Remote ischemic conditioning may improve graft function following kidney transplantation: a systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Remote ischemic conditioning (RIC) has the potential to benefit graft function following kidney transplantation by reducing ischemia-reperfusion injury; however, the current clinical evidence is inconclusive. This meta-analysis with trial sequential analysis (TSA) aimed to determine whether RIC improves graft function after kidney transplantation. METHODS: A comprehensive search was conducted on PubMed, Cochrane Library, and EMBASE databases until June 20, 2023, to identify all randomized controlled trials that examined the impact of RIC on graft function after kidney transplantation. The primary outcome was the incidence of delayed graft function (DGF) post-kidney transplantation. The secondary outcomes included the incidence of acute rejection, graft loss, 3- and 12-month estimated glomerular filtration rates (eGFR), and the length of hospital stay. Subgroup analyses were conducted based on RIC procedures (preconditioning, perconditioning, or postconditioning), implementation sites (upper or lower extremity), and graft source (living or deceased donor). RESULTS: Our meta-analysis included eight trials involving 1038 patients. Compared with the control, RIC did not significantly reduce the incidence of DGF (8.8% vs. 15.3%; risk ratio = 0.76, 95% confidence interval [CI], 0.48-1.21, P = 0.25, I2 = 16%), and TSA results showed that the required information size was not reached. However, the RIC group had a significantly increased eGFR at 3 months after transplantation (mean difference = 2.74 ml/min/1.73 m2, 95% CI: 1.44-4.05 ml/min/1.73 m2, P < 0.0001, I2 = 0%), with a sufficient evidence suggested by TSA. The secondary outcomes were comparable between the other secondary outcomes. The treatment effect of RIC did not differ between the subgroup analyses. CONCLUSION: In this meta-analysis with trial sequential analysis, RIC did not lead to a significant reduction in the incidence of DGF after kidney transplantation. Nonetheless, RIC demonstrated a positive correlation with 3-month eGFR. Given the limited number of patients included in this study, well-designed clinical trials with large sample sizes are required to validate the renoprotective benefits of RIC. TRIAL REGISTRATION: This systematic review and meta-analysis was registered at the International Prospective Register of Systematic Reviews (Number CRD42023464447).

The Use of Diffusion Tensor Imaging in the Identification of Acute Rejection and Chronic Allograft Nephropathy After Renal Transplantation.

BACKGROUND: Identifying the cause of renal allograft dysfunction is important for the clinical management of kidney transplant recipients. PURPOSE: To evaluate the diagnostic efficiency of diffusion tensor imaging (DTI) for identifying allografts with acute rejection (AR) and chronic allograft nephropathy (CAN). STUDY TYPE: Prospective. SUBJECTS: Seventy-seven renal transplant patients (aged 42.5 ± 9.5 years), including 29 patients with well-functioning stable allografts (Control group), 25 patients diagnosed with acute rejection (AR group), and 23 patients diagnosed with chronic allograft nephropathy (CAN group). FIELD STRENGTH/SEQUENCE: 1.5 T/T2-weighted imaging and DTI. ASSESSMENT: The serum creatinine, proteinuria, pathologic results, and fractional anisotropy (FA) values were obtained and compared among the three groups. STATISTICAL TEST: One-way analysis of variance; correlation analysis; independent-sample t-test; intraclass correlation coefficients and receiver operating characteristic curves. Statistical significance was set to a P-value <0.05. RESULTS: The AR and CAN groups presented with significantly elevated serum creatinine as compared with the Control group (191.8 ± 181.0 and 163.1 ± 115.8 µmol/L vs. 82.3 ± 20.9 µmol/L). FA decreased in AR group (cortical/medullary: 0.13 ± 0.02/0.31 ± 0.07) and CAN group (cortical/medullary: 0.11 ± 0.02/0.27 ± 0.06), compared with the Control group (cortical/medullary: 0.15 ± 0.02/0.35 ± 0.05). Cortical FA in the AR group was higher than in the CAN group. The area under the curve (AUC) for identifying AR from normal allografts was 0.756 and 0.744 by cortical FA and medullary FA, respectively. The AUC of cortical FA and medullary FA for differentiating CAN from normal allografts was 0.907 and 0.830, respectively. The AUC of cortical FA and medullary FA for distinguishing AR and CAN from normal allografts was 0.828 and 0.785, respectively. Cortical FA was able to distinguish between AR and CAN with an AUC of 0.728. DATA CONCLUSION: DTI was able to detect patients with dysfunctional allografts. Cortical FA can further distinguish between AR and CAN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Multi-omics network characterization reveals novel microRNA biomarkers and mechanisms for diagnosis and subtyping of kidney transplant rejection.

