, including age, gender, BMI, and ICU durations. Donor microbiological results, recipient perioperative infections, and early post-transplant and first-year clinical outcomes were analyzed. Compared to the control group, drowned donors had significantly increased positive fungal cultures (36.84% vs.13.15%, p = 0.039). Recipients in the drowned group had significantly higher rates of gram-negative bacteria (GNB) and multidrug-resistant GNB infections (23.68% vs.5.26%, 18.42% vs. 3.95%, both p < 0.05). Other colonization and infections were also numerically more frequent in the drowned group. Drowned donor recipients receiving inadequate antibiotic prophylaxis had more perioperative bloodstream infections, higher DGF incidences, and more first-year respiratory tract infections and recipient loss than those receiving adequate prophylaxis (all p < 0.05). Clinical outcomes were similar between the adequate group and the control group. Drowned donors could be suitable options under wide-spectrum and adequate antimicrobial prophylaxis.

为评估死亡供肾血栓和其诱导的受体血栓性微血管病（dir-TMA）对受体移植肾功能的影响，我们回顾性分析了33例活检病理显示微血栓的供体信息及受体预后。根据血栓累及肾小球范围是否大于50%，将33例供体分为弥漫血栓组（n=18）和局灶血栓组（n=15）。结果显示，弥漫血栓组的移植物延迟复功（DGF）发生率显著高于局灶血栓组（P=0.027），肾移植术后1个月，肾小球滤过率（eGFR）估值水平显著低于局灶血栓组（P=0.042）。此外，根据受体是否发生了dir-TMA，将33例受体进一步分为dir-TMA组（n=20）和non-dir-TMA组（n=13）。结果显示，dir-TMA 组受体肾移植术后0至9天的血小板和术后4天至1年的血红蛋白明显低于non-dir-TMA组；dir-TMA受体的DGF发生率高于non-dir-TMA组（50.0% vs. 15.4%，P=0.067），且肾移植术后1月、3月、6月和12月的肾功能均显著差于non-dir-TMA组。此外，根据受体是否接受血浆治疗，将20例发生dir-TMA的受体分为血浆治疗亚组和无血浆治疗亚组。分析表明，血浆治疗亚组受体在移植术后1月、3月、6月和12个月的肾功能均显著差于无血浆治疗亚组。综上，供肾弥漫血栓会增加受体DGF风险，但不影响移植肾功能。临床需关注发生dir-TMA受体的血小板和血红蛋白下降及肾功能恶化，有必要采用更多研究用以评估血浆疗法的效果。

Organ-on-a-chip systems have been increasingly recognized as attractive platforms to assess toxicity and to develop new therapeutic agents. However, current organ-on-a-chip platforms are limited by a “single pot” design, which inevitably requires holistic analysis and limits parallel processing. Here, we developed a digital organ-on-a-chip by combining a microwell array with cellular microspheres, which significantly increased the parallelism over traditional organ-on-a-chip for drug development. Up to 127 uniform liver cancer microspheres in this digital organ-on-a-chip format served as individual analytical units, allowing for analysis with high consistency and quick response. Our platform displayed evident anti-cancer efficacy at a concentration of 10 μM for sorafenib, and had greater alignment than the “single pot” organ-on-a-chip with a previous in vivo study. In addition, this digital organ-on-a-chip demonstrated the treatment efficacy of natural killer cell-derived extracellular vesicles for liver cancer at 50 μg/mL. The successful development of this digital organ-on-a-chip platform provides high-parallelism and a low-variability analytical tool for toxicity assessment and the exploration of new anticancer modalities, thereby accelerating the joint endeavor to combat cancer. Graphic abstract

We herein report the case of a kidney transplant patient with recurrence of obstructive nephropathy that was not diagnosed as adenine phosphoribosyltransferase (APRT) deficiency until gene testing identified a pathogenic homozygous variant three years after renal transplantation. Subsequently, the patient was treated with allopurinol, and the allograft function increased progressively to normal. In addition, 20 cases of APRT deficiency in renal transplant recipients were also reviewed. We hope this case increases awareness of APRT deficiency in repeated obstructive nephropathy post-transplantation, which is a treatable disease for which the misdiagnosis or delayed diagnosis should be avoided.

