The impact of preservation solutions for static cold storage on kidney transplantation outcomes: Results of a Brazilian nationwide multicenter study.

This study evaluated the current practices of selecting cold storage preservation solutions in Brazil and their impact on delayed graft function (DGF) incidence and 1-year outcomes in kidney transplant recipients. A retrospective cohort study was conducted, including 3,134 brain-dead deceased donor kidney transplants performed between 2014 and 2015 in 18 Brazilian centers. The most commonly used preservation solution was Euro-collins (EC, 55.4%), followed by Histidine-tryptophan-ketoglutarate (HTK, 30%) and Institut Georges Lopez (IGL-1, 14.6%). The incidence of DGF was 54.4%, with 11.7% of patients requiring dialysis for more than 14 days, indicating prolonged DGF. Upon adjusting for confounding variables, HTK demonstrated a significantly lower risk of DGF than EC (OR 0.7350.82500.926), as did IGL-1 (OR 0.6050.7120.837). Similar protective effects were observed for prolonged DGF when comparing HTK (OR 0.4780.5990.749) and IGL-1 (OR 0.4780.6810.749) against EC. No significant association was found between preservation solutions and 1-year death-censored graft survival. In conclusion, EC was the most frequently used cold storage perfusion solution, demonstrating a higher incidence and duration of DGF compared with HTK and IGL-1, but with no impact on 1-year graft survival.

Preloading peri-implant crestal bone loss: A retrospective study of incidence and related factors.

BACKGROUND: The aim of this study was to evaluate the incidence of preloading crestal bone loss (PLCBL) and to identify the patient-related and implant-related factors associated with PLCBL. METHODS: This retrospective cohort examined the dental records of patients who received at least one dental implant. PLCBL was defined as a reduction ⩾0.5 mm and severe PLCBL (primary variable) as a reduction ⩾1.5 mm in mesial and/or distal bone level, measured from the day of implant placement to uncovering or abutment installation/crown delivery. The incidence of PLCBL and patient and implant variables were recorded. Bivariate analysis and binary logistic regression identified factors associated with PLCBL ⩾0.5 mm and ⩾1.5 mm. RESULTS: A total of 746 dental implants placed in 361 patients from January 2011 to July 2021 was included in the analyses. Of the implants assessed, 24.4% (n = 182) exhibited PLCBL ⩾ 0.5 mm and 10.5% (n = 78) presented severe PLCBL (i.e., ⩾1.5 mm). Males (odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.11-3.07), patients with diabetes (OR = 3.33, 95% CI = 1.73-6.42), and those allergic to penicillin (OR = 3.13, 95% CI = 1.57-6.22) were more likely to experience severe PLCBL (p < 0.05). Implants placed in the anterior area (OR = 2.08, 95% CI = 1.16-3.73), with bone-level platform-abutment connection (OR = 4.73, 95% CI = 1.94-11.49) and inserted supracrestally (OR = 3.77, 95% CI = 1.84-7.72), presented a greater risk of developing severe PLCBL (p < 0.05). Implants placed in a previously grafted area presented a lower likelihood of developing severe PLCBL (OR = 0.489, 95% CI = 0.28-0.84). CONCLUSION: The incidence of PLCBL ⩾ 0.5 mm and ⩾1.5 mm was 24.4% and 10.5%, respectively. Male sex, diabetes, allergy to penicillin, anterior location, bone-level platform-abutment connection, and supracrestal implant placement are potential risk factors for severe PLCBL. A previously grafted area is a potential protective factor.

Multiple-target Therapy for Posttransplant Focal Segmental Glomerulosclerosis.

Background: There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results. Methods: This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients. Results: Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis. Conclusions: In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.

The Second International Consensus Guidelines on the Management of BK Polyomavirus in Kidney Transplantation.

