Hematopoietic cell-based and non-hematopoietic cell-based strategies for immune tolerance induction in living-donor renal transplantation: A systematic review

IntroductionDespite its use to prevent acute rejection, lifelong immunosuppression can adversely impact long-term patient and graft outcomes. In theory, immunosuppression withdrawal is the ultimate goal of kidney transplantation, and is made possible by the induction of immunological tolerance. The purpose of this paper is to review the safety and efficacy of immune tolerance induction strategies in living-donor kidney transplantation, both chimerism-based and non-chimerism-based. The impact of these strategies on transplant outcomes, including acute rejection, allograft function and survival, cost, and immune monitoring, will also be discussed.Materials and methodsDatabases such as PubMed, Scopus, and Web of Science, as well as additional online resources such as EBSCO, were exhaustively searched. Adult living-donor kidney transplant recipients who developed chimerism-based tolerance after concurrent bone marrow or hematopoietic stem cell transplantation or those who received non-chimerism-based, non-hematopoietic cell therapy using mesenchymal stromal cells, dendritic cells, or regulatory T cells were studied between 2000 and 2021. Individual sources of evidence were evaluated critically, and the strength of evidence and risk of bias for each outcome of the transplant tolerance study were assessed.ResultsFrom 28,173 citations, 245 studies were retrieved after suitable exclusion and duplicate removal. Of these, 22 studies (2 RCTs, 11 cohort studies, 6 case-control studies, and 3 case reports) explicitly related to both interventions (chimerism- and non-chimerism-based immune tolerance) were used in the final review process and were critically appraised. According to the findings, chimerism-based strategies fostered immunotolerance, allowing for the safe withdrawal of immunosuppressive medications. Cell-based therapy, on the other hand, frequently did not induce tolerance except for minimising immunosuppression. As a result, the rejection rates, renal allograft function, and survival rates could not be directly compared between these two groups. While chimerism-based tolerance protocols posed safety concerns due to myelosuppression, including infections and graft-versus-host disease, cell-based strategies lacked these adverse effects and were largely safe. There was a lack of direct comparisons between HLA-identical and HLA-disparate recipients, and the cost implications were not examined in several of the retrieved studies. Most studies reported successful immunosuppressive weaning lasting at least 3 years (ranging up to 11.4 years in some studies), particularly with chimerism-based therapy, while only a few investigators used immune surveillance techniques. The studies reviewed were often limited by selection, classification, ascertainment, performance, and attrition bias.ConclusionsThis review demonstrates that chimerism-based hematopoietic strategies induce immune tolerance, and a substantial number of patients are successfully weaned off immunosuppression. Despite the risk of complications associated with myelosuppression. Non-chimerism-based, non-hematopoietic cell protocols, on the other hand, have been proven to facilitate immunosuppression minimization but seldom elicit immunological tolerance. However, the results of this review must be interpreted with caution because of the non-randomised study design, potential confounding, and small sample size of the included studies. Further validation and refinement of tolerogenic protocols in accordance with local practice preferences is also warranted, with an emphasis on patient selection, cost ramifications, and immunological surveillance based on reliable tolerance assays

A narrative review of vaccine-induced thrombotic thrombocytopenia in organ donation and transplantation: Current evidence and implications

Vaccine-induced thrombotic thrombocytopenia (VITT) has been recently linked with coronavirus disease (COVID-19) vaccines. It becomes crucial for the transplant communities to have a rigorous approach for accepting VITT donors, as the reports of such transplantation have been associated with thrombotic complications, graft loss, and deaths. The magnitude of facing a VITT donor in transplantation practices is unknown and also the management protocol. However, as per the limited data, it is better to avoid such transplants, and in the case of emergency transplants, the risk-benefit ratio should be weighed. All transplantation from VITT donors should be appropriately counseled before procurement. The organs should undergo deliberate examination for functionality by clinical, laboratory, and radiological parameters. In doubtful cases, a preimplantation biopsy is mandated to rule out any thrombosis. VITT donors are suggested to be treated with newer oral anti-coagulation and intravenous immunoglobulin. Platelet transfusion is best avoided in a VITT donor. There is no established protocol for any modification in surgical procedure, anesthesia, or immunosuppressive medicines in the recipients. The recipients should undergo extensive clinical and laboratory monitoring for any possible complications. No prophylactic therapy is recommended at present but candidates with a history of any COVID-19 vaccine within 30 days, should be avoided. In summary, the evidence for diagnosis and management of VITT donors is based only on a few reports, but with current knowledge, it is advisable to take a multidisciplinary approach to assess all benefits and risks before accepting or discarding organs

