Adherencia al tratamiento en pacientes con trasplante renal y su relación con los niveles plasmáticos de inmunosupresores

Introducción: La adherencia al tratamiento inmunosupresor en los pacientes trasplantados renales es un factor clave para la supervivencia del injerto, así como para la calidad de vida de estos pacientes. Objetivo: Analizar la adherencia terapéutica de los pacientes con trasplante renal y su relación con el nivel plasmático de inmunosupresores. Material y Método: Se realizó un estudio observacional, descriptivo, transversal, en una población de trasplantados renales entre diciembre 2021 y enero 2022, del Servicio de Nefrología del Hospital Universitario Marqués de Valdecilla. Para determinar la adherencia al tratamiento inmunosupresor se utilizó el cuestionario simplificado de adherencia a la medicación (SMAQ). Se recogieron otras variables socio-clínicas: edad, sexo, tiempo transcurrido desde el último trasplante, trasplantes renales previos, tipo de trasplante (renal o combinado), nefropatía de base, niveles de inmunosupresores en sangre, inmunosupresor pautado y número total de medicamentos prescritos. En los pacientes con tacrolimus e ImTOR se recogieron niveles de las últimas 5 analíticas, y se calculó la desviación estándar y el coeficiente de variabilidad. Resultados: Se estudiaron 100 pacientes: 7% trasplante combinado riñón-páncreas, 92% tacrolimus como inmunosupresor principal, no adherentes el 29% (sin diferencias por sexo). No se encontraron diferencias estadísticamente significativas entre los niveles de inmunosupresores en sangre y la adherencia al tratamiento inmunosupresor, ni para la totalidad, ni por subgrupos. Conclusiones: La tasa de no adherentes en nuestra muestra es del 29%. No hemos encontrado una asociación estadísticamente significativa entre los niveles de inmunosupresores en sangre y la adherencia al tratamiento

Improvement in the definition of anti-HLA antibody profile in highly sensitized patients

The definition of anti-HLA antibody profile in highly sensitized patients on a waiting list is crucial when virtual crossmatch is used in organ allocation systems, but also when used to identify the true deleterious anti-HLA antibodies. Here we propose different levels of risk based on the results of anti-HLA antibody testing in neat serum (N) and after sera dilution (DIL) and C1q test in 18 highly sensitized patients. This group was heterogeneous in terms of anti-HLA antibody titers and their ability to fix complement. After dilution, 15 out of 18 patients (83.3%) showed a reduction of positive bead counts whereas 4 patients showed a prozone effect and complement fixation was demonstrated. The high dilution of sera and ascertaining the complement fixation allow the accurate definition of risk anti-HLA antibody profiles in highly sensitized patients, as demonstrated in 5 of the sensitized patients who were transplanted

COVID-19-related collapse of transplantation systems: A heterogeneous recovery?

The coronavirus disease‐2019 (COVID‐19) pandemic has pushed healthcare systems to the limit worldwide. Hospital resources have been compromised, especially in intensive care units (ICUs). Regarding that, some nephrologists have alerted about the potential shortages of our ability to deliver kidney replacement therapy to all patients who need it (1). Simultaneously, two reports have highlighted the collapse of organ transplantation figures in several countries such as France (91%), the US (51%) and Spain (87%), mainly due to a reduction in the number of transplants from deceased donors

Detection of antibodies to denatured human leucocyte antigen molecules by single antigen Luminex

