Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 354
Filter
1.
World J Gastroenterol ; 29(19): 3013-3026, 2023 May 21.
Article in English | MEDLINE | ID: covidwho-20233965

ABSTRACT

BACKGROUND: Prolonged symptoms after corona virus disease 2019 (Long-COVID) in dialysis-dependent patients and kidney transplant (KT) recipients are important as a possible risk factor for organ dysfunctions, especially gastrointestinal (GI) problems, during immunosuppressive therapy. AIM: To identify the characteristics of GI manifestations of Long-COVID in patients with dialysis-dependent or KT status. METHODS: This observational, prospective study included patients with COVID-19 infection, confirmed by reverse transcription polymerase chain reaction, with the onset of symptoms between 1 January 2022 and 31 July 2022 which was explored at 3 mo after the onset, either through the out-patient follow-up or by telephone interviews. RESULTS: The 645 eligible participants consisted of 588 cases with hemodialysis (HD), 38 patients with peritoneal dialysis (PD), and 19 KT recipients who were hospitalized with COVID-19 infection during the observation. Of these, 577 (89.5%) cases agreed to the interviews, while 64 (10.9%) patients with HD and 4 (10.5%) cases of PD were excluded. The mean age was 52 ± 11 years with 52% women. The median dialysis duration was 7 ± 3 and 5 ± 1 years for HD and PD groups, respectively, and the median time post-transplantation was 6 ± 2 years. Long-COVID was identified in 293/524 (56%) and 21/34 (62%) in HD and PD, respectively, and 7/19 (37%) KT recipients. Fatigue was the most prevalent (96%) of the non-GI tract symptoms, whereas anorexia (90.9%), loss of taste (64.4%), and abdominal pain (62.5%) were the first three common GI manifestations of Long-COVID. Notably, there were 6 cases of mesenteric panniculitis from 19 patients with GI symptoms in the KT group. CONCLUSION: Different from patients with non-chronic kidney disease, there was a high prevalence of GI manifestations of Long-COVID in dialysis-dependent patients and KT recipients. An appropriate long-term follow-up in these vulnerable populations after COVID-19 infection is possibly necessary.


Subject(s)
COVID-19 , Gastrointestinal Diseases , Kidney Failure, Chronic , Kidney Transplantation , Humans , Female , Adult , Middle Aged , Male , Renal Dialysis/adverse effects , Kidney Transplantation/adverse effects , Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Prospective Studies , Post-Acute COVID-19 Syndrome , Cohort Studies , Gastrointestinal Diseases/diagnosis , Gastrointestinal Diseases/epidemiology , Gastrointestinal Diseases/etiology
2.
Clin Transplant ; 37(5): e14936, 2023 05.
Article in English | MEDLINE | ID: covidwho-20233393

ABSTRACT

BACKGROUND: The optimal treatment for chronic active antibody-mediated rejection (ca-AMR) remains unclear. Tocilizumab (TCZ), a monoclonal antibody against IL-6, has been proposed as a therapeutic option. We reported our experience treating ca-AMR with TCZ either as the first line option or as a rescue therapy. METHODS: We studied 11 adult kidney transplant recipients with biopsy-proven ca-AMR and preserved kidney function (eGFR 57 ± 18) who were treated with TCZ (8 mg/kg IV monthly). All biopsies were prompted by abnormal surveillance biomarker testing with DSA and/or dd-cfDNA. Clinical monitoring included dd-cfDNA and DSA testing every 3 months during the treatment with TCZ. RESULTS: In this cohort, ca-AMR was diagnosed at a median of 90 months (range 14-224) post-transplant, and 4 of 11 patients had DSA negative ca-AMR. Patients received a minimum of 3 months of TCZ, with 6 patients receiving at least 12 months of TCZ. Dd-cfDNA was elevated in all patients, with a median 2.24% at the start of TCZ treatment. After 6 months of TCZ treatment, 8/11 patients had dd- cfDNA <1%, and 3/11 had values <0.5%. Among those who completed at least 12 months of TCZ, dd-cfDNA decreased by 29% at 6 months (p = .05) and 47% by 12 months (p = .04). DSA also stabilized and, by 12 months, was reduced by 29% (p = .047). Graft function remained stable with no graft loss during treatment. There was a nonsignificant trend towards proteinuria reduction. During the course of treatment with tocilizumab, two patients experienced moderate to severe infections. CONCLUSIONS: In our early short-term experience, TCZ appears to reduce graft injury as measured by dd-cfDNA and modulate the immune response as evident by a modest reduction in immunodominant DSA MFI. Allograft function and proteinuria also stabilized.


