Identifying Factors Predicting Kidney Graft Survival in Chile Using Elastic-Net-Regularized Cox's Regression.

Background and Objectives: We developed a predictive statistical model to identify donor-recipient characteristics related to kidney graft survival in the Chilean population. Given the large number of potential predictors relative to the sample size, we implemented an automated variable selection mechanism that could be revised in future studies as more national data is collected. Materials and Methods: A retrospective multicenter study was conducted to analyze data from 822 adult kidney transplant recipients from adult donors between 1998 and 2018. To the best of our knowledge, this is the largest kidney transplant database to date in Chile. A procedure based on a cross-validated regularized Cox regression using the Elastic Net penalty was applied to objectively identify predictors of death-censored graft failure. Hazard ratios were estimated by adjusting a multivariate Cox regression with the selected predictors. Results: Seven variables were associated with the risk of death-censored graft failure; four from the donor: age (HR = 1.02, 95% CI: 1.00-1.03), male sex (HR = 0.64, 95% CI: 0.46-0.90), history of hypertension (HR = 1.49, 95% CI: 0.98-2.28), and history of diabetes (HR = 2.04, 95% CI: 0.97-4.29); two from the recipient: years on dialysis log-transformation (HR = 1.29, 95% CI: 0.99-1.67) and history of previous solid organ transplantation (HR = 2.02, 95% CI: 1.18-3.47); and one from the transplant: number of HLA mismatches (HR = 1.13, 95% CI: 0.99-1.28). Only the latter is considered for patient prioritization in deceased kidney allocation in Chile. Conclusions: A risk model for kidney graft failure was developed and trained for the Chilean population, providing objective criteria which can be used to improve efficiency in deceased kidney allocation.

Clinical Efficacy of SARS-CoV-2 Vaccination in Hemodialysis Patients.

Introduction: The COVID-19 pandemic is a global public health problem. Patients with end-stage renal disease on hemodialysis are at a higher risk of infection and mortality than the general population. Worldwide, a vaccination campaign has been developed that has been shown to reduce severe infections and deaths in the general population. However, there are currently limited data on the clinical efficacy of vaccinations in the hemodialysis population. Methods: A national multicenter observational cohort was performed in Chile to evaluate the clinical efficacy of anti-SARS-CoV-2 vaccination in end-stage renal disease patients on chronic hemodialysis from February 2021 to August 2021. In addition, the BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines were evaluated. The efficacy of vaccination in preventing SARS-CoV-2 infection, hospitalizations, and deaths associated with COVID-19 was determined. Results: A total of 12,301 patients were evaluated; 10,615 (86.3%) received a complete vaccination (2 doses), 490 (4.0%) received incomplete vaccination, and 1196 (9.7%) were not vaccinated. During follow-up, 1362 (11.0%) patients developed COVID-19, and 150 died (case fatality rate: 11.0%). The efficacy of the complete vaccination in preventing infection was 18.1% (95% confidence interval [CI]:11.8-23.8%), and prevention of death was 66.0% (95% CI:60.6-70.7%). When comparing both vaccines, BNT162b2 and CoronaVac were effective in reducing infection and deaths associated with COVID-19. Nevertheless, the BNT162b2 vaccine had higher efficacy in preventing infection (42.6% vs. 15.0%) and deaths (90.4% vs. 64.8%) compared to CoronaVac. Conclusion: The results of our study suggest that vaccination against SARS-CoV-2 in patients on chronic hemodialysis was effective in preventing infection and death associated with COVID-19.

Online Continuing Medical Education for the Latin American Nephrology Community.

A continuing medical education (CME) course was implemented for Latin American nephrologists in 2013. The topic was Immunopathology in native and transplanted kidneys. The course was given in Spanish and Portuguese. The activities included a distance education seven-week asynchronous online modality with multiple educational strategies. Thirty hours of study workload were estimated to complete the course. Four hundred and ninety-eight physicians coming from 18 countries registered for the course; 442 of them participated in it. Of those who participated, 51% received a certificate of completion and 29% a certificate of participation. Sixty-five percent of registrants participated in the case discussions. Eighty-six percent were very satisfied and 13% were satisfied. Lack of time to devote to the course was the main limitation expressed (62%), while Internet access or difficulties in the use of technology were considered by only 12 and 6% of participants, respectively. There was a significant increase in knowledge between before and after the course; the average grade increased from 64 to 83%. In conclusion, technology-enabled education demonstrated potential to become an instrument for Latin American nephrologists.

MicroRNA Profiling of B Cell Subsets from Systemic Lupus Erythematosus Patients Reveals Promising Novel Biomarkers.

