Global trends in chronic kidney disease-related mortality: a systematic review protocol.

INTRODUCTION: In recent decades, all-cause mortality has increased among individuals with chronic kidney disease (CKD), influenced by factors such as aetiology, standards of care and access to kidney replacement therapies (dialysis and transplantation). The recent COVID-19 pandemic also affected mortality over the past few years. Here, we outline the protocol for a systematic review to investigate global temporal trends in all-cause mortality among patients with CKD at any stage from 1990 to current. We also aim to assess temporal trends in the mortality rate associated with the COVID-19 pandemic. METHODS AND ANALYSIS: We will conduct a systematic review of studies reporting mortality for patients with CKD following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We will search electronic databases, national and multiregional kidney registries and grey literature to identify observational studies that reported on mortality associated with any cause for patients with CKD of all ages with any stage of the disease. We will collect data between April and August 2023 to include all studies published from 1990 to August 2023. There will be no language restriction, and clinical trials will be excluded. Primary outcome will be temporal trends in CKD-related mortality. Secondary outcomes include assessing mortality differences before and during the COVID-19 pandemic, exploring causes of death and examining trends across CKD stages, country classifications, income levels and demographics. ETHICS AND DISSEMINATION: A systematic review will analyse existing data from previously published studies and have no direct involvement with patient data. Thus, ethical approval is not required. Our findings will be published in an open-access peer-reviewed journal and presented at scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42023416084.

Long-term outcome of pediatric renal transplantation with donors younger than 6 years.

BACKGROUND: Renal transplantation is currently the best treatment option for patients with end-stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long-term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient. METHODS: Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications. RESULTS: A total of 43 transplants were performed with donors aged 3-6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow-up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow-up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications. CONCLUSIONS: Renal transplants of grafts equal to or less than 6 years old have good short-term and acceptable long-term results in pediatric patients.

Post-Transplant Fecal Carriage of Antibiotic Resistant and B-Lactamases-Producing Enterobacteriales among Renal Transplant Recipients.

BACKGROUND: The intestinal colonization and transmission of antibiotic-resistant Enterobacteriales to renal transplant recipients may pose a threat to them because they are profoundly immunocompromised and vulnerable to infection. Hence, it is crucial to identify these antibiotic-resistant fecal Enterobacteriales harboring high-risk populations. The objective of this study was to determine antibiotic resistance as well as ß-lactamases production in fecal Enterobacteriales among renal transplant recipients. METHODS: The stool samples, one collected from each transplant recipient, were processed for isolation and identification of Enterobacteriales and were tested for their antibiotic susceptibility, extended-spectrum ß-lactamase, and metallo-ß-lactamase production by standard methods. RESULTS: A total of 103 Enterobacteriales comprising of Escherichia coli (86.4%), Klebsiella species (11.7%), and Citrobacter species (1.9%) were isolated and more than 60% of the E. coli were found resistant to ceftazidime and ciprofloxacin and around half of the Klebsiella species were resistant to ceftazidime and fluroquinolones. The extended-spectrum ß-lactamase production was seen in 3.4% and 8.3% and metallo-ß-lactamase production in 24.7% and 33.3% of E. coli and Klebsiella species, respectively. The high proportion of ß-lactamase-producers were resistant to piperacillin-tazobactam, meropenem, gentamicin, and amikacin than ß-lactamases non-producers. CONCLUSION: Since the antibiotic resistance is higher in fecal Enterobacteriales, each renal transplant recipient should be screened for these highly resistant intestinal colonizers after transplantation in order to prevent infections and to reduce the rate of transplant failure due to infections.

Comprehensive molecular and cellular characterization of endoplasmic reticulum stress-related key genes in renal ischemia/reperfusion injury.

