Publications by authors named "Marta Crespo"

127 Publications

Protocol for Optimizing the Use of Kidneys From Donors With Seropositivity for Hepatitis C Virus in Seronegative Recipients.

Transplant Proc 2021 Oct 14. Epub 2021 Oct 14.

Department of Nephrology, Hospital Virgen del Rocío, Sevilla, Spain.

Background: The rapid identification of the viral load from hepatitis C virus (HCV) in seropositive donors enables the determination of their infection capacity and the subsequent design of a strategy to optimize the use of direct-action antivirals (DAA) in seronegative recipients. In 2017, we designed an optimization protocol; this study aims to assess its efficacy and safety.

Methods: This is a prospective, multicenter observational study that complies with the Declarations of Helsinki and Istanbul. Donors were HCV seropositive. The HCV and human immunodeficiency virus loads were immediately determined in the donors. For viremic donors, recipients were treated with DAA for 8 weeks. For nonviremic donors, DAA was started if a viral load was detected during the follow-up period. The minimum follow-up period was 6 months posttransplant.

Results: This study recruited 28 donors. Just over half of the donors (n = 15; 53.5%) had a nonactive history of injection drug use. Eight (22.4%) donors were viremic, and 20 (87.6%) were nonviremic; 13 (65%) had been treated previously. Nine grafts were ineligible for the protocol. We performed a total of 47 transplants. Procedure I (viremic donors) was performed in 13 recipients (27.7%). Posttransplant viremia was observed in 6 participants. Posttransplant viremia was low (<100 IU/mL) in 4 participants but high (36,000 and 138,000 IU/mL) in 2 participants who had initiated DAA after the transplant; all these patients had a sustained viral response. Seroconversion was observed in 11 of 13 (84.6%) patients. Procedure II (nonviremic donors) was undertaken in 34 (82.3%) patients. No positive viral loads were observed. Seroconversion occurred in 7 of 34 (20.5%) recipients. All recipients maintained kidney function at 6 months posttransplant, except 1 patient with a graft that had never been functional and another patient who died of pancreatitis. Both patients had received kidneys from nonviremic donors.

Conclusions: Our experience supports the efficacy and safety of this protocol.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2021.09.013DOI Listing
October 2021

Deciphering Transplant Outcomes of Expanded Kidney Allografts donated after controlled Circulatory Death in the Current Transplant Era. A Call for Caution.

Transpl Int 2021 Oct 9. Epub 2021 Oct 9.

Kidney Transplant Unit, Nephrology Department, Hospital Universitari de Bellvitge, L' Hospitalet de Llobregat, Barcelona, Spain.

Outcomes of kidney transplantation (KT) after controlled circulatory death (cDCD) with highly expanded criteria donors (ECD) and recipients have not been thoroughly evaluated. We analyzed in a multi-center cohort of 1,161 consecutive KT, granular baseline donor and recipient factors predicting transplant outcomes, selected by bootstrapping and Cox proportional hazards, and were validated in a contemporaneous European KT cohort (n=1,585). 74.3% were DBD and 25.7% cDCD-KT. ECD-KT showed the poorest graft survival rates, irrespective of cDCD or DBD (Log-Rank<0.001). Besides standard ECD classification, dialysis vintage, older age and previous cardiovascular recipient events together with low class-II-HLA match, long cold ischemia time and combining a diabetic donor with a cDCD predicted graft loss (C-Index 0.715, 95%CI 0.675-0.755). External validation showed good prediction accuracy (C-Index 0.697, 95%CI 0.643-0.741). Recipient older age, male gender, dialysis vintage, previous cardiovascular events and receiving a cDCD independently predicted patient death. Benefit/risk assessment of undergoing KT was compared to concurrent waitlisted candidates, and despite the fact that undergoing KT outperformed remaining waitlisted, remarkably high mortality rates were predicted if KT was undertaken under the worst risk-prediction model. Strategies to increase the donor pool, including cDCD transplants with highly expanded donor and recipient candidates should be performed with caution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.14131DOI Listing
October 2021

SARS-CoV-2 Infection Modulates ACE2 Function and Subsequent Inflammatory Responses in Swabs and Plasma of COVID-19 Patients.

Viruses 2021 08 28;13(9). Epub 2021 Aug 28.

IrsiCaixa-AIDS Research Institute, Health Research Institute Germans Trias i Pujol (IGTP), Universitat Autònoma de Barcelona, 08916 Badalona, Spain.

Angiotensin converting enzyme 2 (ACE2) is a host ectopeptidase and the receptor for the SARS-CoV-2 virus, albeit virus-ACE2 interaction goes far beyond viral entry into target cells. Controversial data exists linking viral infection to changes in ACE2 expression and function, which might influence the subsequent induction of an inflammatory response. Here, we tested the significance of soluble ACE2 enzymatic activity longitudinally in nasopharyngeal swabs and plasma samples of SARS-CoV-2 infected patients, along with the induction of inflammatory cytokines. Release of soluble functional ACE2 increases upon SARS-CoV-2 infection in swabs and plasma of infected patients, albeit rapidly decreasing during infection course in parallel with gene expression. Similarly, SARS-CoV-2 infection also induced the expression of inflammatory cytokines. These changes positively correlated with the viral load. Overall, our results demonstrate the existence of mechanisms by which SARS-CoV-2 modulates ACE2 expression and function, intracellular viral sensing and subsequent inflammatory response, offering new insights into ACE2 dynamics in the human upper respiratory tract and pointing towards soluble ACE2 levels as a putative early biomarker of infection severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/v13091715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8471465PMC
August 2021

Negative immune responses to two-dose mRNA COVID-19 vaccines in renal allograft recipients assessed with simple antibody and interferon gamma release assay cellular monitoring.