The anti-HLA antibody detection has been improved in sensitivity and specificity with solid-phase antigen bead (SAB) assays based on Luminex. However, false positive results due to denatured HLA (dHLA) may arise after single antigen test. The aim of this study was to compare the performance of the two Luminex technology-based anti-HLA detection kits available in the market in showing undesired anti-HLA antibody results. A prospective cohort was assessed for anti-HLA antibodies with single antigen A manufacturer (AM) kit and a comparison cohort with single antigen B manufacturer (BM) kit. A total of 11 out of 90 patients in a prospective cohort presented monospecific HLA-I antibodies with AM, and 5 out of 11 confirmed monospecific reaction with BM. Despite the confirmation of monospecific reaction with both manufacturers, 80% were assigned as dHLA reaction by specific crossmatch. Further comparative cohorts detected four out of six monospecific reactions with BM that were confirmed as possible dHLA reactions. A positive SAB test should rule out a reaction against a dHLA molecule, thus avoidance of prolonged waitlist periods or misattribution of anti-HLA reactions after transplantation

High Pretransplant BAFF Levels and B-cell Subset Polarized towards a Memory Phenotype as Predictive Biomarkers for Antibody-Mediated Rejection

Antibody-mediated rejection (AbMR) is one of the leading causes of graft loss in kidney transplantation and B cells play an important role in the development of it. A B-cell activating factor (BAFF) is a cytokine involved in B cell ontogeny. Here, we analyzed whether B cell maturation and the e ect of B cell soluble factors, such as BAFF could be involved in AbMR. Serum BAFF levels and B and T cell subpopulations were analyzed 109 kidney transplant patients before transplantation and at 6 and 12 months after kidney transplantation. Pretransplant serum BAFF levels as well as memory B cell subpopulations were significantly higher in those patients who su ered clinical AbMR during the first 12 months after kidney transplantation. Similar results were observed in the prospective analysis of patients with subclinical antibody-mediated rejection detected in the surveillance biopsy performed at 12 months after kidney transplantation. A multivariate analysis confirmed the independent role of BAFF in the development of AbMR, irrespective of other classical variables. Pretransplant serum BAFF levels could be an important non-invasive biomarker for the prediction of the development of AbMR and posttransplant increased serum BAFF levels contribute to AbMR

Regulatory T-cell Number in Peripheral Blood at 1 Year Posttransplant as Predictor of Long-term Kidney Graft Survival

Background: Regulatory T (Treg) cells play a role in limiting kidney transplant rejection and can potentially promote long-term transplant tolerance. There are no large prospective studies demonstrating the utility of peripheral blood Treg cells as biomarkers for long-term graft outcome in kidney transplantation. The aim of our study was to analyze the influence of the absolute number of peripheral blood Treg cells after transplantation on long-term death-censored graft survival. Methods: We monitored the absolute numbers of Treg cells by flow cytometry in nonfrozen samples of peripheral blood in 133 kidney transplant recipients, who were prospectively followed up to 2 years after transplantation. Death-censored graft survival was determined retrospectively in January 2017. Results: The mean time of clinical follow-up was 7.4 ± 2.9 years and 24.1% patients suffered death-censored graft loss (DCGL). Patients with high Treg cells 1 year after transplantation and above the median value (14.57 cells/mm3), showed better death-censored graft survival (5-year survival, 92.5% vs 81.4%, Log-rank P = .030). One-year Treg cells showed a receiver operating characteristic - area under curve of 63.1% (95% confidence interval, 52.9-73.2%, P = 0.026) for predicting DCGL. After multivariate Cox regression analysis, an increased number of peripheral blood Treg cells was a protective factor for DCGL (hazard ratio, 0.961, 95% confidence interval, 0.924-0.998, P = 0.041), irrespectively of 1-year proteinuria and renal function. Conclusions: Peripheral blood absolute numbers of Treg cells 1 year after kidney transplantation predict a better long-term graft outcome and may be used as prognostic biomarkers

Urinary C-X-C Motif Chemokine 10 Is Related to Acute Graft Lesions Secondary to T Cell- and Antibody-Mediated Damage