BACKGROUND: Kidney transplantation is an optimal method for treatment of end-stage kidney failure. However, kidney transplant rejection (KTR) is commonly observed to have negative effects on allograft function. MicroRNAs (miRNAs) are small non-coding RNAs with regulatory role in KTR genesis, the identification of miRNA biomarkers for accurate diagnosis and subtyping of KTR is therefore of clinical significance for active intervention and personalized therapy. METHODS: In this study, an integrative bioinformatics model was developed based on multi-omics network characterization for miRNA biomarker discovery in KTR. Compared with existed methods, the topological importance of miRNA targets was prioritized based on cross-level miRNA-mRNA and protein-protein interaction network analyses. The biomarker potential of identified miRNAs was computationally validated and explored by receiver-operating characteristic (ROC) evaluation and integrated "miRNA-gene-pathway" pathogenic survey. RESULTS: Three miRNAs, i.e., miR-145-5p, miR-155-5p, and miR-23b-3p, were screened as putative biomarkers for KTR monitoring. Among them, miR-155-5p was a previously reported signature in KTR, whereas the remaining two were novel candidates both for KTR diagnosis and subtyping. The ROC analysis convinced the power of identified miRNAs as single and combined biomarkers for KTR prediction in kidney tissue and blood samples. Functional analyses, including the latent crosstalk among HLA-related genes, immune signaling pathways and identified miRNAs, provided new insights of these miRNAs in KTR pathogenesis. CONCLUSIONS: A network-based bioinformatics approach was proposed and applied to identify candidate miRNA biomarkers for KTR study. Biological and clinical validations are further needed for translational applications of the findings.

Preoperative Anemia as a Simple Prognostic Factor in Patients with Urinary Bladder Cancer.

BACKGROUND To evaluate the incidence of preoperative anemia and its prognostic role in patients with urinary bladder cancer (BC). MATERIAL AND METHODS A total of 317 patients diagnosed with BC were enrolled in this retrospective cohort study. Univariate and multivariate analysis was used to identify independent prognostic factors and Kaplan-Meier survival analysis was applied to examine the influence of anemia on survival. RESULTS 109 patients (34.4%) were anemic with a median preoperative hemoglobin of 114 g/L (interquartile range 104 to 122.5). After a median of 6 years follow-up (range: 2 to 8 years), the median recurrence-free survival (RFS), progression-free survival (PFS), and overall survival (OS) in anemic patients were significantly lower than non-anemic patients (p≤0.001). Multivariate Cox analysis indicated that anemia remained an independent predictor of RFS and OS (p=0.010, 0.007). CONCLUSIONS Anemic patients with BC are likely to have a shorter RFS and OS than non-anemic patients, and anemia is an independent predictor of RFS and OS.

Arterial spin labeling combined with T1 mapping for assessment of kidney function and histopathology in patients with long-term renal transplant survival after kidney transplantation.

Background: The long-term survival of kidney transplants is often influenced by various factors, among which renal allograft rejection is the most notable factor. A noninvasive and reliable imaging biomarker correlating with kidney function and histopathology would facilitate longitudinal long-term follow-up of renal allografts. The aim of the study is to investigate the value of arterial spin labeling (ASL) combined with T1 mapping for assessing kidney function in patients with long-term renal transplant survival, and to establish radiological and histopathologic correlations between the magnetic resonance imaging (MRI) measurements and kidney allograft biopsy findings. Methods: Kidney transplant recipients who were admitted to the Department of Urology in First Affiliated Hospital of Soochow University between January and December 2022 were prospectively consecutively recruited [group A, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; group B, 30≤ eGFR <60 mL/min/1.73 m2; group C, eGFR <30 mL/min/1.73 m2], and part of them underwent biopsies. All patients underwent ASL and T1 mapping. MRI parameters were calculated and analyzed. Results: A total of 63 patients (Group A, 30 cases; Group B, 20 cases; and Group C, 13 cases) were included in this cross-sectional study. Cortical T1 increased, whereas renal blood flow (RBF) and ΔT1 [100% × (cortical T1 - medullary T1)/cortical T1] decreased with the decrease of eGFR. The RBF, cortical T1, and ΔT1 values were moderately correlated with eGFR (r=0.569, -0.573, and 0.672, respectively). The MRI parameters were moderately correlated with Banff scores, which determined renal allograft rejection and chronicity. The area under the curve (AUC) for the discrimination of groups A versus B and groups A versus C were 0.740 [95% confidence interval (CI): 0.597-0.854, P=0.004] and 0.923 (95% CI: 0.800-0.982, P<0.001), respectively, using ASL; 0.873 (95% CI: 0.749-0.950, P<0.001) and 0.926 (95% CI: 0.803-0.983, P<0.001), respectively, using T1 mapping; and 0.892 (95% CI: 0.771-0.962, P<0.001) and 0.956 (95% CI: 0.846-0.995, P<0.001), respectively, using multi-parameter MRI. The AUC for discrimination between groups B and C was 0.729 (95% CI: 0.546-0.868, P=0.02) using ASL. Conclusions: The RBF, cortical T1, and ΔT1 can serve as new imaging biomarkers of kidney function and histopathological microstructure.