BK polyomavirus (BKPyV) remains a significant challenge after kidney transplantation. International experts reviewed current evidence and updated recommendations according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). Risk factors for BKPyV-DNAemia and biopsy-proven BKPyV-nephropathy include recipient older age, male sex, donor BKPyV-viruria, BKPyV-seropositive donor/-seronegative recipient, tacrolimus, acute rejection, and higher steroid exposure. To facilitate early intervention with limited allograft damage, all kidney transplant recipients should be screened monthly for plasma BKPyV-DNAemia loads until month 9, then every 3 mo until 2 y posttransplant (3 y for children). In resource-limited settings, urine cytology screening at similar time points can exclude BKPyV-nephropathy, and testing for plasma BKPyV-DNAemia when decoy cells are detectable. For patients with BKPyV-DNAemia loads persisting >1000 copies/mL, or exceeding 10 000 copies/mL (or equivalent), or with biopsy-proven BKPyV-nephropathy, immunosuppression should be reduced according to predefined steps targeting antiproliferative drugs, calcineurin inhibitors, or both. In adults without graft dysfunction, kidney allograft biopsy is not required unless the immunological risk is high. For children with persisting BKPyV-DNAemia, allograft biopsy may be considered even without graft dysfunction. Allograft biopsies should be interpreted in the context of all clinical and laboratory findings, including plasma BKPyV-DNAemia. Immunohistochemistry is preferred for diagnosing biopsy-proven BKPyV-nephropathy. Routine screening using the proposed strategies is cost-effective, improves clinical outcomes and quality of life. Kidney retransplantation subsequent to BKPyV-nephropathy is feasible in otherwise eligible recipients if BKPyV-DNAemia is undetectable; routine graft nephrectomy is not recommended. Current studies do not support the usage of leflunomide, cidofovir, quinolones, or IVIGs. Patients considered for experimental treatments (antivirals, vaccines, neutralizing antibodies, and adoptive T cells) should be enrolled in clinical trials.

The effectiveness of a 6-month intervention with sit-stand workstation in office workers: Results from the SUFHA cluster randomized controlled trial.

BACKGROUND: Prolonged periods of sitting have been linked to negative health outcomes. Implementation of sit-stand desks in the workplace has been one strategy to reduce prolonged sitting. OBJECTIVE: To assess the effectiveness of sit-stand workstations on reducing sitting time and improving other health outcomes of office-based workers. METHODS: 39 Portuguese office workers were randomized into a 6-month parallel-group cluster RCT consisting by the implementation of sit-stand desks in the workplace. The primary outcome of sitting time was assessed using ActivPAL. Secondary outcomes included biometric, psychological, and diet-related variables. All outcomes were assessed at baseline and 6 months for the whole sample and at 3 months for a sub-sample of the intervention group (n = 11). RESULTS: No significant time*group interaction was found for the primary or secondary outcomes, apart from waist circumference favoring the control group (Δ-1.81 cm, pinteraction = 0.04). There were significant changes within the intervention group for sitting time (-44.0 min/day), prolonged sitting (>30 min) (-45.3 min/day) and standing time (51.7 min/day) at 3 months in the sub-sample and in prolonged sitting (>30 min) (-26 min/day) in the full intervention group (p < 0.05). Changes were also observed within the intervention group for percent body fat (Δ-3.7%) and ratings of quality of life (Δ2.2), musculoskeletal discomfort (Δ-4.9), overall fatigue (Δ-2.2), and the need for recovery after work (Δ-1.7) at 6-month follow-up (p < 0.05). CONCLUSION: Although not being effective for reducing sitting time, the implementation of sit-stand desks in the Portuguese workspace was shown to be feasible over the long term, received well by users, and may offer other health benefits. TRIAL REGISTRATION: OSF Registration, OSF.IO/JHGPW. Registered 15 November 2022. https://doi.org/10.17605/OSF.IO/JHGPW.

Assessing the influence of graft loss on 4-year patient survival after simultaneous pancreas-kidney transplantation: Kaplan-Meier versus Competing Risk Analysis model.

