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Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p < 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p < 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p < 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA > 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs.

Resumen: La infección por el SARS-CoV-2 (COVID-19) ha supuesto un importante impacto en la actividad trasplantadora en nuestro país. Era esperable que la mortalidad y el riesgo de complicaciones asociadas a la COVID-19 en el receptor de trasplante renal (TR) fueran mayores debido a su condición de inmunosupresión y a las frecuentes comorbilidades asociadas. Desde el inicio de la pandemia en marzo del 2020 hemos mejorado rápidamente nuestro conocimiento acerca de la epidemiología, características clínicas y manejo de la COVID-19 postrasplante, redundando en un mejor pronóstico para nuestros pacientes. Las unidades de TR han sabido adaptar sus programas a esta nueva realidad, normalizándose la actividad tanto de donación como de trasplante en nuestro país.Este manuscrito presenta una propuesta de actualización de las recomendaciones generales para la prevención y el tratamiento de la infección en esta población tan vulnerable como son los receptores de un trasplante renal. Abstract: SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant (KT) recipients were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country.This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT.

SARS-CoV-2 infection (COVID-19) has had a significant impact on transplant activity in our country. Mortality and the risk of complications associated with COVID-19 in kidney transplant recipients (KT) were expected to be higher due to their immunosuppressed condition and the frequent associated comorbidities. Since the beginning of the pandemic in March 2020 we have rapidly improved our knowledge about the epidemiology, clinical features and management of COVID-19 post-transplant, resulting in a better prognosis for our patients. KT units have been able to adapt their programs to this new reality, normalizing both donation and transplantation activity in our country.This manuscript presents a proposal to update the general recommendations for the prevention and treatment of infection in this highly vulnerable population such as KT. Resumen: La infección por el SARS-CoV-2 (COVID-19) ha supuesto un importante impacto en la actividad trasplantadora en nuestro país. Era esperable que la mortalidad y el riesgo de complicaciones asociadas a la COVID-19 en el receptor de trasplante renal (TR) fueran mayores debido a su condición de inmunosupresión y a las frecuentes comorbilidades asociadas. Desde el inicio de la pandemia en marzo del 2020 hemos mejorado rápidamente nuestro conocimiento acerca de la epidemiología, características clínicas y manejo de la COVID-19 post-trasplante, redundando en un mejor pronóstico para nuestros pacientes. Las unidades de trasplante renal han sabido adaptar sus programas a esta nueva realidad, normalizándose la actividad tanto de donación como de trasplante en nuestro país.Este manuscrito presenta una propuesta de actualización de las recomendaciones generales para la prevención y el tratamiento de la infección en esta población tan vulnerable como son los receptores de un trasplante renal.

Continuous immunosuppression after organ transplantation is associated with an increased risk of developing keratinocyte neoplastic lesions. Topical photodynamic therapy represents a therapeutic approach for different keratinocyte neoplastic lesions. However, the specific efficacy and safety of this treatment in this immunocompromised population remains largely unknown. In this case report series, we show the efficacy and safety of photodynamic therapy with BF-200 ALA gel using red-light and daylight in immunocompromised patients. Out of 8 patients presented here, 1 was treated for 8 basal cell carcinomas, 1 for 2 Bowen´s disease lesions and 6 were treated for field cancerization including 4 to 10 actinic keratoses. Treatment response rates were above 75 %. The adverse events, including pain, did not differ from those already described for PDT. These data suggest that PDT with BF-200 ALA gel could be an effective and safe option to add to the treatment portfolio for neoplastic keratinocyte lesions in this high-risk population.