Background and objectives: Post-transplantation diabetes mellitus (PTDM) is a common complication following kidney transplantation that significantly impacts long-term clinical outcomes. The current study aimed to develop a practical model for predicting the risk of PTDM based on glucose status on day 3 after kidney transplantation.Methods: This study enrolled 300 kidney transplant recipients between October 2018 and July 2019. All recipients were randomly assigned to either development or validation cohorts in a 2:1 ratio. Univariate logistic regression was used for predictor selection. The nomogram was created using a multivariate logistic regression model and calibrated by the receiver operating characteristic curves (ROC), the calibration curves, and the decision-curve analysis. The validation model externally validated the model.Results: The cumulative probability of developing PTDM within one-year of a kidney transplant was 11%. Univariate and multivariate logistic regression analyses identified hyperglycemia on day 3 (OR 2.02, 95% CI: 1.34-3.07, p < 0.001) and recipient age (OR 1.09, 95% CI: 1.02-1.15, p = 0.007) as independent risk factors for PTDM. The calculated potential predictive risk for PTDM was found to be in perfect agreement with the observed prevalence of PTDM. When compared to the previously used glucose statute on day 5, our model had better predictive performance. Moreover, higher risk of PTDM was associated with a lower recovery rate of graft function.Conclusion: Our study confirmed that the prediction model based on day 3 blood glucose levels can provide an early and accurate prediction of PTDM. This model will assist our clinicians in identifying and intervening in high-risk patients on time to prevent PTDM.

Background To evaluate the outcome of kidney recipients with ureteral stenosis after treatment with open surgery under magnetic resonance urography (MRU) localization. Methods We assessed 2,256 consecutive kidney transplant recipients between October 2010 and December 2018. Ureteral stenosis was detected by ultrasound, confirmed and positioned by Magnetic Resonance Urography. All patients underwent open ureteral reconstruction. The ureteral stenosis was located according to the location on the MRU during the operation. Surgical complications and recurrence rate were recorded in the stenosis group. Outcomes were compared with those of a matched control group of transplant recipients with no history of ureteric stenosis. Results The incidence of ureteral stenosis in our center was 3.1% (70/2,256). Sixty-four cases (91.4%) were confirmed to have distal stenosis and were reconstructed with ureterovesical re-implantation; six cases (8.6%) were confirmed to have mid-distal stenosis and were subjected to ureteroureterostomy with the use of native ureter. The overall success rate was 100% and the graft function was salvaged in all cases. There was no recurrence of stenosis after a mean follow-up of 38.9±26.3 months. The complication rate was 5.7%. The 110-month graft survival and patient survival were not significantly different between the stenosis and control groups.Conclusions: MRU is an effective method for non-invasive and accurate diagnosis of ureteral stenosis in kidney transplant recipients. Open ureteral reconstruction surgery under MRU localization for treatment of ureter stenosis after kidney transplantation had a high success rate, low recurrence rate and high safety.

Antibody-mediated rejection (ABMR) is a major cause of dysfunction and loss of transplanted kidney. The current treatments for ABMR involve nonspecific inhibition and clearance of T/B cells or plasma cells. However, the prognosis of patients following current treatment is poor. T follicular helper cells (Tfh) play an important role in allograft-specific antibodies secreting plasma cell (PC) development. Tfh cells are therefore considered to be important therapeutic targets for the treatment of antibody hypersecretion disorders, such as transplant rejection and autoimmune diseases. Tacrolimus (Tac), the primary immunosuppressant, prevents rejection by reducing T cell activation. However, its administration should be closely monitored to avoid serious side effects. In this study, we investigated whether Tac delivery to helper T (CD4 + ) cells using functionalized mesoporous nanoparticles can block Tfh cell differentiation after alloantigen exposure. Results showed that Tac delivery ameliorated humoral rejection injury in rodent kidney graft by suppressing Tfh cell development, PC, and donor-specific antibody (DSA) generation without causing severe side effects compared with delivery through the drug administration pathway. This study provides a promising therapeutic strategy for preventing humoral rejection in solid organ transplantation. The specific and controllable drug delivery avoids multiple disorder risks and side effects observed in currently used clinical approaches.

BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL, P

Recent studies have confirmed the role of plasma donor-derived cell-free DNA (ddcfDNA) as a reliable non-invasive biomarker for allograft injury after kidney transplantation. Whereas the variability of plasma ddcfDNA levels among recipients has limited their clinical use. This study aimed to explore the intrinsic factors associated with plasma ddcfDNA elevation by investigating the impact of Banff lesions and inflammatory infiltrates on ddcfDNA levels in kidney transplant recipients. From March 2017 to September 2019, a total of 106 kidney transplant recipients with matched allograft biopsies were included, consisting of 13 recipients with normal/nonspecific changes, 13 recipients with borderline changes, 60 with T cell-mediated rejection, and 20 with antibody-mediated rejection. Histologic classification was performed according to the Banff 2017 criteria by two experienced pathologists. Plasma ddcfDNA fractions ranged from 0.12% to 10.22%, with a median level of 0.91%. Banff histology subelements including glomerulitis, intimal arteritis, and severe interstitial inflammation were correlated with increased plasma ddcfDNA levels. The inflammatory cell infiltrate in the allografts was phenotyped by immunochemistry and automatically counted by digital image recognition. Pearson correlation analysis revealed a significant positive correlation between macrophage infiltrations in allografts and plasma ddcfDNA levels. Additionally, macrophage extracellular trap (MET) activity was significantly associated with the rise in plasma ddcfDNA levels. Our findings demonstrated that plasma ddcfDNA could reflect the inflammatory state in renal allografts and suggested the potential role of METs in the pathogenesis of allograft injury.