Randomized prospective trial of tubeless versus conventional minimally invasive percutaneous nephrolithotomy.

PURPOSE: To evaluate the effectiveness and safety of minimally invasive percutaneous nephrolithotomy (mPCNL) without nephrostomy drainage tubes. METHODS: We prospectively enrolled 32 eligible patients with kidney stones at our hospital. Patients were randomly assigned to a conventional mPCNL group (ureteric Double-J stents and nephrostomy drainage tubes) or a tubeless mPCNL group (ureteric catheter but no drainage tubes). A single experienced surgeon performed all operations. RESULTS: At baseline, the two groups had similar age, maximum stone diameter, and gender distribution. There were no significant differences in operation time, presence of postoperative fever, stone clearance, and level of postoperative serum hemoglobin. However, the tubeless mPCNL group had significantly shorter hospital stays (3 vs. 4 days, p = 0.032) and significantly less back pain (5 patients vs. 14 patients, p = 0.003) than the conventional mPCNL group. CONCLUSIONS: No significant differences were found between conventional and tubeless mPCNL in safety issues and stone clearance rate. However, patients treated with tubeless mPCNL had shorter hospitalization stays and were less likely to experience back pain.

Soluble FGL2 induced by tumor necrosis factor-α and interferon-γ in CD4+ T cells through MAPK pathway in human renal allograft acute rejection.

BACKGROUND: Acute rejection (AR), initiated by alloreactive CD4(+) T cells, hampers allograft survival. Soluble fibrinogen-like protein 2 (sFGL2) is a novel effector of CD4(+) T cells. We previously found that serum sFGL2 significantly increased in renal allograft recipients with AR. In this study, sFGL2 secretion by CD4(+) T cells and its mechanism were further explored both in vivo and in vitro. MATERIALS AND METHODS: Forty cases of living-related renal transplant recipients with biopsy-proven AR or stable renal function were collected and detected serum sFGL2, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and peripheral CD4(+) T cells. In vitro, the isolated human CD4(+) T cells were stimulated by TNF-α or IFN-γ. sFGL2 in the supernatant and mitogen-activated protein kinase (MAPK) proteins in the CD4(+) T cells were investigated. Approval for this study was obtained from the Ethics Committee of Fudan University. RESULTS: sFGL2, TNF-α, IFN-γ, and CD4(+) T cells were significantly increased in the peripheral blood of renal allograft recipients with AR. Stimulation with 1000 U/mL TNF-α or 62.5 U/mL IFN-γ for 48 h provided an optimal condition for CD4(+) T cells to secrete sFGL2 in vitro. Phosphorylated (p-) c-Jun N-terminal kinase was remarkably upregulated in the activated CD4(+) T cells, whereas no significant changes were found in p-p38 MAPK or p-ERK1/2 expression. Furthermore, inhibition of c-Jun N-terminal kinase significantly reduced sFGL2 secretion by CD4(+) T cells. CONCLUSIONS: sFGL2 secretion by CD4(+) T cells can be induced with TNF-α and IFN-γ stimulation through MAPK signaling in renal allograft AR. Our study suggests that sFGL2 is a potential mediator in the pathogenesis of allograft rejection.

Risk Factors and Short-Term Prognosis of Lymphocele After Kidney Transplant.

