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1.
Clin Transplant ; 38(7): e15390, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38973774

ABSTRACT

BACKGROUND: Extended-spectrum beta-lactamase-producing gram-negative rods (ESBL-GNR) are a rising cause of bacteremia in kidney transplant recipients (KT). The study purpose was to examine patient mortality, allograft survival, estimated glomerular filtration rate (eGFR) at the end of 1 year, and readmission rates while looking at treatment strategies among KTs with ESBL-GNR and non-ESBL-GNR bacteremia at our institution. METHODS: This study was a retrospective, cohort analysis of KTs with gram-negative bacteremia from January 1, 2020, to December 31, 2021. The primary outcome of the study was mortality. Patient outcomes were assessed for 365 days after positive blood cultures. RESULTS: The study included 63 patients. Of these, 18 (29%) patients had bacteremia caused by an ESBL-GNR and 45 (71%) patients had bacteremia caused by a non-ESBL-GNR. Patient survival at 90 days was 94% in the ESBL-GNR group and 96% in the non-ESBL-GNR group. Ciprofloxacin was the most common antimicrobial therapy at discharge (68.9%) in the non-ESBL-GNR group whereas ertapenem was the most common in the ESBL-GNR group (44.5%). Median eGFR at discharge was 41 mL/min/1.73 m2 in the ESBL-GNR group and 48 mL/min/1.73 m2 in the non-ESBL-GNR group. Ninety-day readmission occurred in 9 (50%) ESBL-GNR patients and 14 (32%) non-ESBL-GNR patients. None of the above comparisons are statistically significant (p > 0.05). Eleven (61%) ESBL-GNR and 2 (4%) non-ESBL-GNR patients used outpatient parenteral antimicrobial therapy (p < 0.001). CONCLUSIONS: Among KTs with ESBL-GNR bacteremia, no significant difference was detected in mortality or allograft function compared to non-ESBL-GNR bacteremia.


Subject(s)
Bacteremia , Gram-Negative Bacteria , Gram-Negative Bacterial Infections , Kidney Transplantation , Postoperative Complications , beta-Lactamases , Humans , Male , Female , Kidney Transplantation/adverse effects , Retrospective Studies , Bacteremia/drug therapy , Bacteremia/microbiology , Bacteremia/mortality , Middle Aged , beta-Lactamases/metabolism , Gram-Negative Bacterial Infections/drug therapy , Prognosis , Follow-Up Studies , Gram-Negative Bacteria/isolation & purification , Gram-Negative Bacteria/drug effects , Risk Factors , Survival Rate , Graft Survival , Glomerular Filtration Rate , Anti-Bacterial Agents/therapeutic use , Kidney Function Tests , Adult , Kidney Failure, Chronic/surgery , Transplant Recipients
2.
Exp Clin Transplant ; 22(5): 392-395, 2024 May.
Article in English | MEDLINE | ID: mdl-38970283

ABSTRACT

We present a challenging clinical case of a 68-year-old female kidney transplant recipient who had a complicated posttransplant course marked by borderline T-cell-mediated rejection and BK virus nephropathy. The treatment for borderline rejection with steroids resulted in overimmunosuppression, and the patient acquired cytomegalovirus infection manifesting as colitis and SARS-CoV-2 infection. This progressed rapidly to collapsing glomerulopathy and allograft failure. This study also highlights the challenges in surveillance with donor-derived cell-free DNA in the setting of allograft injury by multiple viral infections.


Subject(s)
BK Virus , COVID-19 , Cytomegalovirus Infections , Graft Rejection , Kidney Transplantation , Polyomavirus Infections , Tumor Virus Infections , Humans , Female , COVID-19/complications , COVID-19/immunology , COVID-19/diagnosis , Aged , Kidney Transplantation/adverse effects , Polyomavirus Infections/immunology , Polyomavirus Infections/virology , Polyomavirus Infections/diagnosis , Cytomegalovirus Infections/immunology , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/virology , Cytomegalovirus Infections/drug therapy , Graft Rejection/immunology , Graft Rejection/virology , BK Virus/pathogenicity , BK Virus/immunology , Tumor Virus Infections/immunology , Tumor Virus Infections/virology , Tumor Virus Infections/diagnosis , Disease Progression , Treatment Outcome , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Coinfection
3.
Exp Clin Transplant ; 22(5): 396-398, 2024 May.
Article in English | MEDLINE | ID: mdl-38970284

ABSTRACT

Renal transplantation is the best modality of treatment for patients with end-stage renal disease. Donor shortage remains a substantial problem, for which different strategies are employed, including acceptance of marginal donors and donor kidneys with anatomic variations. We performed a successful kidney transplant of a donor kidney that had complete duplication of the ureter. After transplant, the recipient had no urinary complications.