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Kidney transplantation is the most effective therapy for patients with end-stage renal disease. However, antibody-mediated rejection (ABMR) threatens long-term survival of renal grafts. Although ABMR can be controlled by donor-specific antibody clearance and B- or (and) plasma-cells inhibition, the treatment often causes severe side effects in patients. Therefore, there is need to explore site-specific scavengers. In this study, a nanovehicle carrying an anti-inflammatory drug is developed with complement component 4d targeting, a specific biomarker expressed on allograft endothelium under ABMR. Moreover, the nanovehicle is endowed with photothermal properties to control drug release. Analysis through systematic in vitro and in vivo toxicity, non-invasive targeted imaging, and in situ remote controlled drug release show the nanovehicle specifically targets allograft kidney endothelium, releases an anti-inflammatory drug, methylprednisolone, locally upon laser irradiation, and promotes recovery of injured endothelium, without affecting systemic inflammation or innate immune responses. This strategy has the potential for future clinical application in ABMR treatment.

Donor-derived cell-free DNA (dd-cfDNA) is a promising biomarker for monitoring allograft status. However, whether dd-cfDNA can reflect real-time anti-rejection treatment effects remains unclear. We prospectively recruited 28 patients with acute renal rejection, including 5 with ABMR, 12 with type IA or type IB rejection, and 11 with type IIA or IIB rejection. dd-cfDNA levels in peripheral blood were measured using human single nucleotide polymorphism (SNP) locus capture hybridization. The percentage of dd-cfDNA (dd-cfDNA%) declined significantly from 2.566 ± 0.549% to 0.773 ± 0.116% (P < .001) after anti-rejection therapy. The dd-cfDNA% decreased steadily over the course of 3 days with daily methylprednisolone injections, but no significant difference in the dd-cfDNA% was observed between the end of anti-rejection therapy and 2 weeks later. Changes in the dd-cfDNA% (∆dd-cfDNA%) demonstrated a positive correlation with estimated glomerular filtration rates at 1 month (ρ = 2.570, P = .022), 3 months (ρ = 3.210, P = .027), and 6 months (ρ = 2.860, P = .019) after therapy. Thus, the dd-cfDNA assay shows prognostic capabilities in therapy outcome and allograft recovery; however, its ability is inhibited by methylprednisolone regardless of the types of rejection. Additionally, a reassessment of frequency intervals for testing is required.

ABO-incompatible living kidney transplantation is nowadays a routine procedure to expand living donor pool. The past decades have seen the evolution of desensitization protocol and immunosuppression regimen. Despite increased bleeding events, infectious complications, and rejection episodes reported in some studies, favorable graft and patient survival rate are now achieved, regardless of various protocols among transplant centers. Several issues such as the usage of rituximab and standardization of blood group antibody titration remain to be settled. The deposition of C4d is no longer the histopathologic hallmark of antibody-mediated rejection, which have inspired innovative strategies of peripheral molecular screening and the improvement of histological diagnosis of AMR (antibody-mediated rejection). The better understanding of the underlying mechanism might facilitate the distinction and therapeutic schemes of AMR.

Background This study aimed to understand the mechanistic role of N-methyl-D-aspartate receptor (NMDAR) in acute fibrogenesis using models of in vivo ureter obstruction and in vitro TGF-β administration. Methods Acute renal fibrosis (RF) was induced in mice by unilateral ureteral obstruction (UUO). Histological changes were observed using Masson’s trichrome staining. The expression levels of NR1, which is the functional subunit of NMDAR, and fibrotic and epithelial-to-mesenchymal transition markers were measured by immunohistochemical and Western blot analysis. HK-2 cells were incubated with TGF-β, and NMDAR antagonist MK-801 and Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist KN-93 were administered for pathway determination. Chronic RF was introduced by sublethal ischemia–reperfusion injury in mice, and NMDAR inhibitor dextromethorphan hydrobromide (DXM) was administered orally. Results The expression of NR1 was upregulated in obstructed kidneys, while NR1 knockdown significantly reduced both interstitial volume expansion and the changes in the expression of α-smooth muscle actin, S100A4, fibronectin, COL1A1, Snail, and E-cadherin in acute RF. TGF-β1 treatment increased the elongation phenotype of HK-2 cells and the expression of membrane-located NR1 and phosphorylated CaMKII and extracellular signal–regulated kinase (ERK). MK801 and KN93 reduced CaMKII and ERK phosphorylation levels, while MK801, but not KN93, reduced the membrane NR1 signal. The levels of phosphorylated CaMKII and ERK also increased in kidneys with obstruction but were decreased by NR1 knockdown. The 4-week administration of DXM preserved renal cortex volume in kidneys with moderate ischemic–reperfusion injury. Conclusions NMDAR participates in both acute and chronic renal fibrogenesis potentially via CaMKII-induced ERK activation.