BACKGROUND: Graft loss increases the risk of patient death after simultaneous pancreas-kidney (SPK) transplantation. The relative risk of each graft failure is complex due to the influence of several competing events. METHODS: This retrospective, single-center study compared 4-year patient survival according to the graft status using Kaplan-Meier (KM) and Competing Risk Analysis (CRA). Patient survival was also assessed according to five eras (Era 1: 2001-2003; Era 2: 2004-2006; Era 3: 2007-2009; Era 4: 2010-2012; Era 5: 2012-2015). RESULTS: Between 2000 and 2015, 432 SPK transplants were performed. Using KM, patient survival was 86.5% for patients without graft loss (n = 333), 93.4% for patients with pancreas graft loss (n = 46), 43.7% for patients with kidney graft loss (n = 16), and 25.4% for patients with pancreas and kidney graft loss (n = 37). Patient survival was underestimated using KM versus CRA methods in patients with pancreas and kidney graft losses (25.4% vs. 36.2%), respectively. Induction with lymphocyte depleting antibodies was associated with 81% reduced risk (HR.19, 95% CI.38-.98, p = .0048), while delayed kidney function (HR 2.94, 95% CI 1.09-7.95, p = .033) and surgical complications (HR 2.94, 95% CI 1.22-7.08, p = .016) were associated with higher risk of death. Four-year patient survival increased from Era 1 to Era 5 (79% vs. 87.9%, p = .047). CONCLUSION: In this cohort of patients, kidney graft loss, with or without pancreas graft loss, was associated with higher mortality after SPK transplantation. Compared to CRA, the KM model underestimated survival only among patients with pancreas and kidney graft losses. Patient survival increased over time.

Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.

BACKGROUND: This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs). METHODS: This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate. RESULTS: A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m2, p = .614). CONCLUSIONS: These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.

Recurrence of membranous nephropathy after kidney transplantation: A multicenter retrospective cohort study.

Membranous nephropathy (MN) is a leading cause of kidney failure worldwide and frequently recurs after transplant. Available data originated from small retrospective cohort studies or registry analyses; therefore, uncertainties remain on risk factors for MN recurrence and response to therapy. Within the Post-Transplant Glomerular Disease Consortium, we conducted a retrospective multicenter cohort study examining the MN recurrence rate, risk factors, and response to treatment. This study screened 22,921 patients across 3 continents and included 194 patients who underwent a kidney transplant due to biopsy-proven MN. The cumulative incidence of MN recurrence was 31% at 10 years posttransplant. Patients with a faster progression toward end-stage kidney disease were at higher risk of developing recurrent MN (hazard ratio [HR], 0.55 per decade; 95% confidence interval [CI], 0.35-0.88). Moreover, elevated pretransplant levels of anti-phospholipase A2 receptor (PLA2R) antibodies were strongly associated with recurrence (HR, 18.58; 95% CI, 5.37-64.27). Patients receiving rituximab for MN recurrence had a higher likelihood of achieving remission than patients receiving renin-angiotensin-aldosterone system inhibition alone. In sum, MN recurs in one-third of patients posttransplant, and measurement of serum anti-PLA2R antibody levels shortly before transplant could aid in risk-stratifying patients for MN recurrence. Moreover, patients receiving rituximab had a higher rate of treatment response.

Computed tomographic findings in TBX4 mutation: a common cause of severe pulmonary artery hypertension in children.

