RESUMEN
BACKGROUND: Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT. METHODS: A single-center prospective cohort of 148 patients undergoing KT between February 2018 and September 2019 that received an individualized infection prevention strategy was compared to a preintervention cohort (n = 159). The bundle comprised a review of the patient's immunization history, infection risk by country of origin, screening for latent tuberculosis infection (LTBI), antimicrobial prophylaxis, and immunological assessment. Individualized recommendations were accordingly provided at a scheduled visit at day +30 after transplantation. RESULTS: The intervention cohort showed a higher compliance rate with the recommended vaccine schedule, screening for geographically restricted infections and LTBI, and intravenous immunoglobulin and vitamin D supplementation (p values <.001). The 1-year incidence rate of infection was lower in the intervention cohort (42.6% vs. 57.9%; p value = .037), as was the rate of infection-related hospitalization (17.6% vs. 32.1%; p value = .003) and the incidence of severe bacterial infection. There were no differences in graft rejection or mortality rates between groups. CONCLUSIONS: A multifaceted intervention, including a bundle of evidence-based practices, enhanced compliance with recommended preventive measures and was correlated with a reduction in the 12-month incidence of infection after KT.
RESUMEN
This study investigates kidney transplant outcomes in highly sensitised patients after implementing a delisting strategy aimed at enabling transplantation despite preformed donor-specific antibodies (preDSA), with the goal of reducing acute antibody-mediated rejection (aAMR) risk. Fifty-three sensitised recipients underwent kidney transplant after delisting prohibited HLA antigens, focusing initially in low MFI antibodies (<5000), except for anti-HLA-DQ. If insufficient, higher MFI antibodies were permitted, especially for those without an immunogenic eplet pattern assigned. Delisting of Complement-fixing antibodies (C1q+) was consistently avoided. Comparison cohorts included 53 sensitised recipients without DSA (SwoDSA) and 53 non-sensitised (NS). The average waiting time prior to delisting was 4.4 ± 1.8 years, with a reduction in cPRA from 99.7 ± 0.5 to 98.1 ± 0.7, followed by transplantation within 7.2 ± 8.0 months (analysed in 34 patients). Rejection rates were similar among preDSA, SwoDSA, and NS groups (16%, 8%, and 11%, respectively; p = 0.46). However, aAMR was higher in the preDSA group (12%, 4%, and 2%, respectively; p = 0.073), only presented in recipients with DSA of MFI >5000. The highest MFI DSA were against HLA-DP (Median: 10796 MFI), with 50% of preDSA aAMR cases due to anti-DP antibodies (n = 3). Graft survival rates at 1 and 5 years in preDSA group were 94%, and 67%, comparable to SwoDSA (94%, and 70%; p = 0.69), being significantly higher in the NS group (p = 0.002). The five-year recipient survival rate was 89%, comparable to SwoDSA and NS groups (p = 0.79). A delisting strategy enables safe kidney transplant in highly sensitised patients with preDSA, with a slight increase in aAMR and comparable graft and patient survivals to non-DSA cohorts.
Asunto(s)
Rechazo de Injerto , Supervivencia de Injerto , Antígenos HLA , Isoanticuerpos , Trasplante de Riñón , Donantes de Tejidos , Humanos , Rechazo de Injerto/inmunología , Masculino , Antígenos HLA/inmunología , Persona de Mediana Edad , Femenino , Isoanticuerpos/sangre , Isoanticuerpos/inmunología , Adulto , Prueba de Histocompatibilidad/métodos , Medicina de Precisión/métodos , AncianoRESUMEN
Cytomegalovirus (CMV)-seropositive kidney transplant recipients (KTRs) with detectable CMV-specific cell-mediated immunity according to the QuantiFERON-CMV assay (QTF-CMV) are expected to have adequate immune protection. Nevertheless, a proportion of patients still develop CMV infection. Human microRNAs (hsa-miRNAs) are promising biomarkers owing to their high stability and easy detection. We performed whole blood miRNA sequencing in samples coincident with the first reactive QTF-CMV after transplantation or cessation of antiviral prophylaxis to investigate hsa-miRNAs differentially expressed according to the occurrence of CMV infection. One-year incidence of CMV viremia was 55.0% (median interval from miRNA sequencing sampling of 29 days). After qPCR validation, we found that hsa-miR-125a-5p was downregulated in KTRs developing CMV viremia within the next 90 days (ΔCt: 7.9 ± 0.9 versus 7.3 ± 1.0; P = .011). This difference was more evident among KTRs preemptively managed (8.2 ± 0.9 versus 6.9 ± 0.8; P < .001), with an area under the receiver operating characteristic curve of 0.865. Functional enrichment analysis identified hsa-miR-125a-5p targets involved in cell cycle regulation and apoptosis, including the BAK1 gene, which was significantly downregulated in KTRs developing CMV viremia. In conclusion, hsa-miR-125a-5p may serve as biomarker to identify CMV-seropositive KTRs at risk of CMV reactivation despite detectable CMV-CMI.