Giant lymph node hyperplasia is the main symptom of Castleman’s disease (CD), which is a rare and easily overlooked lymphoproliferative disease that mimics both benign and malignant lesions. Several cases of CD after renal transplantation have been reported in the literature. A 43-year-old man was admitted to our medical center with high serum globulin levels after receiving a living donor kidney transplant. A lymph node biopsy raised suspicion for multicentric CD. Because of the poor therapeutic effect of reduction of immunosuppression, the patient was treated with CHOP chemotherapy comprising four cycles of monthly cyclophosphamide (750 g/m 2 , day 1), vincristine (1.4 g/m 2 , day 1), doxorubicin (50 g/m 2 , day 1), and prednisone (60 mg/m 2 , daily). Following the treatment, his serum globulin levels decreased to the normal range. At the 2-year follow-up examination, the abdominal, axillary, and inguinal lymph nodes had significantly decreased in size. Without a pathological diagnosis, multicentric CD after renal transplantation can be easily ignored and misdiagnosed. If the clinical signs cannot be relieved by minimizing the dose of common immunosuppressants, the CHOP regimen may be a better option. Biological agents may be added in patients with positive immunohistochemistry staining and good economic conditions.

Donor-derived cell-free DNA (ddcfDNA) is reported to be a promising noninvasive biomarker for acute rejection in organ transplant. However, studies on monitoring ddcfDNA dynamics during the early periods after organ transplantation are scarce. Our study assessed the dynamic variation in ddcfDNA in early period with various types and status of kidney transplantation. Target region capture sequencing used identifies ddcfDNA level in 21 kidney transplant recipients. Median ddcfDNA level was 20.69% at the initial time post-transplant, and decreased to 5.22% on the first day and stayed at the stable level after the second day. The ddcfDNA level in DCD (deceased donors) group (44.99%) was significantly higher than that in LDRT (living donor) group (10.24%) at initial time, P

Background It is not clear whether renal allograft removal affects the outcome of renal retransplantation. This study aimed to determine the effect of allograft nephrectomy (AN) and no-AN (No AN) on renal retransplantation. Methods A systematic review and meta-analysis were conducted using MEDLINE, Embase and the Cochrane Library. Observational studies or randomized controlled trials including renal retransplantation recipients with AN or No-AN were included. The primary outcomes were graft survival, patient survival, acute rejection (AR) and delayed graft dysfunction; the secondary outcomes were positive panel reactive antibody rate and serum creatinine level at 1 year after retransplantation, cold ischemia time and time of hemodialysis before recent transplantation. Pooled estimates of odds ratios (ORs) and the weighted mean difference for outcomes were calculated. Results A total of 13 studies divided into 20 trials including 1923 patients were analyzed. The No-AN group had a significantly higher 3-year graft survival rate {OR 0.48 [95% confidence interval (CI) 0.34-0.69], 10 studies, n = 1030} and 5-year graft survival rate [OR 0.65 (95% CI 0.44-0.97), 16 studies, n = 1878] than the AN group. The rates of 5-year patient survival [OR 1.82 (95% CI 1.14-2.90), 5 studies, n = 749], positive panel reactive antibody [OR 3.08 (95% CI 2.08-4.56), 12 studies, n = 1225], AR [OR 1.59 (95% CI 1.21-2.09), 15 studies, n = 1388] and delayed graft dysfunction [OR 1.66 (95% CI 1.20-2.03), 8 studies, n = 879] were all significantly higher in the AN group. Compared with the No-AN group, cold ischemia time was longer in the AN group [weighted mean difference 1.84 (95% CI 0.90-2.79), 7 studies, n = 919]. The rate of 1-year graft survival and 10-year graft survival, serum creatinine levels at 1 year after retransplantation and the time of hemodialysis before recent transplantation were similar between the AN and No-AN groups. Conclusions We recommend allowing the failed graft to remain unless symptoms dictate the need for surgery. We also suggest donor-specific antibody dynamic monitoring and better human leukocyte antigen matching for improved long-term outcome of retransplantation.