Subject(s)
Kidney Transplantation , Tissue Donors , Ureter , Humans , Kidney Transplantation/adverse effects , Ureter/abnormalities , Ureter/surgery , Treatment Outcome , Kidney/abnormalities , Kidney/surgery , Male , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/diagnosis , Adult , Donor Selection , Female , Middle Aged
4.
Exp Clin Transplant ; 22(5): 351-357, 2024 May.
Article in English | MEDLINE | ID: mdl-38970278

ABSTRACT

OBJECTIVES: With the increase in life expectancy and the aging of the population, chronic kidney disease has become increasingly prevalent in our environment. Kidney transplantation remains the gold standard treatment for end-stage renal disease, but the supply of renal grafts has not been able to keep pace with growing demand. Because of this rationale, organ selection criteria have been extended (expanded criteria donation), and alternative donation types, such as donation after circulatory death, have been evaluated. These approaches aim to increase the pool of potential donors, albeit with organs of potentially lower quality. Various forms of donations, including donation after circulatory death, have also undergone assessment. This approach aims to augment the pool of potential donors, notwithstanding the compromised quality of organs associated with such methods. Diverse strategies have been explored to enhance graft function, with one of the most promising being the utilization of pulsatile machine perfusion. MATERIALS AND METHODS: We conducted a retrospective analysis on 28 transplant recipients who met the inclusion criterion of sharing the same donor, wherein one organ was preserved by cold storage and the other by pulsatile machine perfusion. We performed statistical analysis on posttransplant recovery parameters throughout the patients' hospitalization, including admission and discharge phases. RESULTS: Statistically significant differences were noted in delayed graft function (P = .04), blood transfusions requirements, and Clavien-Dindo complications. Furthermore, an overall trend of improvement in discharge parameters and hospital stay was in favor of the pulsatile machine perfusion group. CONCLUSIONS: The use of pulsatile machine perfusion as a method of renal preservation results in graft optimization, leading to earlier recovery and fewer complications compared with cold storage in the context of donation after circulatory death.


Subject(s)
Delayed Graft Function , Kidney Transplantation , Perfusion , Pulsatile Flow , Recovery of Function , Humans , Kidney Transplantation/adverse effects , Retrospective Studies , Treatment Outcome , Time Factors , Male , Female , Perfusion/methods , Perfusion/adverse effects , Middle Aged , Adult , Delayed Graft Function/etiology , Delayed Graft Function/prevention & control , Risk Factors , Tissue Donors/supply & distribution , Organ Preservation/methods , Organ Preservation/adverse effects , Donor Selection , Heart Arrest/diagnosis , Heart Arrest/physiopathology , Heart Arrest/etiology
5.
Asian J Endosc Surg ; 17(3): e13355, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38956792

ABSTRACT

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.


Subject(s)
Kidney Transplantation , Laparoscopy , Living Donors , Nephrectomy , Humans , Nephrectomy/methods , Kidney Transplantation/methods , Female , Retrospective Studies , Male , Laparoscopy/methods , Adult , Middle Aged , Retroperitoneal Space/surgery , Graft Survival , Treatment Outcome , Tissue and Organ Harvesting/methods
6.
Zhonghua Yi Xue Za Zhi ; 104(27): 2483-2501, 2024 Jul 16.
Article in Chinese | MEDLINE | ID: mdl-38978373

ABSTRACT

Tissue matching is one of the key factors affecting the success of kidney transplantation and long-term graft survival. At present, the development of tissue matching technology and its application in the laboratory of transplant centers in China is different. In order to promote the standardization of clinical diagnosis and treatment of kidney transplantation tissue matching, the Chinese Transplantation Branch of the Chinese Medical Association, the Kidney Transplantation Branch of the China Medical Care International Exchange Promotion Association, and the Transplantation Technology Branch of the Chinese Medical Biotechnology Association jointly initiated the guidelines for clinical application of tissue matching techniques for kidney transplantation in China. This guide grades the quality of evidence and the strength of recommendation for each clinical issue using the 2009 Oxford Centre for Evidence-Based Medicine Grading and Strength of Recommendation criteria. Aiming at 15 clinical problems related to the laboratory detection technology and clinical application of kidney transplantation tissue matching, a total of 21 recommendations were put forward in line with China's clinical diagnosis and treatment practice, aiming at promoting tissue matching before kidney transplantation, improving the long-term survival time of recipients and transplanted kidneys, and giving play to the application value of precision medicine in the field of kidney transplantation.