Subject(s)
Cell-Free Nucleic Acids , Kidney Transplantation , Adult , Humans , Kidney Transplantation/adverse effects , Isoantibodies , Proteinuria
3.
Curr Opin Organ Transplant ; 28(3): 197-206, 2023 06 01.
Article in English | MEDLINE | ID: covidwho-2328276

ABSTRACT

PURPOSE OF REVIEW: The deceased donor organ pool has broadened beyond young, otherwise healthy head trauma victims. But an abundance of donated organs only benefits patients if they are accepted, expeditiously transported and actually transplanted. This review focuses on postdonation challenges and opportunities to increase the number of transplants through improved organ utilization. RECENT FINDINGS: We build upon recently proposed changes in terminology for measuring organ utilization. Among organs recovered for transplant, the nonuse rate (NUR REC ) has risen above 25% for kidneys and pancreata. Among donors, the nonuse rate (NUR DON ) has risen to 40% for livers and exceeds 70% for thoracic organs. Programme-level variation in offer acceptance rates vastly exceeds variation in the traditional, 1-year survival benchmark. Key opportunities to boost utilization include donation after circulatory death and hepatitis C virus (HCV)+ organs; acute kidney injury and suboptimal biopsy kidneys; older and steatotic livers. SUMMARY: Underutilization of less-than-ideal, yet transplant-worthy organs remains an obstacle to maximizing the impact of the U.S. transplant system. The increased risk of inferior posttransplant outcomes must always be weighed against the risks of remaining on the waitlist. Advanced perfusion technologies; tuning allocation systems for placement efficiency; and data-driven clinical decision support have the potential to increase utilization of medically complex organs.


Subject(s)
Heart Transplantation , Kidney Transplantation , Organ Transplantation , Tissue and Organ Procurement , Humans , United States , Organ Transplantation/adverse effects , Tissue Donors , Kidney Transplantation/adverse effects
5.
Front Immunol ; 13: 951576, 2022.
Article in English | MEDLINE | ID: covidwho-2313576

ABSTRACT

After kidney transplantation, patients exhibit a poor response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. However, the efficacy and adverse effects of vaccines based on different platforms in these patients remain unclear. We prospectively analyzed both anti-spike protein antibody and cellular responses 1 month after the first and second doses of SARS-CoV-2 vaccines in 171 kidney transplant patients. Four vaccines, including one viral vector (ChAdOx1 nCov-19, n = 30), two mRNA (mRNA1273, n = 81 and BNT162b2, n = 38), and one protein subunit (MVC-COV1901, n = 22) vaccines were administered. Among the four vaccines, mRNA1273 elicited the strongest humoral response and induced the highest interferon-γ levels in patients with a positive cellular response against the spike protein. Antiproliferative agents were negatively associated with both the antibody and cellular responses. A transient elevation in creatinine levels was noted in approximately half of the patients after the first dose of mRNA1273 or ChadOx1, and only one of them presented with borderline cellular rejection without definite causality to vaccination. In conclusion, mRNA1273 had better immunogenicity than the other vaccines. Further, renal function needs to be carefully monitored after vaccination, and vaccination strategies should be tailored according to the transplant status and vaccine characteristics.


Subject(s)
COVID-19 Vaccines , COVID-19 , Kidney Transplantation , Antibodies, Viral , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , ChAdOx1 nCoV-19 , Creatinine , Humans , Interferon-gamma , Kidney Transplantation/adverse effects , Protein Subunits , RNA, Messenger , SARS-CoV-2 , Transplant Recipients , Vaccination , Viral Vaccines
6.
Exp Clin Transplant ; 20(Suppl 3): 85-88, 2022 05.
Article in English | MEDLINE | ID: covidwho-2309190

