QuantiFERON-CMV as a Predictor of CMV Events During Preemptive Therapy in CMV-seropositive Kidney Transplant Recipients.

BACKGROUND: Prevention of cytomegalovirus (CMV) infection after kidney transplantation is costly and burdensome. METHODS: Given its promising utility in risk stratification, we evaluated the use of QuantiFERON-CMV (QFCMV) and additional clinical variables in this prospective cohort study to predict the first clinically significant CMV infection (CS-CMV, ranging from asymptomatic viremia requiring treatment to CMV disease) in the first posttransplant year. A cost-effectiveness analysis for guided prevention was done. RESULTS: One hundred adult kidney transplant recipients, CMV IgG + , were given basiliximab induction and maintained on steroid/mycophenolate/tacrolimus with weekly CMV monitoring. Thirty-nine patients developed CS-CMV infection (viral syndrome, n = 1; end-organ disease, n = 9; and asymptomatic viremia, n = 29). A nonreactive or indeterminate QFCMV result using the standard threshold around day 30 (but not before transplant) was associated with CS-CMV rates of 50% and 75%, respectively. A higher QFCMV threshold for reactivity (>1.0 IU interferon-γ/mL) outperformed the manufacturer's standard (>0.2 IU interferon-γ/mL) in predicting protection but still allowed a 16% incidence of CS-CMV. The combination of recipient age and type of donor, along with posttransplant QFCMV resulted in a prediction model that increased the negative predictive value from 84% (QFCMV alone) to 93%. QFCMV-guided preemptive therapy was of lower cost than preemptive therapy alone ( P < 0.001, probabilistic sensitivity analysis) and was cost-effective (incremental net monetary benefit of 210 USD) assuming willingness-to-pay of 2000 USD to avoid 1 CMV disease. CONCLUSIONS: Guided CMV prevention by the prediction model with QFCMV is cost-effective and would spare from CMV surveillance in 42% of patients with low risk for CS-CMV.

Coronary Artery Disease Assessment and Cardiovascular Events in Middle-Aged Patients on Hemodialysis.

OBJECTIVE: To explore whether, in younger patients on dialysis with longer life expectancy, assessment of coronary artery disease (CAD) could identify individuals at higher risk of events and revascularization might improve outcomes in selected patients contrary to what had been observed in elderly patients. METHODS: From August 1997 to January 2019, 2265 patients with stage 5 chronic kidney disease were prospectively referred for cardiovascular assessment. For this study, we selected 1374 asymptomatic patients aged between 18 and 64 years. After clinical risk stratification and cardiac scintigraphy by single-photon emission computed tomography, 866 patients underwent coronary angiography. The primary end point was the composite incidence of nonfatal/fatal major adverse cardiovascular events during a follow-up period of 0.1 to 189.7 months (median, 26 months). The secondary end point was all-cause mortality. RESULTS: The primary end point occurred in 327 (23.8%) patients. Clinically stratified high-risk patients had a 3-fold increased risk of the primary end point. The prevalence of abnormal findings on perfusion scans was 29.2% (n=375), and significant CAD was found in 449 (51.8%) of 866 patients who underwent coronary angiography. An abnormal finding on myocardial perfusion scan and the presence of CAD were significantly associated with a 74% and 22% increased risk of cardiovascular events, respectively. In patients undergoing percutaneous coronary intervention or coronary artery bypass grafting (n=99), there was an 18% reduction in the risk of all-cause death relative to patients receiving medical treatment (P=.03). CONCLUSION: In this cohort of middle-aged, asymptomatic patients on dialysis, assessment of CAD identified individuals at higher risk of events, and coronary intervention was associated with reducing the risk of death in selected patients.

Peripheral Artery Disease Diagnosed by Pulse Palpation as a Predictor of Coronary Artery Disease in Patients with Chronic Kidney Disease.