Am J Transplant 2021 Sep 22. Epub 2021 Sep 22.

Department of Nephrology, Hospital del Mar, Barcelona, Spain.

Studies are urgently needed to characterize immunogenicity, efficacy, and safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in kidney transplant (KT) recipients, excluded from major clinical trials. Complex ELISPOT and other cellular response techniques have been applied, but simpler tools are needed. An easy-to-use real-world monitoring of SARS-CoV-2 IgG antibodies against the Spike protein and QuantiFERON SARS-CoV-2 IFNγ release assay (IGRA) were performed at baseline and 28 days after the second dose in KT recipients and controls (dialysis patients and healthy ones). All healthy controls and >95% dialysis controls became positive for anti-S IgG antibodies, while only 63.3% of KT patients seroconverted with a very low antibody level. A positive IGRA was documented in 96.9% of controls, 89.3% peritoneal dialysis, 77.6% hemodialysis, 61.3% of KT patients transplanted more than 1 year ago and only 36% of those transplanted within the previous 12 months. Overall, 100% of healthy controls, 95.4% of dialysis patients and 78.8% KT recipients developed any immune response (humoral and/or cellular) against SARS-CoV-2. KT patients showed low rates of immune responses to mRNA Coronavirus infectious disease 2019 vaccines, especially those with recent transplantations. Simple humoral and cellular monitoring is advisable, so that repeated doses may be scheduled according to the results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16854DOI Listing
September 2021

Assessment of Pre-Donation Glomerular Filtration Rate: Going Back To Basics A Position Paper from the DESCARTES Working Group of the ERA-EDTA.

Nephrol Dial Transplant 2021 Sep 14. Epub 2021 Sep 14.

Department of Medicine and Surgery, University of Parma, Italy.

The 2017 version of the KDIGO (Kidney Disease: Improving Global Outcomes) guidelines is the most recent international framework for the evaluation and care of living kidneys donors. Along with the call for an integrative approach evaluating the long-term end-stage kidney disease risk for the future potential donor, several recommendations are formulated regarding the predonation glomerular filtration rate (GFR) adequacy with no or little consideration for the donor candidate's age and for the importance of using reference methods of GFR measurements. Herein, we question the position of the KDIGO guidelines and discuss the rationale and modalities for a more basic, but not less demanding GFR evaluation susceptible to enable a more efficient selection of the potential kidney donor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfab259DOI Listing
September 2021

Long-Term Evolution of the Adaptive NKG2C NK Cell Response to Cytomegalovirus Infection in Kidney Transplantation: An Insight on the Diversity of Host-Pathogen Interaction.

J Immunol 2021 10 1;207(7):1882-1890. Epub 2021 Sep 1.

Universitat Pompeu Fabra, Barcelona, Spain;

Human CMV infection is frequent in kidney transplant recipients (KTR). Pretransplant Ag-specific T cells and adaptive NKG2C NK cells associate with reduced incidence of infection in CMV KTR. Expansions of adaptive NKG2C NK cells were reported in posttransplant CMV-infected KTR. To further explore this issue, NKG2C NK, CD8, and TcRγδ T cells were analyzed pretransplant and at different time points posttransplant for ≥24 mo in a cohort of CMV KTR ( = 112), stratified according to CMV viremia detection. In cryopreserved samples from a subgroup ( = 49), adaptive NKG2C NK cell markers and T cell subsets were compared after a longer follow-up (median, 56 mo), assessing the frequencies of CMV-specific T cells and viremia at the last time point. Increased proportions of NKG2C NK, CD8, and TcRγδ T cells were detected along posttransplant evolution in viremia(+) KTR. However, the individual magnitude and kinetics of the NKG2C NK response was variable and only exceptionally detected among viremia(-) KTR, presumably reflecting subclinical viral replication events. NKG2C expansions were independent of zygosity and associated with higher viral loads at diagnosis; no relation with other clinical parameters was perceived. Increased proportions of adaptive NKG2C NK cells (CD57, ILT2, FcεRIγ) were observed after resolution of viremia long-term posttransplant, coinciding with increased CD8 and Vδ2 γδ T cells; at that stage CMV-specific T cells were comparable to viremia(-) cases. These data suggest that adaptive NKG2C NK cells participate with T cells to restore CMV replication control, although their relative contribution cannot be discerned.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2100055DOI Listing
October 2021

Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.

Nutrients 2021 Jul 26;13(8). Epub 2021 Jul 26.

Department of Nephrology, Hospital del Mar, IMIM Hospital del Mar Medical Research Institute, RD16/0009/0013 (ISCIII FEDER REDinREN), 08003 Barcelona, Spain.

Background: In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients.

Methods: A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain.

Results: The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival.

Conclusions: Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu13082559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401800PMC
July 2021

Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial.

J Am Soc Nephrol 2021 08;32(8):2083-2098

Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria

Background: Post-transplantation diabetes mellitus (PTDM) might be preventable.

Methods: This open-label, multicenter randomized trial compared 133 kidney transplant recipients given intermediate-acting insulin isophane for postoperative afternoon glucose ≥140 mg/dl with 130 patients given short-acting insulin for fasting glucose ≥200 mg/dl (control). The primary end point was PTDM (antidiabetic treatment or oral glucose tolerance test-derived 2 hour glucose ≥200 mg/dl) at month 12 post-transplant.