ABSTRACT

OBJECTIVES: In children with end-stage renal disease, chronic liver failure, or acute liver failure, liver transplant and kidney transplant are the most effective modalities for better clinical outcomes compared with other therapies. However, children are particularly susceptible to surgical complications, so pediatric solid-organ transplants should be reserved for centers with substantial experience and multidisciplinary expertise. Here, we assessed liver and kidney transplants performed at our center in 2021. MATERIALS AND METHODS: From November 3, 1975, to December 31, 2021, we performed 701 liver transplants and 3290 kidney transplants. From January 1, 2021, to December 31, 2021, we performed 21 liver transplants (19 in children) and 114 kidney transplants (12 in children). We recorded age, sex, body mass index, comorbidities, etiologies, laboratory values, and clinical outcomes. RESULTS: For the year 2021, we performed 19 pediatric liver transplants and 12 pediatric kidney transplants. Mean age of liver recipients was 3.4 years, and 8 were male patients. The most common etiology was biliary atresia (n = 7). All liver grafts were from living related donors who were first-degree (n = 16) or second- degree (n = 3) relatives of the recipients. Mean hospital stay was 17.6 days. All but 2 liver transplant recipients were discharged successfully (2 died from sepsis in the early postoperative period). Mean age of kidney transplant recipients was 14.1 years, and 4 were male patients. The most common etiology was vesicoureteral reflux (n = 3). One kidney graft was from a deceased donor, with the rest from living related donors who were first-degree relatives of the recipients (n = 11; mother for 8 recipients and father for 3 recipients). Mean hospital stay was 4.3 days. All kidney transplant recipients were discharged successfully. CONCLUSIONS: Solid-organ transplants for young children are often complex but can be performed successfully at experienced transplant centers.


Subject(s)
Kidney Transplantation , Adolescent , Child , Child, Preschool , Female , Graft Survival , Humans , Kidney Transplantation/adverse effects , Liver , Living Donors , Male , Tissue Donors , Treatment Outcome
7.
Transplant Proc ; 55(5): 1121-1124, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2290793

ABSTRACT

BACKGROUND: In the normal population, a high monocyte chemoattractant protein (MCP-1) level is an important biomarker for the progression of COVID-19. This study investigated whether MCP-1 level can determine the disease prognosis in kidney transplant (KT) patients with COVID-19. METHODS: A total of 89 patients, including 49 KT patients (group 1) diagnosed with COVID-19 who required hospitalization, and 40 KT patients who did not have COVID-19 disease (group 2), were included. Demographic characteristics and laboratory results of the patients were recorded. The serum reserved for MCP-1 was stored at -80°C and studied blindly by a single microbiologist at the end of the study. RESULTS: While the mean age of the patients was 51.0 years (40.0-59.50) in group 1, it was 48.0 years (40.75-54.75) in group 2 (P > .05). In terms of the female sex, it was 36 (73.5%) and 27 (67.5%) in group 1 and group 2, respectively (P > .05). Similarly, there was no significant difference between the 2 groups regarding primary disease and basal graft function (P > .05). There was a statistically significant difference in inflammation indicators in group 1 compared with group 2 (P < .05). A correlation was found between inflammation indicators and COVID-19 (P < .05). However, no significant correlation was detected between COVID-19 disease and MCP-1 levels in both groups (P > .05). Also, according to basal MCP-1 levels, we did not find a significant difference between survival and nonsurvival patients (164.0 pg/mL [146.0-202.0] vs 156.0 pg/mL [143.0-173.0], respectively (P > .05). CONCLUSION: Monocyte chemoattractant protein, an indicator of inflammation, was not found to predict the prognosis of COVID-19 disease in kidney recipients.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Female , Middle Aged , Chemokine CCL2/metabolism , Kidney Transplantation/adverse effects , Prognosis , Monocyte Chemoattractant Proteins , Inflammation , Transplant Recipients
8.
Am J Case Rep ; 24: e938730, 2023 Apr 23.
Article in English | MEDLINE | ID: covidwho-2300844