There is a need of simple, inexpensive, and reliable noninvasive testing to predict coronary artery disease (CAD) in patients with chronic kidney disease (CKD), where the prevalence of cardiovascular (CV) events and death is elevated. We analyzed the association between peripheral artery disease (PAD) and CAD in 201 patients with stage 5 CKD on dialysis using a prospective observational cohort. Diagnosis of PAD by both palpation and USD were significantly correlated. In patients with PAD diagnosed by palpation, CAD was observed in 80%, while in those diagnosed by USD, CAD was present in 79.1%. The absence of a pulse by palpation predicted CAD with a sensitivity of 55% and a specificity of 76%; USD showed a sensitivity of 62% and specificity of 60% to predict CAD. The risk of combined serious CV events and death was significantly higher in subjects with PAD diagnosed by palpation, but not by USD. PAD assessed by palpation also correlated with the occurrence of multivessel CAD and with the probability of coronary intervention. Both methods are moderately useful for predicting CAD, but PAD diagnosis by palpation was a better predictor of combined CV events and death and was also associated with CAD severity and likelihood of intervention.

Interdialytic Blood Pressure and Risk of Cardiovascular Events and Death in Hemodialysis Patients.

INTRODUCTION: Normal (120-140 mm Hg) systolic peridialysis blood pressure (BP) is associated with higher mortality in hemodialysis (HD) patients. AIM: We explored the relationship between hypertension and BP on outcomes using data collected at the interdialytic period. METHODS: This was a single-center observational cohort study with 2672 HD patients. BP was determined at inception, in mid-week, between 2 consecutive dialysis sessions. Hypertension was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Endpoints were major CV events and all-cause mortality. RESULTS: During a median follow-up of 31 months, 761 patients (28%) experienced CV events and 1181 (44%) died. Hypertensive patients had lower survival free of CV than normotensive patients (P = 0.031). No difference occurred in the incidence of death between groups. Compared with the reference category of SBP ≥ 171 mmHg, the incidence of cardiovascular events was reduced in patients with SBP 101-110 (HR 0.647, 95% CI 0.455 to 0.920), 111-120 (HR 0.663, 95%CI 0.492 to 0.894), 121-130 (HR 0.747, 95%CI 0.569 to 0.981), and 131-140 (HR 0.757, 95%CI 0.596 to 0.962). On multivariate analysis, systolic and diastolic BP were not independent predictors of CV events or death. Normal interdialytic BP was not associated with mortality or CV events, and hypertension predicted an increased probability of CV complications. CONCLUSIONS: Interdialytic BP may be preferred to guide treatment decisions, and HD patients should be treated according to guidelines for the general population until specific BP targets for this population are identified.

A Machine Learning Prediction Model for Immediate Graft Function After Deceased Donor Kidney Transplantation.

BACKGROUND: After kidney transplantation (KTx), the graft can evolve from excellent immediate graft function (IGF) to total absence of function requiring dialysis. Recipients with IGF do not seem to benefit from using machine perfusion, an expensive procedure, in the long term when compared with cold storage. This study proposes to develop a prediction model for IGF in KTx deceased donor patients using machine learning algorithms. METHODS: Unsensitized recipients who received their first KTx deceased donor between January 1, 2010, and December 31, 2019, were classified according to the conduct of renal function after transplantation. Variables related to the donor, recipient, kidney preservation, and immunology were used. The patients were randomly divided into 2 groups: 70% were assigned to the training and 30% to the test group. Popular machine learning algorithms were used: eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine, Gradient Boosting classifier, Logistic Regression, CatBoost classifier, AdaBoost classifier, and Random Forest classifier. Comparative performance analysis on the test dataset was performed using the results of the AUC values, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. RESULTS: Of the 859 patients, 21.7% (n = 186) had IGF. The best predictive performance resulted from the eXtreme Gradient Boosting model (AUC, 0.78; 95% CI, 0.71-0.84; sensitivity, 0.64; specificity, 0.78). Five variables with the highest predictive value were identified. CONCLUSIONS: Our results indicated the possibility of creating a model for the prediction of IGF, enhancing the selection of patients who would benefit from an expensive treatment, as in the case of machine perfusion preservation.