// Zaiyou Dai 1, 2, 3, 4, * , Luxi Ye 1, 2, 3, * , Dajin Chen 1, 2, 3 , Xing Zhang 1, 2, 3 , Meifang Wang 1, 2, 3 , Rending Wang 1, 2, 3 , Jianyong Wu 1, 2, 3 and Jianghua Chen 1, 2, 3 1 Department of The Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China 2 Key Laboratory of Kidney Disease Prevention and Control Technology, Zhejiang, China 3 The Third Grade Laboratory under The National State, Administration of Traditional Chinese Medicine, Zhejiang, China 4 Department of Nephrology, The First People’s Hospital of Wenling, Zhejiang, China * These authors have contributed equally to this work Correspondence to: Jianyong Wu, email: wujianyong@medmail.com.cn Keywords: proteinuria, living donor renal transplantation, transplant outcome Received: March 17, 2017 Accepted: April 27, 2017 Published: July 15, 2017 ABSTRACT Background: Proteinuria is an indicator of subsequent renal function decline in most nephropathies and early proteinuria has been assumed to be a risk factor of poor kidney transplant outcomes. However, there is no information about the effect of earlier-proteinuria at the first week on short-term graft function after living donor renal transplantation. Methods: Retrospective cohort study of 439 living donor kidney transplants to analyze the effect of early proteinuria at 7-day post-transplantation on short-term prognosis of living donor renal transplantation. Patients were stratified into 2 groups according to the definition of earlier-proteinuria: Group A as proteinuria < 0.4 g/24h and Group B as proteinuria ≥ 0.4 g/24h, and differences over the first year post-transplantation were analyzed. Results: Patients with earlier-proteinuria ≥ 0.4 g/24h had a significantly higher 1-year proteinuria and lower 1-year graft function post-transplantation. Discrepancies of weight ratio of donor-recipient and mean artery pressure difference of recipient to donor influenced the urine protein excretion at the 7-day post-transplantation. Conclusions: Earlier-proteinuria at 7-day after living donor renal transplantation was associated with short-term graft function. To eliminate the functional discrepancies between living donors and recipients could be viewed as a solution of reducing earlier-proteinuria.

Long-term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β-catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg-1 of the β-catenin inhibitor ICG-001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μm ICG-001 (HG+ICG) for 48 h. We found greater thickness of the parietal peritoneum in the PDF-treated mice. Additionally, lower expression of E-cadherin, higher expression of Vimentin, β-catenin, and Snail, and activation of β-catenin was observed in the mice and in HG-treated mPECs, all of which were reversed by ICG-001. The changes in E-cadherin and Vimentin indicated occurrence of the epithelial-to-mesenchymal transition (EMT). Thus, β-catenin signaling participates in the process of HG-induced peritoneal fibrosis, and the EMT of peritoneal epithelial cells is one of the underlying mechanisms of this pathological change.

Background/Aims: Infection with Acinetobacter baumannii was emerging as one of the leading causes of mortality after donation after cardiac death transpalantion. Methods: We reported a case of a recipient who underwent DCD renal transplantation and later got infected by A.baumannii. Etests were done to verify the susceptibility test results in clinic. Whole-genome analysis was applied to investigate the resistant mechanism at gene level. Results: The pathogen was isolated from his draining liquid the day after the surgery, and susceptibility test reavealed that it was sensitive to tigecycline. However, the isolate obtained from the draining liquid became tigecycline-resistant after fifteen-day administration of tigecycline. The Susceptibility tests showed that the pathogen recovered from tigecycline resistance and became intermediated to tigecycline. Whole-Genome analysis revealed the genetic level change leading to tigecycline resistance and we identified the location of mutation by comparing the whole genome sequence of the isolates. Three loci were figured out which may contribute to drug resistance, including genes encoding HTH domain protein, MFS transporter and AdeS. Conclusion: Understanding the genetic characteristics associated with drug resistance mechanism and antimicrobial profiles of pathogen is important in controlling infection outbreak and preventing serious complications and gives a new insight into the development of antimicrobial agents.

Podocytes play important roles in the progression of diabetic kidney disease (DKD) and these roles are closely associated with cytoskeletal actin dynamics. N-Methyl-d-aspartate receptors (NMDARs), which consist of two functional NR1 subunits and two regulatory NR2 subunits, are widely expressed in the brain but are also found in podocytes. Here, we found increased NR1 expression in two diabetic mouse models and in podocytes incubated in high glucose (HG). In diabetic mice, knockdown of NR1 using lentivirus carrying NR1-shRNA ameliorated the pathological features associated with DKD, and reversed the decreased expression of synaptopodin and Wilms' tumour-1. In podocytes incubated with HG, NR1 was secreted from the endoplasmic reticulum and this was blocked by bisindolylmaleimide I. NR1 knockdown decreased the cell shape remodelling, cell collapse, bovine serum albumin permeability, and migration induced by HG. After HG incubation, levels of cell division control protein 42 (Cdc42) and its active form increased, and a significantly higher Cdc42-GTP level, increased Cdc42 translocation onto the leading edges, and lower migration ability were found in podocytes with NR1 knockdown. Increases in the number and length of filopodia were found in podocytes with NR1 knockdown but these were abolished by Cdc42-GTP blockade with ML141. In conclusion, the activation of NMDARs plays an important role in DKD by reducing Cdc42-GTP activation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Background Chronic refractory dialysis hypotension (CRDH) is a serious issue in dialysis patients waiting for transplants. It leads to fatal clinical outcomes and disqualification from kidney transplantation. Kidney transplantation from pediatric donor to adult patient with lower blood pressure (BP) may be an option. No related study has been reported and we conducted this study to first evaluate the effect of pediatric donor kidney transplantation in CRDH recipients. Methods Ten single-kidney transplantations from small pediatric donors after cardiac death in our center between August 2016 and April 2018 were described. Half were CRDH recipients (group A) with intradialytic and interdialytic systolic blood pressure (SBP) below 100 mmHg. Each was paired with no-CRDH recipient (control, group B) from the same donor. The operation method of vascular anastomosis and ureterocystoneostomy was the same as that of adult donors. Clinical characteristics, post-operative treatment and outcomes of all recipients were retrieved. Postoperative BP, graft function and size were compared between two groups. The follow-up time was up to April 2019. Results There was no acute rejection (AR), graft loss or death in all recipients after transplantation. Their renal function was recovered despite three transient delayed graft function (DGF). There was no significant difference in serum creatinine (SCr) or graft size (P=0.84, 0.94) after transplantation between two groups. For all CRDH recipients, the postoperative SBP was above 100 mmHg (except one, 90-130 mmHg). The BP one year after transplantation was maintained at 110-125/70-85 mmHg. Conclusions kidney transplantation from small pediatric donors may be feasible to CRDH recipients and their BP may return to normal after transplantation.