ABSTRACT

BACKGROUND Vaccine-induced thrombosis and thrombocytopenia is a rare immune disorder documented after adenoviral vector ChAdOx1 nCOV-19 (AstraZeneca) and Ad26.COV2-S (Janssen) vaccine administration against severe acute respiratory syndrome coronavirus 2. It is a rare adverse effect with an incidence of 1 case per 100 000 exposures. The disorder represents altered immune response with proliferation of antibodies that bind to platelet factor 4 (PF4), leading to formation of thrombi and consumptive coagulopathy. Thrombosis combined with thrombocytopenia generally occurs in the first month following vaccination and can lead to fatal outcome, even in young, previously healthy individuals. These young adults ultimately may become solid organ donors. The main concerns with vaccine-induced thrombosis and thrombocytopenia solid organ donors are anti-PF4 antibodies transmission potential, risk of early major graft thrombosis, and serious bleeding. CASE REPORT In our center, 2 kidney transplantations were performed from a single brain-dead vaccine-induced thrombosis and thrombocytopenia donor following Ad26.COV2-S COVID-19 (Janssen) vaccine in October 2021, which represents the first 2 cases of kidney transplantation from a deceased vaccine-induced thrombosis and thrombocytopenia donor after immunization with Ad26.COV2-S (Janssen) vaccine. Both recipients were closely monitored in the early post-transplantation period and after discharge from the hospital. To date, both recipients have a good functioning allograft, without any evidence of vaccine-induced thrombosis and thrombocytopenia transmission. CONCLUSIONS Our results are consistent with those of previously published cases of successful vaccine-induced thrombosis and thrombocytopenia donor solid organ transplantation. Kidney allografts transplanted from vaccine-induced thrombosis and thrombocytopenia donors can have a good overall function with favorable outcomes.


Subject(s)
COVID-19 , Kidney Transplantation , Thrombocytopenia , Thrombosis , Young Adult , Humans , COVID-19 Vaccines/adverse effects , Ad26COVS1 , Kidney Transplantation/adverse effects , ChAdOx1 nCoV-19 , Tissue Donors , Thrombocytopenia/chemically induced , Thrombosis/etiology
9.
Transplantation ; 107(5): 1136-1138, 2023 05 01.
Article in English | MEDLINE | ID: covidwho-2305609

ABSTRACT

BACKGROUND: Immunocompromised patients have been at an increased risk of succumbing to coronavirus disease 2019 (COVID-19) since the beginning of the pandemic. METHODS: Here, we analyzed mortality and case fatality data from dialysis and kidney transplant patients, and compared each with an age-matched subgroup of the general population. RESULTS: We found that both patients on dialysis and kidney transplant patients remain at increased risk of succumbing to COVID-19 despite all available countermeasures. CONCLUSIONS: The analyses underline the need for additional protection for this vulnerable population.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , COVID-19/epidemiology , Renal Dialysis/adverse effects , Kidney Transplantation/adverse effects , Pandemics/prevention & control , Immunocompromised Host , Transplant Recipients
10.
J Bras Nefrol ; 44(3): 376-382, 2022.
Article in English, Portuguese | MEDLINE | ID: covidwho-2303093

ABSTRACT

INTRODUCTION: Kidney transplant recipients are a subgroup of patients at higher risk of critical forms of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection and poor outcomes due to immunosuppression treatment. Herein, we present data from a single center cohort of kidney transplant recipients with SARS-CoV-2 infection. METHODS: In a prospective study, baseline characteristics, clinical features, antiviral and immunosuppression management were compared between outpatients and hospitalized patients, during a one-year period. RESULTS: Seventy-seven kidney transplant recipients were analyzed, including outpatients and hospitalized patients, with a median age of 57.7 (IQR 49.7-64.9) years. Twenty-eight (36.4%) were managed as outpatients, while 49 (63.6%) patients required hospital admission. Among hospitalized patients, 18.4% were admitted in ICU, 49% had AKI, and 20.4% died. Immunosuppression adjustments were performed in 95.9% of hospitalized patients, with dose of anti-metabolites adjusted in 83.7%, mTOR inhibitors in 14.3%, calcineurin inhibitors in 12.2%, and corticosteroid therapy in 81.6%. CONCLUSION: Among hospitalized patients, immunosuppression management included reduction or withdrawal of anti-metabolite and increase of corticosteroid dose. AKI occurred in almost half of patients and mortality in hospitalized patients reached 20%, reflecting greater disease severity than the general population.


Subject(s)
Acute Kidney Injury , COVID-19 , Kidney Transplantation , Acute Kidney Injury/etiology , Antiviral Agents/therapeutic use , Calcineurin Inhibitors , Humans , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Middle Aged , Prospective Studies , Retrospective Studies , SARS-CoV-2
11.
Am J Transplant ; 23(6): 744-758, 2023 06.
Article in English | MEDLINE | ID: covidwho-2286568

ABSTRACT

Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBDNEG; n = 42 anti-RBDLO), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+%, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P < .001). Day 30 spike-specific CD8+% was negative in 91% KTRs (vs 20% HCs; P = .07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2-reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P = .11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P = .001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P = .037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical. (NCT04969263).