BACKGROUND: Mutations in the T-Box 4 (TBX4) gene are a lesser-known cause of heritable pulmonary arterial hypertension (PAH). Patients with heritable PAH typically have worse outcomes when compared with patients with idiopathic PAH, yet little is known about the phenotypical presentation of this mutation. OBJECTIVE: This article reviews the pattern of chest CT findings in pediatric patients with PAH and TBX4 mutations and compares their radiographic presentation with those of age-matched patients with PAH but without TBX4 mutations. MATERIALS AND METHODS: A retrospective chart review of the pulmonary arterial hypertension database was performed. Pediatric patients with PAH-confirmed TBX4 mutations and an available high CT were included. Fifteen (9 females) patients met the inclusion criteria. Fourteen (8 females) age-matched controls with diagnosed PAH but without TBX4 mutations were also evaluated. The median age at diagnosis was 7.4 years (range: 0.1-16.4 years). Demographic information and clinical outcomes were collected. CTs of the chest were reviewed for multiple airway, parenchymal, and structural abnormalities (16 imaging findings in total). Chi-square tests were used to compare the prevalence of each imaging finding in the TBX4 cohort compared to the control group. RESULTS: Patients with TBX-4 mutations had increased presence of peripheral or subpleural irregularity (73% vs 0%, P < 0.01), cystic lucencies (67% vs 7%, P < 0.01), and linear or reticular opacity (53% vs 0%, P < 0.01) compared to the control group. Ground glass opacities, bronchiectasis, and centrilobular nodules were not significantly different between the two patient groups (P > 0.05). CONCLUSION: TBX4 mutations have distinct imaging phenotypes in pediatric patients with PAH. Compared to patients without this mutation, patients with TBX-4 genes typically present with peripheral or subpleural irregularity, cystic lucencies, and linear or reticular opacity.

A Head-to-head Comparison of De Novo Sirolimus or Everolimus Plus Reduced-dose Tacrolimus in Kidney Transplant Recipients: A Prospective and Randomized Trial.

BACKGROUND: Mammalian target of rapamycin inhibitors (mTORi), sirolimus (SRL) and everolimus (EVR), have distinct pharmacokinetic/pharmacodynamics properties. There are no studies comparing the efficacy and safety of de novo use of SRL versus EVR in combination with reduced-dose calcineurin inhibitor. METHODS: This single-center prospective, randomized study included first kidney transplant recipients receiving a single 3 mg/kg antithymocyte globulin dose, tacrolimus, and prednisone, without cytomegalovirus (CMV) pharmacological prophylaxis. Patients were randomized into 3 groups: SRL, EVR, or mycophenolate sodium (MPS). Doses of SRL and EVR were adjusted to maintain whole blood concentrations between 4 and 8 ng/mL. The primary endpoint was the 12-mo incidence of the first CMV infection/disease. RESULTS: There were 266 patients (SRL, n = 86; EVR, n = 90; MPS, n = 90). The incidence of the first CMV event was lower in the mTORi versus MPS groups (10.5% versus 7.8% versus 43.3%, P < 0.0001). There were no differences in the incidence of BK polyomavirus viremia (8.2% versus 10.1% versus 15.1%, P = 0.360). There were no differences in survival-free from treatment failure (87.8% versus 88.8% versus 93.3%, P = 0.421) and incidence of donor-specific antibodies. At 12 mo, there were no differences in kidney function (75 ± 23 versus 78 ± 24 versus 77 ± 24 mL/min/1.73 m 2 , P = 0.736), proteinuria, and histology in protocol biopsies. Treatment discontinuation was higher among patients receiving SRL or EVR (18.6% versus 15.6% versus 6.7%, P = 0.054). CONCLUSIONS: De novo use of SRL or EVR, targeting similar therapeutic blood concentrations, shows comparable efficacy and safety. The reduced incidence of CMV infection/disease and distinct safety profile of mTORi versus mycophenolate were confirmed in this study.

Long COVID Among Kidney Transplant Recipients Appears to Be Attenuated During the Omicron Predominance.