Subject(s)
Kidney Transplantation , Humans , China , Graft Survival , Histocompatibility Testing , Tissue Donors , Tissue and Organ Procurement
7.
Transplantation ; 108(7): e139-e147, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38985979

ABSTRACT

BACKGROUND: Polyclonal rabbit antithymocyte globulins (ATGs) are commonly used in organ transplantation as induction. Anti- N -glycolylneuraminic acid carbohydrate antibodies which develop in response to rabbit carbohydrate antigens might lead to unwanted systemic inflammation. LIS1, the first new generation of antilymphocyte globulins (ALGs) derived from double knockout swine, lacking carbohydrate xenoantigens was already tested in nonhuman primates and rodent models. METHODS: This open-label, single-site, dose escalation, first-in-human, phase 1 study evaluated the safety, T cell depletion, pharmacokinetics, and pharmacodynamics of LIS1. In an ascending dose cohort (n = 5), a primary kidney transplant recipient at low immunologic risk (panel reactive antibody [PRA] < 20%), received LIS1 for 5 d at either 0.6, 1, 3, 6, or 8 mg/kg. After each patient completed treatment, the data safety monitoring board approved respective dose escalation. In the therapeutic dose cohort (n = 5) in patients with PRA <50% without donor specific antibodies, 2 patients received 8 mg/kg and 3 patients 10 mg/kg. RESULTS: CD3 + T cell depletion <100/mm 3 at day 2 was observed in all patients who received 6, 8, and 10 mg/kg of LIS1. The terminal half-life of LIS1 was 33.7 d with linearity in its disposition. Lymphocyte repopulation was fast and pretransplant lymphocyte subpopulation counts recovered within 2-4 wk. LIS1 was well tolerated, neither cytokine release syndrome nor severe thrombocytopenia or leukopenia were noticed. Antibodies to LIS1 were not detected. CONCLUSIONS: In this first-in-human trial, genome-edited swine-derived polyclonal LIS1 ALG was well tolerated, did not elicit antidrug antibodies, and caused time-limited T cell depletion in low- and medium-risk kidney transplant recipients.


Subject(s)
Antilymphocyte Serum , Kidney Transplantation , Kidney Transplantation/adverse effects , Humans , Animals , Antilymphocyte Serum/immunology , Male , Middle Aged , Swine , Female , Adult , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , Lymphocyte Depletion/methods , Graft Rejection/immunology , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Treatment Outcome , Galactosyltransferases
9.
Cochrane Database Syst Rev ; 7: CD004925, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979749

ABSTRACT

BACKGROUND: Major urological complications (MUCs) after kidney transplantation contribute to patient morbidity and compromise graft function. The majority arise from vesicoureteric anastomosis and present early after transplantation. Ureteric stents have been successfully used to treat such complications. A number of centres have adopted a policy of universal prophylactic stenting at the time of graft implantation to reduce the incidence of urine leaks and ureteric stenosis. Stents are associated with specific complications, and some centres advocate a policy of only stenting selected anastomoses. This is an update of our review, first published in 2005 and last updated in 2013. OBJECTIVES: To examine the benefits and harms of routine ureteric stenting to prevent MUCs in kidney transplant recipients. SEARCH METHODS: We contacted the Information Specialist and searched the Cochrane Kidney and Transplant's Specialised Register (up to 19 June 2024) using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Our meta-analysis included all randomised controlled trials (RCTs) and quasi-RCTs designed to examine the impact of using stents for kidney transplant recipients. We aimed to include studies regardless of the type of graft, the technique of ureteric implantation, or the patient group. DATA COLLECTION AND ANALYSIS: Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Twelve studies (1960 patients) were identified. One study was deemed to be at low risk of bias across all domains. The remaining 11 studies were of low or medium quality, with a high or unclear risk of bias in at least one domain. Universal prophylactic ureteric stenting versus control probably reduces major urological complications (11 studies: 1834 participants: RR 0.30, 95% CI 0.16 to 0.55; P < 0.0001; I2 = 16%; moderate certainty evidence; number needed to treat (17)); this benefit was confirmed in the only study deemed to be at low risk of bias across all domains. This benefit was also seen for the individual components of urine leak and ureteric obstruction. Universal prophylactic ureteric stent insertion reduces the risk of MUC in the subgroup of studies with short duration (≤ 14 days) of stenting (2 studies, 480 participants: RR 0.39, 95% CI CI 0.21 to 0.72; P = 0.003; I2 = 0%) and where stenting was continued for > 14 days (8 studies, 124 participants: RR 0.22, 95% CI 0.08 to 0.61; P = 0.004; I2 = 29%). It is uncertain whether stenting has an impact on the development of urinary tract infection (UTI) (10 studies, 1726 participants: RR 1.32, 95% CI 0.97 to 1.80; P = 0.07; I² = 60%; very low certainty evidence due to risk of bias, heterogeneity and imprecision). Subgroup analysis showed that the risk of UTI did not increase if short-duration stenting was used (9 days) and that there was no impact on UTI risk when the prophylactic antibiotic regime co-trimoxazole 480 mg/day was used. Stents appear generally well tolerated, although studies using longer stents (≥ 20 cm) for longer periods (> 6 weeks) had more problems with encrustation and migration. There was no evidence that the presence of a stent resulted in recurrent or severe haematuria (8 studies, 1546 participants: RR 1.09, 95% CI 0.59 to 2.00; P = 0.79; I2 = 33%). The impact of stents on graft and patient survival and other stent-related complications remains unclear as these outcomes were either poorly reported or not reported at all. AUTHORS' CONCLUSIONS: Routine prophylactic stenting probably reduces the incidence of MUCs, even when the duration of stenting is short (≤ 14 days). Further high-quality studies are required to assess optimal stent duration. Studies comparing selective stenting and universal prophylactic stenting, whilst difficult to design and analyse, would address the unresolved quality of life and economic issues.