Results: In the intention-to-treat population, PTDM rates at 12 months were 12.2% and 14.7% in treatment versus control groups, respectively (odds ratio [OR], 0.82; 95% confidence interval [95% CI], 0.39 to 1.76) and 13.4% versus 17.4%, respectively, at 24 months (OR, 0.71; 95% CI, 0.34 to 1.49). In the per-protocol population, treatment resulted in reduced odds for PTDM at 12 months (OR, 0.40; 95% CI, 0.16 to 1.01) and 24 months (OR, 0.54; 95% CI, 0.24 to 1.20). After adjustment for polycystic kidney disease, per-protocol ORs for PTDM (treatment versus controls) were 0.21 (95% CI, 0.07 to 0.62) at 12 months and 0.35 (95% CI, 0.14 to 0.87) at 24 months. Significantly more hypoglycemic events (mostly asymptomatic or mildly symptomatic) occurred in the treatment group versus the control group. Within the treatment group, nonadherence to the insulin initiation protocol was associated with significantly higher odds for PTDM at months 12 and 24.

Conclusions: At low overt PTDM incidence, the primary end point in the intention-to-treat population did not differ significantly between treatment and control groups. In the per-protocol analysis, early basal insulin therapy resulted in significantly higher hypoglycemia rates but reduced odds for overt PTDM-a significant reduction after adjustment for baseline differences-suggesting the intervention merits further study. NCT03507829.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1681/ASN.2021010127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8455276PMC
August 2021

Non-HLA Antibodies and Epitope Mismatches in Kidney Transplant Recipients With Histological Antibody-Mediated Rejection.

Front Immunol 2021 6;12:703457. Epub 2021 Jul 6.

Department of Nephrology, Hospital del Mar, Barcelona, Spain.

Background: Correlation between antibody-mediated rejection (ABMR) and circulating HLA donor-specific antibodies (HLA-DSA) is strong but imperfect in kidney transplant (KT) recipients, raising the possibility of undetected HLA-DSA or non-HLA antibodies contributing to ABMR. Detailed evaluation of the degree of HLA matching together with the identification of non-HLA antibodies in KT may help to decipher the antibody involved.

Methods: We retrospectively assessed patients with transplant biopsies scored following Banff'15 classification. Pre- and post-transplant serum samples were checked for HLA and non-HLA antibodies [MICA-Ab, angiotensin-II type-1-receptor (ATR)-Ab, endothelin-1 type-A-receptor (ETAR)-Ab and crossmatches with primary aortic endothelial cells (EC-XM)]. We also analyzed HLA epitope mismatches (HLA-EM) between donors and recipients to explore their role in ABMR histology (ABMR) with and without HLA-DSA.

Results: One-hundred eighteen patients with normal histology (n = 19), ABMR (n = 52) or IFTA (n = 47) were studied. ABMR patients were HLA-DSA (n = 38, 73%) or HLA-DSA (n = 14, 27%). Pre-transplant HLA-DSA and ATR-Ab were more frequent in ABMR compared with IFTA and normal histology cases (p = 0.006 and 0.003), without differences in other non-HLA antibodies. Only three ABMRDSA cases showed non-HLA antibodies. ABMRDSA and ABMRDSA cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMRDSA but not with ABMRDSA. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 [1.31-10.37], p = 0.013) and ATR-Ab (OR: 5.47 [1.78-16.76], p = 0.003) were independent predictors of ABMRDSA.

Conclusions: In conclusion, pre-transplant ATR-Ab is frequently found in ABMRDSA patients. However, ATR-Ab, MICA-Ab, ETAR-Ab or EC-XM are rarely found among ABMRDSA patients. Pre-transplant ATR-Ab may act synergistically with preformed or HLA-DSA to produce ABMRDSA but not ABMRDSA. HLA epitope mismatch associates with ABMRDSA compared with ABMRDSA, suggesting factors other than HLA are responsible for the damage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.703457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300190PMC
July 2021

Live donor kidney transplantation. Situation analysis and roadmap.

Nefrologia (Engl Ed) 2021 Jul 19. Epub 2021 Jul 19.

Clínica Universitaria de Navarra, Pamplona, España.

Living donor kidney transplantation (LDKT) is the best treatment option for end stage renal disease in terms of both patient and graft survival. However, figures on LDKT in Spain that had been continuously growing from 2005 to 2014, have experienced a continuous decrease in the last five years. One possible explanation for this decrease is that the significant increase in the number of deceased donors in Spain during the last years, both brain death and controlled circulatory death donors, might have generated the false idea that we have coped with the transplant needs. Moreover, a greater number of deceased donor kidney transplants have caused a heavy workload for the transplant teams. Furthermore, the transplant teams could have moved on to a more conservative approach to the information and assessment of patients and families considering the potential long-term risks for donors in recent papers. However, there is a significant variability in the LDKT rate among transplant centers and regions in Spain independent of their deceased donor rates. This fact and the fact that LDKT is usually a preemptive option for patients with advanced chronic renal failure, as time on dialysis is a negative independent factor for transplant outcomes, lead us to conclude that the decrease in LDKT depends on other factors. Thus, in the kidney transplant annual meeting held at ONT site in 2018, a working group was created to identify other causes for the decrease of LDKT in Spain and its relationship with the different steps of the process. The group was formed by transplant teams, a representative of the transplant group of the Spanish Society of Nephrology (SENTRA), a representative of the Spanish Society of Transplants (SET) and representatives of the Spanish National Transplant Organization (ONT). A self-evaluation survey that contains requests about the phases of the LDKT processes (information, donor work out, informed consent, surgeries, follow-up and human resources) were developed and sent to 33 LDKT teams. All the centers answered the questionnaire. The analysis of the answers has resulted in the creation of a national analysis of strengths, weaknesses, opportunities, threats (SWOT) of the LDKT program in Spain and the development of recommendations targeted to improve every step of the donation process. The work performed, the conclusions and recommendations provided, have been reflected in the following report: Spanish living donor kidney transplant program assessment: recommendations for optimization. This document has also been reviewed by a panel of experts, representatives of the scientific societies (Spanish Society of Urology (AEU), Spanish Society of Nephrology Nursery (SEDEN), Spanish Society of Immunology (SEI/GETH)) and the patient association ALCER. Finally, the report has been submitted to public consultation, reaching ample consensus. In addition, the transplant competent authorities of the different regions in Spain have adopted the report at institutional level. The work done and the recommendations to optimize LDKT are summarized in the present manuscript, organized by the different phases of the donation process.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nefro.2021.03.008DOI Listing
July 2021

Use and Safety of Remdesivir in Kidney Transplant Recipients With COVID-19.

