Challenges and opportunities in research on BK virus infection after renal transplantation.

Renal transplantation is one of the primary approaches for curing end-stage kidney disease. With advancements in immunosuppressive agents, the short-term and long-term survival rates of transplanted kidneys have significantly improved. However, infections associated with potent immunosuppression have remained a persistent challenge. Among them, BK virus (BKV) reactivation following renal transplantation leading to BK virus-associated nephropathy (BKVAN) is a major cause of graft dysfunction. However, we still face significant challenges in understanding the pathogenesis, prevention, diagnosis, and treatment of BKVAN. These challenges include: 1. The mechanism of BKV reactivation under immunosuppressive conditions has not been well elucidated, leading to difficulties in breakthroughs in clinical research on prevention, diagnosis, and treatment. 2. Lack of proper identification of high-risk individuals, and effective personalized clinical management strategies. 3.Lack of early and sensitive diagnostic markers. 4. Lack of direct and effective treatment options due to the absence of specific antiviral drugs. The purpose of this review is to summarize the current status and cutting-edge advancements in BKV-related research, providing new methods and perspectives to address future research challenges.

Integrated Cognitive Ergonomics of the Remote Evaluation of the Grafts with Robotics and Machine Organ Perfusion Technology in Solid Organ Transplantation.

AIM: To extend reliability of the integrated Tele-Radiological (TRE) and Tele-Pathological (TPE) evaluation of the Renal Graft (RG) of Prometheus Digital Medical Device (pn 2003016) via integration with Machine Organ Perfusion and Tele-Robotics (Stamoulis Rb) in Organ Transplantation. MATERIAL AND METHODS: A sensitivity-specificity analysis by a simulation of the TRE of RG on 15 MR abdominal images by a radiologist and of the TPE of RG by 26 specialists based on 130 human RG images assessing damages and lesions. RESULTS: The integrated analysis of TRE and TPE of RG showed: Sensitivity=96.7%, Specificity=100% and Accuracy=97.6%. Integration of Machine Organ Perfusion based results pattern recognition and AI programming offers deep learning and improves morbidity-mortality and organ viability prognosis. CONCLUSION: The TRE integrated with TPE and AI programming of RG machine organ perfusion based results pattern recognition by AI programming and Deep Learning supported virtual benching is feasible and seems more reliable for instant morbidity-mortality and organ viability prognosis in renal transplant decision support and operational planning.

Potential biomarkers of recurrent FSGS: a review.

Focal segmental glomerulosclerosis (FSGS), a clinicopathological condition characterized by nephrotic-range proteinuria, has a high risk of progression to end-stage renal disease (ESRD). Meanwhile, the recurrence of FSGS after renal transplantation is one of the main causes of graft loss. The diagnosis of recurrent FSGS is mainly based on renal puncture biopsy transplants, an approach not widely consented by patients with early mild disease. Therefore, there is an urgent need to find definitive diagnostic markers that can act as a target for early diagnosis and intervention in the treatment of patients. In this review, we summarize the domestic and international studies on the pathophysiology, pathogenesis and earliest screening methods of FSGS and describe the functions and roles of specific circulating factors in the progression of early FSGS, in order to provide a new theoretical basis for early diagnosis of FSGS recurrence, as well as aid the exploration of therapeutic targets.

Successful Kidney Transplantation in a Young Male with Type 2 Xanthinuria.

Type-II Xanthanuria is an genetic disorder associated with diminished serum uric acid levels. Patients with xanthanuria has absence of xanthine oxidase or xanthine dehydrogenase activity, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Deficiency of these enzyme leads to elevated levels of xanthine in urine which further leads to precipitation of xanthine in urine which further helps to formation of renal stones and ultimately leads to chronic kidney disease and end stage renal disease. We report a 23 years old male, who reached ESRD due to Type 2 xanthinuria, which was confirmed by genetic studies, who later successfully underwent renal transplant surgery and currently having normal life with functioning graft.

Exhaustion of T cells after renal transplantation.