Background: Non-invasive biomarkers of graft rejection are needed to optimize the management and outcomes of kidney transplant recipients. Urinary excretion of IFN-g-related chemokine CXCL10 is clearly associated with clinical and subclinical T cell-mediated graft inflammation, but its relationship with antibody-mediated damage has not been fully addressed. Further, the variables influencing levels of urinary CXCL10 excretion are unknown. Material/Methods: A total of 151 kidney graft biopsies (92 surveillance and 59 indication biopsies) and 151 matched urine samples obtained before biopsy were prospectively analyzed. T cell-mediated rejection (TCMR) and antibody-mediated rejection (AbMR) were defined according to the 2017 Banff classification criteria. Urinary CXCL10 levels were measured by ELISA and corrected by urinary creatinine. Results: Banff scores ?t?, ?i?, ?g?, and ?ptc? were significantly related to urinary CXCL10 levels. Multivariate analysis showed that ?t? (b=0.107, P=0.001) and ?ptc? (b=0.093, P=0.002) were significantly associated with urinary CXCL10. Donor specific antibodies (DSAs) were related to the high excretion of urinary CXCL10 at 1 year after transplantation (odds ratio [OR] 17.817, P=0.003). Urinary CXCL10 showed good discrimination ability for AbMR (AUC-ROC 0.760, P=0.001). The third tertile of urinary CXCL10 remained significantly associated with AbMR (OR 4.577, 95% confidence interval 1.799?11.646, P=0.001) after multivariate regression analysis. Conclusions: DSA was the only variable clearly related to high urinary CXCL10 levels. Urinary CXCL10 is a good non-invasive candidate biomarker of AbMR and TCMR, supplying information independent of renal function and other variables normally used to monitor kidney transplant

Measurement of galactosyl-deficient IgA1 by the monoclonal antibody KM55 contributes to predicting patients with IgA nephropathy with high risk of long-term progression

Backgroundandobjective:About25%ofpatientswithIgAnephropathy(IgAN)progresstostage5chronickidneydisease(CKD)afteryearsofevolution.Varioustoolshavebeendevelopedinrecentyearsdesignedtopredictwhichofthepatientswillhadpooreroutcomes.Thevalueofcirculatinggalactosyl-deficientIgA1(Gd-IgA1)hasbeenrelatedtoaworseevolutionofIgANinseveralstudies.TherearealsosomepublicationsthatrelatehigherAPRILvalueswithaworseevolution.Recently,anewmethodhasbeendevelopedthatallowsmeasuringthevalueofcirculatingGd-IgA1inasimplerwaythanthosepreviouslyavailable.TheobjectiveofthisstudyistoanalyzetheinfluenceofcirculatingGd-IgA1,measuredbythismethod,ontheprogressionofIgAN.Materialsandmethods:Forty-ninepatientswithadiagnosisofIgANdemonstratedbyrenalbiopsywereselectedinourcenter,withouthavingreceivedpriorimmunosuppressivetreat-ment,forwhomfrozenserumwasavailable.Themedianfollow-upwas4years.Gd-IgA1wasmeasuredbylectin-independentELISAwiththemonoclonalantibodyKM55(IgA1kitCat.No.30111694.IBLInt.,Hamburg,Germany).Likewise,APRILlevelswerealsomeasuredinthesepatients.Results:19(38.8%)patientsreachedstage5CKD.ThefourthquartileofcirculatingGd-IgA1wasrelatedtoahighercumulativeriskofreachingstage5CKDintheKaplan?Meieranalysis(riskatthe5thyear39.4%vs.24.3%,logrankp=0.019).TheGd-IgA1valuewasrelatedto anincreasedriskofCKDstage5(HR1.147,95%CI1.035?1.270,p=0.009),regardlessofglomerularfiltrationrate,proteinuria,thepercentageofsclerosedglomeruliandthevalueofsegmentalsclerosis.WedidnotfindsignificantdifferencesintheAPRILvalues.Conclusions:ThevalueofcirculatingGd-IgA1measuredbythemonoclonalantibodyKM55isrelatedtoaworseevolutionofpatientswithIgANindependentlyofothervariables,soitcouldbeincludedinthestudyofpatientstoimprovethepredictionoftheriskofdiseaseprogression