Asunto(s)
Infecciones por Citomegalovirus , Citomegalovirus , Trasplante de Riñón , MicroARNs , Humanos , Trasplante de Riñón/efectos adversos , MicroARNs/genética , MicroARNs/sangre , Infecciones por Citomegalovirus/virología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/etiología , Masculino , Citomegalovirus/genética , Persona de Mediana Edad , Femenino , Estudios de Seguimiento , Factores de Riesgo , Biomarcadores/sangre , Pronóstico , Rechazo de Injerto/etiología , Rechazo de Injerto/virología , Fallo Renal Crónico/cirugía , Complicaciones Posoperatorias/diagnóstico , Viremia/virología , Viremia/diagnóstico , Viremia/epidemiología , Adulto , Supervivencia de Injerto , Pruebas de Función RenalRESUMEN
We measured cytomegalovirus (CMV)-specific antibodies that neutralize epithelial cell infection (CMV-AbNEIs) in 101 CMV-seropositive kidney transplant recipients (KTRs) at baseline and post-transplant months 3 and 6. All the patients received antithymocyte globulin and 3-month valganciclovir prophylaxis. There were no significant differences in pre-transplant AbNEIs titers between KTRs that developed or did not develop any-level CMV infection or the composite of high-level infection and/or disease. One-year CMV infection-free survival was comparable between KTRs with or without pre-transplant CMV-AbNEIs. No differences were observed by months 3 and 6 either. We observed no protective role for CMV-AbNEIs among CMV-seropositive KTRs undergoing T-cell-depleting induction.
RESUMEN
Infection is a common complication in kidney transplant recipients (KTRs). The usefulness of antimicrobial stewardship programs (ASP) and hospital-acquired infection control (HAIC) initiatives in the general inpatient population is well established. We performed a quasi-experimental study to evaluate a joint ASP/HAIC initiative focused on KTRs. A dedicated ASP team optimized antimicrobial prescriptions in consecutive KTRs during the intervention period (June 2015-March 2016). A multifaceted, evidence-based HAIC program was concurrently implemented. Results were compared with the preceding period (June 2014-March 2015). We included 96 and 100 KTRs in the intervention and preintervention periods, respectively. There was a reduction in the consumption of meropenem (rate ratio [RR]: 0.63; 95% confidence interval [CI]: 0.53-0.75; P <.0001), ceftazidime (RR: 0.31; 95% CI: 0.21-0.45; P <.0001), vancomycin (RR: 0.65; 95% CI: 0.53-0.8; P <.0001), and ciprofloxacin (RR: 0.66; 95% CI: 0.55-0.81; P <.0001) and an increase of fosfomycin (RR: 1.80; 95% CI: 1.17-2.76; P =.008) during the intervention period. The incidence of cystitis (RR: 0.30; 95% CI: 0.28-0.33; P <.001) and upper urinary tract infection (RR: 0.56; 95% CI: 0.33-0.95; P =.04) decreased. A specific ASP/HAIC initiative was effective in optimizing antimicrobial use and reducing the incidence of common bacterial infections among KTRs.