Subject(s)
Kidney Transplantation , Postoperative Complications , Randomized Controlled Trials as Topic , Stents , Ureter , Humans , Stents/adverse effects , Kidney Transplantation/adverse effects , Ureter/surgery , Postoperative Complications/prevention & control , Ureteral Obstruction/prevention & control , Intraoperative Care/methods
10.
Sci Rep ; 14(1): 15818, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982209

ABSTRACT

The presence of donor-specific antibodies (DSA) such as antibodies directed against donor class I human leucocyte antigen (e.g., HLA-A) is a major barrier to kidney transplant success. As a proof of concept, functionalized magnetic nanoparticles have been designed to eliminate DSA from saline, blood and plasma of healthy donors and sensitized patients. Specific HLA-A1 protein was covalently bound to functionalized cobalt nanoparticles (fNP), human serum albumin (HSA) as control. fNP were added to anti-HLA class I-spiked saline, spiked volunteers' whole blood, and to whole blood and plasma of sensitized patients ex vivo. Anti-HLA-A1 antibody levels were determined with Luminex technology. Antibodies' median fluorescent intensity (MFI) was defined as the primary outcome. Furthermore, the impact of fNP treatment on blood coagulation and cellular uptake was determined. Treatment with fNP reduced MFI by 97 ± 2% and by 94 ± 4% (p < 0.001 and p = 0.001) in spiked saline and whole blood, respectively. In six known sensitized anti-HLA-A1 positive patients, a reduction of 65 ± 26% (p = 0.002) in plasma and 65 ± 33% (p = 0.012) in whole blood was achieved. No impact on coagulation was observed. A minimal number of nanoparticles was detected in peripheral mononuclear blood cells. The study demonstrates-in a first step-the feasibility of anti-HLA antibody removal using fNP. These pilot data might pave the way for a new personalized DSA removal technology in the future.


Subject(s)
Isoantibodies , Magnetite Nanoparticles , Humans , Magnetite Nanoparticles/chemistry , Isoantibodies/immunology , Isoantibodies/blood , Kidney Transplantation , Tissue Donors , Female , Proof of Concept Study , Male , Antibodies/immunology
11.
Clin Transplant ; 38(7): e15395, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39023087