Kidney Int Rep 2021 Sep 6;6(9):2305-2315. Epub 2021 Jul 6.

Department of Nephrology, Hospital del Mar, Institute Mar for Medical Research (IMIM), Red de Investigación Renal (REDinREN) (RD16/0009/0013), Barcelona, Spain.

Introduction: Remdesivir has demonstrated antiviral activity against coronavirus, shortening the time to recovery in adults hospitalized with moderate/severe COVID-19. Severe adverse events such as acute kidney injury have been reported. Scant data are available on the use and safety of remdesivir in kidney transplant recipients.

Methods: We present a multicenter cohort study of 51 kidney transplant recipients with COVID-19 treated with remdesivir. Outcomes and safety were assessed.

Results: Mean age at diagnosis was 60 years, with a median time since kidney transplant of 4.5 years. Mean time since admission to remdesivir was 2 days. Twenty-eight patients (54.9%) required mechanical ventilation (19 noninvasive). Mortality was 18.9% and markedly higher if aged ≥65 years (45% vs. 3.2% in younger patients). Acute kidney injury was present in 27.7% of patients, but was diagnosed in 50% before treatment. No patients required remdesivir discontinuation because of adverse events. We did not find significant hepatoxicity or systemic symptoms resulting from the drug.

Conclusion: In our cohort of kidney transplant recipients, remdesivir was well tolerated and safe in renal and hepatic toxicity, but randomized trials are needed to assess its efficacy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ekir.2021.06.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257403PMC
September 2021

COVID-19 in Solid Organ Transplant Recipients in Spain Throughout 2020: Catching the Wave?

Transplantation 2021 10;105(10):2146-2155

Organización Nacional de Trasplantes, Madrid, Spain.

Background: Few studies have analyzed differences in clinical presentation and outcomes in solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) across different pandemic waves.

Methods: In this multicenter, nationwide, prospective study, we compared demographics and clinical features, therapeutic management, and outcomes in SOT recipients diagnosed with COVID-19 in Spain before (first wave) or after (second wave) 13 July 2020.

Results: Of 1634 SOT recipients, 690 (42.2%) and 944 (57.8%) were diagnosed during the first and second periods, respectively. Compared with the first wave, recipients in the second were younger (median: 63 y [interquartile range, IQR: 53-71] versus 59 y [IQR: 49-68]; P < 0.001) and less likely to receive anti-severe acute respiratory syndrome coronavirus 2 drugs (81.8% versus 8.1%; P < 0.001), with no differences in immunomodulatory therapies (46.8% versus 47.0%; P = 0.931). Adjustment of immunosuppression was less common during the second period (76.4% versus 53.6%; P < 0.001). Hospital admission (86.7% versus 58.1%; P < 0.001), occurrence of acute respiratory distress syndrome (34.1% versus 21.0%; P < 0.001), and case-fatality rate (25.8% versus 16.7%; P < 0.001) were lower in the second period. In multivariate analysis, acquiring COVID-19 during the first wave was associated with an increased risk of death (OR: 1.47; 95% confidence interval [CI], 1.12-1.93; P = 0.005), although this impact was lost in the subgroup of patients requiring hospital (OR: 0.97; 95% CI, 0.73-1.29; P = 0.873) or intensive care unit admission (OR: 0.65; 95% CI, 0.35-1.18; P = 0.157).

Conclusions: We observed meaningful changes in demographics, therapeutic approaches, level of care, and outcomes between the first and second pandemic waves. However, outcomes have not improved in the more severe cases of posttransplant COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8487705PMC
October 2021

Immunoguided Discontinuation of Prophylaxis for Cytomegalovirus Disease in Kidney Transplant Recipients Treated with Antithymocyte Globulin: A Randomized Clinical Trial.

Clin Infect Dis 2021 Jun 22. Epub 2021 Jun 22.

Maimónides Institute for Biomedical Research of Cordoba (IMIBIC)/Reina Sofía University Hospital/University of Cordoba (UCO), Cordoba, Spain.

Background: Antiviral prophylaxis is recommended in cytomegalovirus (CMV)-seropositive kidney transplant (KT) recipients receiving antithymocyte globulin (ATG) as induction. An alternative strategy of premature discontinuation of prophylaxis after CMV-specific cell-mediated immunity (CMV-CMI) recovery (immunoguided prevention) has not been studied. The aim of this study was to evaluate whether it is effective and safe to discontinue prophylaxis when CMV-CMI is detected and to continue with preemptive therapy.

Methods: In this open-label, non-inferiority clinical trial, patients were randomized 1:1 to follow immunoguided strategy, receiving prophylaxis (valganciclovir 900 mg daily) until CMV-CMI recovery or to receive fixed-duration prophylaxis until day +90. After prophylaxis, preemptive therapy (valganciclovir 900 mg twice daily) was indicated in both arms until month 6. The primary and secondary outcomes were incidence of CMV disease and replication, respectively, within the first 12 months. Desirability of outcome ranking (DOOR) assessed two deleterious events (CMV disease/replication and neutropenia).