Asunto(s)
Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Infección Hospitalaria , Trasplante de Riñón , Humanos , Programas de Optimización del Uso de los Antimicrobianos/métodos , Trasplante de Riñón/efectos adversos , Infección Hospitalaria/tratamiento farmacológico , Infección Hospitalaria/etiología , Infección Hospitalaria/prevención & control , Hospitales , Control de Infecciones , Atención a la Salud , Antibacterianos/uso terapéuticoRESUMEN
The best method for monitoring cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) among high-risk kidney transplant (KT) recipients remains uncertain. We assessed CMV-CMI by intracellular cytokine staining (ICS) by flow cytometry and a commercial interferon (IFN)-γ release assay (QuantiFERON®-CMV [QTF-CMV]) at posttransplant months 3, 4, and 5 in 53 CMV-seropositive KT recipients that had received induction therapy with antithymocyte globulin (ATG) and a 3-month course of valganciclovir prophylaxis. The discriminative capacity (areas under receiver operating characteristics curve [auROCs]) and diagnostic accuracy to predict immune protection against CMV infection from the discontinuation of prophylaxis to month 12 were compared between both methods. There was significant although moderate correlations between CMV-specific IFN-γ-producing CD8+ T-cell counts enumerated by ICS and IFN-γ levels by QTF-CMV at months 3 (rho: 0.493; p = 0.005) and 4 (rho: 0.440; p = 0.077). The auROCs for CMV-specific CD4+ and CD8+ T-cells by ICS were nonsignificantly higher than that of QTF-CMV (0.696 and 0.733 vs. 0.678; p = 0.900 and 0.692, respectively). The optimal cut-off of ≥0.395 CMV-specific CD8+ T-cells yielded a sensitivity of 86.4%, specificity of 54.6%, positive predictive value of 79.2% and negative predictive value of 66.7% to predict protection. The corresponding estimates for QTF-CMV (IFN-γ levels ≥0.2 IU/mL) were 78.9%, 37.5%, 75.0%, and 42.9%, respectively. The enumeration of CMV-specific IFN-γ-producing CD8+ T-cells at the time of cessation of prophylaxis performed slightly better than the QTF-CMV assay to predict immune protection in seropositive KT recipients previously treated with ATG.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Riñón , Humanos , Citomegalovirus , Trasplante de Riñón/efectos adversos , Citocinas , Linfocitos T CD8-positivos , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/prevención & control , Inmunidad Celular , Receptores de Trasplantes , Ensayo de Inmunoadsorción EnzimáticaRESUMEN
INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) represents a histologic pattern of glomerular injury that may be due to several aetiologies. Few studies have comprehensively analysed the recurrence of MPGN according to the current classification system. METHODS: We collected a multicentre, retrospective cohort of 220 kidney graft recipients with biopsy-proven native kidney disease due to MPGN between 1981 and 2021 in 11 hospitals. Demographic, clinical and histologic parameters of prognostic interest were collected. The main outcomes were time to kidney failure, time to recurrence of MPGN and disease remission after recurrence. RESULTS: The study group included 34 complement-mediated and 186 immune complex-mediated MPGN. A total of 81 patients (37%) reached kidney failure in a median follow-up of 79 months. The main predictors of this event were the development of rejection episodes and disease recurrence. In all, 54 patients (25%) had a disease recurrence in a median of 16 months after kidney transplantation. The incidence of recurrence was higher in patients with dysproteinaemia (67%) and complement-mediated MPGN (62%). In the multivariable model, complement-mediated MPGN emerged as a predictor of recurrence. A total of 33 patients reached kidney failure after recurrence. The main determinants of no remission were early time to recurrence (<15 months), estimated glomerular filtration rate <30 mL/min/1.73 m2 and serum albumin <3.5 g/dL at the time of recurrence. CONCLUSIONS: One-fourth of the patients with native kidney disease due to MPGN developed clinical recurrence in the allograft, especially in cases with complement-mediated disease or in those associated with dysproteinaemia. The kidney outcomes of disease recurrence with currently available therapies are heterogeneous and thus more effective and individualized therapies are needed.
Asunto(s)
Glomerulonefritis Membranoproliferativa , Glomerulonefritis , Fallo Renal Crónico , Trasplante de Riñón , Humanos , Complejo Antígeno-Anticuerpo , Proteínas del Sistema Complemento , Glomerulonefritis/complicaciones , Fallo Renal Crónico/terapia , Recurrencia , Estudios RetrospectivosRESUMEN
The case discussed involves a 69-year-old Thai woman who underwent orthotopic heart transplantation 9 months before this event. She presented with fever without localizing signs or symptoms. However, her chest images revealed mass-like consolidation in the left upper lobe. Blood culture and lung tissue identified Rhodococcus equi. She was successfully treated with a combination of antimicrobial therapy, optimization of immunosuppressants, and surgical resection.