OBJECTIVES: Lymphocele is a frequent complication after kidney transplant and needs attention. This study was undertaken to analyze perioperative risk factors and short-term outcomes associated with lymphocele after kidney transplant. MATERIALS AND METHODS: Our single-center study retrospectively analyzed 264 recipients of kidney allografts from January 2018 to October 2021. Patients were classified into 2 groups according to the occurrence of lymphocele. Perioperative clinical data and follow-up indicators were compared between groups. RESULTS: The incidence of lymphocele after kidney transplant was 19.7%. Univariate analysis showed that percentage of male patients, hypothermic machine perfusion proportion, and postoperative hemoglobin and albumin were lower and flow velocity of renal artery was higher in the lymphocele group compared with the control group. Multivariate logistic regression revealed that postoperative hemoglobin <95 g/L (odds ratio = 2.01; 95% confidence interval, 1.01-4.05; P = .03) was an independent risk factor and hypothermic machine perfusion (odds ratio = 0.27; 95% confidence interval, 0.08-0.96; P = .04) was a protective factor for the determination of lymphocele. Comparisons of related complications indicated that drainage tube and urinary catheter removal times were longer and urinary tract infection and moderate to severe anemia proportions were higher in the lymphocele group. Follow-up data showed that postoperative 1-month serum creatinine was higher and 1-month estimated glomerular filtration rate was lower in lymphocele group compared with the control group, but no significant differences were shown at 12 months. CONCLUSIONS: Postoperative hemoglobin may be a risk factor and hypothermic machine perfusion may be a protective factor for lymphocele after kidney transplant. Lymphocele only temporarily affects short-term kidney function, especially during hospitalization.

Resistive index of prostate capsular arteries: a newly identified parameter to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia.

PURPOSE: We evaluated the association of the resistive index of the prostate capsular arteries and bladder outlet obstruction severity in men with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 74 patients histologically diagnosed with benign prostatic hyperplasia were ultimately enrolled in this prospective study. Urodynamics were performed by a urologist to determine bladder outlet obstruction. Baseline parameters measured in patients with benign prostatic hyperplasia were the prostate capsular artery resistive index, International Prostate Symptom Score, quality of life score, total prostate and transition zone volume, and the transition zone index. ROC curves were produced to calculate the ROC AUC and evaluate the diagnostic performance of the prostate capsular artery resistive index, International Prostate Symptom Score, obstructive symptoms, total prostate and transition zone volume, and the transition zone index for bladder outlet obstruction. RESULTS: Significant difference between patients with and without bladder outlet obstruction was observed in the resistive index, which showed the highest coefficient with the degree of obstruction (r = 0.712, p <0.0001). At a cutoff of 0.69 the resistive index distinguished patients with and without bladder outlet obstruction with 78% sensitivity and 86.4% specificity. The prostate capsular artery resistive index had the maximum AUC of 0.823. CONCLUSIONS: The prostate capsular artery resistive index is significantly higher in patients with benign prostatic hyperplasia related bladder outlet obstruction than in those without such obstruction. The resistive index might serve as a novel indicator to diagnose and assess bladder outlet obstruction in patients with benign prostatic hyperplasia.

Erythropoietin ameliorates renal ischemia and reperfusion injury via inhibiting tubulointerstitial inflammation.

BACKGROUND: Tubulointerstitial inflammation is the characteristics of renal ischemia reperfusion injury (IRI) that is inevitable in kidney transplantation. Erythropoietin (EPO) has recently been shown to have protective effects on renal IRI by anti-apoptosis and anti-oxidation. Here, the effect and mechanism of EPO on renal IRI were further investigated, with a focus on tubulointerstitial inflammation. MATERIALS AND METHODS: Male Sprague-Dawley rats were administrated with saline or EPO prior to IRI induced by bilateral renal pedicle clamping. Twenty-four hours following reperfusion, the effects of EPO on renal IRI were assessed by renal function and structure, tubulointerstitial myeloperoxidase (MPO) positive neutrophils, and proinflammatory mediator gene expression. The translocation and activity of NF-κB in renal tissues were also evaluated. RESULTS: Compared with control groups, the EPO treated group exhibited lower serum urea and creatinine levels, limited tubular necrosis with a lower score of renal histological lesion. MPO positive cells in the tubulointerstitial area were greatly increased by IRI, but significantly reduced by the treatment of EPO. The gene expression of proinflammatory cytokines (IL-1ß, IL-6, IL-10, and TNF-α) and chemokine (MCP-1) was also significantly decreased by EPO. In addition, less activation and nuclear-translocation of NF-κB was observed in the kidney treated by EPO as well. CONCLUSION: EPO improved renal function and structure in IRI rats via reducing neutrophils in the tubulointerstitium, the production of proinflammatory cytokines and chemokine, as well as the activation and nuclear-translocation of NF-κB. EPO may have potential clinical applications as an anti-inflammation agent clinically for a wide range of injury.

Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a Donation-After-Cardiac-Death Kidney Transplant: A Randomized Clinical Trial.

Importance: Delayed graft function (DGF) is a risk factor for acute rejection and graft failure after kidney transplant. Previous studies have suggested that dexmedetomidine may be renoprotective, but whether the use of dexmedetomidine would improve kidney allograft function is unknown. Objective: To investigate the effects of perioperative dexmedetomidine on DGF following a donation-after-cardiac-death (DCD) kidney transplant. Design, Setting, and Participants: This single-center, double-blind, placebo-controlled randomized clinical trial was conducted at The First Affiliated Hospital of Soochow University in Suzhou, China. Adults (18 years or older) who were scheduled for DCD kidney transplant were enrolled between September 1, 2019, and January 28, 2021, and then randomized to receive either dexmedetomidine or normal saline (placebo). One-year postoperative outcomes were recorded. All analyses were based on the modified intention-to-treat population. Interventions: Patients who were randomized to the dexmedetomidine group received a 24-hour perioperative dexmedetomidine intravenous infusion (0.4 µg/kg/h intraoperatively and 0.1 µg/kg/h postoperatively). Patients who were randomized to the normal saline group received an intravenous infusion of the placebo with the same dose regimen as the dexmedetomidine. Main Outcomes and Measures: The primary outcome was the incidence of DGF, defined as the need for dialysis in the first posttransplant week. The prespecified secondary outcomes were in-hospital repeated dialysis in the first posttransplant week, in-hospital acute rejection, and serum creatinine, serum cystatin C, estimated glomerular filtration rate, need for dialysis, and patient survival on posttransplant day 30. Results: Of the 114 patients enrolled, 111 completed the study (mean [SD] age, 43.4 [10.8] years; 64 male patients [57.7%]), of whom 56 were randomized to the dexmedetomidine group and 55 to the normal saline group. Dexmedetomidine infusion compared with normal saline reduced the incidence of DGF (17.9% vs 34.5%; odds ratio [OR], 0.41; 95% CI, 0.17-0.98; P = .04) and repeated dialysis (12.5% vs 30.9%; OR, 0.32; 95% CI, 0.13-0.88; P = .02, which was not statistically significant after multiple testing corrections), without significant effect on other secondary outcomes. Dexmedetomidine vs normal saline infusion led to a higher median (IQR) creatinine clearance rate on postoperative days 1 (9.9 [4.9-21.2] mL/min vs 7.9 [2.0-10.4] mL/min) and 2 (29.6 [9.7-67.4] mL/min vs 14.6 [3.8-45.1] mL/min) as well as increased median (IQR) urine output on postoperative days 2 (106.5 [66.3-175.6] mL/h vs 82.9 [27.1-141.9] mL/h) and 7 (126.1 [98.0-151.3] mL/h vs 107.0 [82.5-137.5] mL/h) and at hospital discharge discharge (110.4 [92.8-121.9] mL/h vs 97.1 [77.5-113.8] mL/h). Three patients (5.5%) from the normal saline group developed allograft failure by the post hoc 1-year follow-up visit. Conclusions and Relevance: This randomized clinical trial found that 24-hour perioperative dexmedetomidine decreased the incidence of DGF after DCD kidney transplant. The findings support the use of dexmedetomidine in kidney transplants. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900025493.

Cyclic Helix B Peptide Prolongs Skin Allograft Survival via Inhibition of B Cell Immune Responses in a Murine Model.

Antibody-mediated rejection (AMR) represents a major cause of allograft dysfunction and results in allograft failure in solid organ transplantation. Cyclic helix B peptide (CHBP) is a novel erythropoietin-derived peptide that ameliorated renal allograft rejection in a renal transplantation model. However, its effect on AMR remains unknown. This study aimed to investigate the effect of CHBP on AMR using a secondary allogeneic skin transplantation model, which was created by transplanting skin from BALB/c mice to C57BL/6 mice with or without CHBP treatment. A secondary syngeneic skin transplantation model, involving transplantation from C57BL/6 mice to C57BL/6 mice, was also created to act as a control. Skin graft rejection, CD19+ B cell infiltration in the skin allograft, the percentages of splenic plasma cells, germinal center (GC) B cells, and Tfh cells, the serum levels of donor specific antibodies (DSAs), and NF-κB signaling in splenocytes were analyzed. Skin allograft survival was significantly prolonged in the CHBP group compared to the allogeneic group. CHBP treatment also significantly reduced the CD19+ B cell infiltration in the skin allograft, decreased the percentages of splenic plasma cells, GC B cells, and Tfh cells, and ameliorated the increase in the serum DSA level. At a molecular level, CHBP downregulated P100, RelB, and P52 in splenocytes. CHBP prolonged skin allograft survival by inhibiting AMR, which may be mediated by inhibition of NF-κB signaling to suppress B cell immune responses, thereby decreasing the DSA level.