Renal transplantation is a life-saving treatment for patients with end-stage renal disease. However, the challenge of transplant rejection and the complications associated with immunosuppressants necessitates a deeper understanding of the underlying immune mechanisms. T cell exhaustion, a state characterized by impaired effector functions and sustained expression of inhibitory receptors, plays a dual role in renal transplantation. While moderate T cell exhaustion can aid in graft acceptance by regulating alloreactive T cell responses, excessive exhaustion may impair the recipient's ability to control viral infections and tumors, posing significant health risks. Moreover, drugs targeting T cell exhaustion to promote graft tolerance and using immune checkpoint inhibitors for cancer treatment in transplant recipients are areas deserving of further attention and research. This review aims to provide a comprehensive understanding of the changes in T cell exhaustion levels after renal transplantation and their implications for graft survival and patient outcomes. We discuss the molecular mechanisms underlying T cell exhaustion, the role of specific exhaustion markers, the potential impact of immunosuppressive therapies, and the pharmaceutical intervention on T cell exhaustion levels. Additionally, we demonstrate the potential to modulate T cell exhaustion favorably, enhancing graft survival. Future research should focus on the distinctions of T cell exhaustion across different immune states and subsets, as well as the interactions between exhausted T cells and other immune cells. Understanding these dynamics is crucial for optimizing transplant outcomes and ensuring long-term graft survival while maintaining immune competence.

Cancer incidence following bariatric surgery in renal transplant recipients: a retrospective multi-center analysis.

BACKGROUND: Obesity, a known independent risk factor for developing malignancy. Additionally, renal transplant recipients (RTR) confer a 2- to 4-fold increased risk of overall malignancies with an excess absolute risk of .7% per year. While transplant recipients are at risk for obesity and malignancy, the effect of bariatric surgery (BS) in the posttransplantation setting is not well known. OBJECTIVES: Our study primarily evaluated the impact of BS on cancer incidence in RTR with severe obesity in the posttransplantation setting. Weight loss outcomes were analyzed secondarily. SETTING: University Hospital. METHODS: A retrospective study using TriNetX database was developed to analyze cancer outcomes in RTR with posttransplantation BS versus RTR without BS from 2000 to 2023. After the exclusion process and propensity matching, both cohorts consisted of 153 patients. RESULTS: RTR-BS had a significantly lower incidence of overall cancer and transplant-related cancers (P < .05). No significant difference was identified in cutaneous, gastrointestinal, and reproductive cancers. Percent Excess Weight Loss (%EWL) was significantly lower in RTR-only cohort (11.4%) versus RTR-BS cohort (57.8%) at 5 years. Sleeve gastrectomy (SG) patients (73.19%) had significantly higher %EWL than Roux en-Y gastric bypass (RYGB) patients (49.33%) at 3 years. No difference in cancer incidence was noted between SG and RYGB patients. CONCLUSION: Postrenal transplantation BS had a diminishing effect on overall and transplant-related cancer incidence in RTR with severe obesity. Significant weight loss was also demonstrated with post-renal transplantation BS.

Renal Aspergillosis Complicating Renal Allograft Transplantation: A Case Report.

Renal aspergillosis is a rare yet potentially devastating complication following renal allograft transplantation. We present the case of a 45-year-old male with a history of crescentic IgA nephropathy who underwent renal allograft transplantation from his mother. Despite initial favorable progress, he developed post-transplant renal dysfunction attributed to active antibody-mediated rejection. Subsequently, he presented with signs of systemic infection and graft dysfunction, leading to the diagnosis of renal aspergillosis. Despite aggressive management, including antifungal therapy and cessation of immunosuppression, the patient progressed to renal graft cortical necrosis, necessitating nephrectomy. This case underscores the challenges in diagnosing and managing renal aspergillosis in transplant recipients and highlights the importance of early recognition and prompt intervention to improve outcomes in such cases.

Renal and cardiac biopsy findings in an adolescent patient with the 3243A>G mitochondrial DNA mutation: Favorable renal prognosis post renal transplantation from the mother.