Asunto(s)
Empiema , Trasplante de Corazón , Absceso Pulmonar , Femenino , Humanos , Anciano , Tailandia , PulmónRESUMEN
Risk stratification for cytomegalovirus (CMV) infection after kidney transplantation (KT) remains to be determined. Since endosomal toll-like receptors (TLRs) are involved in viral sensing, we investigated the impact of common single-nucleotide polymorphisms (SNPs) located within TLR3 and TLR9 genes on the occurrence of overall and high-level (≥1,000 IU/ml) CMV infection in a cohort of 197 KT recipients. Homozygous carriers of the minor allele of TLR3 (rs3775291) had higher infection-free survival compared with reference allele carriers (60.0% for TT versus 42.3% for CC/CT genotypes; P-value = 0.050). Decreased infection-free survival was observed with the minor allele of TLR9 (rs352139) (38.2% for TC/CC versus 59.3% for TT genotypes; P-value = 0.004). After multivariable adjustment, the recessive protective effect of the TLR3 (rs3775291) TT genotype was confirmed (adjusted hazard ratio [aHR]: 0.327; 95% CI: 0.167-0.642; P-value = 0.001), as was the dominant risk-conferring effect of TLR9 (rs352139) TC/CC genotypes (aHR: 1.865; 95% CI: 1.170-2.972; P-value = 0.009). Carriers of the TLR9 (rs352139) TC/CC genotypes showed lower CMV-specific interferon-γ-producing CD4+ T-cell counts measured by intracellular cytokine staining compared with the TT genotype (median of 0.2 versus 0.7 cells/µl; P-value = 0.003). In conclusion, TLR3/TLR9 genotyping may inform CMV infection risk after KT.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Riñón , Humanos , Infecciones por Citomegalovirus/genética , Trasplante de Riñón/efectos adversos , Polimorfismo de Nucleótido Simple , Receptor Toll-Like 3/genética , Receptor Toll-Like 9/genéticaRESUMEN
BACKGROUND: Increasing evidence suggests that infection with the nonpathogenic human pegivirus type 1 (HPgV-1) exerts a clinical benefit in human immunodeficiency virus (HIV) patients, which could be attributable to immunomodulatory effects. Whether this impact can be extrapolated to kidney transplantation (KT) remains largely unknown. METHODS: We measured plasma HPgV-1 RNA by real-time polymerase chain reaction targeting the 5' untranslated region at various points (pretransplantation, day 7, months 1, 3, 6, and 12) in 199 KT recipients. Study outcomes included posttransplant serious infection, immunosuppression-related adverse event (opportunistic infection and/or de novo cancer), and acute graft rejection. RESULTS: HPgV-1 infection was demonstrated in 52 (26.1%) patients, with rates increasing from 14.7% at baseline to 19.1% by month 12 (p-value = .071). De novo infection occurred in 13.8% of patients with no detectable HPgV-1 RNA before transplantation. Double-organ (liver-kidney or kidney-pancreas) transplantation (odds ratio [OR]: 5.62; 95% confidence interval [CI]: 1.52-20.82) and donation after brain death (OR: 2.21; 95% CI: 1.00-4.88) were associated with posttransplant HPgV-1 infection, whereas pretransplant hypertension was protective (OR: 0.23; 95% CI: 0.09-0.55). There were no significant differences in the incidence of study outcomes according to HPgV-1 status. Plasma HPgV-1 RNA levels at different points did not significantly differ between patients that subsequently developed outcomes and those remaining free from these events. No correlation between HPgV-1 RNA and immune parameters or torque teno virus DNA load was observed either. CONCLUSION: Unlike patients living with HIV, HPgV-1 infection does not seem to influence patient or graft outcomes after KT.