Results: A total of 150 CMV-seropositive KT recipients were randomly assigned. There was no difference in the incidence of CMV disease (0% vs. 2.7%; P = 0.149) and replication (17.1% vs. 13.5%; log-rank test, P = 0.422) between both arms. Incidence of neutropenia was lower in the immunoguided arm (9.2% vs. 37.8%; OR, 6.0; P < 0.001). A total of 66.1% of patients in the immunoguided arm showed a better DOOR, indicating a greater likelihood of a better outcome.

Conclusions: Prophylaxis can be prematurely discontinued in CMV-seropositive KT patients receiving ATG when CMV-CMI is recovered since no significant increase in the incidence of CMV replication or disease is observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/cid/ciab574DOI Listing
June 2021

Renin-Angiotensin System Blockers and the Risk of COVID-19-Related Mortality in Patients with Kidney Failure.

Clin J Am Soc Nephrol 2021 07 4;16(7):1061-1072. Epub 2021 Jun 4.

Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background And Objectives: There is concern about potential deleterious effects of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). Patients with kidney failure, who often use ACEis/ARBs, are at higher risk of more severe COVID-19. However, there are no data available on the association of ACEi/ARB use with COVID-19 severity in this population.

Design, Setting, Participants, & Measurements: From the European Renal Association COVID-19 database (ERACODA), we retrieved data on kidney transplant recipients and patients on dialysis who were affected by COVID-19, between February 1 and October 1, 2020, and had information on 28-day mortality. We used Cox proportional-hazards regression to calculate hazard ratios for the association between ACEi/ARB use and 28-day mortality risk. Additionally, we studied the association of discontinuation of these agents with 28-day mortality.

Results: We evaluated 1511 patients: 459 kidney transplant recipients and 1052 patients on dialysis. At diagnosis of COVID-19, 189 (41%) of the transplant recipients and 288 (27%) of the patients on dialysis were on ACEis/ARBs. A total of 88 (19%) transplant recipients and 244 (23%) patients on dialysis died within 28 days of initial presentation. In both groups of patients, there was no association between ACEi/ARB use and 28-day mortality in both crude and adjusted models (in transplant recipients, adjusted hazard ratio, 1.12; 95% confidence interval [95% CI], 0.69 to 1.83; in patients on dialysis, adjusted hazard ratio, 1.04; 95% CI, 0.73 to 1.47). Among transplant recipients, ACEi/ARB discontinuation was associated with a higher mortality risk after adjustment for demographics and comorbidities, but the association was no longer statistically significant after adjustment for severity of COVID-19 (adjusted hazard ratio, 1.36; 95% CI, 0.40 to 4.58). Among patients on dialysis, ACEi/ARB discontinuation was not associated with mortality in any model. We obtained similar results across subgroups when ACEis and ARBs were studied separately, and when other outcomes for severity of COVID-19 were studied, , hospital admission, admission to the intensive care unit, or need for ventilator support.

Conclusions: Among kidney transplant recipients and patients on dialysis with COVID-19, there was no significant association of ACEi/ARB use or discontinuation with mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2215/CJN.18961220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425613PMC
July 2021

Impact of a Nosocomial COVID-19 Outbreak on a Non-COVID-19 Nephrology Ward during the First Wave of the Pandemic in Spain.

Antibiotics (Basel) 2021 May 22;10(6). Epub 2021 May 22.

Infectious Diseases Service, Hospital del Mar, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Universitat Autònoma de Barcelona (UAB), CEXS-Universitat Pompeu Fabra, 08003 Barcelona, Spain.

Introduction: The aim of this study was to analyze a nosocomial coronavirus disease 2019 (COVID-19) outbreak that occurred on a polyvalent non-COVID-19 ward at a tertiary care university hospital in Spain during the first wave of the pandemic and to describe the containment measures taken. The outbreak affected healthcare workers (HCWs) and kidney disease patients including transplant patients and those requiring maintenance hemodialysis.

Methods: The outbreak investigation and report were conducted in accordance with the Orion statement guidelines.

Results: In this study, 15 cases of COVID-19 affecting 10 patients and 5 HCWs were identified on a ward with 31 beds and 43 HCWs. The patients had tested negative for severe acute respiratory syndrome coronavirus 2 infection on admission. One of the HCWs was identified as the probable index case. Five patients died (mortality rate, 50%). They were all elderly and had significant comorbidities. The infection control measures taken included the transfer of infected patients to COVID-19 isolation wards, implementation of universal preventive measures, weekly PCR testing of patients and HCWs linked to the ward, training of HCWs on infection control and prevention measures, and enhancement of cleaning and disinfection. The outbreak was contained in 2 weeks, and no new cases occurred.

Conclusion: Nosocomial COVID-19 outbreaks can have high attack rates involving both patients and HCWs and carry a high risk of patient mortality. Hospitals need to implement effective infection prevention and control strategies to prevent nosocomial COVID-19 spread.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics10060619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224553PMC
May 2021

Sex differences in cancer risk and outcomes after kidney transplantation.

Transplant Rev (Orlando) 2021 07 1;35(3):100625. Epub 2021 May 1.

Department of Nephrology, Hospital del Mar, Barcelona, Spain.