Desensitization using IVIG alone for living-donor kidney transplant: impact on donor-specific antibodies / Dessensibilização usando somente IgIV para transplante renal com doador vivo: impacto nos anticorpos específicos contra o doador

Abstract Introduction: Sensitization to human leukocyte antigen is a barrier to. Few data have been published on desensitization using polyvalent human intravenous immunoglobulin (IVIG) alone. Methods: We retrospectively reviewed the of 45 patients with a positive complement-dependent cytotoxicity crossmatch (CDCXM) or flow cytometry crossmatch (FCXM) against living donors from January 2003 to December 2014. Of these, 12 were excluded. Patients received monthly IVIG infusions (2 g/kg) only until they had a negative T-cell and B-cell FCXM. Results: During the 33 patients, 22 (66.7%) underwent living donor kidney transplantation, 7 (21.2%) received a deceased donor graft, and 4 (12.1%) did not undergo transplantation. The median class I and II panel reactive antibodies for these patients were 80.5% (range 61%-95%) and 83.0% (range 42%-94%), respectively. Patients (81.8%) had a positive T-cell and/or B-cell CDCXM and 4 (18.2%) had a positive T-cell and/or B-cell FCXM. Patients underwent transplantation after a median of 6 (range 3-16). The median donor-specific antibody mean fluorescence intensity sum was 5057 (range 2246-11,691) before and 1389 (range 934-2492) after desensitization (p = 0.0001). Mean patient follow-up time after transplantation was 60.5 (SD, 36.8) months. Nine patients (45.0%). Death-censored graft survival at 1, 3, and 5 years after transplant was 86.4, 86.4, and 79.2%, respectively and patient survival was 95.5, 95.5, and 83.7%, respectively. Conclusions: Desensitization using IVIG alone is an effective strategy, allowing successful transplantation in 87.9% of these highly sensitized patients.

Resumo Introdução: Sensibilização HLA é uma barreira ao transplante em pacientes sensibilizados. Há poucos dados publicados sobre dessensibilização utilizando somente imunoglobulina intravenosa humana polivalente (IgIV). Métodos: Revisamos retrospectivamente prontuários de 45 pacientes com prova cruzada positiva por citotoxicidade dependente do complemento (CDCXM) ou citometria de fluxo (FCXM) contra doadores vivos, de Janeiro/2003-Dezembro/2014. Destes, excluímos 12. 33 pacientes receberam infusões mensais de IgIV (2 g/kg) apenas até apresentarem FCXM células T e B negativa. Resultados: Durante dessensibilização, 22 pacientes (66,7%) realizaram transplante renal com doador vivo, 7 (21,2%) receberam enxerto de doador falecido, 4 (12,1%) não realizaram transplante. A mediana do painel de reatividade de anticorpos classes I e II para estes pacientes foi 80,5% (intervalo 61%-95%) e 83,0% (intervalo 42%-94%), respectivamente. 18 pacientes (81,8%) apresentaram CDCXM célula T e/ou B positiva; 4 (18,2%) apresentaram FCXM célula T e/ou B positiva. Pacientes realizaram transplante após mediana de 6 (intervalo 3-16) infusões. A mediana da somatória da intensidade média de fluorescência do anticorpo específico contra o doador foi 5057 (intervalo 2246-11.691) antes e 1389 (intervalo 934-2492) após dessensibilização (p = 0,0001). O tempo médio de acompanhamento do paciente pós transplante foi 60,5 (DP, 36,8) meses. Nove pacientes (45,0%) não apresentaram rejeição e 6 (27,3%) apresentaram rejeição mediada por anticorpos. Sobrevida do enxerto censurada para óbito em 1, 3, 5 anos após transplante foi 86,4; 86,4; 79,2%, respectivamente, e sobrevida do paciente foi 95,5; 95,5; 83,7%, respectivamente. Conclusões: Dessensibilização utilizando apenas IgIV é uma estratégia eficaz, permitindo transplante bem-sucedido em 87,9% destes pacientes altamente sensibilizados.

Increasing transplantability in Brazil: time to discuss Kidney Paired Donation / Doação renal pareada no Brasil: tempo para reflexão

Abstract Introduction: Kidney transplantation (KT) is the best treatment for chronic kidney disease. In Brazil, there are currently more than 26 thousand patients on the waitlist. Kidney Paired Donation (KPD) offers an incompatible donor-recipient pair the possibility to exchange with another pair in the same situation, it is a strategy to raise the number of KT. Discussion: KPD ceased being merely an idea over 20 years ago. It currently accounts for 16.2% of living donors KT (LDKT) in the USA and 8% in Europe. The results are similar to other LDKT. It is a promising alternative especially for highly sensitized recipients, who tend to accumulate on the waitlist. KPD is not limited to developed countries, as excellent results were already published in India in 2014. In Guatemala, the first LDKT through KPD was performed in 2011. However, the practice remains limited to isolated cases in Latin America. Conclusion: KPD programs with different dimensions, acceptance rules and allocation criteria are being developed and expanded worldwide to meet the demands of patients. The rise in transplantability brought about by KPD mostly meets the needs of highly sensitized patients. The Brazilian transplant program is mature enough to accept the challenge of starting its KPD program, intended primarily to benefit patients who have a low probability of receiving a transplant from a deceased donor.