Asunto(s)
Infecciones por Flaviviridae , Virus GB-C , Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Cinética , Receptores de TrasplantesRESUMEN
Primary infection and/or reactivation of cytomegalovirus (CMV) in kidney transplant recipients (KTR) favor rejection and mortality. T follicular helper cells (TFH) could contribute to protection against CMV. Circulatory TFH (cTFH) were studied pretransplant and early posttransplant in 90 CMV seropositive KTR not receiving antithymocyte globulin or antiviral prophylaxis, followed-up for 1 year. Patients who presented CMV infection had significantly lower cTFH and activated cTFH pretransplant and early posttransplant. Pretransplant activated cTFH were also lower within patients who developed CMV disease. Pre- and 14 days posttransplant activated cTFH were an independent protective factor for CMV infection (HR 0.41, p = .01; and 0.52, p = .02, respectively). KTR with low cTFH 7 days posttransplant (<11.9%) had lower CMV infection-free survival than patients with high cTFH (28.2% vs. 67.6%, p = .002). cTFH were associated with CMV-specific neutralizing antibodies (Nabs). In addition, IL-21 increased interferon-γ secretion by CMV-specific CD8+ T cells in healthy controls. Thus, we show an association between cTFH and lower incidence of CMV infection, probably through their cooperation in CMV-specific Nab production and IL-21-mediated enhancement of CD8+ T cell activity. Moreover, monitoring cTFH pre- and early posttransplant could improve CMV risk stratification and help select KTR catalogued at low/intermediate risk who could benefit from prophylaxis.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Riñón , Linfocitos T CD8-positivos , Infecciones por Citomegalovirus/epidemiología , Humanos , Incidencia , Trasplante de Riñón/efectos adversos , Linfocitos T Colaboradores-Inductores , Receptores de TrasplantesRESUMEN
No disponible
Asunto(s)
Humanos , Masculino , Anciano , Infecciones por Coronavirus/complicaciones , Neumonía Viral/complicaciones , Pandemias , Pericarditis/virología , Trasplante de RiñónRESUMEN
OBJECTIVES: This study focused on the role that BK polyomavirus (BKPyV) genotypes can play in the development of BKPyV-associated complications in renal transplant recipients. METHODS: A retrospective observational study (January 2015 to April 2018) was conducted by analyzing BKPyV genotypes in 180 blood samples with detectable BKPyV viral load (VL) > 1000 copies/mL, from 63 renal transplant recipients. VL and BKPyV genotypes detections were based on real-time PCR (rt-PCR)-specific assays. RESULTS: Forty-four patients (44/63 [69.8%]) were men, and the median age was 55.0 (interquartile range 49.0-66.0 years). Eleven patients had clinical manifestations (11/63 [17.5%]). The most frequently detected genotypes were I (14/63 [22.2%]) and II (13/63 [20.6%]). Half of the patients (33/63 [52.4%]) had a mixed genotype, most with genotypes I and II (25/33 [75.8%]). Patients with infection by mixed genotypes showed VLs that were detected earlier (in the first year after transplantation) than those with a single genotype (25/33 [75.8%] vs 13/30 [43.3%], P = .009) and demonstrated greater risk of developing clinical manifestations associated with BKPyV (odds ratio 12.609, 95% confidence interval 1.503-105.807). Moreover, patients with first BKPyV VL > 10 000 copies/mL more frequently presented mixed genotypes (12/16 [75.0%] vs 21/47 [44.7%], P = .036). CONCLUSIONS: The probability of developing clinical manifestations is higher in infections by mixed genotypes. Therefore, the detection of BKPyV genotypes by rt-PCR can provide relevant information to stratify patients' risk of BKPyV-associated complications and guide the clinical management of BKPyV infection in kidney transplant recipients.