ABSTRACT

BACKGROUND: Medical distrust may hinder kidney transplantation (KT) access. Among KT candidates evaluated for waitlisting, we identified factors associated with high distrust levels and quantified their association with waitlisting. METHODS: Among 812 candidates (2018-2023), we assessed distrust using the Revised Health Care System Distrust Scale across composite, competence, and values subscales. We used linear regression to quantify the associations between candidate and neighborhood-level factors and distrust scores. We used Cox models to quantify the associations between distrust scores and waitlisting. RESULTS: At KT evaluation, candidates who were aged 35-49 years (difference = 1.97, 95% CI: 0.78-3.16), female (difference = 1.10, 95% CI: 0.23-1.97), and Black (difference = 1.47, 95% CI: 0.47-2.47) were more likely to report higher composite distrust score. For subscales, candidates aged 35-49 were more likely to have higher competence distrust score (difference = 1.14, 95% CI: 0.59-1.68) and values distrust score (difference = 0.83, 95% CI: 0.05-1.61). Race/ethnicity (Black, difference = 1.42, 95% CI: 0.76-2.07; Hispanic, difference = 1.52, 95% CI: 0.35-2.69) was only associated with higher values distrust scores. Female candidates reporting higher rescaled values distrust scores (each one point) had a lower chance of waitlisting (aHR = 0.78, 95% CI: 0.63-0.98), whereas this association was not observed among males. Similarly, among non-White candidates, each 1-point increase in both rescaled composite (aHR = 0.87, 95% CI: 0.77-0.99) and values (aHR = 0.82, 95% CI: 0.68-0.99) distrust scores was associated with a lower chance of waitlisting, while there was no association among White candidates. CONCLUSION: Female, younger, and non-White candidates reported higher distrust scores. Values distrust may contribute to the long-standing racial/ethnic and gender disparities in access to KT. Implementing tailored strategies to reduce distrust in transplant care may improve KT access for groups that experience persistent disparities.


Subject(s)
Kidney Transplantation , Trust , Waiting Lists , Humans , Female , Male , Kidney Transplantation/psychology , Middle Aged , Adult , Prognosis , Follow-Up Studies , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/psychology
12.
Clin Transplant ; 38(7): e15373, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39023085

ABSTRACT

BACKGROUND: Alternate complement dysregulation postrenal transplantation can result in thrombotic microangiopathy (TMA). There is a scarcity of data regarding outcomes based on the timing of TMA post-transplant, coupled with a lack of follow-up biopsy findings post TMA diagnosis. This study aims to assess allograft and patient outcomes in individuals developing early TMA, defined within 4 months post-transplantation, and explore any differences in follow-up surveillance biopsies compared to a non-TMA group. DESIGN: This is a single center retrospective study between January 1, 2002 and October 10, 2019. Patients who developed TMA within 4 months post-transplantation were compared to a propensity matched non-TMA group. RESULTS: Thirty-one patients developed TMA within 4 months of renal transplantation. Index TMA biopsy featured noticeable glomerular, and vascular lesions along with acute tubular injury. Four-month surveillance biopsy showed significant glomerulitis, transplant glomerulopathy and chronic interstitial fibrosis as compared to non-TMA group. However, at 1 year, these differences were no longer significant. There was no significant difference in patient survival (TMA vs. non-TMA, p = 0.083); however, death censored graft survival was significantly lower in the TMA group (p < 0.001). TMA patients had a significantly lower estimated glomerular filtration rate at 4 months and at 1 year as compared to the non-TMA group. CONCLUSION: Early onset TMA post renal transplant leads to decreased renal function and lower graft survival. Early recognition and prompt treatment may help in reducing the adverse outcomes.


Subject(s)
Graft Rejection , Graft Survival , Kidney Transplantation , Postoperative Complications , Thrombotic Microangiopathies , Humans , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/pathology , Kidney Transplantation/adverse effects , Female , Male , Retrospective Studies , Middle Aged , Follow-Up Studies , Prognosis , Postoperative Complications/etiology , Graft Rejection/etiology , Graft Rejection/pathology , Adult , Glomerular Filtration Rate , Risk Factors , Kidney Function Tests , Survival Rate , Kidney Failure, Chronic/surgery
13.
Clin Transplant ; 38(7): e15383, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39023092

ABSTRACT

BACKGROUND: Antibody-mediated rejection (ABMR) poses a barrier to long-term graft survival and is one of the most challenging events after kidney transplantation. Removing donor specific antibodies (DSA) through therapeutic plasma exchange (PLEX) is a cornerstone of antibody depletion but has inconsistent effects. Imlifidase is a treatment currently utilized for desensitization with near-complete inactivation of DSA both in the intra- and extravascular space. METHODS: This was a 6-month, randomized, open-label, multicenter, multinational trial conducted at 14 transplant centers. Thirty patients were randomized to either imlifidase or PLEX treatment. The primary endpoint was reduction in DSA level during the 5 days following the start of treatment. RESULTS: Despite considerable heterogeneity in the trial population, DSA reduction as defined by the primary endpoint was 97% for imlifidase compared to 42% for PLEX. Additionally, imlifidase reduced DSA to noncomplement fixing levels, whereas PLEX failed to do so. After antibody rebound in the imlifidase arm (circa days 6-12), both arms had similar reductions in DSA. Five allograft losses occurred during the 6 months following the start of ABMR treatment-four within the imlifidase arm (18 patients treated) and one in the PLEX arm (10 patients treated). In terms of clinical efficacy, the Kaplan-Meier estimated graft survival was 78% for imlifidase and 89% for PLEX, with a slightly higher eGFR in the PLEX arm at the end of the trial. The observed adverse events in the trial were as expected, and there were no apparent differences between the arms. CONCLUSION: Imlifidase was safe and well-tolerated in the ABMR population. Despite meeting the primary endpoint of maximum DSA reduction compared to PLEX, the trial was unsuccessful in demonstrating a clinical benefit of imlifidase in this heterogenous ABMR population. TRIAL REGISTRATION: EudraCT number: 2018-000022-66, 2020-004777-49; ClinicalTrials.gov identifier: NCT03897205, NCT04711850.