Significance of examined lymph-node count in accurate staging and long-term survival in patients undergoing radical prostatectomy: a population-based study.

PURPOSE: The number of examined lymph node (ELN) is regarded as the critical quality index for cancer care. We scrutinize the relationship among ELN number, accurate staging, and long-term survival in prostate cancer (Pca). METHODS: Population-based data on Pca patients in 2004-2015 from the US SEER database were investigated. The connection among ELN number and stage migration, overall survival (OS), and prostate cancer-specific survival (CSS) were evaluated by performing multivariable-adjusted logistic, Cox proportional hazards, and fine-gray competing-risk regression models, respectively. LOWESS smoother was used to fit the series of ELN number, odds ratios (OR), and hazard ratios (HR), while the Chow test was used to resolve the structural breakpoints. Subgroup and interaction analyses were performed in different risk populations. RESULTS: Overall, 84,838 patients were analyzed. Serial improvements were seen in stage migration (OR, 1.072, P < 0.001), OS (HR, 0.991; P < 0.001), and CSS (HR, 0.983; P < 0.001) per additional ELN after adjusting for confounders. Subgroup analysis revealed that the ELN number gains the most staging and survival benefits in high-risk population (P for interaction < 0.001). Cut-point analyses suggested that an optimal number of 12 ELNs, which was verified by the cumulative incidence curve, had a strong capability to distinguish different probabilities of CSS. CONCLUSIONS: Higher quantities of ELNs are related to more-accurate nodal staging and long-term survival of Pca patients undergoing RP. We highlight that 12 ELNs are the optimal cut-point for the high-risk population to investigate the quality of LN detection and stratifying postoperative prognosis.

Long non-coding RNA MIR4435-1HG promotes cancer growth in clear cell renal cell carcinoma.

BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in cancer development, yet their roles in renal carcinoma remain unclear. OBJECTIVE: We performed this study in order to investigate the expression and roles of lncRNAs in renal cell carcinoma. METHODS: In this study, we investigated the expression of lncRNAs in renal cell carcinoma through microarray analysis. Quantitative real-time PCR was performed to measure the expression of lncRNAs. Gain- or loss-of-function experiments were performed to investigate the roles of lncRNAs in cell proliferation and apoptosis. RNA pull-down and western blotting were performed to explore the underlying mechanism. RESULTS: The microarray analysis identified an upregulated lncRNA MIR4435-1HG in renal carcinoma. The expression level of MIR4435-1HG was correlated with TNM stage, tumor size, and Fuhrman grade. High expression of MIR4435-1HG indicated poor prognosis. MIR4435-1HG knockdown inhibited cell proliferation, and suppressed the migrating and invasive capacity of renal carcinoma cells. RNA pull-down followed by mass spectrometry revealed an interaction between MIR4435-1HG and pyruvate carboxylase, which was later corroborated by western blotting. CONCLUSIONS: MIR4435-1HG plays a critical role in the oncogenesis of renal cell carcinoma and may serve as a potential biomarker for renal cell carcinoma.

Resection of adult polycystic kidney with retroperitoneal laparoscopic technique assisted by arterial embolization.

BACKGROUND: Traditional surgical methods have high complication rate and large injury in the resection of adult polycystic kidney. We investigated the effect of retroperitoneal laparoscopic resection of adult polycystic kidney assisted by arterial embolization. METHODS: The data of adult polycystic kidney patients who underwent laparoscopic surgery assisted by arterial embolization from November 2015 to November 2018 in our hospital were retrospectively analyzed, and the data of patients who underwent open surgery during the same period were collected. The basic data, surgical conditions, postoperative recover situation, and complications of the two groups were compared. RESULTS: There was no significant difference in the basic situation between the laparoscopic operation group and open operation (control) group. The bleeding volume, hospitalization time, and the length of incision in the laparoscopic operation group were significantly better than those in the open operation (control) group, but the operation time was significantly longer than that in the open operation group. There was no significant difference in drainage tube extraction time, bed rest time and blood transfusion rate between the two groups. There was no significant difference in the complication rate between the two groups. CONCLUSIONS: Arterial interventional embolization-assisted retroperitoneal laparoscopy is an effective method for the resection of polycystic kidney.