Background: Renal ischemia-reperfusion injury (RIRI) is an inevitable complication in the process of kidney transplantation and lacks specific therapy. The study aims to determine the underlying mechanisms of RIRI to uncover a promising target for efficient renoprotection. Method: Four bulk RNA-seq datasets including 495 renal samples of pre- and post-reperfusion were collected from the GEO database. The machine learning algorithms were utilized to ascertain pivotal endoplasmic reticulum stress genes. Then, we incorporated correlation analysis and determined the interaction pathways of these key genes. Considering the heterogeneous nature of bulk-RNA analysis, the single-cell RNA-seq analysis was performed to investigate the mechanisms of key genes at the single-cell level. Besides, 4-PBA was applied to inhibit endoplasmic reticulum stress and hence validate the pathological role of these key genes in RIRI. Finally, three clinical datasets with transcriptomic profiles were used to assess the prognostic role of these key genes in renal allograft outcomes after RIRI. Results: In the bulk-RNA analysis, endoplasmic reticulum stress was identified as the top enriched pathway and three endoplasmic reticulum stress-related genes (PPP1R15A, JUN, and ATF3) were ranked as top performers in both LASSO and Boruta analyses. The three genes were found to significantly interact with kidney injury-related pathways, including apoptosis, inflammatory response, oxidative stress, and pyroptosis. For oxidative stress, these genes were more strongly related to oxidative markers compared with antioxidant markers. In single-cell transcriptome, the three genes were primarily upregulated in endothelium, distal convoluted tubule cells, and collecting duct principal cells among 12 cell types of renal tissues in RIRI. Furthermore, distal convoluted tubule cells and collecting duct principal cells exhibited pro-inflammatory status and the highest pyroptosis levels, suggesting their potential as main effectors of three key genes for mediating RIRI-associated injuries. Importantly, inhibition of these key genes using 4-phenyl butyric acid alleviated functional and histological damage in a mouse RIRI model. Finally, the three genes demonstrated highly prognostic value in predicting graft survival outcomes. Conclusion: The study identified three key endoplasmic reticulum stress-related genes and demonstrated their prognostic value for graft survival, providing references for individualized clinical prevention and treatment of postoperative complications after renal transplantation.

Open bypass revascularisation for endovascular-resistant transplant renal artery stenosis secondary to mechanical renal artery kinking.

Transplant renal artery stenosis (TRAS) represents a significant vascular complication subsequent to renal transplantation. This pathology is associated with grave implications including graft dysfunction and mortality. Early identification and therapeutical intervention are imperative for preserving graft longevity and achieving optimal clinical outcomes. We detail the case of a male in his 20s, following renal transplantation, who encountered recurrent TRAS, aetiologically linked to mechanical arterial kinking. Initial management using endovascular techniques yielded insufficient resolution. Consequently, the persistence of endovascular-resistant stenosis necessitated a surgical bypass intervention using the great saphenous vein, granting a 2-year period devoid of restenosis. The existing literature emphasises the indispensability of discerning the appropriate juncture for transitioning from endovascular to surgical management in TRAS cases. The robustness and durability of bypass grafts present an efficacious therapeutical strategy in contemporaneous practice.

Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation. A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes. Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.

Electrocauterization versus Ligation of Lymphatic Vessels to Prevent Lymphocele Development after Kidney Transplantation-A Meta-Analysis.

Background: Lymphoceles are amongst the most common complications following kidney transplantation. Therefore, effective strategies to prevent their development are needed. The ligation of lymphatic vessels has proven to be a successful concept for that purpose. However, whether electrocauterization or suture ligation is more effective is unclear. Methods: We conducted a meta-analysis using a random effects model with the log risk ratio as the primary outcome measure. Additionally, an analysis using a random effects model with the raw mean difference in lymphatic sealing time between suture ligation and electrocauterization was performed. Adequate studies were found in a literature search conducted in PubMed, CENTRAL and Web of Science as well as from independent sources. Results: A total of 8 studies including 601 patients were included in the analysis. The estimated average log risk ratio based on the random effects model was µ = -0.374 (95% CI: -0.949 to 0.201), which did not differ significantly from zero (z = -1.28, p = 0.2). The lymphatic sealing time was 7.28 (95% CI:1.25-13.3) minutes shorter in the electrocauterization group. Conclusions: We conclude that neither technique is superior for the purpose of lymphocele prevention post kidney transplantation, and secondary criteria like time savings, cost and surgeons' preference should be considered in the decision for an optimal outcome.