Figure S1. Timeline. (DOC 70 kb)

Background The purpose of this case report is to increase the awareness of tigecycline-induced pancreatitis specifically in renal transplant patients predisposed to the condition. Case presentation A 48-year-old woman developed a donor-derived infection after kidney transplantation, resulting in a ruptured graft renal artery, followed by peritoneal drainage, blood and urine culture infections. Due to multiple drug resistance Acinetobacter baumannii cultured from the preservation fluid and blood, she was treated with tigecycline at the 8th post-transplant day combined with other antibiotics. After 15 days of tigecycline treatment, she was observed with recurrent fever and abdominal distension with a rise in pancreatic enzymes. CT scans showed acute pancreatitis with grade D on Balthazar score, no necrosis visible without contrast injection. These facts were sufficient to hint that pancreatitis was slowly becoming prominent. After withdrawal of tigecycline, CT scans showed that exudation around the pancreas were relieved, and blood amylase returned to the normal range in a week. Conclusions Clinicians should pay attention to clinical signs and symptoms and the level of serum pancreatic enzymes in order to monitor the development of pancreatitis. If necessary, abdominal CT scans should be performed regularly when given tigecycline. Electronic supplementary material The online version of this article (10.1186/s12879-018-3103-z) contains supplementary material, which is available to authorized users.

Infection after renal transplantation remains a major cause of morbidity and death, especially infection from the extensively drug-resistant bacteria, A. baumannii. A total of fourteen A. baumannii isolates were isolated from the donors’ preserved fluid from DCD (donation after cardiac death) renal transplantation and four isolates in the recipients’ draining liquid at the Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from March 2013 to November 2014. An outbreak of A. baumannii emerging after DCD renal transplantation was tracked to understand the transmission of the pathogen. PFGE displayed similar DNA patterns between isolates from the same hospital. Antimicrobial susceptibility tests against thirteen antimicrobial agents were determined using the K-B diffusion method and eTest. Whole-genome sequencing was applied to investigate the genetic relationship of the isolates. With the clinical data and research results, we concluded that the A. baumannii isolates 3R1 and 3R2 was probably transmitted from the donor who acquired the bacteria during his stay in the ICU, while isolate 4R1 was transmitted from 3R1 and 3R2 via medical manipulation. This study demonstrated the value of integration of clinical profiles with molecular methods in outbreak investigation and their importance in controlling infection and preventing serious complications after DCD transplantation.

Erosion of the peritoneal dialysis (PD) catheter into the bowel is very rare. Some patients experience serious consequences such as peritonitis, difficulties in draining, and feculent dialysate effluent with watery diarrhea, but some patients develop no symptoms. Most cases have occurred upon insertion of a stylet-catheter. Perforation by a PD catheter is distinctly unusual. Here, we report a 72-year-old man who presented with a plastic tube protruding from the anus after defecating. We diagnosed the patient with delayed rectal perforation by a PD catheter. We compare our patient with similar patients identified by a search of the English-language literature indexed at PubMed (keywords: “perforation,” “erosion,” “peritoneal dialysis,” “catheter”) and a search for references within articles identified in the primary search.

Background. Some adult patients with minimal change nephrotic syndrome (MCNS) who are refractory to steroid treatment or combination with immunosuppressive drug developed reversible acute renal failure (ARF) due to persistent severe hypoalbuminemia and proteinuria. It is a challenge to find rescue therapies that are effective and safe in treating such difficult patients. Methods. In this prospective observational study, 13 patients with adult-onset MCNS, all unresponsive to treatment with a steroid or a steroid with other immunosuppressive drugs, were studied from January 2005 to February 2009. All patients developed ARF before enrollment. Oral tacrolimus (TAC) was started at 1 mg/day (target trough levels of 3–6 ng/mL) before serum creatinine (SCr) decreased to ≤133 μmol/L, and then increased doses were given (target trough level of 5–10 ng/mL) when SCr decreased to ≤133 μmol/L. Primary outcome variables were remission, and recovery from ARF. Secondary outcome variables were time to recovery from ARF, time to remission, relapse rate, changes in SCr and estimated glomerular filtration rate (eGFR). Results. One patient discontinued TAC due to deterioration of ARF, and 12 patients recovered from ARF. The mean time to recovery from ARF was 15.8 ± 4.4 days. Nine patients (69.2%) experienced complete remission (CR) and two patients (15.4%) experienced partial remission (PR). The mean time to PR and CR was 4.8 ± 2.7 and 9.4 ± 2.3 weeks, respectively. After a mean follow-up of 69.6 months, 36.4% (4/11) of patients who had remission experienced relapses. One patient who was resistant to TAC therapy had a doubling of serum creatinine concentration during follow-up. Conclusions. TAC may be a suitable therapeutic option for treatment of adult-onset refractory MCNS with reversible ARF.