We investigated the pathogenesis of a perihilar variant of focal segmental glomerulosclerosis detected by kidney biopsy in a 16-year-old male. The disease was refractory to steroid therapy, and at the second kidney biopsy, abnormal mitochondrial proliferation was newly observed in the podocytes. The patient also developed late-onset hearing loss and had a family history of diabetes, and genetic testing confirmed the mitochondrial DNA mutation 3243A>G (48%). Eight months after hemodialysis was started, encephalopathy occurred presumably due to rapid dehydration. After changing dialysis into continuous ambulatory peritoneal dialysis, encephalopathy was resolved, but the patient developed myocardial hypertrophy, probably because of the myocardial overreaction to congestion. A myocardial biopsy showed mitochondrial proliferation in the myocardium. After renal transplantation from his mother with a heteroplasmy of 4%, the cardiomyopathy improved, and the renal function has remained stable for 4 years. We speculated that the abnormal mitochondrial morphology in the kidney and heart may be characteristic of mitochondrial genetic disease, and renal transplantation from the mother with a low heteroplasmy was considered desirable for mitochondrial nephropathy with poor prognosis.

Diagnosis of light­chain deposition disease after renal transplantation: A case report and literature review.

Light chain deposition disease (LCDD) is a rare, clonal plasma cell proliferative condition. The deposition of nonamyloid monoclonal immunoglobulin light chains predominantly affects the kidneys, which may lead to end-stage renal disease, eventually requiring renal replacement therapy. The present study reported a rare case of LCDD that was confirmed after renal transplantation. A 49-year-old man initially presented with heavy proteinuria, hypoproteinemia, hyperlipidemia and renal insufficiency. The patient was diagnosed with nephrotic syndrome and pathological examination revealed fibrillary glomerulonephritis in 2014. Treatment was started with prednisolone. About 5 years later, the patient began to receive continuous hemodialysis due to worsening serum creatinine levels. Renal allograft transplantation was performed in 2020 and dialysis independence was achieved. Laboratory findings before renal transplantation revealed that serum and urine immunofixation electrophoresis was negative. Allograft kidney biopsy established the pathological diagnosis of LCDD at >1 year after renal transplantation for renal dysfunction. The treatment is challenging due to the lack of generally accepted standard treatment practices. Administration of bortezomib combined with dexamethasone was started. As anemia and renal failure developed progressively, the treatment was switched to anti-CD38 antibody and continuous hemodialysis was restarted. The best response achieved was hematological partial response and relief of anemia. However, the patient's renal function did not improve and he remains to have end-stage kidney disease. LCDD is easily missed in cases in which serum and urine immunofixation electrophoresis is negative. Hence, early recognition of LCCD based on kidney biopsy is important. To the best of our knowledge, the use of anti-CD38 antibody therapy in patients with LCDD is rarely reported. Anti-CD38 antibody is effective in treating LCDD, but it may not reverse the marked deterioration of renal function.

Cytomegalovirus-Associated Colitis as a Cause of Lower Gastrointestinal Bleeding in Kidney Transplant Recipients: A Single-Centered Study.

Introduction Cytomegalovirus (CMV) is the most common viral pathogen affecting patients undergoing solid organ transplantation. It is often the most important infection for patients who have undergone kidney transplantation. Clinical presentations of cytomegalovirus infection range from asymptomatic infection to organ-specific involvement. This study aimed to determine the frequency of cytomegalovirus-associated colitis in kidney transplant recipients (KTRs) presenting with lower gastrointestinal bleeding. Methods After the approval of the ethical review committee of the Sindh Institute of Urology and Transplantation (ERC-SIUT), this cross-sectional study was conducted at the Department of Hepatogastroenterology at the Sindh Institute of Urology and Transplantation from January 2021 to December 2021. All the KTRs (six months after the transplantation) of either gender and aged between 18 and 65 years, presenting with lower gastrointestinal (GI) bleeding as per the operational definition, were enrolled in the study. Those patients who were either unfit for the endoscopy or refused to give consent were excluded from the study. Colonic biopsies were reviewed by a consultant histopathologist for the features of CMV infection. Results A total of 95 renal transplant recipients of either gender or age above 18 to 65 years with lower GI bleeding were included in the study. Among them, 84 (88.4%) were males, while 11 (11.6%) were females. The mean age of the patients included in the study was 37±11 years. The most common presenting complaint was fresh bleeding per rectum, which was observed in 73 (76.8%). The most common findings observed on colonoscopy in KTRs with bleeding per rectum were colonic ulcers and erosions noted in 41 (43.1%) and 36 (37.3%) patients, respectively. On histopathology, CMV colitis was noted in 21 (22.1%) patients. On comparison of different baseline variables, the presence of fresh bleeding per rectum and the presence of both ulcers and erosions on colonoscopy were the factors significantly associated with CMV colitis in KTRs. Conclusion CMV colitis is a prevalent condition in KTRs, presenting with lower GI bleeding. Despite the significant occurrence, the levels of CMV viremia were not associated with CMV colitis, suggesting that diagnosis should rely on histopathological confirmation. Prophylaxis during periods of high immunosuppression is crucial to reducing the incidence of CMV infections and improving both graft function and patient survival.