Resumo Introdução: O transplante renal (TxR) é sabidamente o melhor tratamento para doença renal crônica. No Brasil, mais de 26 mil pacientes aguardam em lista atualmente. A doação renal pareada (DRP) oferece a um par de doador/receptor incompatível a possibilidade de trocar com outro par na mesma situação, representando uma estratégia para aumentar o número de TxR. Discussão: A DRP deixou de ser apenas uma ideia há mais de 20 anos. Atualmente é responsável por 16,2% dos TxR com doador vivo (TxRDV) nos EUA e 8% na Europa. Os resultados são semelhantes a outros TxRDV. Essa modalidade representa uma alternativa promissora, especialmente para os receptores hipersensibilizados que tendem a se acumular em lista de espera. A DRP não está limitada a países desenvolvidos. Em 2014, a Índia já publicava excelentes resultados. Na Guatemala, o primeiro TxRDV através de DRP aconteceu em 2011. Porém, a prática permanece limitada a casos isolados na América Latina. Conclusão: Programas de DRP com diferentes dimensões, regras para aceitação e critérios para alocação estão sendo desenvolvidos e expandidos mundialmente com o objetivo de atender às demandas dos pacientes. O aumento na capacidade de transplantar trazido pela DRP vem ao encontro especialmente das necessidades dos pacientes hipersensibilizados. O programa de TxR brasileiro tem maturidade para assumir o desafio de iniciar o programa de DRP, com o objetivo de beneficiar principalmente seus pacientes que estão em maior desvantagem por apresentarem baixas chances de transplante com doadores falecidos.

The impact of mTOR inhibitors in the regression of left ventricular hypertrophy in elderly kidney transplant recipients.

End-stage kidney disease is frequently associated with left ventricular hypertrophy (LVH), a condition more prevalent in the elderly, that may increase mortality after renal transplantation (RTx). Previous studies suggested that mTOR inhibitors (mTORi) can improve LVH, but this has never been tested in elderly kidney transplant recipients. In this prospective randomized clinical trial, we analyzed the impact of Everolimus (EVL) on the reversal of LVH after RTx in elderly recipients (≥60 years) submitted to different immunosuppressive regimens: EVL/lowTacrolimus (EVL group, n = 53) or mycophenolate sodium/regularTacrolimus (MPS group, n = 47). Patients performed echocardiograms (Echo) up to 3 months after RTx and then annually. At baseline, mean age was 65±3 years in both groups and LVH was observed in 63.6% of patients in EVL group and in 61.8% of MPS group. Last Echo was performed at mean time of 47 and 49 months after RTx in EVL and MPS groups, respectively (P = .34). LVH regression was observed in 23.8% (EVL group) and 19% (MPS group) of patients (P = 1.00). Mean eGFR, blood pressure, and use of RAS blockers were similar between groups throughout follow-up. EVL did not improve LVH in this cohort, and this lack of benefit may be attributed to concomitant use of TAC, senescence, or both.

Association Between Total Cell Free DNA and SARS-CoV-2 In Kidney Transplant Patients: A Preliminary Study.