OBJECTIVE It remains debated whether reduced doses of chronic calcineurin inhibitors benefit graft survival. METHODS This retrospective study analyzed 60 first cadaveric renal transplant recipients who received cyclosporine (CSA), mycophenolate mofetil (MMF) and prednisone (CMP group) and 71 recipients who received reduced-dose CSA with prednisone and MMF (RCMP group). All recipients were followed for at least 96 months. The Modification of Diet in Renal Disease (MDRD) glomerular filtration rate (GFR) calculated at different time points, graft survival, the incidence of chronic allograft nephropathy (CAN) and the acute rejection rate within six months were analyzed and compared between the two groups. RESULTS The incidence of acute rejection within six months post-transplant was 15.5% (11/71) in the RCMP group and 13.3% (8/60) in the CMP group. This difference was not significant (p=0.727). The MDRD-calculated GFR in the CMP group reached a peak at 24 months post-transplant (66.6 ± 20.2 mL/min/1.73 m(2)) then decreased gradually. In contrast, in the RCMP group, the GFR reached a peak at 36 months post-transplant (76.9 ± 19.6 mL/min/1.73 m(2)). The GFR from month 36 to month 96 was significantly higher in the RCMP group than in the CMP group. The Kaplan-Meier calculated death-censored graft survival in the RCMP group was significantly higher than that observed in the CMP group, with an estimated cumulative proportion surviving at 96 months of 95.5% in the RCMP group and 83.5% in the CMP group. The incidence of CAN within 96 months was 5.6% (4/71) in the RCMP group vs. 16.7% (10/60) in the CMP group (p=0.042). CONCLUSION An RCMP regimen can significantly improve the long-term GFR level and benefit graft survival.

// Yingying Lu 1,* , Bingjue Li 1,* , Qixia Shen 1 , Rending Wang 1 , Zhimin Chen 1 , Hong Jiang 1 and Jianghua Chen 1 1 Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, 310003, P.R. China * These authors have contributed equally to this work Correspondence to: Jianghua Chen, email: // Hong Jiang, email: // Keywords : CD20+ B cell, kidney transplantation, acute rejection, graft loss, steroid resistance Received : September 23, 2016 Accepted : March 04, 2017 Published : March 15, 2017 Abstract The effects of CD20+ B-cell infiltration during acute rejection on graft outcomes are controversial. The objective of this systematic review and meta-analysis was to clarify this issue. We performed a systematic literature search for studies published up to January 14, 2016. A total of 5 studies, with 200 patients, were included. The presence of CD20+ B cells in renal biopsies during allograft rejection was associated with graft loss and steroid resistance. No association of CD20+ B-cell infiltration with C4d-positive staining of the peritubular capillaries in renal biopsies was found in the analysis of patients who experienced kidney graft rejection. In conclusion, CD 20+ B cell infiltration during allograft rejection was associated with an increased risk of graft loss and steroid resistance.

Background. It is controversial whether lymphocyte infiltration exhibited in biopsy specimens is associated with transplant outcomes. This study focused on the effect of CD20-positive B cell infiltration in biopsy specimens from allografts with acute cellular rejection (ACR) in a Chinese population.Methods. Altogether, 216 patients transplanted from Sep. 2001 to Dec. 2014 with biopsy-proved ACR (Banff I or Banff II) were included in the analysis. Biopsies were immunostained for CD20 and C4d. Baseline information, serum creatinine and GFR before and after treatment, steroid resistance, response to treatment, graft loss, and survival were analyzed.Results. Eighty-three patients were classified into CD20-negative group, and 133 patients were classified into CD20-positive group. Significantly more CD20-negative patients (49/83, 59.0%) received steroid plus antibody therapy compared with the CD20-positive group (52/133, 39.1%) (P=0.004). The response to treatment for ACR did not differ between these two groups. The CD20-positive group had less graft loss (18.8% versus 32.5%,P=0.022) and a better graft survival rate. Further exploration of the infiltration degree suggested that it tended to be positively related to graft survival, but this did not reach statistical significance.Conclusion. CD20-positive B cell infiltration in renal allograft biopsies with ACR is associated with less steroid resistance and better graft survival. The presence of CD20-positive B cells is protective for renal allografts.