Kidney transplant recipients (KTRs) experience a two- to four-fold increased risk of developing and dying from cancer compared with the general population. High cancer risk results from the interaction of both modifiable and non-modifiable factors. This mapping review explores the impact of sex disparity on cancer's increased incidence and mortality after kidney transplantation (KT). In terms of age, population-based studies indicate that younger recipients of both sexes experience a higher risk of cancer, but this is more pronounced in young women. On the contrary, older men are more likely to be diagnosed with cancer, although their increased risk is not statistically significant compared with the general population. Regarding cancer type, studies show an increased risk of Kaposi sarcoma, gynecologic and lung cancer in women, and bladder and kidney cancer in men. Immune-related cancers such as pos-transplant lymphoproliferative disorders and melanoma are increased in both sexes. Mortality also shows differences between sexes. Although cancer is the second cause of death in both male and female KTRs, studies show higher overall mortality in men and elderly recipients. However, the relative risk of cancer mortality compared with the general population is higher at a younger age, with disparate results regarding sex. Female KTRs appear to die at a younger age than males when compared with the general population. Differences in cancer rates by sex after renal transplantation need further studies. A better understanding of sex-specific differences in cancer epidemiology after KT could help nephrologists to better address pre-transplant counseling, to establish early surveillance programs, and to plan modifiable risk factors such as immunosuppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.trre.2021.100625DOI Listing
July 2021

Immunological and genetic kinetics from diagnosis to clinical progression in chronic lymphocytic leukemia.

Biomark Res 2021 May 20;9(1):37. Epub 2021 May 20.

Department de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.

Background: Mechanisms driving the progression of chronic lymphocytic leukemia (CLL) from its early stages are not fully understood. The acquisition of molecular changes at the time of progression has been observed in a small fraction of patients, suggesting that CLL progression is not mainly driven by dynamic clonal evolution. In order to shed light on mechanisms that lead to CLL progression, we investigated longitudinal changes in both the genetic and immunological scenarios.

Methods: We performed genetic and immunological longitudinal analysis using paired primary samples from untreated CLL patients that underwent clinical progression (sampling at diagnosis and progression) and from patients with stable disease (sampling at diagnosis and at long-term asymptomatic follow-up).

Results: Molecular analysis showed limited and non-recurrent molecular changes at progression, indicating that clonal evolution is not the main driver of clinical progression. Our analysis of the immune kinetics found an increasingly dysfunctional CD8 T cell compartment in progressing patients that was not observed in those patients that remained asymptomatic. Specifically, terminally exhausted effector CD8 T cells (T-betEomesPD1) accumulated, while the the co-expression of inhibitory receptors (PD1, CD244 and CD160) increased, along with an altered gene expression profile in T cells only in those patients that progressed. In addition, malignant cells from patients at clinical progression showed enhanced capacity to induce exhaustion-related markers in CD8 T cells ex vivo mainly through a mechanism dependent on soluble factors including IL-10.

Conclusions: Altogether, we demonstrate that the interaction with the immune microenvironment plays a key role in clinical progression in CLL, thereby providing a rationale for the use of early immunotherapeutic intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s40364-021-00290-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138982PMC
May 2021

Activation of final complement components after kidney transplantation as a marker of delayed graft function severity.

Clin Kidney J 2021 Apr 10;14(4):1190-1196. Epub 2020 Oct 10.

Department of Nephrology, Hospital del Mar, Barcelona, Catalunya, Spain.

Background: Ischaemia-reperfusion (I/R) damage is a relevant cause of delayed graft function (DGF). Complement activation is involved in experimental I/R injury, but few data are available from kidney transplant (KT) patients. We studied the dynamics of membrane attack complex (C5b-9) as a soluble fraction (SC5b-9) and the histological deposit pattern of C3b, complement Factor H (FH) and C5b-9 in DGF patients.

Methods: We evaluated SC5b-9 levels in 59 recipients: 38 with immediate graft function and 21 with DGF. The SC5b-9 was measured at admission for KT and 7 days after KT. DGF-kidney biopsies ( = 12) and a control group of 1-year protocol biopsies without tissue damage ( = 4) were stained for C5b-9, C3b and FH.

Results: SC5b-9 increased significantly in DGF patients (Day 0: 6621 ± 2202 mAU/L versus Day 7: 9626 ± 4142  mAU/L; P = 0.006), while it remained stable in non-DGF patients. Days 0-7 increase >5% was the better cut-off associated with DGF versus non-DGF patient discrimination (sensitivity = 81%). In addition, SC5b-9 increase was related to DGF duration and worse graft function, and independently associated with DGF occurrence. SC5b-9, C3b and FH stains were observed in tubular epithelial cells basal membrane. DGF-kidney biopsies showed a more frequently high-intensity stain, a higher number of tubules with positive stain and larger perimeter of tubules with positive stains for SC5b-9, C3b and FH than control patients.

Conclusions: Both SC5b-9 levels and SC5b-9, C3b and FH deposits in tubular epithelial cells basal membrane are highly expressed in patients experiencing DGF. SC5b-9 levels increase could be useful as a marker of DGF severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfaa147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023215PMC
April 2021

Kidney transplantation outcomes from elderly donors after circulatory death: a comparison with elderly brain-dead donors.

Clin Kidney J 2021 Apr 10;14(4):1181-1189. Epub 2020 Sep 10.

Department of Nephrology, Hospital del Mar, Barcelona, Spain.

Background: The use of kidneys from elderly controlled donation after circulatory death (cDCD) donors has increased significantly in recent years. Concerns about outcomes achieved with these elderly cDCD kidneys have arisen. We aimed to compare outcomes from elderly cDCD kidney transplant recipients (KTrs) and elderly donation after brain death donors (DBDs) in KTrs.

Methods: We conducted a single-centre retrospective study including 87 cDCD-KTrs (46 from donors ≥65 years of age and 41 from <65 years) and 126 DBD-KTrs from donors ≥65 years of age from 2013 through 2017). Young cDCD-KTrs were used as controls. The median follow-up was 27.1 months for all cDCD-KTrs and 29.7 months for DBD-KTrs ≥65 years of age.