BackgroundRenal transplantation is the treatment of choice for most cases of end-stage renal disease. Recipients need to lead a healthy lifestyle to minimize the potential side effects of immunosuppressive drugs and improve transplant outcomes. There is not much evidence about the best way to increase adherence to healthy lifestyles in kidney transplant recipients, so one of the objectives set by the nursing team is to train people to acquire the necessary skills and tools to be able to take care of themselves. In this sense, the consensual development of appropriate materials may be useful and of interest. ObjectiveThe aim of this study was to develop an information guide for adults with kidney transplants to be assessed in a subsequent clinical trial as an intervention to increase adherence to healthy habits. MethodsWe used a 3-step, methodological, sequential approach: (1) training from a group of experts and item consensus; (2) review of the medical literature available; and (3) use of the Delphi technique with on-site meetings. A total of 5 nurses from the Community of Madrid Kidney Transplantation Unit in Spain were asked to participate. The patients’ lifestyle factors that, according to the medical literature available and experts’ opinions, have the greatest impact on the survival of the transplanted organ and the recipients themselves were all described. ResultsAfter using the modified Delphi method to reach a consensus on the items to be included and the information needed in each, an information guide for adult kidney transplant patients was developed. This guide facilitates the structuring of health care, information, and recommendations necessary for effective self-care for each person. The result is considered to be an easy-to-understand tool, useful for transplant doctors and nurses, in simple language, with information based on the latest scientific-medical evidence published to date, aspects of which will be evaluated in a clinical trial designed for this purpose. ConclusionsCurrently, this guide is the main intervention variable of a clinical trial (registered on ClinicalTrials.gov; NCT05715580) aimed at improving compliance with healthy habits in kidney transplant recipients in the Community of Madrid, Spain. The method used in its development has been useful and agile, and the result is a guide that can be easily updated periodically following the same procedure. International Registered Report Identifier (IRRID)DERR1-10.2196/46961

Resumen: La enfermedad antimembrana basal glomerular (EMBG) es un trastorno autoinmune caracterizado por la presencia de anticuerpos antimembrana basal glomerular (AMBG), hemorragia pulmonar, glomerulonefritis necrotizante y depósito lineal de inmunoglobulinas en inmunofluorescencia directa. La predisposición genética, entre otros factores, posee un papel importante en el desarrollo de la enfermedad. Estudios previos han demostrado que el antígeno leucocitario humano (HLA), HLA-DR15 y HLA- DR4, se asocian con mayor riesgo de presentarla, mientras que el HLA-DR1 y HLA-DR7 han demostrado ser factor de protección frente a su desarrollo.Describimos el primer caso de dos hermanos no gemelos con EMBG con tipaje HLA idéntico, con factor de riesgo HLA-DR4 y factor de protección HLA-DR7. Planteamos la importancia de analizar el tipaje de histocompatibilidad en hermanos de pacientes con EMBG, para determinar el grado de susceptibilidad genética y plantear en ellos un seguimiento estrecho, con el objetivo de lograr un diagnóstico y tratamiento precoces en caso de presentar la enfermedad. Abstract: Anti-glomerular basement membrane disease (AGBM) is an autoinmune disorder characterized by the presence of anti-glomerular basement membrane (anti-GBM) antibodies, alveolar hemorrhage, necrotizing glomerulonephritis, and linear deposition of immunoglobulins through direct inmunofluorescence. Genetic predisposition, among other factors, plays an important role in the development of the disease. Previous studies have shown that HLA-DR15 and HLA-DR4 increase the risk of presenting it, while HLA-DR1 and HLA-DR7 protect against its development.We describe the first case of two non-twin siblings with AGBM and identical HLA, with HLA-DR4 as risk factor and HLA-DR7 as protection factor. We propose the importance of analyzing HLA in siblings of patients with AGBM, to determine the degree of genetic susceptibility and to carry out a close follow-up on them, with the aim of achieving an early diagnosis and treatment in case of presenting the disease.

Anti glomerular basement membrane disease (AGBM) is an autoinmune disorder characterised by the presence of anti-glomerular basement membrane (Anti-GBM) antibodies, alveolar hemorrhage, necrotizing glomerulonephritis, and linear deposition of immunoglobulins through direct inmunofluorescence. Genetic predisposition, among other factors, plays an important role in the development of the disease. Previous studies have shown that HLA-DR15 and HLA-DR4 increase the risk of presenting it, while HLA-DR1 and HLA-DR7 protect against its development.We describe the first case of two non-twin siblings with AGBM and identical HLA, with HLA-DR4 as risk factor and HLA-DR7 as protection factor. We propose the importance of analysing HLA in siblings of patients with AGBM, to determine the degree of genetic susceptibility and to carry out a close follow-up on them, with the aim of achieving an early diagnosis and treatment in case of presenting the disease. Resumen: La enfermedad antimembrana basal glomerular (EMBG) es un trastorno autoinmune caracterizado por la presencia de anticuerpos anti-membrana basal glomerular (AMBG), hemorragia pulmonar, glomerulonefritis necrotizante y depósito lineal de inmunoglobulinas en inmunofluorescencia directa. La predisposición genética, entre otros factores, posee un papel importante en el desarrollo de la enfermedad. Estudios previos han demostrado que el HLA-DR15 y HLA- DR4 se asocian con mayor riesgo de presentarla, mientras que el HLA-DR1 y HLA-DR7 han demostrado ser factor de protección frente a su desarrollo.Describimos el primer caso de dos hermanos no gemelos con EMBG con tipaje HLA idéntico, con factor de riesgo HLA-DR4 y factor de protección HLA-DR7. Planteamos la importancia de analizar el tipaje de histocompatibilidad en hermanos de pacientes con EMBG, para determinar el grado de susceptibilidad genética y plantear en ellos un seguimiento estrecho, con el objetivo de lograr un diagnóstico y tratamiento precoces en caso de presentar la enfermedad.