Long‐term exposure to peritoneal dialysate with high glucose (HG) leads to peritoneal fibrosis and thus decreases dialysis efficiency. In this study, we explored the role of β‐catenin in this process. C57BL/6 mice received daily intraperitoneal injection with 10% of the body weight of saline (control), 4.25% glucose peritoneal dialysis fluid (PDF), or PDF combined with 5 mg·kg−1 of the β‐catenin inhibitor ICG‐001 (PDF+ICG) for 30 days. Also, mice peritoneal epithelial cells (mPECs) were cultured in 4.25% glucose (HG) or combined with 10 μm ICG‐001 (HG+ICG) for 48 h. We found greater thickness of the parietal peritoneum in the PDF‐treated mice. Additionally, lower expression of E‐cadherin, higher expression of Vimentin, β‐catenin, and Snail, and activation of β‐catenin was observed in the mice and in HG‐treated mPECs, all of which were reversed by ICG‐001. The changes in E‐cadherin and Vimentin indicated occurrence of the epithelial‐to‐mesenchymal transition (EMT). Thus, β‐catenin signaling participates in the process of HG‐induced peritoneal fibrosis, and the EMT of peritoneal epithelial cells is one of the underlying mechanisms of this pathological change.

Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study — 67.5% (27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0% (20/40) had low estimated glomerular filtration rate (eGFR) (2). We compared the efficacy and adverse effects of TAC (0.04–0.08 mg/kg/d)/prednisone for 12 months (TAC group, n = 20) with intravenous CYC (750 mg/m2 per month)/prednisone for six months followed by azathioprine (Aza) (100 mg/day)/prednisone for six months (CYC group, n = 20). The TAC target concentration was 6–8 ng/mL or 4–6 ng/mL, respectively, when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency. In the TAC group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy ( P 2 at baseline to 93.75 ± 28.52 mL/min/1.73m2 after 12 months, P = 0.001. In the CYC group, two patients developed end-stage renal disease (ESRD), three patients experienced serious pneumonia, and one patient died. Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease, and with less-severe adverse events compared with CYC followed Aza therapy. Further larger sample studies are needed to confirm our conclusion.

Wu J, Li H, Huang H, Wang R, Wang Y, He Q, Chen J. Slope of changes in renal function in the first year post-transplantation and one-yr estimated glomerular filtration rate together predict long-term renal allograft survival. Clin Transplant 2010: 24: 862–868. © 2010 John Wiley & Sons A/S. Abstract: Background: Few studies have examined the predictive value of the slope of changes in renal function in the first year post-transplantation when combined with one-yr estimated glomerular filtration rate (eGFR). Methods: We reviewed 1062 recipients who underwent renal transplantations from deceased donors between January 1992 and June 2003. Recipients were stratified into four groups: (a) one-yr eGFR −2 mL/min/month, (c) one-yr eGFR >45 mL/min and slope 45 mL/min and slope >−2 mL/min/month. Survival was assessed by Kaplan-Meier analysis and the significance of variables with the Cox proportional hazard model. Results: Both the slopes of eGFR changes and one-yr eGFR were significantly associated with survival in univariate analysis. The hazard ratio of graft loss was 2.645 when one-yr eGFR was −2 mL/min/month had five- and 10-yr graft survival rates similar to those with one-yr eGFR >45 mL/min. Conclusions: Long-term graft survival was related to one-yr eGFR and the slope of changes in eGFR within the first year. Their combination provides a more discriminatory predictive value.

Podocytes play important roles in the progression of diabetic kidney disease (DKD) and these roles are closely associated with cytoskeletal actin dynamics. N-Methyl-d-aspartate receptors (NMDARs), which consist of two functional NR1 subunits and two regulatory NR2 subunits, are widely expressed in the brain but are also found in podocytes. Here, we found increased NR1 expression in two diabetic mouse models and in podocytes incubated in high glucose (HG). In diabetic mice, knockdown of NR1 using lentivirus carrying NR1-shRNA ameliorated the pathological features associated with DKD, and reversed the decreased expression of synaptopodin and Wilms' tumour-1. In podocytes incubated with HG, NR1 was secreted from the endoplasmic reticulum and this was blocked by bisindolylmaleimide I. NR1 knockdown decreased the cell shape remodelling, cell collapse, bovine serum albumin permeability, and migration induced by HG. After HG incubation, levels of cell division control protein 42 (Cdc42) and its active form increased, and a significantly higher Cdc42-GTP level, increased Cdc42 translocation onto the leading edges, and lower migration ability were found in podocytes with NR1 knockdown. Increases in the number and length of filopodia were found in podocytes with NR1 knockdown but these were abolished by Cdc42-GTP blockade with ML141. In conclusion, the activation of NMDARs plays an important role in DKD by reducing Cdc42-GTP activation. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John WileySons, Ltd.