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.

Population pharmacokinetics of everolimus in renal transplant recipients receiving long-term multiple immunosuppressive therapy.

Everolimus is used for immunosuppression after renal transplantation. This study aimed to develop a population pharmacokinetic (PopPK) model of everolimus using therapeutic drug monitoring (TDM) data of patients under long-term multiple immunosuppressive therapy, including tacrolimus. To develop the model, 185 renal transplant recipients with 3358 everolimus blood concentrations during a median postoperative period of 35.3 months were included. The PopPK model is described as a one-compartment model with first-order absorption. The population mean of apparent clearance is 8.92 L/h (relative standard error = 3.6%), and this negatively correlated with the dose-normalized concentration (C/D) of tacrolimus and hematocrit value, and positively correlated with a daily dose of everolimus (i.e. TDM effect). The usefulness of dose adjustment using the final popPK model was assessed by a simulation study. The ratio of the first trough measurement within the therapeutic range of 3-8 ng/mL increased from 69.8% in the original dose to 87.9% in the individual dose calculated by the final PopPK model. The tacrolimus C/D ratio before initiating everolimus therapy and the hematocrit value were useful to estimate the initial dose of everolimus and can improve the safety and effectiveness of immunosuppressive therapy involving everolimus.

Torque Teno Virus (TTV) in Renal Transplant Recipients: Species Diversity and Variability.

Torque Teno Virus (TTV) is a nonpathogenic and ubiquitous ssDNA virus, a member of the Anelloviridae family. TTV has been postulated as a biomarker in transplant patients. This study aimed to determine the TTV species diversity and variability in renal transplant recipients and to associate species diversity with the corresponding TTV viral load. From 27 recipients, 30 plasma samples were selected. Viral load was determined using two real-time PCR assays, followed by RCA-NGS and ORF1 phylogenetic analysis. The TTV diversity was determined in all samples. Variability was determined in three patients with two sequential samples (pre- and post-transplantation). Most of the samples presented multiple TTV species, up to 15 different species were detected. In the pre-transplant samples (n = 12), the most prevalent species were TTV3 (75%) and TTV13 (75%), and the median number of species per sample was 5 (IQR: 4-7.5). TTV3 was also the most prevalent (56%) in the post-transplant samples (n = 18), and the median number of species was 2 (IQR: 1.8-5.5). No significant correlation between the number of species and viral load was found. The number and type of TTV species showed total variability over time. We report high TTV species diversity in Argentinian recipients, especially in pre-transplant period, with total intra-host variability. However, we found no significant correlation between this high diversity and TTV viral load.

Talaromycosis from Wuhan: two-case report and literature review.

Background: Talaromycosis is a serious opportunistic infectious disease caused by Talaromyces marneffei, which mostly occurs in immunocompromised patients. The disease is mainly prevalent in tropical countries and regions of Southeast Asia and South Asia, but non-endemic areas also have patients with Talaromycosis. The disease has no characteristic clinical manifestations and is difficult to diagnose. Delayed diagnosis often leads to death. Case presentation: Both patients had cellular immunodeficiency. Case 1 had a history of acquired immune deficiency syndrome, and case 2 had a history of renal transplantation and glucose-6-phosphate dehydrogenase deficiency. They all had fever, anemia, fatigue, and skin lesions. Case 1 had gastrointestinal bleeding, enlarged lymph nodes, and hepatosplenomegaly. Case 2 had cough and dyspnea. Both patients had thrombocytopenia and hypoalbuminemia; an increased neutrophil ratio, procalcitonin, and C-reactive protein; and abnormal liver function and coagulation dysfunction. Case 1 sputum culture, blood culture, and bronchoalveolar lavage fluid were positive for T. marneffei. T. marneffei was detected in the blood culture of case 2, with infection of Candida parapsilosis and Pneumocystis jirovecii. Chest computed tomography scan mainly showed pulmonary exudative lesions. Although these two patients were actively treated, they died of poor efficacy. Conclusion: Talaromycosis has an insidious onset, long course, atypical clinical symptoms, imaging performance and laboratory results, difficult diagnosis, and high mortality. Therefore, it is important to promptly consider and treat Talaromycosis in immunocompromised patients upon infection in order to reduce mortality.