Asunto(s)
Virus BK , Enfermedades Renales , Trasplante de Riñón , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Anciano , Virus BK/genética , Genotipo , Humanos , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/diagnóstico , Infecciones por Polyomavirus/epidemiología , Estudios Retrospectivos , Receptores de Trasplantes , Infecciones Tumorales por Virus/epidemiologíaRESUMEN
BACKGROUND: Immunomodulatory effects attributable to cytomegalovirus (CMV) would predispose to BK polyomavirus (BKPyV) infection after kidney transplantation (KT), although available evidence is conflicting. It has been suggested that (val)ganciclovir therapy may increase the risk of BKPyV viremia and BKPyV-associated nephropathy (BKPyVAN) as a result of drug-induced T-cell impairment. METHODS: We investigated whether CMV replication and/or (val)ganciclovir exposure (either as prophylaxis or treatment) were associated with the development of BKPyV viremia or BKPyVAN in a prospective cohort of 399 KT recipients. CMV infection (any level or high-level viremia and area under the curve of DNAemia) and (val)ganciclovir exposure (any duration of therapy and cumulative days of treatment) during the first post-transplant year were explored through separate landmark survival analyses. RESULTS: Cumulative incidence of BKPyV viremia and BKPyVAN after a median follow-up of 551 days was 23.1% and 2.5%, respectively. One-year rates of CMV infection and (val)ganciclovir therapy were 47.4% and 54.1%, respectively. No differences were observed in BKPyV viremia- or BKPyVAN-free survival according to previous CMV infection or (val)ganciclovir exposure in any of the landmark analyses. Adjusted Cox models confirmed this lack of association. CONCLUSION: Our findings do not confirm the existence of a relevant impact of CMV infection or (val)ganciclovir therapy on the risk of post-transplant BKPyV events.
Asunto(s)
Virus BK , Infecciones por Citomegalovirus , Trasplante de Riñón , Nefritis Intersticial , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Antivirales/efectos adversos , Infecciones por Citomegalovirus/epidemiología , Ganciclovir/efectos adversos , Humanos , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/epidemiología , Estudios Prospectivos , Valganciclovir , Viremia/epidemiologíaRESUMEN
BACKGROUND: The magnitude and kinetics of severe acute respiratory syndrome coronavirus 2-specific cell-mediated immunity (SARS-CoV-2-CMI) in kidney transplant (KT) recipients remain largely unknown. METHODS: We enumerated SARS-CoV-2-specific interferon-γ-producing CD69+ CD4+ and CD8+ T cells at months 4 and 6 from the diagnosis of coronavirus disease 2019 (COVID-19) in 21 KT recipients by intracellular cytokine staining. Overlapping peptides encompassing the SARS-CoV-2 spike (S) glycoprotein N-terminal 1- to 643-amino acid sequence and the membrane protein were used as stimulus. SARS-CoV-2 IgG antibodies targeting the S1 protein were assessed by ELISA at month 6. RESULTS: Detectable (≥0.1%) SARS-CoV-2-specific CD4+ T-cell response was found in 57.1% and 47.4% of patients at months 4 and 6. Corresponding rates for CD8+ T cells were 19.0% and 42.1%, respectively. Absolute SARS-CoV-2-specific T-cell counts increased from month 4 to month 6 in CD8+ (P = 0.086) but not CD4+ subsets (P = 0.349). Four of 10 patients with any detectable response at month 4 had lost SARS-CoV-2-CMI by month 6, whereas 5 of 9 patients mounted SARS-CoV-2-CMI within this period. All but 2 patients (89.5%) tested positive for SARS-CoV-2 IgG. Patients lacking detectable SARS-CoV-2-specific CD4+ response by month 6 were more likely to be under tacrolimus (100.0% versus 66.7%; P = 0.087) and to have received tocilizumab for the previous COVID-19 episode (40.0% versus 0.0%; P = 0.087). CONCLUSIONS: Although still exploratory and limited by small sample size, the present study suggests that a substantial proportion of KT recipients exhibited detectable SARS-CoV-2-CMI after 6 months from COVID-19 diagnosis.