BACKGROUND: Kidney transplant (KT) recipients are at high risk for developing severe COVID-19. Lowering immunosuppression levels in KT recipients with COVID-19 encourages native immune responses but can raise the risk of rejection. Donor-derived cell-free DNA (dd-cfDNA), reported as a fraction of total cfDNA, is a proven biomarker for KT rejection. Total cfDNA levels are elevated in patients with COVID-19, which may depress dd-cfDNA fractions, potentially leading to missed rejections. METHODS: A retrospective analysis of 29 KT recipients hospitalized with COVID-19 between April and November 2020 examined total and dd-cfDNA levels. Blood samples were collected after onset of COVID-19, with follow-up samples collected from a subset of patients, when infection had likely subsided. RESULTS: After COVID-19 diagnosis, the median total cfDNA level was elevated (7.9 multiples of median [MoM]). A significant decrease in total cfDNA levels was observed between the first and second time points (6.2 MoM, 1.0 MoM; P <001). A significant positive association was identified between total cfDNA levels and COVID-19 severity (P = .02; R2 = .19). Two patients with biopsy-proven acute cellular rejection had dd-cfDNA fractions below the 1% cutoff for rejection (0.20% and 0.78%), with elevated total cfDNA levels of 7.9 MoM and 41.8 MoM, respectively. CONCLUSIONS: In this preliminary study, total cfDNA levels were elevated in KT patients with COVID-19, subsiding after resolution of infection. High total cfDNA levels may confound dd-cfDNA results, leading to failure to identify rejection. Considering total cfDNA levels is important in interpretation of dd-cfDNA tests for assessment of rejection in KT patients with COVID-19 or other infection.

Performance of two methods of carbapenem-resistant Enterobacterales surveillance on a kidney transplant ward: selective culture of and real-time PCR directly from rectal swabs.

BACKGROUND: Infection with carbapenem-resistant Enterobacterales (CRE) is associated with a high mortality rate in kidney transplant recipients, and colonization with CRE is one of the major risk factors for CRE infection. There is, therefore, a need to improve the capacity to detect colonization with CRE among inpatients. METHODS: In this prospective study, we compared the performance of real-time PCR for carbapenemase directly from rectal swabs with that of conventional CRE surveillance culture in all patients admitted to a kidney transplant ward between February 2019 and March 2020. Surveillance culture and real-time PCR were performed at admission and weekly until hospital discharge. Two perineum-rectal swabs were collected: one for culture and one for PCR. RESULTS: We collected 905 paired samples for CRE surveillance from 399 patients, of whom 347 (87.0%) were kidney transplant recipients and 52 were waiting list patients. CRE was detected by culture and/or PCR in 75 patients (18.8%). Positivity for CRE was identified by PCR in 62 (15.5%) of the 399 patients and by culture in 55 (13.8%); 20 (5.0%) of the patients tested positive only on PCR, and 13 (3.3%) tested positive only on culture. The most common carbapenemase and species were, respectively, blaKPC (in 85.5%) and Klebsiella pneumoniae (in 80.0%). Infection with CRE occurred in 21.6% of the colonized patients, those cases occurred only among kidney transplant recipients. None of the patients who tested negative on culture developed CRE infection. CONCLUSION: In conclusion, the two methods are complementary and could be useful in a scenario of high CRE prevalence.

Desensitization using IVIG alone for living-donor kidney transplant: impact on donor-specific antibodies.

INTRODUCTION: Sensitization to human leukocyte antigen is a barrier to. Few data have been published on desensitization using polyvalent human intravenous immunoglobulin (IVIG) alone. METHODS: We retrospectively reviewed the of 45 patients with a positive complement-dependent cytotoxicity crossmatch (CDCXM) or flow cytometry crossmatch (FCXM) against living donors from January 2003 to December 2014. Of these, 12 were excluded. Patients received monthly IVIG infusions (2 g/kg) only until they had a negative T-cell and B-cell FCXM. RESULTS: During the 33 patients, 22 (66.7%) underwent living donor kidney transplantation, 7 (21.2%) received a deceased donor graft, and 4 (12.1%) did not undergo transplantation. The median class I and II panel reactive antibodies for these patients were 80.5% (range 61%-95%) and 83.0% (range 42%-94%), respectively. Patients (81.8%) had a positive T-cell and/or B-cell CDCXM and 4 (18.2%) had a positive T-cell and/or B-cell FCXM. Patients underwent transplantation after a median of 6 (range 3-16). The median donor-specific antibody mean fluorescence intensity sum was 5057 (range 2246-11,691) before and 1389 (range 934-2492) after desensitization (p = 0.0001). Mean patient follow-up time after transplantation was 60.5 (SD, 36.8) months. Nine patients (45.0%). Death-censored graft survival at 1, 3, and 5 years after transplant was 86.4, 86.4, and 79.2%, respectively and patient survival was 95.5, 95.5, and 83.7%, respectively. CONCLUSIONS: Desensitization using IVIG alone is an effective strategy, allowing successful transplantation in 87.9% of these highly sensitized patients.

