There are no approved treatments for chronic antibody mediated rejection (ABMR). We conducted a multicenter, prospective, randomized, placebo‐controlled, double‐blind clinical trial to evaluate ...efficacy and safety of intravenous immunoglobulins (IVIG) combined with rituximab (RTX) (EudraCT 2010‐023746‐67). Patients with transplant glomerulopathy and anti‐HLA donor‐specific antibodies (DSA) were eligible. Patients with estimated glomerular filtration rate (eGFR) <20 mL/min per 1.73m2 and/or severe interstitial fibrosis/tubular atrophy were excluded. Patients were randomized to receive IVIG (4 doses of 0.5 g/kg) and RTX (375 mg/m2) or a wrapped isovolumetric saline infusion. Primary efficacy variable was the decline of eGFR at one year. Secondary efficacy variables included evolution of proteinuria, renal lesions, and DSA at 1 year. The planned sample size was 25 patients per group. During 2012‐2015, 25 patients were randomized (13 to the treatment and 12 to the placebo group). The planned patient enrollment was not achieved because of budgetary constraints and slow patient recruitment. There were no differences between the treatment and placebo groups in eGFR decline (−4.2 ± 14.4 vs. −6.6 ± 12.0 mL/min per 1.73 m2, P‐value = .475), increase of proteinuria (+0.9 ± 2.1 vs. +0.9 ± 2.1 g/day, P‐value = .378), Banff scores at one year and MFI of the immunodominant DSA. Safety was similar between groups. These data suggest that the combination of IVIG and RTX is not useful in patients displaying transplant glomerulopathy and DSA.
Intravenous immunoglobulins and rituximab did not modify glomerular filtration rate decline, daily proteinuria, HLA donor‐specific antibody intensity, and graft histological damage at one year in a prospective, randomized, placebo‐controlled clinical trial.
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.
Simple antibody quantification and interferon‐γ release assay demonstrates low humoral and cellular responses in kidney transplant recipients compared to to healthy controls and dialysis patients after 2 dose mRNA SARS‐CoV‐2 vaccination.
COVID‐19 in elderly kidney transplant recipients Crespo, Marta; Pérez‐Sáez, María J.; Redondo‐Pachón, Dolores ...
American journal of transplantation,
October 2020, Letnik:
20, Številka:
10
Journal Article
Recenzirano
Odprti dostop
The SARS‐Cov‐2 infection disease (COVID‐19) pandemic has posed at risk the kidney transplant (KT) population, particularly the elderly recipients. From March 12 until April 4, 2020, we diagnosed ...COVID‐19 in 16 of our 324 KT patients aged ≥65 years old (4.9%). Many of them had had contact with healthcare facilities in the month prior to infection. Median time of symptom onset to admission was 7 days. All presented with fever and all but one with pneumonia. Up to 33% showed renal graft dysfunction. At infection diagnosis, mTOR inhibitors or mycophenolate were withdrawn. Tacrolimus was withdrawn in 70%. The main treatment combination was hydroxychloroquine and azithromycin. A subset of patients was treated with anti‐retroviral and tocilizumab. Short‐term fatality rate was 50% at a median time since admission of 3 days. Those who died were more frequently obese, frail, and had underlying heart disease. Although a higher respiratory rate was observed at admission in nonsurvivors, symptoms at presentation were similar between both groups. Patients who died were more anemic, lymphopenic, and showed higher D‐dimer, C‐reactive protein, and IL‐6 at their first tests. COVID‐19 is frequent among the elderly KT population and associates a very early and high mortality rate.
The authors report early and high mortality rates for elderly kidney transplant recipients.