Incidence and risk factors of infections following kidney transplantation.

BACKGROUND: For patients with End-Stage Renal Disease (ESRD), kidney transplantation stands as the superior alternative to dialysis, exhibiting enhancements in both quality of life and survival rates. The objective of this study is to ascertain the prevalence of infections and associated risk factors within the initial two years post-renal transplant. METHOD: A retrospective study of all renal transplant recipients who underwent renal transplantation at king Abdullah medical city in Makkah, Saudi Arabia from January 1st, 2018, till end of December 2021 followed up for two years. RESULTS: A total of 43 patients were included in the study, The participants who experienced infectious episodes had a higher mean age, averaging 45.26 ± 14, in contrast to those who did not, averaging 38.75 ± 12. Most of the patients included in the study were male, 70 % of the total population. However, most infectious complications occurred in women (77 % vs. 30 %, respectively, p-value 0.004). Regarding the mode of dialysis before the transplantation, most of the patients were maintained on hemodialysis (76.7 %), and the mean duration of dialysis was longer on those presented with infections within two years post-transplant compared to those without it (3.26 ± 1.6 vs. 2 ± 1.14 years respectively). The incidence of the infections was 44.2 % (19 individuals). The most common presented infections in the patients within two years post renal transplant were urinary tract infections (20.9 %), with a high recurrence rate reaching 11.6 %. This was followed by Coronavirus disease (COVID-19) and Cytomegalovirus (CMV). CONCLUSION: This study sheds light on the prevalence of infectious complications following renal transplantation and highlights specific risk factors associated with these infections. Understanding these patterns can aid in the development of preventive strategies and optimized care for transplant recipients during the early post-transplant period.

The relationship between compliance with immunosuppressive therapy and religious attitudes of kidney transplant patients.

OBJECTIVE: This study was conducted to examine the relationship between adherence to immunosuppressive therapy and religious attitudes of kidney transplant patients. METHOD: The research was conducted descriptively with patients followed in the transplantation clinic of the between 2015 and 2019. The sample consisted of 142 patients who met the study criteria. Before starting the study, necessary permissions were obtained from the institution, ethics committee and patients. RESULTS: There was a significant relationship between marital status, educational status, income status and the mean score of the immunosuppressive treatment adherence scale, and between family type and the mean score of the religious attitude scale (p < 0.05). Of these results only; It was determined that there was a significant relationship between the priority order of drugs in life, duration of renal failure and time after transplantation and drug compliance scale average score (p < 0.05). Those who do not want to donate their kidneys to their relatives, those who do not want to donate organs when they die, those whose religious beliefs affect drug compliance, the duration of kidney failure is between 1 and 12 months and the period after transplantation 13- It was determined that those who had 60 months had a "more positive religious attitude" (p < 0.05). CONCLUSION: It was found that the mean score of the immunosuppressive treatment compliance scale of kidney transplant patients was at a good level, while the mean score of religious attitude was below the middle level. In addition, there was no significant relationship between the mean score of the immunosuppressive treatment compliance scale and the mean score of the religious attitude scale.

Subclinical rejection and allograft survival in kidney transplantation: protocol for a systematic review and meta-analysis.