BACKGROUND: Omicron variant has been associated with milder cases of COVID-19 among kidney transplant recipients. However, little is known about postacute sequelae, referred to as Long COVID. METHODS: Prospective, single-center cohort study investigating prevalence and risk factors for Long COVID among kidney transplant recipients during the omicron predominance in Brazil. The analysis included adult patients with confirmed SARS-CoV-2 infection between January 5, 2022, and July 18, 2022, were alive, had a functioning kidney transplant 3 mo after symptom onset, and answered a telephonic survey about physical complains of Long COVID. RESULTS: From the 1529 eligible, 602 (39%) patients responded the survey. Sixteen percent reported a previous SARS-CoV-2 infection, and 85% had been fully vaccinated. The prevalence of Long COVID was 52%, with the most common complaints being weakness (46%), myalgia (41%), dizziness (33%), and headache (31%). Among employed patients, 94% were able to resume their normal work activities. In multivariable analysis, female gender (hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.51-3.02; P < 0.0001), previous SARS-CoV-2 infection (HR, 3.55; 95% CI, 1.91-6.60; P < 0.0001), fatigue (HR, 2.32; 95% CI, 1.18-4.55; P = 0.014), myalgia (HR, 1.48; 95% CI, 1.03-2.15; P = 0.036) during the acute phase, and hospitalization because of COVID-19 (HR, 1.71; 95% CI, 1.06-2.76; P = 0.028) were independently associated with Long COVID. CONCLUSIONS: In the "omicron era," Long COVID among kidney transplant recipients exhibited milder characteristics and had a less significant impact on their ability to resume normal life activities. The risk factors for persistent symptoms were similar to those observed in the general population except for the vaccination status, underscoring the importance of closer monitoring in special subgroups.

The cardiorespiratory system of miniature frogs.

Anurans of the genus Brachycephalus are among the smallest vertebrates in the world, due to an extreme process of miniaturization. As an example of this process, Brachycephalus species show loss of fingers, loss of the eardrum and middle ear, bone fusions, and the presence of paravertebral plates and parotic plaque. However, no studies addressing the consequences of miniaturization on internal organs, such as the lungs and heart, are currently available. Thus, this study aimed to investigate if overall small body size has affected the cardiorespiratory system. We investigated, via dissections, individuals of four Brachycephaloidea species: Brachycephalus rotenbergae, B. pitanga, Eleutherodactylus johnstonei, and Ischnocnema parva. We observed that B. rotenbergae and B. pitanga present a reduction of the atrial septum and absence of the carotid body. On the other hand, despite being a member of the sister genus to Brachycephalus (both genera belong to the Brachycephalidae), individuals of Ischnocnema present a heart with a complete septum and carotid body; this is also observed in E. johnstonei (Eleutherodactylidae). We observed that B. rotenbergae and B. pitanga have thin skin with a one to two cell thick germ layer, and their lungs likely exhibit lower blood supply when compared to individuals of the E. johnstonei and I. parva species. Based on the observed structures, we suggest that in species of Brachycephalus, respiration is performed mainly through the skin, and their lungs may have a reduced respiratory function.

Natural history and prognostic factors of candidemia in kidney transplant recipients: A retrospective, multinational study.

BACKGROUND: The natural history of candidemia in kidney transplant recipients (KTR) remains poorly understood. This study aimed to evaluate mortality, prognostic factors and overall graft loss after candidemia in KTRs. METHODS: This is a retrospective multicentre study enrolling all KTRs ≥15 years old with candidemia diagnosed at hospitals in Brazil, Spain and Italy from 2010 to 2020. Primary endpoints were mortality rates at 14 and 30 days. Secondary endpoints were prognostic factors of 14-day mortality and overall graft loss. RESULTS: We enrolled 93 KTRs of which 75 were from Brazil. The mean time interval from transplantation to the onset of candidemia was 45.2 ± 61.5 months. 42% of all patients were on haemodialysis, 31.3% had an episode of sepsis and 39% underwent surgery within 30 days before fungemia. European patients were more likely to receive echinocandin (32 vs. 72%, p < .001). 22.7% of Brazilian patients did not receive any antifungal before death. All-cause mortality at 14 days was higher in Brazil (41.3 vs. 11.1%, p = .016). Candida colonisation (OR 6.91 [95% CI: 1.08-44.3], p = .042) and hypotension (OR 4.87 [95% CI: 1.62-14.66], p = .005) were associated with 14-day mortality. Echinocandin treatment had a protective effect (OR 0.19 [95% CI: 0.05-0.73], p = .015). Graft loss at 90 days occurred in 48% of patients (70.7 in Brazil vs. 22.2% in Europe, p < .01). CONCLUSIONS: Candidemia in KTR is usually documented late after engraftment in patients requiring HD, surgical procedures and dysbiosis secondary to antibiotic use. Mortality was higher in Brazil. Echinocandin therapy was associated with improved survival.