Increasing transplantability in Brazil: time to discuss Kidney Paired Donation.

INTRODUCTION: Kidney transplantation (KT) is the best treatment for chronic kidney disease. In Brazil, there are currently more than 26 thousand patients on the waitlist. Kidney Paired Donation (KPD) offers an incompatible donor-recipient pair the possibility to exchange with another pair in the same situation, it is a strategy to raise the number of KT. DISCUSSION: KPD ceased being merely an idea over 20 years ago. It currently accounts for 16.2% of living donors KT (LDKT) in the USA and 8% in Europe. The results are similar to other LDKT. It is a promising alternative especially for highly sensitized recipients, who tend to accumulate on the waitlist. KPD is not limited to developed countries, as excellent results were already published in India in 2014. In Guatemala, the first LDKT through KPD was performed in 2011. However, the practice remains limited to isolated cases in Latin America. CONCLUSION: KPD programs with different dimensions, acceptance rules and allocation criteria are being developed and expanded worldwide to meet the demands of patients. The rise in transplantability brought about by KPD mostly meets the needs of highly sensitized patients. The Brazilian transplant program is mature enough to accept the challenge of starting its KPD program, intended primarily to benefit patients who have a low probability of receiving a transplant from a deceased donor.

Invasive coronary artery disease assessment and myocardial infarction in patients on renal replacement therapy.

BACKGROUND: The incidence of myocardial infarction (MI) is elevated in patients receiving renal replacement therapy (RRT). We hypothesized that an invasive strategy of assessment of coronary artery disease (CAD) will identify patients more prone to developing MI. METHODS: This was a single-center observational cohort study that included 1678 patients receiving RRT (hemodialysis and renal transplantation) assessed for CAD prospectively and analyzed retrospectively. Endpoints were the incidence of MI and death. RESULTS: The median follow-up was 43 months, and 180 patients experienced an MI with a mortality rate of 74%. Multivariate analysis showed that diabetes (HR 1.633; 95% CI 1.165-2.289), prior MI (HR 1.724; 95% CI 1.153-2.579), and CAD (HR 2.073; 95% CI 1.400-3.071) were predictors of MI. Altered myocardial scan did not correlate with MI. At the discretion of the attending physicians, 20/180 patients (11%) underwent coronary intervention that was associated with a higher cumulative survival (Log-rank 0.007). CONCLUSION: Patients with CAD suffered an MI more frequently, independently of symptoms and risk factors for MI, including noninvasive testing. Because of the elevated rate of the lethality of MI, invasive coronary studies may be indicated in select patients on RRT. Once an MI occurs, our data suggest that an invasive therapeutic approach is warranted.

Diastolic and systolic left ventricular dysfunction and mortality in chronic kidney disease patients on haemodialysis.

AIMS: Left ventricular diastolic dysfunction (LVDD) and LV systolic dysfunction (LVSD) are prevalent in CKD, but their prognostic relevance is debatable. We intent to verify whether LVDD and LVSD are independently predictive of all-cause mortality and if they have comparable or different effects on outcomes. METHODS: A retrospective analysis was conducted of the echocardiographic data of 1285 haemodialysis patients followed up until death or transplantation. LVDD was classified into 4 grades of severity. Endpoint was all-cause mortality. RESULTS: During a follow-up of 30 months, 419/1285 (33%) patients died, 224 (53%) due to CV events. LVDD occurred in 75% of patients, grade 1 DD was the prevalent diastolic abnormality, and pseudonormal pattern was the predominant form of moderate-severe DD. Moderate-severe LVDD (HR 1.379, CI% 1.074-1.770) and LVSD (HR 1.814, CI% 1.265-2.576) independently predicted death; a graded, progressive association was found between LVDD categories and the risk of death; and the impact of isolated severe-moderate LVDD on the risk of death was comparable to that exercised by isolated compromised LV systolic function. CONCLUSION: Moderate-severe LVDD and LVSD were independently associated with a higher probability of death and had a similar impact on survival. A progressive association was observed between LVDD grades and mortality.

An Open-label Randomized Controlled Parallel-group Pilot Study Comparing the Immunogenicity of a Standard-, Double-, and Booster-dose Regimens of the 2014 Seasonal Trivalent Inactivated Influenza Vaccine in Kidney Transplant Recipients.