Subject(s)
Graft Rejection , Graft Survival , Isoantibodies , Kidney Failure, Chronic , Kidney Transplantation , Plasmapheresis , Humans , Graft Rejection/etiology , Graft Rejection/immunology , Graft Rejection/prevention & control , Female , Male , Middle Aged , Follow-Up Studies , Isoantibodies/blood , Isoantibodies/immunology , Adult , Prognosis , Kidney Failure, Chronic/surgery , Kidney Failure, Chronic/therapy , Kidney Function Tests , Postoperative Complications , Glomerular Filtration Rate , Risk Factors , Transplant Recipients
14.
Transpl Int ; 37: 12995, 2024.
Article in English | MEDLINE | ID: mdl-39010891

ABSTRACT

Antibody-mediated rejection (ABMR) remains one of the main causes of long-term graft failure after kidney transplantation, despite the development of powerful immunosuppressive therapy. A detailed understanding of the complex interaction between recipient-derived immune cells and the allograft is therefore essential. Until recently, ABMR mechanisms were thought to be solely caused by adaptive immunity, namely, by anti-human leucocyte antigen (HLA) donor-specific antibody. However recent reports support other and/or additive mechanisms, designating monocytes/macrophages as innate immune contributors of ABMR histological lesions. In particular, in mouse models of experimental allograft rejection, monocytes/macrophages are readily able to discriminate non-self via paired immunoglobulin receptors (PIRs) and thus accelerate rejection. The human orthologs of PIRs are leukocyte immunoglobulin-like receptors (LILRs). Among those, LILRB3 has recently been reported as a potential binder of HLA class I molecules, shedding new light on LILRB3 potential as a myeloid mediator of allograft rejection. In this issue, we review the current data on the role of LILRB3 and discuss the potential mechanisms of its biological functions.


Subject(s)
Graft Rejection , Kidney Transplantation , Receptors, Immunologic , Graft Rejection/immunology , Humans , Kidney Transplantation/adverse effects , Animals , Receptors, Immunologic/immunology , Mice , HLA Antigens/immunology , Monocytes/immunology , Antigens, CD/immunology , Macrophages/immunology
15.
Appl Microbiol Biotechnol ; 108(1): 402, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38951204

ABSTRACT

Delayed graft function (DGF) is a frequently observed complication following kidney transplantation (KT). Our prior research revealed dynamic shifts in salivary microbiota post-KT with immediate graft function (IGF), yet its behavior during DGF remains unexplored. Five recipients with DGF and 35 recipients with IGF were enrolled. Saliva samples were collected during the perioperative period, and 16S rRNA gene sequencing was performed. The salivary microbiota of IGFs changed significantly and gradually stabilized with the recovery of renal function. The salivary microbiota composition of DGFs was significantly different from that of IGFs, although the trend of variation appeared to be similar to that of IGFs. Salivary microbiota that differed significantly between patients with DGF and IGF at 1 day after transplantation were able to accurately distinguish the two groups in the randomForest algorithm (accuracy = 0.8333, sensitivity = 0.7778, specificity = 1, and area under curve = 0.85), with Selenomonas playing an important role. Bacteroidales (Spearman's r = - 0.4872 and p = 0.0293) and Veillonella (Spearmen's r = - 0.5474 and p = 0.0125) were significantly associated with the serum creatinine in DGF patients. Moreover, the significant differences in overall salivary microbiota structure between DGF and IGF patients disappeared upon long-term follow-up. This is the first study to investigate the dynamic changes in salivary microbiota in DGFs. Our findings suggested that salivary microbiota was able to predict DGF in the early stages after kidney transplantation, which might help the perioperative clinical management and early-stage intervention of kidney transplant recipients. KEY POINTS: • Salivary microbiota on the first day after KT could predict DGF. • Alterations in salivary taxa after KT are related to recovery of renal function.