Background: IgG4 is the least immunogenic subclass of IgG. Immunization with mRNA vaccines against SARS-CoV-2, unlike other vaccines, induces an increase in IgG4 against the spike protein in healthy populations. This study investigated whether immunosuppressive therapy affects the immune response, focusing on IgG subclass changes, to four doses of mRNA vaccine in kidney transplant recipients (KTRs). Methods: This study includes 146 KTRs and 23 dialysis patients (DPs) who received three mRNA-1273 vaccine doses and a BNT162b2 booster. We evaluated anti-spike IgG titers and subclasses, T-CD4+ and T-CD8+ cellular responses, and serum neutralizing activity (SNA). Results: At the fourth dose, 75.8% of COVID-19 naïve KTRs developed humoral and cellular responses (vs. 95.7% in DPs). There was a correlation between anti-spike IgG titers/subclasses and SNA (p < 0.001). IgG subclass kinetics after the third/fourth dose differed between COVID-19 naïve KTRs and DPs. Immunosuppressive therapy influenced IgG subclasses: mTOR inhibitors (mTORi) positively influenced IgG1 and IgG3 (p < 0.05), while mycophenolic acid negatively affected IgG1, IgG3, and IgG4 (p < 0.05). SNA is correlated with breakthrough infections after four doses of vaccine in KTRs. mTORi was the only factor associated with SNA > 65% in naïve KTRs [4.29 (1.21–15.17), p = 0.024]. Conclusions: KTRs show weaker cellular and humoral immune responses to mRNA vaccines and a class shift towards non-inflammatory anti-S IgG4 upon booster doses. IgG subclasses show a positive correlation with SNA and are influenced by immunosuppression. Increased SNA after four doses of vaccine is protective against infection. mTORi may benefit non-responding KTRs. [ABSTRACT FROM AUTHOR]

The management of diabetes and renal failure is changing thanks to the appearance of new drugs such as glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT2i) that have benefits in terms of survival and cardiorenal protection. Based on the potential mechanisms of GLP1-RA, kidney transplant recipients (KTRs) could benefit from their effects. However, high-quality studies are needed to demonstrate these benefits, in the transplant population, especially those related to cardiovascular benefits and renal protection. Studies with SGLT2i performed in KTRs are much less potent than in the general population and therefore no benefits in terms of patient or graft survival have been clearly demonstrated in this population to date. Additionally, the most frequently observed side effects could be potentially harmful to this population profile, including severe or recurrent urinary tract infections and impaired kidney function. However, benefits demonstrated in KTRs are in line with a known potential effects in cardiovascular and renal protection, which may be essential for the outcome of transplant recipients. Better studies are still needed to confirm the benefits of these new oral antidiabetics in the renal transplant population. Understanding the characteristics of these drugs may be critical for KTRs to be able to benefit from their effects without being damaged. This review discusses the results of the most important published studies on KTRs with GLP1-RA and SGLT2i as well as the potential beneficial effects of these drugs. Based on these results, approximate suggestions for the management of diabetes in KTRs were developed.