Excess mortality among kidney transplant recipients: Impact of COVID-19-related deaths during the pandemic.

BACKGROUND: Because COVID-19 has been associated with high lethality rates among kidney transplant recipients (KTR), but also with a severe disruption and delays in overall healthcare, this study aims to evaluate the excess mortality in the pandemic era among KTR in a high-volume Brazilian transplant center. METHODS: This study used data from a single center that provides follow-up on all its transplant recipients. The population of interest included all the patients who were transplanted between August 31, 1983 and December 31, 2022 and who were live from January 1, 2014. Using the "AutoRegressive Integrated Moving Average" forecasting algorithm, the expected mortality for the pandemic era (2020-2022) was modeled from the pre-pandemic era (2014-2019). RESULTS: There were 12 077 KTRs at risk of dying in the entire observation period. In the pre-pandemic era, there were 21 deaths per 1000 patients at risk. In the pandemic era, there were 1429 observed deaths (rate of 47 deaths per 1000 patients at risk) versus the expected 587 deaths, resulting in an absolute number of 842 excess deaths, or an observed-to-expected ratio of 2.4, or an absolute rate of 26 deaths in excess per 1000 patients at risk. The excess deaths exhibited a temporal pattern mirroring that of the surges in new cases and lethality rates of COVID-19. COVID-19-related deaths drove 94% of excess mortality in the pandemic era. CONCLUSION: In this large cohort of KTR under centralized follow-up, more than twofold excess mortality was primarily driven by COVID-19-related deaths, highlighting the vulnerability of this population to the most severe presentation of SARS-CoV-2 infection.

Use of sirolimus as an adjuvant therapy for kidney transplant recipients with high-risk cutaneous squamous cell carcinomas: a prospective non-randomized controlled study / Uso do sirolimo como terapia adjuvante para receptores de transplante renal com carcinoma espinocelular cutâneo de alto risco: um estudo prospectivo controlado não randomizado

ABSTRACT Introduction: Previous research demonstrated benefits of late conversion to mTOR inhibitors against cutaneous squamous cell carcinomas (cSCC) in kidney transplant recipients (KTR), despite of poor tolerability. This study investigated whether stepwise conversion to sirolimus monotherapy without an attack dose modified the course of disease with improved tolerability. Methods: This prospective exploratory study included non-sensitized KTR with more than 12-months post-transplant, on continuous use of calcineurin inhibitors (CNI)-based therapy, and with poor-prognosis cSCC lesions. Incidence densities of high-risk cSCC over 3-years after conversion to sirolimus-monotherapy were compared to a non-randomized group with high-risk cSCC but unsuitable/not willing for conversion. Results: Forty-four patients were included (83% male, mean age 60 ± 9.7years, 62% with skin type II, mean time after transplantation 9 ± 5.7years). There were 25 patients converted to SRL and 19 individuals kept on CNI. There was a tendency of decreasing density of incidence of all cSCC in the SRL group and increasing in the CNI group (1.49 to 1.00 lesions/patient-year and 1.74 to 2.08 lesions/patient-year, p = 0.141). The density incidence of moderately differentiated decreased significantly in the SRL group while increasing significantly in the CNI group (0.31 to 0.11 lesions/patient-year and 0.25 to 0.62 lesions/patient-year, p = 0.001). In the SRL group, there were no sirolimus discontinuations, no acute rejection episodes, and no de novo DSA formation. Renal function remained stable. Conclusions: This study suggests that sirolimus monotherapy may be useful as adjuvant therapy of high-risk cSCC in kidney transplant recipients. The conversion strategy used was well tolerated and safe regarding key mid-term transplant outcomes.