Subject(s)
Delayed Graft Function , Kidney Transplantation , Microbiota , RNA, Ribosomal, 16S , Saliva , Humans , Kidney Transplantation/adverse effects , Saliva/microbiology , Male , Female , Middle Aged , RNA, Ribosomal, 16S/genetics , Adult , Bacteria/classification , Bacteria/isolation & purification , Bacteria/genetics
16.
BMC Nephrol ; 25(1): 214, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956529

ABSTRACT

BACKGROUND: Live donor kidney transplantation is the preferred kidney replacement therapy for eligible patients but requires thorough donor evaluation to minimise risks. Contemporary guidelines recommend split kidney function measurement in living donors only when there is a significant kidney size discrepancy, yet the evidence for this is poor, and practice varies nationally. This study evaluates the efficacy of CT-derived kidney metrics in detecting significant functional asymmetry. METHODS: We conducted a retrospective cohort analysis of 123 prospective living kidney donors at a regional transplant centre from June 2011 to October 2014, utilising CT to determine kidney and cortical volumes and lengths. Asymmetric kidney function (AKF), defined by > 10% function difference on DMSA scans, was correlated with CT measurements to calculate the diagnostic accuracy of current guidelines. RESULTS: Among the prospective donors, the median age was 42 years, and 59.3% were female. The median split kidney function difference was 4%, with 25 individuals exhibiting > 10% AKF. Kidney length discrepancy proved to be a poor indicator of AKF (sensitivity: 28%, specificity: 84%). While negative predictive values for cortical and kidney volumes were high (96% and 93%, respectively), sensitivity was low, and specificity and positive predictive value did not meet satisfactory thresholds. CONCLUSIONS: CT-derived metrics of kidney length, cortical, and total volume show limited sensitivity and specificity in identifying significant AKF. These findings provide evidence to support revised guideline development in the assessment of living kidney donors.


Subject(s)
Kidney Transplantation , Kidney , Living Donors , Tomography, X-Ray Computed , Humans , Female , Male , Retrospective Studies , Adult , Kidney/diagnostic imaging , Middle Aged , Kidney Function Tests/methods , Cohort Studies , Organ Size
17.
Med Sci Monit ; 30: e944285, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946121

ABSTRACT

BACKGROUND Thrombosis poses a grave threat to patients undergoing kidney transplants, with a heightened risk of mortality. While previous studies have established a link between COVID-19 and thrombosis, the specific association between COVID-19 and thrombosis in this patient population remains unexplored. MATERIAL AND METHODS We conducted a retrospective analysis utilizing data from 394 individuals who underwent kidney transplantation within the period of September 1, 2015, to April 1, 2023. To evaluate overall survival, we employed Kaplan-Meier analysis and utilized a logistic regression model for risk analysis. Furthermore, we developed a prediction model and assessed its accuracy through calibration curves. RESULTS Out of the 394 patients included in our study, a total of 51 individuals experienced thrombosis, resulting in 2 deaths. Our analysis revealed that COVID-19 infection significantly increased the risk of thrombosis (odds ratio [OR] 8.60, 95% confidence interval 3.13-24.74, P<0.01). Additionally, the use of cyclosporine was found to elevate the risk of death (OR 20.86, 95% CI 7.93-59.24, P<0.01) according to multifactorial analysis. Logistic models were employed to screen variables, and predictive models were constructed based on the presence of COVID-19 infection and the usage of cyclosporine. A nomogram was developed, demonstrating promising accuracy in estimating the risk of thrombosis during internal validation, with a corrected C-index of 0.869. CONCLUSIONS Our study suggests that both COVID-19 infection and the use of cyclosporine can serve as reliable predictors of thrombosis risk in patients undergoing renal transplantation. Furthermore, we developed a mortality risk prediction model based on COVID-19 in assessing thrombosis.