Subject(s)
COVID-19 , Kidney Transplantation , Humans , SARS-CoV-2/genetics , COVID-19/epidemiology , COVID-19/prevention & control , Kidney Transplantation/adverse effects , RNA, Messenger/genetics , Transplant Recipients , mRNA Vaccines , Receptors, Antigen, T-Cell , Antibodies, Viral
12.
Clin Nephrol ; 99(6): 307-310, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2281975

ABSTRACT

BACKGROUND AND AIMS: Electrolyte and acid-base disturbances are common in kidney transplant recipients, but there are few reports of low-solute hyponatremia or beer potomania in this population. We report herein a case of low-solute hyponatremia in a kidney transplant recipient with impaired graft function, highlighting key issues in diagnosis and management of low-solute hyponatremia, as well as exploring the pathophysiology of hyponatremia after kidney transplantation. CASE PRESENTATION: A 51-year-old man who had received a cadaveric renal transplant 18 years before presented with symptomatic hyponatremia and seizure. Workup for an underlying intracranial pathology was negative, and subsequent biochemical workup suggested low-solute hyponatremia with potomania, arising from dietary modifications taken by the patient while self-isolating during the COVID-19 pandemic. Correction of hyponatremia was successful with conservative management with close monitoring. CONCLUSION: This case illustrates key points in the diagnosis and management of low-solute hyponatremia and highlights the pathophysiology of hyponatremia after kidney transplantation.


Subject(s)
COVID-19 , Hyponatremia , Kidney Transplantation , Male , Humans , Middle Aged , Hyponatremia/diagnosis , Hyponatremia/etiology , Hyponatremia/therapy , Kidney Transplantation/adverse effects , Pandemics , Beer
13.
Clin Exp Nephrol ; 27(5): 445-453, 2023 May.
Article in English | MEDLINE | ID: covidwho-2256462

ABSTRACT

BACKGROUND: Vulnerable populations, such as hemodialysis (HD) patients and kidney transplant (RTx) recipients, have priority for anti-COVID-19 vaccination, because of their impaired immune status. Here, we investigated the immune response after vaccination with BNT162b2 (two doses plus booster) in HD and RTx patients. METHODS: A prospective, observational study was started in two homogeneous groups of 55 HD and 51 RTx patients previously matched from a cohort of 336 patients. Anti-RBD IgG levels, assayed after the second dose with BNT162b2 mRNA, were used to stratify subjects into quintiles. After the second dose and after booster, anti-RBD and IGRA test were evaluated in RTx and HD, belonging to the first and fifth quintiles. RESULTS: After the second dose of vaccine, the median circulating levels of anti-RBD IgG were significantly higher in HD (1456 AU/mL) compared to RTx (27.30 AU/mL). IGRA test showed significantly higher values in the HD (382 mIU/mL) compared with the RTx (73 mIU/mL). After the booster, humoral response increased significantly in both HD (p = 0.0002) and RTx groups (p = 0.009), whereas the T-cellular immunity remained essentially stable in most patients. In RTx patients with a low humoral response after the second dose, the third dose did not significantly strengthen either humoral or cellular immunity. CONCLUSIONS: For HD and RTx, there is great variability in the humoral response to anti-COVID-19 vaccination, with a stronger response in the HD group. The booster dose was ineffective at reinforcing the humoral and cellular immune response in most RTx patients hyporesponsive to the second dose.


Subject(s)
COVID-19 Vaccines , COVID-19 , Kidney Transplantation , Renal Dialysis , Humans , Antibodies, Viral , BNT162 Vaccine , Immunoglobulin G , Kidney Transplantation/adverse effects , Prospective Studies , Transplant Recipients , Vaccines , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects
14.
Transpl Infect Dis ; 25(2): e14052, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2253991