Tolerance induction with donor hematopoietic stem cell infusion in kidney transplantation: a single-center experience in China with a 10-year follow-up.

BACKGROUND: Immunosuppressive therapy after life-saving kidney transplantation increases the risk of infection, cardiovascular diseases, metabolic diseases, and cancer. To date, four centers (three in the USA and one in South Korea) have reported clinical tolerance trials in kidney transplantation. We performed the first Chinese clinical trial in which kidney transplantation was combined with donor hematopoietic stem cell (DHSC) infusion to induce tolerance. This study summarizes the 10-year follow-up results. METHODS: From 2009 to 2017, 11 donor/recipient pairs underwent living-related kidney transplantation combined with DHSC infusion. Two of the pairs were human leukocyte antigen (HLA)-matched, and nine were HLA-mismatched. DHSCs were mobilized using granulocyte colony-stimulating factor (G-CSF) and harvested 1 day before transplantation. The recipients received consecutive total lymphoid irradiation (TLI) for 3 days before kidney transplantation. The induction drug was anti-thymocyte globulin (ATG). DHSCs were infused on days 2, 4, and 6 post surgery. All patients were followed-up until Dec 2019. Routine laboratory examinations, chimerism, biopsies, and mixed lymphocyte reactions were performed. RESULTS: One HLA-matched recipient had 30-50% chimerism, while the other patients had less than 1% chimerism. Recipients had donor-specific hyporesponsiveness (DSH) while sustaining normal reactivity to non-donors in mixed lymphocyte reactions. All recipients were followed up for 717-3,918 days. One recipient lost allograft function, and 10 recipients had stable renal function. None of the 11 recipients developed myelosuppression or graft-versus-host disease (GVHD) post transplantation. Our protocol did not increase the risk of infection. Allograft biopsy confirmed that one patient had mild rejection with Banff grade IA, while the other ten recipients did not develop rejection. Five patients were able to reduce the dose of their immunosuppressive therapy. CONCLUSIONS: Our immune tolerance induction protocol, which used DHSC infusion and TLI, achieved low dose immunosuppression with long-term stable kidney allograft survival in Chinese patients.

The Predictive Value of Preoperative High-Sensitive C-Reactive Protein/Albumin Ratio in Systemic Inflammatory Response Syndrome After Percutaneous Nephrolithotomy.

OBJECTIVE: The aim of the study was to evaluate the predictive value of preoperative high-sensitive C-reactive protein/albumin (hs-CRP/Alb) ratio in systemic inflammatory response syndrome (SIRS) after percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: We retrospectively reviewed 556 patients who underwent PCNL at our institution between August 2015 and February 2018. The primary endpoint for the study was the development of SIRS after operation. A univariate and multivariate logistic regression analysis was used to identify the independent factors associated with the post-PCNL SIRS. Receiver operating characteristic (ROC) curves were constructed and the areas under the curve (AUC) were calculated to compare the discriminatory ability of systemic inflammation biomarkers. RESULTS: Among the 556 patients who underwent PCNL, 123 patients (22.1%) developed SIRS. Multivariate analysis revealed that female gender (OR 1.691; 95% CI 1.045-2.735; p = 0.032), positive urine culture (OR 1.972; 95% CI 1.204-3.231; p < 0.01), hs-CRP/Alb ratio (OR 6.925; 95% CI 4.244-11.300; p < 0.01), neutrophil to lymphocyte ratio (NLR) (OR 2.476; 95% CI 1.471-4.167; p < 0.01), and prognostic nutritional index (PNI) (OR 0.559; 95% CI 0.338-0.924; p = 0.023) were independent predictors of post-PCNL SIRS. The optimal cutoff value of the hs-CRP/Alb ratio was 0.06 from the ROC analysis. The elevated hs-CRP/Alb ratio was significantly associated with female gender, positive urine culture, hs-CRP, albumin, leukocyte, neutrophil, monocyte, platelet, hemoglobin, creatinine, NLR, lymphocyte to monocyte ratio (LMR), platelet to lymphocyte ratio (PLR), PNI, high-sensitive modified Glasgow prognostic score (hs-mGPS), development of sepsis, ICU admission, and length of stay (all p < 0.05). In addition, the hs-CRP/Alb ratio had a higher AUC (0.791) with a sensitivity of 76.4% and a specificity of 73.2% than NLR (0.669), LMR (0.633), PLR (0.594), PNI (0.629), and hs-mGPS (0.739). CONCLUSIONS: The preoperative hs-CRP/Alb ratio is independently predictive for the development of SIRS after PCNL. Moreover, compared with other systemic inflammation biomarkers, the preoperative hs-CRP/Alb ratio shows a better predictive value.