An autophagy-associated diagnostic signature based on peripheral blood for antibody-mediated rejection in renal transplantation.

BACKGROUND: Antibody-mediated rejection (ABMR) emerged as a major cause of graft loss in renal transplantation. Needle biopsy is the gold standard for diagnosis of ABMR in renal allografts. Thus, noninvasive diagnosis methods of ABMR with high accuracy are urgently needed to prevent unnecessary biopsies. METHODS: We collected peripheral blood transcriptome data from two independent renal transplantation cohorts with patients with ABMR, stable well-functioning transplants (STA), and T-cell mediated rejection (TCMR). Differentially expressed genes (DEGs) were identified by comparing the ABMR group with the STA group. In addition, functional enrichment analysis and gene set enrichment analysis were performed to seek new key underlying mechanisms in ABMR. Subsequently, we utilized a Boruta algorithm and least absolute shrinkage and selection operator logistic algorithm to establish a diagnostic model which was then evaluated and validated in an independent cohort. RESULTS: According to functional enrichment analysis, autophagy was found to be the primary upregulated biological process in ABMR. Based on algorithms, three autophagy-associated genes, ubiquitin specific peptidase 33 (USP33), Ras homolog mTORC1 binding (RHEB), and ABL proto-oncogene 2 (ABL2), were selected to establish the diagnostic model in the training cohort. This autophagy-related gene model possessed good diagnostic value in distinguishing ABMR from STA blood samples in the training cohort (AUC = 0.907) and in the validation cohort (AUC = 0.972). In addition, this model also showed good discernibility in distinguishing ABMR from TCMR in the training and validation cohorts (AUCs = 0.908 and 0.833). CONCLUSION: We identified and validated an autophagy-associated diagnostic model with high accuracy for renal transplant patients with ABMR. Our study provided a new potential test for the non-invasive diagnosis of ABMR in clinical practice and highlighted the importance of autophagy in ABMR.

Laparoscopic Surgery for Sigmoid Colon Cancer in a Patient With a History of Two Renal Transplantations and Peritoneal Dialysis.

The development of transplantation technology has improved the prognosis of transplantation surgery; however, the negative impact of immunosuppressive drugs has increased the number of patients with cancer after transplantation. Recently, minimally invasive surgery has become more common for cancer treatment. We report our experience of performing laparoscopic sigmoid colon resection for a patient with a history of two renal transplantations and peritoneal dialysis. A 42-year-old male patient who developed purpura nephropathy underwent renal transplantation at ages eight and 34 years. He had been on peritoneal dialysis for five years before the second transplantation. The patient was referred to our department with the chief complaint of sudden abdominal pain. After an examination of imaging, we obtained a diagnosis of sigmoid colon cancer. Despite a history of peritoneal dialysis, laparoscopic sigmoid colon resection was successfully performed without complications after confirming that there were no adhesions in the abdominal cavity. The left lower port position had to be adjusted because the transplanted kidney protruded into the left iliac fossa. No postoperative complications and graft loss occurred. In this case, laparoscopic surgery was effective in lowering the risk of damage to the transplanted kidney and safely performing the procedure. The number of colorectal cancer cases in renal transplant patients is expected to increase, and some of these patients will have a history of peritoneal dialysis, which may make surgery more difficult. The successful outcome of this case highlights that laparoscopic surgery could be viable for patients with such a complex medical history.