ABSTRACT

BACKGROUND: Before the availability of mRNA vaccines, many transplant centers chose to significantly reduce maintenance immunosuppression in kidney transplant recipients (KTRs) with SARS-CoV-2 infection. The extent to which this increases the risk of allosensitization is unclear. METHODS: In this observational cohort study, we analyzed 47 KTRs from March 2020 to February 2021 who underwent substantial reduction of maintenance immunosuppression during SARS-CoV-2 infection. KTRs were followed at 6 and 18 months concerning the development of de novo donor-specific anti-HLA (human leukocyte antigen) antibodies (DSA). The HLA-derived epitope mismatches were calculated using the predicted indirectly recognizable HLA-epitopes (PIRCHE-II) algorithm. RESULTS: In total, 14 of 47 KTRs (30%) developed de novo HLA antibodies after the reduction of maintenance immunosuppression. KTRs with higher total PIRCHE-II scores and higher PIRCHE-II scores for the HLA-DR locus were more likely to develop de novo HLA antibodies (p = .023, p = .009). Furthermore, 4 of the 47 KTRs (9%) developed de novo DSA after reduction of maintenance immunosuppression, which were exclusively directed against HLA-class II antigens and also showed higher PIRCHE-II scores for HLA-class II. The cumulative mean fluorescence intensity of 40 KTRs with preexisting anti-HLA antibodies and 13 KTRs with preexisting DSA at the time of SARS-CoV-2 infection remained stable after the reduction of maintenance immunosuppression (p = .141; p = .529). CONCLUSIONS: Our data show that the HLA-derived epitope mismatch load between donor and recipient influences the risk of de novo DSA development when immunosuppression is temporarily reduced. Our data further suggest that reduction in immunosuppression should be made more cautiously in KTRs with high PIRCHE-II scores for HLA-class II antigens.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Epitopes , Kidney Transplantation/adverse effects , Graft Rejection/prevention & control , Histocompatibility Testing , SARS-CoV-2 , HLA Antigens , Antibodies , Tissue Donors , Immunosuppression Therapy , Histocompatibility Antigens Class II , Transplant Recipients , Graft Survival
15.
Trials ; 24(1): 213, 2023 Mar 22.
Article in English | MEDLINE | ID: covidwho-2262440

ABSTRACT

BACKGROUND: Immunosuppression after kidney transplantation is mainly guided via plasma tacrolimus trough level, which cannot sufficiently predict allograft rejection and infection. The plasma load of the non-pathogenic and highly prevalent torque teno virus (TTV) is associated with the immunosuppression of its host. Non-interventional studies suggest the use of TTV load to predict allograft rejection and infection. The primary objective of the current trial is to demonstrate the safety, tolerability and preliminary efficacy of TTV-guided immunosuppression. METHODS: For this purpose, a randomised, controlled, interventional, two-arm, non-inferiority, patient- and assessor-blinded, investigator-driven phase II trial was designed. A total of 260 stable, low-immunological-risk adult recipients of a kidney graft with tacrolimus-based immunosuppression and TTV infection after month 3 post-transplantation will be recruited in 13 academic centres in six European countries. Subjects will be randomised in a 1:1 ratio (allocation concealment) to receive tacrolimus either guided by TTV load or according to the local centre standard for 9 months. The primary composite endpoint includes the occurrence of infections, biopsy-proven allograft rejection, graft loss, or death. The main secondary endpoints include estimated glomerular filtration rate, graft rejection detected by protocol biopsy at month 12 post-transplantation (including molecular microscopy), development of de novo donor-specific antibodies, health-related quality of life, and drug adherence. In parallel, a comprehensive biobank will be established including plasma, serum, urine and whole blood. The date of the first enrolment was August 2022 and the planned end is April 2025. DISCUSSION: The assessment of individual kidney transplant recipient immune function might enable clinicians to personalise immunosuppression, thereby reducing infection and rejection. Moreover, the trial might act as a proof of principle for TTV-guided immunosuppression and thus pave the way for broader clinical applications, including as guidance for immune modulators or disease-modifying agents. TRIAL REGISTRATION: EU CT-Number: 2022-500024-30-00.


Subject(s)
Kidney Transplantation , Torque teno virus , Adult , Humans , Tacrolimus/adverse effects , Kidney Transplantation/adverse effects , Quality of Life , Immunosuppression Therapy , Graft Rejection/diagnosis , Graft Rejection/prevention & control , Immunosuppressive Agents/adverse effects
16.
Transplant Proc ; 55(3): 514-520, 2023 Apr.
Article in English | MEDLINE | ID: covidwho-2279905