Results: Donors >65 years of age represented more than half of our global cDCD cohort (52.9%). KTs from elderly cDCDs had similar rates of delayed graft function, primary non-function and vascular complications compared with young cDCD-KTrs and elderly DBD-KTrs. Short and medium-term graft survival from elderly cDCD kidneys are excellent and are comparable to those from young cDCD and elderly DBD kidneys (90% young cDCD versus 88% elderly cDCD versus 80% elderly DBD at 36 months, P = 0.962 and 0.180, respectively). Although recipients from cDCDs ≥65 years of age showed lower 3-year patient survival (78% versus 87% in elderly DBD-KTrs; P = 0.01), recipient age was the only determinant of patient survival [hazard ratio 1.10 (95% confidence interval 1.02-1.17); P < 0.01], without any influence of donor characteristics.

Conclusions: The use of kidneys from elderly cDCDs is increasing in Spain. Short- and medium-term graft outcomes are similar when comparing kidneys from elderly cDCDs and DBDs. Recipient age is the only determinant of patient survival. Additional studies are needed to assess long-term outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ckj/sfaa114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8023186PMC
April 2021

Tacrolimus, Sirolimus and Everolimus Doses in HIV-Infected Solid-Organ Recipients, Requiring a Cobicistat-Based Antiretroviral Regimen: Report of Three Cases and Review.

Infect Dis Ther 2021 Jun 8;10(2):1055-1064. Epub 2021 Apr 8.

HIV Unit and Infectious Diseases Service, Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.

People living with HIV should be considered candidates for solid-organ transplantation (SOT). However, managing HIV-infected patients undergoing SOT represents a major challenge due to the potential drug-drug interactions between antiretroviral drugs and immunosuppressive agents, particularly when resorting to antiretroviral drugs that require pharmacokinetic enhancers. We report three cases of cobicistat-tacrolimus co-administration, two of which also include the co-administration of mTOR inhibitors, in HIV-positive patients undergoing SOT (2 kidney and 1 liver recipient). We review previously reported cases and provide recommendations for initial management following transplantation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40121-021-00430-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027707PMC
June 2021

Role of C5aR1 and C5L2 Receptors in Ischemia-Reperfusion Injury.

J Clin Med 2021 Mar 2;10(5). Epub 2021 Mar 2.

Department of Nephrology, Parc de Salut Mar, 08003 Barcelona, Spain.

The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of , genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, = 12) and compared with a control group ( = 8). We observed higher immunofluorescence expression of C5aR1, MAC and FH as higher expression of genes related to tubular injury, inflammatory and profibrotic pathways and of in the hypoxic cells; whereas, gene expression was unaffected by the hypoxic stimulus. Regarding KB, C5aR1 was detected in the apical and basal membrane of tubular epithelial cells, whereas C5L2 deposits were observed in endothelial cells of peritubular capillaries (PTC). DGF-KB showed more frequently diffuse C5aR1 staining and C5L2 compared to controls. In conclusion, C5aR1 expression is increased by hypoxia and IRI, both in vitro and in human biopsies with an acute injury. C5L2 expression in PTC could be related to endothelial cell damage during IRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10050974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957510PMC
March 2021

Stratifying the humoral risk of candidates to a solid organ transplantation: a proposal of the ENGAGE working group.

Transpl Int 2021 06 22;34(6):1005-1018. Epub 2021 Apr 22.

Service de Transplantation, Néphrologie et Immunologie Clinique, Hôpital Edouard Herriot, Lyon, France.

Detection of circulating antibodies directed against human leukocyte antigen (HLA) molecules, which corresponds to the current definition of 'sensitized patient', has been shown to have a severe impact on both access to transplantation and, if the anti-HLA antibodies are specific to the selected donor, survival of the graft. However, not all donor-specific antibodies (DSA) are equally harmful to the graft and progress in the understanding of humoral memory has led to the conclusion that absence of DSA at transplantation does not rule out the possibility that the patient has a preformed cellular humoral memory against the graft (thereby defining a category of DSA-negative sensitized recipients). Technological progress has led to the generation of new assays that offer unprecedented precision in exploring the different layers (serological and cellular) of alloimmune humoral memory. Based on this recent knowledge, the EuropeaN Guidelines for the mAnagement of Graft rEcipients (ENGAGE) working group to propose an updated definition of sensitization in candidates for solid organ transplantation - one that moves away from the current binary division towards a definition based on homogenous strata with similar humoral risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/tri.13874DOI Listing
June 2021

The effect of anti‑HLA class I antibodies on the immunological properties of human glomerular endothelial cells and their modification by mTOR inhibition or GCN2 kinase activation.

Mol Med Rep 2021 05 24;23(5). Epub 2021 Mar 24.

Department of Nephrology, Faculty of Medicine, University of Thessaly, Larissa 41110, Greece.