Cytomegalovirus (CMV) infection constitutes a complication for kidney transplant recipients (KTR) and CMV‐specific T cells reduce the risk of viral replication in seropositive patients. CMV promotes ...the adaptive differentiation and expansion of an NK cell subset, hallmarked by expression of the CD94/NKG2C receptor with additional characteristic features. We previously reported an association of pretransplant NKG2C+ NK cells with a reduced incidence of CMV infection. We have strengthened the analysis in cryopreserved peripheral blood mononuclear cells from an enlarged KTR cohort (n = 145) with homogeneous immunosuppression, excluding cases at low risk of infection (ie, CMV D−R−) or receiving antiviral prophylaxis. Moreover, adaptive NKG2C+ NK cell–associated markers (ie, NKG2A, CD57, Immunoglobulin‐like transcript 2 LIR1 or LILRB1, FcεRI γ chain, and Prolymphocytic Leukemia Zinc Finger transcription factor) as well as T lymphocyte subsets were assessed by multicolor flow cytometry. The relation of NKG2C+ NK cells with T cells specific for CMV antigens was analyzed in pretransplant patients (n = 29) and healthy controls (n = 28). Multivariate Cox regression and Kaplan‐Meier analyses supported that NKG2C+ NK cells bearing adaptive markers were specifically associated with a reduced incidence of posttransplant symptomatic CMV infection; no correlation between NKG2C+ NK cells and CMV‐specific T cells was observed. These results support that adaptive NKG2C+ NK cells contribute to control CMV infection in KTR.
Detection of “memory‐like” NKG2C+ NK cells in CMV‐positive renal transplant recipients is inversely related to the risk of posttransplant symptomatic CMV infection, supporting their contribution to antiviral defense.
CMV infection in kidney transplant recipients (KTRs) has been associated with an increased risk for graft loss and reduced host survival. CMV promotes persistent expansions of NK cells expressing the ...CD94/NKG2C receptor. The NKG2C (KLRC2) gene is frequently deleted, and copy number influences the adaptive response of NKG2C
NK cells. The distribution of NKG2C
NK cells and NKG2C genotypes (NKG2C
, NKG2C
, NKG2C
) were studied in cross-sectional (n = 253) and prospective (n = 122) KTR cohorts. Assessment of CMV viremia was restricted to symptomatic cases in the retrospective study, but was regularly monitored in the prospective cohort. Overall, the proportions of NKG2C
NK cells were significantly higher in KTRs who had suffered posttransplant symptomatic CMV infection in the cross-sectional study. Yet, along the prospective follow-up (3, 6, 12, and 24 mo), posttransplant NKG2C
NK cell expansions were not observed in every patient with detectable viremia who received preemptive antiviral therapy, suggesting that the adaptive NK cell response may be inversely related with the degree of CMV control. Remarkably, the incidence of posttransplant viremia was reduced among cases with high pretransplant levels of NKG2C
NK cells. The NKG2C genotype distribution was comparable in KTR and healthy controls, and greater proportions of NKG2C
cells were detected in NKG2C
than in NKG2C
patients. Yet, a trend toward increased NKG2C
and reduced NKG2C
frequencies associated with symptomatic infection was appreciated in both cohorts. Altogether, our results indirectly support that adaptive NKG2C
NK cells are involved in the control of CMV in KTRs.
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.
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 (AT
R)-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.
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 AT
R-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 ABMR
DSA
cases showed non-HLA antibodies. ABMR
DSA
and ABMR
DSA
cases showed similar biopsy changes and graft-survival. Both total class II and DRB1 HLA-EM were associated with ABMR
DSA
but not with ABMR
DSA
. Multivariate analysis showed that pre-transplant HLA-DSA (OR: 3.69 1.31-10.37, p = 0.013) and AT
R-Ab (OR: 5.47 1.78-16.76, p = 0.003) were independent predictors of ABMR
DSA
.
In conclusion, pre-transplant AT
R-Ab is frequently found in ABMR
DSA
patients. However, AT
R-Ab, MICA-Ab, ETAR-Ab or EC-XM
are rarely found among ABMR
DSA
patients. Pre-transplant AT
R-Ab may act synergistically with preformed or
HLA-DSA to produce ABMR
DSA
but not ABMR
DSA
. HLA epitope mismatch associates with ABMR
DSA
compared with ABMR
DSA
, suggesting factors other than HLA are responsible for the damage.
Summary
Delayed graft function (DGF) is associated with poorer graft survival and higher rate of acute rejection (AR). It is unknown whether this negative influence relies on the increased risk of AR ...or the DGF itself. The different Kidney Donor Profile Index (KDPI) values may also play a role in this interaction. Retrospective study aimed to evaluate the impact of DGF on graft function and graft survival in a subset of KT recipients (2004–2017). We also analyzed the relationship between KDPI and DGF. The study includes 601 KT, 226 of them (37%) developed DGF. Graft survival was lower in patients with DGF compared with non‐DGF patients. Multivariable analysis revealed DGF as risk factor for graft loss, independently of the presence or not of acute rejection. Between DGF patients, we observed poorer graft survival in patients with higher KDPI value (>85%). We observed a trend of a greater impact of KDPI in patients with DGF, although this interaction was not statistically significant. Additionally, we observed poorer 12‐month graft function in DGF patients. DGF is related to poorer graft survival independently of the developed acute rejection. This negative impact might be influenced by high KDPI values.