Role of high resolution computed tomography of chest in posttransplant pulmonary infection

Aim of This Study: This study aims to describe the utility of high-resolution computed tomography (HRCT) of chest in renal transplant recipients in patients with pulmonary infection. Materials and Methods: We retrospectively analyzed the findings of HRCT of chest in 48 postrenal transplant patients with documented pulmonary infection from September 2013 to August 2014. All patients underwent detailed investigations including specific pathological tests, chest X-ray, sputum analysis, bronchoalveolar lavage and pleural fluid analysis as and when required. HRCT was done in all patients on Somatom sensation 64 scan. The spectrum of causative organism and utility of HRCT was studied. Results: Out of 48 patients, the causative organism was confirmed by microbiology in 27 patients. These include 14 patients with Gram-negative bacteria, 5 patients with Gram-positive bacteria, 8 patients with fungal infection, and 3 patients with Mycobacterium tuberculosis infection confirmed on sputum analysis. The causative organism was confirmed to be cytomegalovirus-based on serological tests in 3 patients. Laboratory investigations could not identify the causative organism in 18 patients, 2 of them were treated with broad spectrum antibiotic, 13 patients with anti-tuberculous drugs, and 3 patients with antifungal therapy based on CT findings. Spectrum of HRCT findings was studied. Conclusion: We found bacterial infection is the most common in postrenal transplant patients followed by M. tuberculosis. Tree in bud appearance is common in M. tuberculosis infection. We found HRCT makes the road of early diagnosis of pulmonary infections smoother when coupled with clinical data

Clinical and laboratory profile of renal amyloidosis: A single-center experience

The kidney is the most common organ involved in systemic amyloidosis. We aimed to study etiology and clinicopathological profile of renal amyloidosis. This was a retrospective study of 40 consecutive adult patients with biopsy-proven renal amyloidosis evaluated over a period of two years. Emphasis was given to describing the clinical presentation, renal function, proteinuria, type of amyloidosis, and its etiology. Mean age of the study cohort was 44 ± 15 years (with a male-to-female ratio of 3:1). Amyloid A (AA) amyloidosis was the most common type of amyloidosis observed in 72.5% of cases. Amyloid light chain (AL) amyloidosis accounted for 17.5% of cases, and the rest remained undetermined. AA amyloidosis had widespread age distribution while AL amyloidosis was confined to those >40 years. Proteinuria was the most common renal manifestation observed in all patients. Nephrotic syndrome was seen in 70% of patients. Mean 24 h proteinuria was 6.4 g. Renal failure was the second most common manifestation seen in 70% of patients, of whom 21.4% required hemodialysis. Tuberculosis (TB) accounted for 90% cases of AA amyloidosis. The most prevalent form was pulmonary TB while the rest accounted for by rheumatoid arthritis and bronchiectasis. Among patients with TB induced amyloidosis, 61.5% had received adequate treatment for TB in the past. All patients with AL amyloidosis had nephrotic range proteinuria, five had renal failure out of which two required dialysis. Cardiac involvement was seen in two patients. AA amyloidosis was the most common type of renal amyloidosis in the present study and pulmonary TB was the most common etiology

Scoring systems and outcome of chronic kidney disease patients admitted in intensive care units

The outcome of chronic kidney disease (CKD) patients admitted to the Intensive Care Unit (ICU) is difficult to predict. This study assessed the outcome of CKD patients admitted to the ICU and evaluated prediction of 30-day mortality using the Acute Physiology and Chronic Health Evaluation (APACHE II), Simplified Acute Physiology Score (SAPS II), and Sequential Organ Failure Assessment (SOFA) score. One hundred consecutive CKD patients admitted to the ICU at a tertiary care hospital, Ahmedabad between 2011 and 2013 were included prospectively. Data on demographics, indication for admission, cause of CKD, use of vasoactive drugs and mechanical ventilation (MV), mode of renal replacement therapy (RRT), and 30-day mortality were recorded. The APACHE II, SAPS II, and SOFA scores were calculated based on the admission characteristics. The mean APACHE II, SAPS II, and SOFA scores were 28.22 ± 7.53, 43.04 ± 16.40, and 10.39 ± 5.20, respectively, and area under receiver operating characteristics curve in predicting 30-day mortality were 0.961, 0.994, and 0.950, respectively. The scores were significantly higher in 30-day nonsurvivors as compared to survivors (P = 0.001). During the ICU stay, MV and vasoactive drugs were required in 57% and 67% of the patients, respectively, and the requirement was significantly greater in nonsurvivors as compared to survivors (P = 0.001). About 85% of patients were on intermittent hemodialysis and 15% of patients were on continuous venovenous hemodiafiltration. Sepsis was the main reason for hospital admission, and the mean length of stay in the ICU was 7.74 ± 5.34 days. The study indicates that all three scores (APACHE II, SAPS II, and SOFA) perform equally well and have equal diagnostic utility in predicting 30-day mortality