ABSTRACT

PURPOSE: To investigate the kinetics and durability of anti-spike glycoprotein (S) immunoglobulin G (IgG) after the second dose of mRNA-based SARS-CoV-2 vaccine in kidney transplant recipients (recipients) compared with those in kidney donors (donors) and healthy volunteers (HVs) and identify factors negatively associated with SARS-CoV-2 vaccine effectiveness in recipients. METHODS: We enrolled 378 recipients with no history of COVID-19 and no anti-S-IgG before the first vaccine and who received a second mRNA-based vaccine dose. Antibodies were detected using an immunoassay more than 4 weeks after the second vaccine dose. Anti-S-IgG <0.8, ≥0.8 to 15, and ≥15 U/mL were considered negative, weak positive, and strongly positive, respectively, whereas anti-nucleocapsid protein IgG was negative. Anti-S-IgG titer was determined in 990 HVs and 102 donors. RESULTS: Anti-S-IgG titers were 154, 2475, and 1181 U/mL in the recipient, HV, and donor groups, respectively, with values significantly lower in recipients. The anti-S-IgG-positivity rate of recipients gradually increased following the second vaccination, suggesting that recipients had a delayed response compared with the HV and donor groups, who had a 100% positivity rate at an earlier time point. Anti-S-IgG titers decreased in donors and HVs, whereas they remained stable in recipients, although at a significantly lower level. Independent negative factors associated with anti-S-IgG titers in recipients were age >60 years and lymphocytopenia (odds ratio: 2.35 and 2.44, respectively). CONCLUSIONS: Kidney transplant recipients demonstrate delayed and attenuated responses, with lower SARS-CoV-2 antibody titers after the second dose of the mRNA-based COVID-19 vaccine.


Subject(s)
COVID-19 , Kidney Transplantation , Humans , Middle Aged , COVID-19 Vaccines/adverse effects , Kidney Transplantation/adverse effects , SARS-CoV-2 , COVID-19/prevention & control , Healthy Volunteers , Antibodies, Viral , Immunoglobulin G , Transplant Recipients , Vaccination
17.
Am J Transplant ; 23(2): 294-297, 2023 02.
Article in English | MEDLINE | ID: covidwho-2278883

ABSTRACT

Lung transplant candidates who are highly sensitized against human leucocyte antigen present an ongoing challenge with regards to finding immunologically acceptable donors. Desensitization strategies aimed at reducing preformed donor-specific antibodies have a number of limitations. Imlifidase, an IgG-degrading enzyme derived from Streptococcus pyogenes, is a novel agent that has been used to convert positive crossmatches to negative in kidney transplant candidates, allowing transplantation to occur. We present the first case of imlifidase use for antibody depletion in a highly sensitized lung transplant candidate who went on to undergo a successful bilateral lung transplant.


Subject(s)
Kidney Transplantation , Lung Transplantation , Humans , Antibodies , Immunosuppressive Agents , Kidney Transplantation/adverse effects , Tissue Donors , HLA Antigens , Lung Transplantation/adverse effects , Histocompatibility Testing , Desensitization, Immunologic , Graft Rejection/drug therapy , Graft Rejection/etiology
18.
Transplant Proc ; 55(2): 342-345, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2276964

ABSTRACT

BACKGROUND: The aim of this case study was to explore the possible link between viral infections and collapsing focal segmental glomerulosclerosis (cFSGS) in patients who underwent kidney transplantation. METHODS: This case study included 3 case reports of patients who underwent kidney transplantation. The case reports were presented clinically and pathohistologically with cFsGS as a possible consequence of viral infections. RESULTS: The first patient developed cFSGS after polymerase chain reaction for SARS-CoV2 was positive twice. He gradually developed terminal stage chronic kidney disease. The second patient developed cFSGS with high range proteinuria after cytomegalovirus infection, which has been treated with 3 lines of antiviral medicaments. The third patient developed cFSGS as a possible consequence of hepatitis B virus infection. CONCLUSIONS: This case study highlighted the importance of viral etiology in the pathway of cFSGS. Pathogenic links between viral infections and concomitant glomerulopathies are challenging, especially in immunocompromised transplanted patients.


Subject(s)
COVID-19 , Glomerulosclerosis, Focal Segmental , Kidney Transplantation , Male , Humans , Glomerulosclerosis, Focal Segmental/complications , Glomerulosclerosis, Focal Segmental/pathology , Kidney Transplantation/adverse effects , RNA, Viral , COVID-19/complications , SARS-CoV-2 , Proteinuria/etiology
19.
Clin Transplant ; 37(2): e14915, 2023 02.
Article in English | MEDLINE | ID: covidwho-2274777