INTRODUCTION: Subclinical rejection (SCR) refers to the presence of acute rejection without accompanying kidney allograft dysfunction. The impact of SCR on long-term graft survival remains a subject of ongoing debate. METHODS AND ANALYSIS: We will perform a systematic search of databases including MEDLINE, Embase and Cochrane Central, from January 1995 to November 2023. We will include English-language studies involving adult kidney transplant patients who investigated SCR. We will exclude studies focused on 'for-cause' biopsies. Both title, abstract screening and full-text screening will be performed by two or more reviewers. The primary outcome of this study will be death-censored allograft loss. The secondary outcome will include development of subsequent rejection. For time-dependent outcomes, we will prioritise HRs and the 95% CIs. In cases where HRs are unavailable, we will calculate risk ratios based on the recorded events. The risk of bias will be assessed using the Cochrane Collaboration's revised tool for assessing the risk of bias in randomised trials and the Newcastle-Ottawa scale for cohort studies. We will employ a random effects model. We will evaluate heterogeneity using the I2 variable. We will assess publication bias by funnel plots, Begg and Mazumdar test, and Egger's test. ETHICS AND DISSEMINATION: Ethics approval does not apply as no original data will be collected. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42023463536.

Renal Transplant Outcomes in Plasma Cell Dyscrasias and AL Amyloidosis after Treatment with Daratumumab.

Background: The morbidity and mortality from AL amyloidosis has significantly improved with the development of novel treatments. Daratumumab is a highly effective treatment for AL amyloidosis, but end-stage kidney disease is a common complication of this condition. Kidney transplantation is the ideal form of renal replacement therapy but has historically been contraindicated in this group of patients. Methods: Given the improved survival and better treatments of both conditions, we argue that it is time to reconsider transplanting these patients. Results: We report our experience of transplanting four patients with AL amyloidosis who had achieved stable remission through treatment with daratumumab. Conclusions: We highlight the key challenges involved and discuss important clinical issues for patients receiving daratumumab, particularly the difficulties with interpreting the crossmatch in light of daratumumab and immunoglobulin therapy interference. We also discuss the complexities involved in balancing the risks of infection, relapse, rejection, and immunosuppression in such patients.

Surgical Strategies for Renal Transplantation: A Pictorial Essay.

This pictorial essay aims to navigate through the complexities and challenges of renal transplantation (RT), by weaving together visual imagery with clinical insights within a comprehensive illustrative surgical guide. Herein, we provide a detailed visual exploration of the intricate anatomy and surgical processes necessary for both renal graft retrieval from the donor and also for an adequate implantation in the recipient. Regarding graft retrieval, after reviewing the relevant retroperitoneal surgical anatomy, and donor nephrectomy techniques, graft preservation and optimal backbench graft dissection principles were meticulously analyzed. Thereafter, the recipient surgical strategy for graft implantation was addressed, focusing on preoperative preparations, the site of implantation selection, exposure, operative bed dissection, graft revascularization, and urinary tract reconstruction. Careful donor and recipient selection, meticulous surgical execution, and rigorous postoperative management clearly hold a pivotal role in optimizing patient outcomes. Fostering a deeper understanding of the surgical nuances and clinical management practices that contribute to successful results post-RT, we hope to provide a useful practical tool for clinicians about to embark on the treacherous road of RT surgery. Innovative technologies and surgical practices that have already significantly improved the safety and effectiveness of RT stand testament to the importance of further scientific inquiry, conceptual developments, and clinical integration. Moving forward, it is essential that the medical community continues to refine these strategies and advocate for equitable access to transplantation, ensuring that advancements in the field translate into real-world benefits for all patients grappling with ESRD. The collaborative efforts of multidisciplinary teams are essential in addressing the complex clinical challenges associated with RT, with the ultimate goal of improving patient survival, enhancing graft longevity, and reducing healthcare disparities.

Safety and graft outcome of right retroperitoneal laparoscopic donor nephrectomy for living donor kidney transplantation: A comparison with left retroperitoneal laparoscopic donor nephrectomy.