The value of cystatin C and urinary and serum neutrophil gelatinase-associated lipocalin during the perioperative period of renal transplantation.

BACKGROUND: The perioperative management of renal transplantation is complex. Our research aimed to study the clinical value of cystatin-C (Cys-C) and urinary and serum neutrophil gelatinase-associated lipocalin (NGAL) during the perioperative period of renal transplantation. METHODS: We collected the clinical information of 47 renal transplantation patients. Urine and serum samples were collected daily until the second week and then weekly until discharge to determine serum NGAL (s-NGAL), urine NGAL (u-NGAL), serum creatinine (s-Cr), and Cys-C levels. Receiver-operating characteristic (ROC) analysis was used, and the area under the curve (AUC) was compared to evaluate the accuracy of the diagnosis of delayed graft function (DGF). Multivariable analysis was used to find the association between the markers and renal function at discharge. RESULTS: In our research, the value of Cys-C, serum NGAL, and urine NGAL were higher in DGF group. In the ROC analysis, Cys-C had the highest AUC (0.939) compared with s-NGAL (0.909), u-NGAL (0.856), and s-Cr (0.747). Multivariable analysis showed that Cys-C levels in the first week after the operation and cold ischemia time were independently associated with estimated glomerular filtration rate (eGFR) at discharge (P<0.05). CONCLUSIONS: Our results showed that Cys-C, serum NGAL, and urine NGAL could reflect renal function sensitively. Cys-C had the highest sum of sensitivity and specificity at 4.77 mg/L, with a sensitivity of 0.818 and specificity of 0.889. The Cys-C level during the first week after the operation was independently associated with eGFR at discharge and could predict the short-term prognosis of renal transplantation patients.

Discovery of potent necroptosis inhibitors targeting RIPK1 kinase activity for the treatment of inflammatory disorder and cancer metastasis.

Necroptosis is a form of regulated necrosis controlled by receptor-interacting kinase 1 (RIPK1 or RIP1), RIPK3 (RIP3), and pseudokinase mixed lineage kinase domain-like protein (MLKL). Increasing evidence suggests that necroptosis is closely associated with pathologies including inflammatory diseases, neurodegenerative diseases, and cancer metastasis. Herein, we discovered the small-molecule PK6 and its derivatives as a novel class of necroptosis inhibitors that directly block the kinase activity of RIPK1. Optimization of PK6 led to PK68, which has improved efficacy for the inhibition of RIPK1-dependent necroptosis, with an EC50 of around 14-22 nM in human and mouse cells. PK68 efficiently blocks cellular activation of RIPK1, RIPK3, and MLKL upon necroptosis stimuli. PK68 displays reasonable selectivity for inhibition of RIPK1 kinase activity and favorable pharmacokinetic properties. Importantly, PK68 provides strong protection against TNF-α-induced systemic inflammatory response syndrome in vivo. Moreover, pre-treatment of PK68 significantly represses metastasis of both melanoma cells and lung carcinoma cells in mice. Together, our study demonstrates that PK68 is a potent and selective inhibitor of RIPK1 and also highlights its great potential for use in the treatment of inflammatory disorders and cancer metastasis.

The performance of the new prognostic grade and stage groups in conservatively treated prostate cancer.

We evaluated the prognosis of the new grade groups and American Joint Committee on Cancer (AJCC) stage groups in men with prostate cancer (PCa) who were treated conservatively. A total of 13 798 eligible men were chosen from the Surveillance Epidemiology and End Results database. The new grade and AJCC stage groups were investigated on prostate biopsy specimens. Kaplan-Meier survival analysis and multivariable hazards models were applied to estimate the association of new grade and stage groups with overall survival (OS) and PCa-specific survival (CSS). Mean follow-up was 42.65 months (95% confidence interval: 42.47-42.84) in the entire cohort. The 3-year OS and CSS rates stepped down for grade groups 1-5 and AJCC stage groups I-IVB, respectively. After adjusting for clinical and pathological characteristics, all grade groups and AJCC stage groups were associated with higher all-cause and PCa-specific mortality compared to the reference group (all P ≤ 0.003). In conclusion, we evaluated the oncological outcome of the new grade and AJCC stage groups on biopsy specimens of conservatively treated PCa. These two novel clinically relevant classifications can assist physicians to determine different therapeutic strategies for PCa patients.