BACKGROUND: Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. METHODS: We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV), and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59), and BDTIIV regimens (58). Antibody titers were determined by hemagglutination inhibition at enrollment and 21 d postvaccination. Seroprotection rates (SPRs), seroconversion rates (SCRs), and geometric mean ratios (GMRs) were analyzed separately for participants with low (<1:40) and high (≥1:40) prevaccination antibody titers. RESULTS: Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided postvaccination blood samples. In the subgroup with high prevaccination antibody titers, all vaccination regimens induced SPR > 70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low prevaccination antibody titers, DDTIIV and BDTIIV regimens induced adequate SCR > 40% and GMR > 2.5 for all antigens, whereas SDTIIV achieved the same outcomes only for influenza B. SPRs were >70% only after DDTIIV (A/H1N1-77.8%) and BDTIIV (A/H3N2-77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR = 2.58; P = 0.021) and A/H3N2 (PR = 2.21; P = 0.004), whereas DDTIIV independently increased seroprotection to A/H1N1 (PR = 2.59; P = 0.021). CONCLUSIONS: Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

An open-label randomized controlled parallel-group pilot study comparing the immunogenicity of a standard-, double- and booster-dose regimens of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients

Background: Immunogenicity of influenza vaccine in transplant recipients is suboptimal and alternative vaccination regimens are necessary. Methods: We compared the immunogenicity of a standard-dose trivalent inactivated influenza vaccination (SDTIIV), double-dose trivalent inactivated influenza vaccination (DDTIIV) and booster-dose trivalent inactivated influenza vaccination (BDTIIV) of the 2014 seasonal trivalent inactivated influenza vaccine in kidney transplant recipients. We randomized 176 participants to SDTIIV (59), DDTIIV (59) and BDTIIV regimens (58). Antibody titres were determined by hemagglutination inhibition at enrollment and 21 days post-vaccination. Seroprotection rates (SPR), seroconversion rates (SCR) and geometric mean ratios (GMR) were analyzed separately for participants with low (<1:40) and high (≥1:40) pre-vaccination antibody titres. Results: Vaccination was confirmed for 172 participants. Immunogenicity analysis was done for 149 participants who provided post-vaccination blood samples. In the subgroup with high pre-vaccination antibody titres, all vaccination regimens induced SPR >70% to all antigens, but SCR and GMR were below the recommendations. In the subgroup with low pre-vaccination antibody titres, DDTIIV and BDTIIV regimens induced adequate SCR >40% and GMR >2,5 for all antigens, while SDTIIV achieved the same outcomes only for influenza B. SPR were >70% only after DDTIIV (A/H1N1 - 77.8%) and BDTIIV (A/H3N2 - 77.8%). BDTIIV regimen independently increased seroprotection to A/H1N1 (PR=2.58; p=0.021) and A/H3N2 (PR=2.21; p=0.004), while DDTIIV independently increased seroprotection to A/H1N1 (PR=2.59; p=0.021). Conclusion: Our results suggest that DDTIIV and BDTIIV regimens are more immunogenic than SDTIIV, indicating the need for head-to-head multicenter clinical trials to further evaluate their efficacy.

Comparative analysis of kidney transplant costs related to recovery of renal function after the procedure / Análise comparativa dos custos do transplante renal relacionados à recuperação da função renal após o procedimento

Abstract Introduction: The number of kidney transplants (KTx) is increasing in Brazil and, consequently, the costs of this procedure increase the country's health budget. We retrospectively evaluated the data of kidney transplant procedures until hospital discharge, according to kidney function recovery after the procedure. Methods: Retrospective analysis of the non-sensitized, 1st KTx from deceased donors performed between Jan/2010 to Dec/2017. Results: Out of the 1300 KTx from deceased donors performed in this period, 730 patients were studied and divided into 3 groups: Immediate Renal Function (IRF) - decrease in serum creatinine ≥ 10% on two consecutive days; Delayed Graft Function (DGF) - decrease in serum creatinine <10% on two consecutive days, without the need for dialysis, and Dialysis (D) - need for dialysis during the first week. Patients in group D stayed longer in the hospital compared to DGF and IRF (21, 11 and 8 days respectively, p < 0.001). More D patients (21%) were admitted to the ICU and performed a greater number of laboratory tests (p < 0.001) and renal biopsies (p < 0.001), in addition to receiving a higher amount of immunosuppressants. Total hospital costs were higher in group D and DGF compared to IRF (U$ 7.021,48; U$ 3.603,42 and U$ 2.642,37 respectively, p < 0.001). Conclusion: The costs of the transplant procedure is impacted by the recovery of kidney function after the transplant. The reimbursement for each of these different kidney function outcomes should be individualized in order to cover their real costs.