In antibody‑mediated rejection (ABMR), the graft endothelium is at the forefront of the kidney transplant against the assault from the recipient's humoral immune system, and is a target of the latter. The present study investigated the effect of antibodies against human leukocyte antigen (HLA) class I (anti‑HLAI) on the immunological properties of human glomerular endothelial cells. Additionally, the effect of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) inhibitor (everolimus), or the general control nonderepressible 2 kinase (GCN2K) activator (halofuginone) on anti‑HLAI antibody‑mediated alterations was assessed. Cell integrity was examined, an lactate dehydrogenase (LDH) release assay was performed and cleaved caspase‑3 levels were determined. Furthermore, cell proliferation was analyzed by performing a bromodeoxyuridine assay and the cellular proteins involved in signal transduction or immune effector mechanisms were assessed via western blotting. IL‑8, monocyte chemoattractive protein‑1 (MCP‑1), von Willebrand factor (vWF) and transforming growth factor‑beta 1 (TGF‑β1) were assayed via ELISA. The results revealed that anti‑HLAI triggered integrin signaling, activated mTOR and GCN2K, preserved cell integrity and promoted cell proliferation. Additionally, by increasing intercellular adhesion molecule 1 (ICAM‑1), HLA‑DR, IL‑8 and MCP‑1 levels, anti‑HLAI enhanced the ability of immune cells to interact with endothelial cells thus facilitating graft rejection. Contrarily, by upregulating CD46 and CD59, anti‑HLAI rendered the endothelium less vulnerable to complement‑mediated injury. Finally, by enhancing vWF and TGF‑β1, anti‑HLAI may render the endothelium prothrombotic and facilitate fibrosis and graft failure, respectively. According to our results, mTORC1 inhibition and GCN2K activation may prove useful pharmaceutical targets, as they prevent cell proliferation and downregulate ICAM‑1, IL‑8, MCP‑1 and TGF‑β1. mTORC1 inhibition also decreases vWF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mmr.2021.11994DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7974416PMC
May 2021

Predictors of severe COVID-19 in kidney transplant recipients in the different epidemic waves: Analysis of the Spanish Registry.

Am J Transplant 2021 07 12;21(7):2573-2582. Epub 2021 Apr 12.

Department of Nephrology, Hospital del Mar, Institute Mar for Medical Research, REDinREN, Barcelona, Spain.

SARS-CoV-2 infection has produced high mortality in kidney transplant (KT) recipients, especially in the elderly. Until December 2020, 1011 KT with COVID-19 have been prospectively included in the Spanish Registry and followed until recovery or death. In multivariable analysis, age, pneumonia, and KT performed ≤6 months before COVID-19 were predictors of death, whereas gastrointestinal symptoms were protective. Survival analysis showed significant increasing mortality risk in four subgroups according to recipient age and time after KT (age <65 years and posttransplant time >6 months, age <65 and time ≤6, age ≥65 and time >6 and age ≥65 and time ≤6): mortality rates were, respectively, 11.3%, 24.5%, 35.4%, and 54.5% (p < .001). Patients were significantly younger, presented less pneumonia, and received less frequently specific anti-COVID-19 treatment in the second wave (July-December) than in the first one (March-June). Overall mortality was lower in the second wave (15.1 vs. 27.4%, p < .001) but similar in critical patients (66.7% vs. 58.1%, p = .29). The interaction between age and time post-KT should be considered when selecting recipients for transplantation in the COVID-19 pandemic. Advanced age and a recent KT should foster strict protective measures, including vaccination.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajt.16579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250925PMC
July 2021

Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation.

Transplantation 2021 03;105(3):648-659

Department of Medicine, University of Wisconsin, Madison, WI.

Background: There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx).

Methods: We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up.

Results: A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of -0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of -9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years.

Conclusions: If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/TP.0000000000003274DOI Listing
March 2021

Long-term risks after kidney donation: how do we inform potential donors? A survey from DESCARTES and EKITA transplantation working groups.

Nephrol Dial Transplant 2021 08;36(9):1742-1753

Antwerp University Hospital, Antwerp, Belgium.

Background: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation.

Methods: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks.

Results: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes.

Conclusions: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfab035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397510PMC
August 2021

A Role for Human Renal Tubular Epithelial Cells in Direct Allo-Recognition by CD4+ T-Cells and the Effect of Ischemia-Reperfusion.

Int J Mol Sci 2021 Feb 9;22(4). Epub 2021 Feb 9.

Department of Nephrology, Faculty of Medicine, University of Thessaly, 41110 Larissa, Greece.

Direct allorecognition is the earliest and most potent immune response against a kidney allograft. Currently, it is thought that passenger donor professional antigen-presenting cells (APCs) are responsible. Further, many studies support that graft ischemia-reperfusion injury increases the probability of acute rejection. We evaluated the possible role of primary human proximal renal tubular epithelial cells (RPTECs) in direct allorecognition by CD4+ T-cells and the effect of anoxia-reoxygenation. In cell culture, we detected that RPTECs express all the required molecules for CD4+ T-cell activation (HLA-DR, CD80, and ICAM-1). Anoxia-reoxygenation decreased HLA-DR and CD80 but increased ICAM-1. Following this, RPTECs were co-cultured with alloreactive CD4+ T-cells. In T-cells, zeta chain phosphorylation and c-Myc increased, indicating activation of T-cell receptor and co-stimulation signal transduction pathways, respectively. T-cell proliferation assessed with bromodeoxyuridine assay and with the marker Ki-67 increased. Previous culture of RPTECs under anoxia raised all the above parameters in T-cells. FOXP3 remained unaffected in all cases, signifying that proliferating T-cells were not differentiated towards a regulatory phenotype. Our results support that direct allorecognition may be mediated by RPTECs even in the absence of donor-derived professional APCs. Also, ischemia-reperfusion injury of the graft may enhance the above capacity of RPTECs, increasing the possibility of acute rejection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms22041733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915934PMC
February 2021

Building a network of TP53 and IGHV testing reference centers across Spain: the Red53 initiative.

Ann Hematol 2021 Mar 6;100(3):825-830. Epub 2021 Jan 6.

Department of Hematology, University Clinic Hospital of Valencia, INCLIVA Institute, Valencia, Spain.

Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00277-020-04331-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7914181PMC
March 2021
-->