An uncommon cause of rapidly progressive renal failure in a lupus patient: Pauci-immune crescentic glomerulonephritis

We report a case of systemic lupus erythematosus (SLE) who presented with rapidly progressive renal failure (RPRF) with positive antinuclear antibody (ANA) and anti-double-stranded DNA (dsDNA) antibody and active urinary sediment in the form of microscopic hematuria and proteinuria. Provisional clinical diagnosis of lupus nephritis was made. Renal biopsy showed pauci-immune crescentic glomerulonephritis, the diagnosis of which was supported by positive serum anti-MPO antibody. Renal biopsy in SLE patients can sometimes reveal varied pathological entities such as antinuclear cytoplasmic antibodies (ANCAs) positive vasculitis, as in our case, which modified our treatment protocol. Thus, in a patient with SLE presenting with RPRF with active urinary sediments, ANCA serology, and renal biopsy with immunofluorescence examination should be performed always

Secondary renal amyloidosis in a patient of pulmonary tuberculosis and common variable immunodeficiency

Common variable immunodeficiency (CVID) usually manifests in the second or third decade of life with recurrent bacterial infections and hypoglobulinemia. Secondary renal amyloidosis with history of pulmonary tuberculosis is rare in CVID, although T cell dysfunction has been reported in few CVID patients. A 40-year-old male was admitted to our hospital with a 3-month history of recurrent respiratory infections and persistent pitting pedal edema. His past history revealed 3 to 5 episodes of recurrent respiratory tract infections and diarrhoea each year since last 20 years. He had been successfully treated for sputum positive pulmonary tuberculosis 8 years back. Laboratory studies disclosed high erythrocyte sedimentation rate (ESR), hypoalbuminemia and nephrotic range proteinuria. Serum immunoglobulin levels were low. CD4/CD8 ratio and CD3 level was normal. C3 and C4 complement levels were normal. Biopsy revealed amyloid A (AA) positive secondary renal amyloidosis. Glomeruli showed variable widening of mesangial regions with deposition of periodic schiff stain (PAS) pale positive of pink matrix showing apple green birefringence on Congo-red staining. Immunohistochemistry was AA stain positive. Immunofluorescence microscopy revealed no staining with anti-human IgG, IgM, IgA, C3, C1q, kappa and lambda light chains antisera. Patient was treated symptomatically for respiratory tract infection and was discharged with low dose angiotensin receptor blocker. An old treated tuberculosis and chronic inflammation due to recurrent respiratory tract infections were thought to be responsible for AA amyloidosis. Thus pulmonary tuberculosis should be considered in differential diagnosis of secondary causes of AA renal amyloidosis in patients of CVID especially in endemic settings

Social media coverage of the 32nd Annual conference of the Indian Society of Organ transplantation 2022: Unity in diversity

Background: The 32nd edition of the Indian Society of Organ Transplantation's yearly conference was recently hosted in Nagpur, coinciding with the 2nd Mid-term Meeting of the Liver Transplantation Society of India and the 15th Annual International Conference of Network and Alliance of Transplant Coordinators. Aims and Objectives: We are delighted to present our insights and observations on the social media coverage of #ISOT22. Materials and Methods: In order to ensure comprehensive coverage, a specialized social media team was assembled by the ISOT. This team comprised of twenty-five dedicated educators who attended the conference live. Social media coverage was done mainly by live-tweeting, taking faculty interviews, and sharing images of presentation slides. Results: Social media played a crucial role in covering the #ISOT22 event, with Twitter being the most extensively used platform. There were 2.318 million impressions with 2037 conference tweets with the hashtag #ISOT2022Nagpur. Total number of participants on Twitter was 177 and average tweets/hour were three. There were twelve average tweets per participant. Conclusions: The use of social media at 32nd Annual Conference offered several benefits, including the dissemination of presented scientific research and engagement with both physical and virtual attendees