Resumo Introdução: O número de transplantes renais (KTx, do inglês kidney transplant) está aumentando no Brasil e, consequentemente, os custos deste procedimento aumentam o orçamento de saúde do país. Avaliamos retrospectivamente dados dos procedimentos de transplantes renais até a alta hospitalar, de acordo com a recuperação da função renal após o procedimento. Métodos: Análise retrospectiva dos 1º KTx de doadores falecidos, não sensibilizados, realizados entre Jan/2010 a Dez/2017. Resultados: Dos 1300 KTx de doadores falecidos realizados neste período, 730 pacientes foram estudados e divididos em 3 grupos: Função Renal Imediata (FRI) - diminuição na creatinina sérica ≥ 10% em dois dias consecutivos; Função Retardada do Enxerto (FRE) - diminuição na creatinina sérica <10% em dois dias consecutivos, sem necessidade de diálise, e Diálise (D) - necessidade de diálise durante a primeira semana. Pacientes no grupo D permaneceram mais tempo no hospital em comparação com FRE e FRI (21, 11 e 8 dias dias respectivamente, p < 0,001). Mais pacientes do grupo D (21%) foram admitidos na UTI e realizaram um maior número de testes laboratoriais (p < 0,001) e biópsias renais (p < 0,001), além de receberem uma quantidade maior de imunossupressores. Os custos hospitalares totais foram mais elevados nos grupos D e FRE em comparação com FRI (U$ 7.021,48; U$ 3.603,42 e U$ 2.642,37 respectivamente, p < 0,001). Conclusão: Os custos do procedimento de transplante são impactados pela recuperação da função renal após o transplante. O reembolso para cada um desses diferentes desfechos da função renal deve ser individualizado a fim de cobrir seus custos reais.

Recurrence of IgA Nephropathy after Kidney Transplantation in Adults.

BACKGROUND AND OBJECTIVES: In patients with kidney failure due to IgA nephropathy, IgA deposits can recur in a subsequent kidney transplant. The incidence, effect, and risk factors of IgA nephropathy recurrence is unclear, because most studies have been single center and sample sizes are relatively small. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a multicenter, international, retrospective study to determine the incidence, risk factors, and treatment response of recurrent IgA nephropathy after kidney transplantation. Data were collected from all consecutive patients with biopsy-proven IgA nephropathy transplanted between 2005 and 2015, across 16 "The Post-Transplant Glomerular Disease" study centers in Europe, North America, and South America. RESULTS: Out of 504 transplant recipients with IgA nephropathy, recurrent IgA deposits were identified by kidney biopsy in 82 patients; cumulative incidence of recurrence was 23% at 15 years (95% confidence interval, 14 to 34). Multivariable Cox regression revealed a higher risk for recurrence of IgA deposits in patients with a pre-emptive kidney transplant (hazard ratio, 3.45; 95% confidence interval, 1.31 to 9.17) and in patients with preformed donor-specific antibodies (hazard ratio, 2.59; 95% confidence interval, 1.09 to 6.19). After kidney transplantation, development of de novo donor-specific antibodies was associated with subsequent higher risk of recurrence of IgA nephropathy (hazard ratio, 6.65; 95% confidence interval, 3.33 to 13.27). Immunosuppressive regimen was not associated with recurrent IgA nephropathy in multivariable analysis, including steroid use. Graft loss was higher in patients with recurrence of IgA nephropathy compared with patients without (hazard ratio, 3.69; 95% confidence interval, 2.04 to 6.66), resulting in 32% (95% confidence interval, 50 to 82) graft loss at 8 years after diagnosis of recurrence. CONCLUSIONS: In our international cohort, cumulative risk of IgA nephropathy recurrence increased after transplant and was associated with a 3.7-fold greater risk of graft loss.