Estenosis arterial del injerto renal: evaluación de la incidencia mediante ecografía doppler, factores de riesgo y análisis de las complicaciones que pueden afectar a la supervivencia del injerto / Transplant renal artery stenosis: Study of incidence using doppler ultrasound, risk factors and analysis is effect in graft outcomes

Introducción y objetivos La estenosis de la arteria del injerto renal (EAR) es una complicación vascular del trasplante renal cuya incidencia estimada es del 13%, la cual puede causar hipertensión arterial refractaria, disfunción renal y muerte prematura en los receptores. Métodos Se realizó un estudio retrospectivo que incluyó a todos los pacientes sometidos a trasplante renal entre 2014 y 2020. Los pacientes fueron evaluados mediante ecografía doppler renal sistemática tras el trasplante. Para identificar los factores de riesgo independientes de la estenosis de la arteria renal tras el trasplante, realizamos un análisis multivariante. Resultados Se incluyeron 724 trasplantes renales, el 12% eran de donante vivo y el 88% de donante fallecido. La edad media en los receptores era de 54,8 años y en los donantes era de 53. Se diagnosticó estenosis de la arteria del injerto renal en 70 (10%) receptores, la mayoría durante los primeros 6 meses después de la intervención. El 51% de los pacientes con estenosis de la arteria del injerto renal se manejaron de manera conservadora. El análisis multivariante mostró que la diabetes mellitus, el rechazo del injerto, la resutura arterial y el índice de masa corporal del donante eran factores de riesgo independientes de estenosis de la arteria renal después del trasplante. La supervivencia de los injertos con estenosis de la arteria del injerto renal fue del 98% a los 6 meses y del 95% a los 2 años. Conclusiones El uso sistemático de la ecografía doppler en el período inmediatamente posterior al trasplante permitió diagnosticar un 10% de estenosis de la arteria del injerto renal en nuestra cohorte. A pesar de los factores de riesgo mencionados anteriormente, un seguimiento y tratamiento adecuados podrían reducir el riesgo de pérdida del injerto en pacientes con estenosis de la arteria del injerto renal. (AU)

Introduction and objectives Transplant renal artery stenosis (TRAS) is a vascular complication after kidney transplantation which estimated incidence is 13%. It could cause refractory arterial hypertension, kidney dysfunction and premature death in transplant recipients. Methods We carried out a retrospective study including every patient who underwent renal transplantation between 2014 and 2020. They were evaluated with a systematic post-transplant renal Doppler ultrasound. To identify independent risk factors for transplant renal artery stenosis we performed a multivariate analysis. Results Seven hundred twenty-four kidney transplants were included, 12% were living donors and 88% were deceased donors. The mean age was 54.8 in recipients and 53 in donors. Transplant renal artery stenosis was diagnosed in 70 (10%) recipients, the majority in the first 6 months after surgery. The 51% of patients with transplant renal artery stenosis were managed conservatively. The multivariate analysis showed diabetes mellitus, graft rejection, arterial resuture and donor body mass index as independent risk factors for transplant renal artery stenosis. Survival of the grafts with transplant renal artery stenosis was 98% at 6 months and 95% at two years. Conclusions The systematic performance of Doppler ultrasound in the immediate post-transplant period diagnosed 10% of transplant renal artery stenosis in our cohort. Despite the above risk factors, an adequate monitoring and treatment could avoid the increased risk of graft loss in patients with transplant renal artery stenosis. (AU)

Intra-operative duplex ultrasound scanning in renal transplantation: protocol and service requirements.