Asunto(s)
COVID-19/inmunología , Inmunidad Celular , Huésped Inmunocomprometido , Trasplante de Riñón/efectos adversos , SARS-CoV-2/inmunología , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , COVID-19/sangre , COVID-19/diagnóstico , Prueba de COVID-19 , Femenino , Estudios de Seguimiento , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Humanos , Inmunosupresores/efectos adversos , Interferón gamma/metabolismo , Masculino , Persona de Mediana Edad , Receptores de Trasplantes , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: The recurrence of proteinuria after kidney transplantation (KT) is a characteristic complication of focal segmental glomerulosclerosis (FSGS). It has been suggested that pre-emptive rituximab might prevent recurrences in patients at risk, but there is no agreement about which factors might help to identify such patients. METHODS: We studied 93 kidney transplants with biopsy-proven idiopathic FSGS in order to analyse if preventive rituximab treatment could decrease recurrences in patients at risk. RESULTS: Fifteen patients (16.1%) presented a recurrence after KT, but when we restricted the analysis to the 34 patients presenting nephrotic syndrome at primary disease onset, the recurrence diagnosis rate increased to 44.1%. All patients with recurrence had complete nephrotic syndrome at the time of diagnosis. After multivariate adjustment, the only significant risk factor for recurrence was the presence of complete nephrotic syndrome at diagnosis. Twelve of the 34 patients at risk for recurrence received rituximab at the time of transplantation. Clinical and analytical characteristics were similar in all patients at risk. The number of recurrences was similar among treated (50%) and non-treated patients (40.9%). CONCLUSIONS: Nephrotic syndrome with hypoalbuminaemia at diagnosis is the most important feature to identify patients at risk of recurrence. Our data suggest that pre-emptive rituximab is not effective to prevent FSGS recurrences.
RESUMEN
Previous reports hypothesized that cytomegalovirus (CMV) may predispose to non-CMV infection after kidney transplantation (KT). We analysed the incidence of non-CMV infection (overall, bacterial and opportunistic) in 291 KT recipients according to the previous development of any level or high-level (≥1,000 IU/ml) CMV viremia. Exposure to CMV replication was assessed throughout fixed intervals covering first the 30, 90, 180 and 360 post-transplant days (cumulative exposure) and non-overlapping preceding periods (recent exposure). Adjusted Cox models were constructed for each landmark analysis. Overall, 67.7 and 50.5% patients experienced non-CMV and CMV infection, respectively. Patients with cumulative CMV exposure had higher incidence of non-CMV infection beyond days 30 (p-value = 0.002) and 90 (p-value = 0.068), although these associations did not remain after multivariable adjustment. No significant associations were observed for the remaining landmark models (including those based on high-level viremia or recent CMV exposure), or when bacterial and opportunistic infection were separately analysed. There were no differences in viral kinetics (peak CMV viremia and area under curve of CMV viral load) either. Our findings do not support the existence of an independent association between previous CMV exposure and the overall risk of post-transplant infection, although results might be affected by power limitations.
Asunto(s)
Infecciones por Citomegalovirus , Trasplante de Riñón , Antivirales , Estudios de Cohortes , Citomegalovirus , Infecciones por Citomegalovirus/epidemiología , Infecciones por Citomegalovirus/etiología , Humanos , Trasplante de Riñón/efectos adversos , Carga Viral , Replicación ViralAsunto(s)
COVID-19/complicaciones , Trasplante de Riñón , Pericarditis/etiología , Anciano , COVID-19/diagnóstico , Prueba de Ácido Nucleico para COVID-19 , Electrocardiografía , Humanos , Huésped Inmunocomprometido , Masculino , Insuficiencia Renal Crónica/sangre , Tratamiento Farmacológico de COVID-19RESUMEN
The clinical characteristics, management, and outcome of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after solid organ transplant (SOT) remain unknown. We report our preliminary experience with 18 SOT (kidney [44.4%], liver [33.3%], and heart [22.2%]) recipients diagnosed with COVID-19 by March 23, 2020 at a tertiary-care center at Madrid. Median age at diagnosis was 71.0 ± 12.8 years, and the median interval since transplantation was 9.3 years. Fever (83.3%) and radiographic abnormalities in form of unilateral or bilateral/multifocal consolidations (72.2%) were the most common presentations. Lopinavir/ritonavir (usually associated with hydroxychloroquine) was used in 50.0% of patients and had to be prematurely discontinued in 2 of them. Other antiviral regimens included hydroxychloroquine monotherapy (27.8%) and interferon-ß (16.7%). As of April 4, the case-fatality rate was 27.8% (5/18). After a median follow-up of 18 days from symptom onset, 30.8% (4/13) of survivors developed progressive respiratory failure, 7.7% (1/13) showed stable clinical condition or improvement, and 61.5% (8/13) had been discharged home. C-reactive protein levels at various points were significantly higher among recipients who experienced unfavorable outcome. In conclusion, this frontline report suggests that SARS-CoV-2 infection has a severe course in SOT recipients.