Subject(s)
COVID-19 , Kidney Transplantation , Thrombosis , Humans , Kidney Transplantation/adverse effects , COVID-19/complications , COVID-19/epidemiology , Thrombosis/etiology , Thrombosis/epidemiology , Male , Female , Middle Aged , Retrospective Studies , Incidence , Adult , Prognosis , Risk Factors , Transplant Recipients , SARS-CoV-2 , Logistic Models , Aged , Cyclosporine/therapeutic use , Kaplan-Meier Estimate
18.
Clin Transplant ; 38(7): e15394, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39001595

ABSTRACT

INTRODUCTION: Broad national or international programs contribute to mitigating the expected longer waiting list (WL) time for sensitized patients but with minor benefits for highly sensitized subjects. Therefore, strategies to prevent high sensitization are urgently required. In this study, we investigated the risk of developing highly sensitized patients with different immunosuppressive (IS) handling after kidney allograft failure (KAF). METHODS: Data from 185 patients with KAF, retransplanted/relisted from 2010 to 2020 in two regions of Italy that share the same regional WL, were analyzed. Patients were categorized according to IS management at 12 months after KAF as follows: patients maintaining IS with calcineurin inhibitors (CNI) (late withdrawal group [LWG], n = 58) and those who withdrew all IS therapy or were on steroids only (early withdrawal group [EWG], n = 127). RESULTS: Patients in the LWG showed lower panel reactive antibodies (PRA) at 12 (29.0% vs. 85.5%, p < 0.001) and 24 months (61.0% vs. 91.0%, p = 0.001), reduced risk of high sensitization (PRA ≥90%) at 12 (9.4% vs. 40.7%, p < 0.001, OR = 0.15) and 24 months (25.6% vs. 57.3%, p = 0.001, OR = 0.26) and almost no very high sensitization (PRA ≥ 98%) at 12 months (1.9% vs. 18.6%, p = 0.003, OR = 0.08) after KAF. In the LWG subgroup analysis, patients who maintained IS for up to 24 months after KAF did not show very high sensitization. The LWG showed shorter active WL times (406 vs. 813 days, p = 0.001) without an increased risk of complications. CONCLUSIONS: CNI maintenance for at least 12 months after KAF could be a useful approach to prevent high sensitization and reduce WL times in patients who are offered retransplantation, without a higher burden of complications.


Subject(s)
Calcineurin Inhibitors , Graft Rejection , Graft Survival , Immunosuppressive Agents , Kidney Transplantation , Humans , Male , Female , Kidney Transplantation/adverse effects , Calcineurin Inhibitors/therapeutic use , Middle Aged , Follow-Up Studies , Graft Rejection/prevention & control , Graft Rejection/etiology , Graft Rejection/immunology , Graft Survival/drug effects , Graft Survival/immunology , Risk Factors , Immunosuppressive Agents/therapeutic use , Prognosis , Kidney Failure, Chronic/surgery , Adult , Glomerular Filtration Rate , Retrospective Studies , Postoperative Complications/prevention & control , Kidney Function Tests , Immunosuppression Therapy/methods
19.
Am J Case Rep ; 25: e944664, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38987998

ABSTRACT

BACKGROUND Isolated iliac aneurysms are rare. Although they grow very slowly, they can rupture when large enough. Rarely, they rupture into an adjacent organ, such as the colon, the bladder, or even an adjacent vein. Cases of aneurysms rupturing into or communicating with an adjacent vein, leading to an arteriovenous fistula, have been reported. However, reports of aneurysms that rupture and communicate with another adjacent artery have not been found in the literature. CASE REPORT A 52-year-old man who underwent a renal transplantation in the left iliac fossa 21 years ago was admitted for chronic left lower abdominal pain that began 1 year ago. He did not have a history of any invasive procedures or severe trauma after the renal transplantation. Duplex ultrasound showed an oval-shaped hypoechoic structure adjacent to the left external iliac artery (EIA), with a swirling motion of blood flow inside. Computed tomography angiography showed an aneurysm of the left EIA, with a size of 35×34×47 mm, closely adjacent to or even communicating with the transplant renal artery (TRA). There was calcification in the aneurysm wall, without surrounding hematoma. The aneurysm was considered to be a true aneurysm, not a pseudoaneurysm. Endovascular therapy was performed. Digital subtraction angiography confirmed the communication between the aneurysm and the TRA. After the EIA was reconstructed with a covered stent, no leakage was demonstrated; however, contrast still flowed into the aneurysm though the TRA. A second covered stent graft was implanted in the TRA. Subsequently, the aneurysm was successfully excluded. CONCLUSIONS The pathogenesis of this strange aneurysm communicating with another adjacent artery is not well established. Stenting of multiple arteries was needed to treat this aneurysm.


Subject(s)
Iliac Aneurysm , Kidney Transplantation , Renal Artery , Humans , Male , Middle Aged , Renal Artery/diagnostic imaging , Iliac Aneurysm/surgery , Iliac Aneurysm/diagnostic imaging , Computed Tomography Angiography
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