RESUMO Introdução: Pesquisas anteriores demonstraram benefícios da conversão tardia para inibidores de mTOR contra carcinomas espinocelulares cutâneos (CECs) em receptores de transplante renal (RTR), apesar da baixa tolerabilidade. Este estudo investigou se a conversão gradual para monoterapia com sirolimo sem dose de ataque modificou o curso da doença com melhor tolerabilidade. Métodos: Esse estudo prospectivo exploratório incluiu RTR não sensibilizados com mais de 12 meses pós-transplante, uso contínuo de terapia imunossupressora baseado em inibidor de calcineurina (CNI) associado a micofenolato de sódio ou azatioprina, com lesões de CECs de mau prognóstico. Comparou-se densidades de incidência de CECs de alto risco durante 3 anos após conversão para monoterapia com sirolimo à um grupo não randomizado com CECs classificados conforme os mesmos critérios de gravidade do grupo sirolimo, mas inadequado/não disposto à conversão. Resultados: Foram incluídos 44 pacientes (83% homens, idade média 60 ± 9,7 anos, 62% com fototipo de pele II, tempo médio pós-transplante 9 ± 5,7 anos). 25 pacientes foram convertidos para SRL e 19 indivíduos mantidos em CNI. Foi observado tendência de diminuição da densidade de incidência de todos CECs no grupo SRL e de aumento no grupo CNI (1,49 a 1,00 lesões/paciente-ano; 1,74 a 2,08 lesões/paciente-ano; p = 0,141). A densidade de incidência de lesões moderadamente diferenciadas diminuiu significativamente no grupo SRL enquanto aumentou significativamente no grupo CNI (0,31 a 0,11 lesões/paciente-ano; 0,25 a 0,62 lesões/paciente-ano; p = 0,001). No grupo SRL não houve descontinuação do sirolimo, nenhum episódio de rejeição aguda e nenhuma formação de DSA de novo. Função renal permaneceu estável. Conclusões: Esse estudo sugere que a monoterapia com sirolimo pode ser útil como terapia adjuvante de CECs de alto risco em RTR. A estratégia de conversão usada foi bem tolerada e segura em relação aos principais desfechos do transplante a médio prazo.

Sex Differences among Overweight/Obese Kidney Transplant Recipients Requiring Oxygen Support Amid the COVID-19 Pandemic.

Background and Objectives: Overweight/obesity puts individuals at greater risk for COVID-19 progression and mortality. We aimed to evaluate the impact of overweight/obesity on oxygen (O2) requirement outcomes of male and female kidney transplant recipients (KTRs) during the COVID-19 pandemic. Materials and Methods: We conducted a retrospective analysis of a cohort of KTRs diagnosed with COVID-19. Participants were stratified based on BMI categories, and data on the need for O2 therapy outcome were collected and analyzed separately for male and female KTRs. Results: In total, 284 KTRs (97 males and 187 females) were included in the study. Overweight/obesity was observed in 60.6% of male KTRs and 71% of female KTRs. Strikingly, overweight/obese women had a significantly higher requirement for supplemental O2 (63.3% vs. 41.7%, OR = 2.45, p = 0.03), particularly among older individuals (OR = 1.05, p = 0.04), smokers (OR = 4.55, p = 0.03), those with elevated lactate dehydrogenase (LDH) levels (OR = 1.01, p = 0.006), and those with lower admission and basal estimated glomerular filtration rate (eGFR) levels. Within this cohort, the necessity for O2 supplementation was correlated with more unfavorable outcomes. These included heightened mortality rates, transfers to the intensive care unit, employment of invasive mechanical ventilation, and the emergence of acute kidney injury requiring hemodialysis. On the other hand, although overweight/obese male KTRs had a higher prevalence of hypertension and higher fasting blood glucose levels, no significant association was found with COVID-19-related outcomes when compared to lean male KTRs. Conclusions: Overweight/obesity is highly prevalent in KTRs, and overweight/obese women demonstrated a higher need for supplemental O2. Therefore, the early identification of factors that predict a worse outcome in overweight/obese female KTRs affected by COVID-19 contributes to risk stratification and guides therapeutic decisions.