Intra-operative duplex ultrasound in renal transplantation was first described in 1998 and whilst reported in problematic cases, there are few reports of its routine use and no current published protocols. Since 2013, we have used intra-operative ultrasound in all renal transplants. The formal protocol used since August 2020 is presented as a reference document for other transplant centres. A Canon Aplio 800 ultrasound system with an i22LH8 hockey-stick transducer is used to image the renal cortex and major vessels, and an i8CX1 matrix transducer to image the graft during and after fascial closure. These transducers are fully sterilised with Sterrad and no sheathing of transducers is required. The transplant surgeon scans within the sterile field with the sonographer guiding imaging and adjusting machine settings. Ultrasound findings are discussed between team members including any requirement for interventions. Ultrasound is performed at three stages of the operation: Stage 1: after clamp release identifying issues of graft vascularity including otherwise unrecognised major vessel and anastomotic abnormalities. Stage 2: following ureteric implantation identifying compromised perfusion due to graft rotation or vessel kinking. Stage 3: after fascial closure identifying compromised perfusion due to external compression. Post-operative scanning, including assessment of the collecting system and bladder, is performed routinely on days 1, 3, 7 and 30. The intervention is effective with no early graft losses or peri-operative vascular thromboses. The requirements for service provision are significant including the availability of additional transducers, and sonographers with expertise in intra-operative scanning able to attend after-hours for extended periods.

Assessment of CTLA-4 Gene Expression Levels on CD8+ T Cells in Renal Transplant Patients and Relation with Serum sCTLA-4 Levels.

CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) is an immune regulator molecule that is expressed on a variety of immune cells, including CD4+ and CD8+ T cells. After realizing the significance of this regulator molecule, researchers began to concentrate on its activation or inhibition in cancer. Even though there have been some studies on organ transplantation and autoimmunity, the role of the CTLA-4 molecule in renal transplantation has not been demonstrated. The goal of this study was to see how CTLA-4 gene expression and serum sCTLA-4 levels affected renal transplant patients. Peripheral blood samples were collected before and 1-3 months after renal transplantation from 29 recipients. CD8+ T lymphocytes were separated using magnetic beads and purity of the cells controlled by Flow cytometry. CTLA-4 mRNA levels were determined by Real-Time PCR while serum sCTLA-4 levels were assessed by ELISA. 55% of the patient had decreased level of CTLA-4 mRNA after transplantation when compared to pre-transplantation levels. Moreover 61% of the patient had lower serum sCTLA-4 levels after transplantation. sCTLA-4 levels were decreased 11% of the patients with rejection episode after transplantation when compared to stabile patients (5%). Kidney rejection is a complicated process influenced by numerous unknown factors. Several parameters should be evaluated together to precise rejection episodes or graft dysfunctions. Further research focused on the other immune checkpoint regulator molecules could give an opportunity to have an idea about the effect of these molecules on renal transplantation.

Expression of Rejection-Associated Transcripts in Early Protocol Renal Transplant Biopsies Is Associated with Tacrolimus Exposure and Graft Outcome.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter's association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) < 0.01, fold (change (FC) > 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 ± 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

Investigating the role of ultrasound-based shear wave elastography in kidney transplanted patients: correlation between non-invasive fibrosis detection, kidney dysfunction and biopsy results-a systematic review and meta-analysis.

INTRODUCTION: Interstitial fibrosis and tubular atrophy are leading causes of renal allograft failure. Shear wave elastography could be a promising noninvasive method for providing information on the state of the kidney, with specific regard to fibrosis but currently available data in the literature are controversial. Our study aimed to analyze the correlation between shear wave elastography and various kidney dysfunction measures. METHODS: This review was registered on PROSPERO (CRD42021283152). We systematically searched three major databases (MEDLINE, Embase, and CENTRAL) for articles concerning renal transplant recipients, shear wave elastography, fibrosis, and kidney dysfunction. Meta-analytical calculations for pooled Pearson and Spearman correlation coefficients (r) were interpreted with 95% confidence intervals (CIs). Heterogeneity was tested with Cochran's Q test. I2 statistic and 95% CI were reported as a measurement of between-study heterogeneity. Study quality was assessed with the QUADAS2 tool. RESULTS: In total, 16 studies were included in our meta-analysis. Results showed a moderate correlation between kidney stiffness and interstitial fibrosis and tubular atrophy, graded according to BANFF classification, on biopsy findings for pooled Pearson (r = 0.48; CI: 0.20, 0.69; I2 = 84%) and Spearman correlations (r = 0.57; CI: 0.35, 0.72; I2 = 74%). When compared to kidney dysfunction parameters, we found a moderate correlation between shear wave elastography and resistive index (r = 0.34 CI: 0.13, 0.51; I2 = 67%) and between shear wave elastography and estimated Glomerular Filtration Rate (eGFR) (r = -0.65; CI: - 0.81, - 0.40; I2 = 73%). All our outcomes had marked heterogeneity. CONCLUSION: Our results showed a moderate correlation between kidney stiffness measured by shear wave elastography and biopsy results. While noninvasive assessment of kidney fibrosis after transplantation is an important clinical goal, there is insufficient evidence to support the use of elastography over the performance of a kidney biopsy.