ABSTRACT

BACKGROUND: The clinical outcomes of ABO-incompatible (ABOi) kidney transplantation have improved with the introduction of desensitization therapy with rituximab. However, rituximab prevents not only antibody-mediated rejection (AMR) but also increases the risk of adverse events, such as infection. For ABOi kidney transplantation in patients with low anti-A/B antibody titers, we previously used a rituximab-free desensitization protocol and then initiated a single dose of 100 mg rituximab in 2016. We retrospectively compared the outcomes of ABOi kidney transplantation in patients with low anti-A/B antibody titers before and after the introduction of rituximab. METHODS: ABOi kidney transplantations (n = 142) in patients with low anti-A/B antibody titers between 2007 and 2021 were included. Patients were divided into two groups (with and without rituximab) for desensitization. The primary outcomes were the incidence of acute AMR and infection. RESULTS: Sixty-six patients were desensitized without rituximab (rituximab-free group), and 76 were pretreated with 100 mg rituximab (rituximab group) before transplantation. The incidence of acute AMR was significantly lower in the rituximab group than in the rituximab-free group (.0% [0/76] vs. 7.6% [5/66], respectively; p = .047). Post-transplantation anti-A/B antibody titers were also lower in the rituximab group than in the rituximab-free group. There was no significant difference in the incidence of adverse events, including infections, between the two groups. CONCLUSION: In ABOi kidney transplantation patients with low anti-A/B antibody titers, the desensitization protocol with a single dose of 100 mg rituximab was effective in preventing acute AMR without increasing the risk of other adverse events.


Subject(s)
Kidney Transplantation , Humans , Rituximab/therapeutic use , Kidney Transplantation/adverse effects , Kidney Transplantation/methods , Retrospective Studies , Treatment Outcome , Antibodies , Blood Group Incompatibility , ABO Blood-Group System , Graft Rejection/drug therapy , Graft Rejection/etiology , Graft Rejection/epidemiology , Graft Survival , Living Donors
20.
Trials ; 23(1): 1042, 2022 Dec 22.
Article in English | MEDLINE | ID: covidwho-2274174

ABSTRACT

BACKGROUND: Chronic active antibody-mediated rejection (AMR) is a major cause of graft loss with no approved drugs for its treatment. Currently, off-label regimens are used, reflecting the high unmet need for effective therapies based on well-controlled trials. Clazakizumab is a high-affinity, humanized monoclonal antibody that binds interleukin-6 and decreases donor-specific antibody (DSA) production and inflammation. Phase 2 pilot studies of clazakizumab in kidney transplant recipients with chronic active AMR suggest modulation of DSA, stabilization of glomerular filtration rate (GFR), and a manageable safety profile. We report the design of the Phase 3 IMAGINE study (NCT03744910) to evaluate the safety and efficacy of clazakizumab for the treatment of chronic active AMR. METHODS: IMAGINE is a multicenter, double-blind trial of approximately 350 kidney transplant recipients with chronic active AMR (Banff chronic glomerulopathy [cg] >0 with concurrent positive human leukocyte antigen DSA) randomized 1:1 to receive clazakizumab or placebo (12.5 mg subcutaneous once every 4 weeks). The event-driven trial design will follow patients until 221 occurrences of all-cause graft loss are observed, defined as return to dialysis, graft nephrectomy, re-transplantation, estimated GFR (eGFR) <15 mL/min/1.73m2, or death from any cause. A surrogate for graft loss (eGFR slope) will be assessed at 1 year based on prior modeling validation. Secondary endpoints will include measures of pharmacokinetics/pharmacodynamics. Recruitment is ongoing across North America, Europe, Asia, and Australia. DISCUSSION: IMAGINE represents the first Phase 3 clinical trial investigating the safety and efficacy of clazakizumab in kidney transplant recipients with chronic active AMR, and the largest placebo-controlled trial in this patient population. This trial includes prognostic biomarker enrichment and uniquely utilizes the eGFR slope at 1 year as a surrogate endpoint for graft loss, which may accelerate the approval of a novel therapy for patients at risk of graft loss. The findings of this study will be fundamental in helping to address the unmet need for novel therapies for chronic active AMR. TRIAL REGISTRATION: ClinicalTrials.gov NCT03744910 . Registered on November 19, 2018.


Subject(s)
Kidney Transplantation , Humans , Kidney Transplantation/adverse effects , Antibodies, Monoclonal, Humanized/adverse effects , Double-Blind Method , Glomerular Filtration Rate , Graft Rejection/drug therapy , Graft Rejection/prevention & control , Isoantibodies , Graft Survival
SELECTION OF CITATIONS
SEARCH DETAIL