The genes CD28, CD86 and CTLA-4 conform the costimulatory (CD28-CD86) or inhibitory (CTLA-4-CD86) signal in T-cell activation. T-cell immune response has a critical role in allograft rejection, and single nucleotide polymorphisms (SNPs) located in these genes have been widely analyzed with controversial results. We analyzed a group of SNPs located in the three genes: CD28: rs3116496; CD86: rs1129055; and CTLA-4: rs231775 and rs3087243 in a cohort of 632 consecutively recruited kidney transplanted subjects. All polymorphisms were genotyped by TaqMan chemistry and the diagnosis of rejection was confirmed by biopsy and categorized according to the Banff classification. The analyses showed a statistically significant protective effect to T cell-mediated rejection (TCMR) in carriers of the CTLA-4 rs3087243*G allele, especially in patients with TCMR Banff ≥2 in the overall cohort and in patients without thymoglobulin induction therapy. Both associations were corroborated as independent factors in the multivariate analysis. Interestingly, associations with rejection were not found for any SNP in patients with thymoglobulin induction therapy. As expected, considering the major role of these genes in T-cell activation, no effect was observed for antibody-mediated rejection (ABMR). In conclusion, the SNP rs3087243 located in the CTLA-4 gene may be considered a useful independent biomarker for TCMR risk especially for severe TCMR in patients who did no received thymoglobulin induction therapy.

The +874 A/T polymorphism in the interferon gamma (IFNG) gene has been associated with Cytomegalovirus (CMV) infection risk in lung and kidney transplant recipients. To replicate this association, we performed a retrospective observational study of this polymorphism and immunosuppressive therapies considering the prophylactic treatment in 600 consecutive kidney transplanted recipients. We found no association of the aforementioned polymorphism with CMV infection in univariate and multivariate analyses regardless of the prophylactic treatment. In addition, the immunosuppressive treatment with mammalian target of rapamycin inhibitors (imTOR) showed a protective effect in all patients independently of prophylaxis. Moreover, in the adjusted model, we found interactions between prophylaxis with high-risk (Donor+/Recipient–, D+/R–) status (p-interaction = 0.01), with thymoglobulin induction therapy (p-interaction = 0.03) and with thymoglobulin anti-rejection therapy (p-interaction = 0.002). Data also revealed that prophylaxis was not an advantage in the not D+/R– and without thymoglobulin therapy group (HR = 0.98, p = 0.95). The benefit of prophylaxis was observed in all groups with thymoglobulin therapy, but it was maximal in the high-risk CMV infection group with both thymoglobulin induction therapy and thymoglobulin anti-rejection therapy (HR = 0.01, p < 0.001). In conclusion, the IFNG +874 polymorphism is not a predictive marker of CMV infection. The protective effect of imTOR is not improved with prophylaxis. Interestingly, the thymoglobulin therapy associated with prophylaxis is not a risk factor for CMV infection, and prophylaxis is not effective in recipients with no high-risk CMV status and without thymoglobulin therapy.

Background Immunoglobulin A nephropathy (IgAN) is the most frequent recurrent disease in kidney transplant recipients and its recurrence contributes to reducing graft survival. Several variables at the time of recurrence have been associated with a higher risk of graft loss. The presence of clinical or subclinical inflammation has been associated with a higher risk of kidney graft loss, but it is not precisely known how it influences the outcome of patients with recurrent IgAN. Methods We performed a multicentre retrospective study including kidney transplant recipients with biopsy-proven recurrence of IgAN in which Banff and Oxford classification scores were available. 'Tubulo-interstitial inflammation' (TII) was defined when 't' or 'i' were ≥2. The main endpoint was progression to chronic kidney disease (CKD) stage 5 or to death censored-graft loss (CKD5/DCGL). Results A total of 119 kidney transplant recipients with IgAN recurrence were included and 23 of them showed TII. Median follow-up was 102.9 months and 39 (32.8%) patients reached CKD5/DCGL. TII related to a higher risk of CKD5/DCGL (3 years 18.0% vs 45.3%, log-rank 7.588, P  = .006). After multivariate analysis, TII remained related to the risk of CKD5/DCGL (HR 2.344, 95% CI 1.119–4.910, P  = .024) independently of other histologic and clinical variables. Conclusions In kidney transplant recipients with IgAN recurrence, TII contributes to increasing the risk of CKD5/DCGL independently of previously well-known variables. We suggest adding TII along with the Oxford classification to the clinical variables to identify recurrent IgAN patients at increased risk of graft loss who might benefit from intensified immunosuppression or specific IgAN therapies. [ABSTRACT FROM AUTHOR]