Impact of Transplantation Timing on Renal Graft Survival Outcomes and Perioperative Complications.

Nighttime organ transplantation aims to decrease cold ischemia duration, yet conflicting data exists on its impact on graft function and perioperative complications. This multicenter TRANSPLANT'AFUF study including 2,854 patients, transplanted between 1 January 2011, and 31 December 2022, investigated nighttime kidney transplantation's impact (8:00 p.m.-8:00 a.m.) versus daytime (8:00 a.m.-8:00 p.m.) on surgical complications and graft survival. Overall, 2043 patients (71.6%) underwent daytime graft, while 811 (28.4%) underwent nighttime graft. No impact was observed of timing of graft surgery on graft survival with a median survival of 98 months and 132 months for daytime and nightime grafting, respectively (p = 0.1749). Moreover, no impact was observed on early surgical complications (Clavien I-II = 20.95% for DG and 20.10% for NG; Clavien III-IV-V = 15.42% for DG and 12.94% for NG; p = 0.0889) and late complications (>30 days) (Clavien I-II = 6.80% for DG and 5.67% for NG; Clavien III-IV-V = 12.78% for DG and 12.82% for NG; p = 0.2444). Noteworthy, we found a significant increase in Maastricht 3 donors' rates in nighttime transplantation (5.53% DG vs. 21.45% NG; p < 0.0001). In conclusion, nighttime kidney transplantation did not impact early/late surgical complications nor graft survival.

H2S alleviates renal ischemia and reperfusion injury by suppressing ERS-induced autophagy.

BACKGROUND: Ischemia/reperfusion injury (IRI) can lead to acute kidney injury and result in high disability and mortality rates. Cystathionine γ-lyase (CSE)-produced hydrogen sulfide (H2S) has been confirmed to play a protective role in renal IRI. While autophagy is involved in renal IRI, its role in the regulation by endoplasmic reticulum stress (ERS) has not been considered. Our study explored the role of CSE/H2S in protecting against renal IRI by regulating ERS-induced autophagy. METHODS: C57/BL6 mice were subjected to 30-min renal ischemia followed by .24-h reperfusion injury (IRI). The H2S donor sodium hydrosulfide hydrate (NaHS) or the CSE inhibitor D,L-propargylglycine (PAG) was injected intraperitoneally (i.p) into the mice. Serum creatinine and urea nitrogen levels were analyzed to evaluate renal function. Renal tubule epithelial cell damage was measured by HE and PAS staining. ERS and microtubule-associated protein light chain 3 (LC3) autophagy (LC3-I to LC3-II conversion) were analyzed by using western blotting. RESULTS: In a C57/BL6 mouse model of acute renal IRI, the application of IRI impaired the renal function, which was accompanied by elevated serum creatinine (P < 0.001) and urea nitrogen levels (P < 0.001). While NaHS pretreatment dramatically attenuated renal IRI, PAG administration exacerbated renal IRI (P < 0.001). Furthermore, NaHS treatment inhibited the ERS-induced increased LC3II/I protein ratio (P < 0.001); increased Beclin-1 protein expression (P < 0.001); PAG pretreatment exacerbated the effects of ERS on both the LC3II/I ratio (P < 0.001) and the Beclin-1 protein expression (P < 0.001). CONCLUSIONS: Our results suggest that the CSE/H2S system is an important therapeutic target for protecting against renal IRI, and it may protect renal tubule epithelial cells from IRI by suppressing ERS-induced autophagy.