Summary
The objective of this review was to assess whether dual kidney transplantation (DKT) is better than single KT (SKT) for optimizing the use of expanded criteria donor kidneys. We did a ...systematic literature search and meta‐analyses when possible, pooling data for calculating relative risks (RR) of major outcomes. Twenty‐five studies met the inclusion criteria. One‐year serum creatinine was better after DKT vs. SKT (mean difference −0.27 −0.37, −0.17, P < 0.001), with less incidence of acute rejection (RR 0.66 0.52, 0.85, P < 0.001) and without differences at five years. Less DGF was seen in DKT (RR 0.88 0.76, 1.02, P = 0.09). Mortality at 1 and 3 years was similar after dual or SKT, but mortality at five years was lower after DKT (RR 0.71 0.53, 0.94, P = 0.02). One‐year graft loss was similar between dual (n = 4158) and SKT (n = 51 800) (RR 0.97 0.87, 1.09, P = 0.62). Three‐ and five‐year graft loss was not considered because of high heterogeneity between studies. In conclusion, short‐term graft function and long‐term patient survival are better in recipients receiving DKT vs. SKT. However, these differences are based on few retrospective reports with a relatively low number of cases. Good quality randomized controlled trials are needed to assess whether the investment of two kidneys in one recipient is justified in face of the current organ shortage.
To analyse the aspects involved in the care of individuals assessed as kidney transplant candidates and to identify the role of nurses in providing specialised care for this population.
Scoping ...review. The results were summarised using a narrative synthesis technique.
A review of the literature published between 2001 and 2021 was conducted between October and November 2021 using PubMed, CINAHL and SciELO.
The research team agreed on a search strategy based on clinical practice guidelines for assessing kidney transplantation candidates. Quantitative, qualitative and mixed methods studies published in peer-reviewed journals in English, Spanish, French and Portuguese were included.
A total of 377 studies were identified, and 49 articles were included after the inclusion and exclusion criteria were applied. The narrative synthesis was structured into four themes: Physical needs; Psychological and quality of life needs; Education and adherence needs; and Nurses' role.
Nursing assessment of kidney transplantation candidates should encompass physical, psychosocial and adherence aspects. A variety of methodologies and resources are available for this assessment. Nurses contribute to coordinating access to kidney transplantation, aiming to improve adherence to an appropriate lifestyle to prevent patients from being excluded from kidney transplantation or suffering from kidney transplantation-related complications.
Based on our findings, we managed to design a nursing care map for kidney transplantation candidates combining the main elements of nursing care that should be incorporated into this process. Advanced practice nursing professionals play a crucial role in accessing renal transplant care.
Introduction: Chronic kidney disease (CKD) increases the risk of mortality during coronavirus disease 2019 (COVID-19) episodes, and some reports have underlined the high incidence and severity of ...this infection in dialysis patients. Information on COVID-19 in nondialysis CKD patients is not available yet. Case Reports: Here we present 7 patients with grade 4–5 CKD who developed symptomatic COVID-19; they comprise 2.6% of our 267 advanced CKD patients. The estimated GFR was between 12 and 20 mL/min during the month prior to COVID-19. The 3 major symptoms were fever, cough, and dyspnea, and 5 patients showed bilateral pneumonia. Hydroxychloroquine, azithromycin, ceftriaxone, and steroids were the most frequently prescribed drugs. Two patients needed noninvasive mechanical ventilation. All patients showed minimal to moderate kidney function deterioration during admission, with an eGFR decline below 5 mL/min in 6 cases. No patient required acute dialysis. Six patients were discharged alive and remained dialysis free athe t the time of reporting, and one 76-year-old patient died. Conclusions: COVID-19 affects grade 4–5 CKD patients, but prognosis may be acceptable if prompt supportive measures are applied. These findings should be confirmed in larger cohorts, and further observations will be needed to understand the full spectrum of clinical features and the optimal approach to COVID-19 in patients with advanced CKD.
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