INTRODUCTION: The left kidney is often preferred for living donor kidney transplantation because of its anatomical advantages. However, the right kidney may be procured due to donor conditions. Few studies have assessed the safety and graft outcome of right retroperitoneal laparoscopic donor nephrectomy (RDN). This study aimed to compare the outcomes between right and left RDN with respect to donor outcome and the graft function of recipients. METHODS: This retrospective study included 230 consecutive living donor kidney transplants performed at our institution between May 2019 and March 2023. We reviewed the outcomes of kidney transplant in the right and left kidneys after RDN. RESULTS: A total of 230 living donor kidney transplants were performed, with 32 donors receiving right RDN (right RDN group) and 198 donors receiving left RDN (left RDN group). The renal veins and ureters were significantly shorter in the right RDN group than in the left RDN group (both p < .001). Donor operation and warm ischemia time were significantly longer in the right RDN group than in the left RDN group (p = .012 and p < .001, respectively). None of the groups exhibited any cases of delayed graft function owing to donor-related reasons. Perioperative changes in the estimated glomerular filtration rate of recipients and death-censored graft survival were not significantly different between the two groups. CONCLUSIONS: In RDN, the outcomes of right donor nephrectomy were comparable to those of left donor nephrectomy in terms of donor safety and recipient renal function.

Outcomes of kidney transplant recipients exposed to Chagas disease under Benznidazole prophylaxis. A single center 10-year experience.

BACKGROUND: Chagas disease (ChD) is endemic in many parts of the world and can be transmitted through organ transplantation or reactivated by immunosuppression. Organs from infected donors are occasionally used for transplantation, and the best way of managing the recipients remains a subject of debate. METHODS: We present a single-center cohort study describing a 10-year experience of kidney transplantation in patients at risk of donor-derived ChD and or reactivation. Patients received prophylactic treatment with Benznidazole and were monitored for transmission or reactivation. Monitoring included assessing direct parasitemia, serology, and polymerase chain reaction (PCR). RESULTS: Fifty-seven kidney transplant recipients (KTRs) were enrolled in the study. Forty-four patients (77.2%) were at risk of primary ChD infection, nine patients (15.8%) were at risk of disease reactivation, and four patients (7.0%) were at risk of both. All patients received Benznidazole prophylaxis, starting on the first day after transplantation. Parasitemia was assessed in 51 patients (89.5%), serology also in 51 patients (89.5%), and PCR in 40 patients (70.2%). None of the patients exhibited clinically or laboratory-detectable signs of disease. A single patient experienced a significant side effect, a cutaneous rash with intense pruritus. At 1-year post-transplantation, the patient and graft survival rates were 96.5% and 93%, respectively. CONCLUSION: In this study, no donor-derived or reactivation of Trypanosoma cruzi infection occurred in KTRs receiving Benznidazole prophylaxis.

Hypomagnesaemia, an independent risk factor for the development of post-transplant diabetes mellitus in liver and renal transplant recipients? A systematic review.

BACKGROUND: Post-transplantation diabetes mellitus (PTDM) is common after solid organ transplantation. In the past decade, there has been increasing interest in the association between hypomagnesaemia and the development of PTDM. This systematic review aimed to investigate the current knowledge regarding the association between hypomagnesaemia and PTDM in adult liver and renal transplant recipients. METHODS: A literature search of five databases, Medline, Embase, ProQuest, Scopus and Google Scholar, as well as article reference lists, was performed. Eligible studies that focused on adult liver and renal transplant recipients without pretransplantation hyperglycaemia or diabetes were included. Other eligibility criteria included quantitative studies which reported magnesium concentrations, studies with at least 6 months of follow-up, and studies published in English. The Newcastle-Ottawa Assessment Tool was used for the quality assessment. RESULTS: In total, 12 studies were included in the final analysis. Eleven focused on renal transplantation and one on liver transplantation. All studies were medium to high quality with eight out of 12 achieving the highest rating of nine. Eight studies found a negative association between either pretransplant or early post-transplant serum magnesium concentration and the risk of PTDM, three studies found no association between these two variables, and one study found a positive association between the magnesium concentration at 8 weeks after transplantation and glycosylated haemoglobin A1C. CONCLUSIONS: Further large-scale prospective studies with at least 6 months of follow-up are needed to confirm these findings, particularly in liver transplantation, to further clarify and explore the relationship between hypomagnesaemia and PTDM.