MicroRNAs control the differentiation and function of B cells, which are considered key elements in the pathogenesis of systemic lupus erythematosus (SLE). However, a common micro(mi)RNA signature has not emerged since published data includes patients of variable ethnic background, type of disease, and organ involvement, as well as heterogeneous cell populations. Here, we aimed at identifying a miRNA signature of purified B cells from renal and non-renal severe SLE patients of Latin American background, a population known to express severe disease. Genome-wide miRNA expression analyses were performed on naive and memory B cells and revealed two categories of miRNA signatures. The first signature represents B cell subset-specific miRNAs deregulated in SLE: 11 and six miRNAs discriminating naive and memory B cells of SLE patients from healthy controls (HC), respectively. Whether the miRNA was up or down-regulated in memory B cells as compared with naive B cells in HC, this difference was abolished in SLE patients, and vice versa. The second signature identifies six miRNAs associated with specific pathologic features affecting renal outcome, providing a further understanding for SLE pathogenesis. Overall, the present work provided promising biomarkers in molecular diagnostics for disease severity as well as potential new targets for therapeutic intervention in SLE.

[Bone mineral metabolism in patients with chronic kidney disease on dialysis in Southern Metropolitan Santiago]. / Caracterización del metabolismo óseo mineral en pacientes con enfermedad renal crónica en hemodiálisis en el Servicio de Salud Metropolitano Sur, Santiago de Chile.

BACKGROUND: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a condition of dialysis patients associated with both morbidity and mortality. Management is based on clinical guidelines with goals that are hard to comply with. AIM: To describe and compare biochemical variables associated with this disorder in two different time periods. MATERIAL AND METHODS: Revision of medical records of 814 patients (49% females) dialyzed during 2009 and 1018 patients (48% females), dialyzed during 2012 in Southern Metropolitan Santiago. Information about serum calcium, phosphorus, parathyroid hormone (PTH) and albumin was retrieved. RESULTS: Median PTH values in 2009 and 2012 were 222.5 and 353.5 pg/ml respectively (p < 0.05). The figures for serum calcium corrected by albumin were 9.0 and 8.5 mg/dl respectively (p < 0.05). The figures for phosphorus were 4.7 and 5.0 mg/dl respectively (p < 0.05). The Calcium x Phosphorus product was 41.4 and 42.5 mg²/dl² (p < 0.05). Of note, the proportion patients with serum calcium below recommended levels (< 8.4 mg/dl) increased from 16% to 40% from 2009 to 2012. The proportion of patients with biochemical variables within recommended ranges was lower in 2012 than in 2009. CONCLUSIONS: There was a low proportion of patients with bone metabolism parameters within ranges recommended by clinical guidelines. These parameters were worst in 2012.

Caracterización del metabolismo óseo mineral en pacientes con enfermedad renal crónica en hemodiálisis en el Servicio de Salud Metropolitano Sur, Santiago de Chile / Bone mineral metabolism in patients with chronic kidney disease on dialysis in Southern Metropolitan Santiago

Background: Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) is a condition of dialysis patients associated with both morbidity and mortality. Management is based on clinical guidelines with goals that are hard to comply with. Aim: To describe and compare biochemical variables associated with this disorder in two different time periods. Material and Methods: Revision of medical records of 814 patients (49% females) dialyzed during 2009 and 1018 patients (48% females), dialyzed during 2012 in Southern Metropolitan Santiago. Information about serum calcium, phosphorus, parathyroid hormone (PTH) and albumin was retrieved. Results: Median PTH values in 2009 and 2012 were 222.5 and 353.5 pg/ml respectively (p < 0.05). The figures for serum calcium corrected by albumin were 9.0 and 8.5 mg/dl respectively (p < 0.05). The figures for phosphorus were 4.7 and 5.0 mg/dl respectively (p < 0.05). The Calcium x Phosphorus product was 41.4 and 42.5 mg²/dl² (p < 0.05). Of note, the proportion patients with serum calcium below recommended levels (< 8.4 mg/dl) increased from 16% to 40% from 2009 to 2012. The proportion of patients with biochemical variables within recommended ranges was lower in 2012 than in 2009. Conclusions: There was a low proportion of patients with bone metabolism parameters within ranges recommended by clinical guidelines. These parameters were worst in 2012.

Gastrointestinal (GI)-Specific patient reported outcomes instruments differentiate between renal transplant patients with or without GI symptoms: results from a South American cohort.

BACKGROUND: Immunosuppressive therapies have burdensome side effects which may lead to sub-therapeutic dosing and non-compliance. Patients on different immunosuppressant regimens may feel less bothered by Gastrointestinal (GI) side effects or report better health-related quality of life (HRQL). We evaluated the reliability and validity of two GI-specific outcome instruments (Gastrointestinal Symptom Rating Scale (GSRS; higher scores = increased severity) and Gastrointestinal Quality of Life Index (GIQLI; higher scores = better GI-specific HRQL)) in renal transplant patients in South America. METHODS: Data from 5 South American centers participating in an international, longitudinal, observational study were analyzed. Patients were > or = 1 month post transplant and on mycophenolate mofetil (MMF) and a calcineurin inhibitor. Patients completed the GSRS, GIQLI, and Psychological General Well-Being (PGWB; higher scores = better HRQL) Index at baseline and at 4-6 weeks. Internal consistency, test-retest reliability and construct and discriminant validity were assessed. RESULTS: Sixty-two participants were enrolled. Mean age was 42 years; mean time since transplant was 3.3 years; 57% were male; 65% received a deceased organ transplant and 68%had GI events. The GSRS and GIQLI demonstrated high internal consistency (Cronbach's alphas 0.72-0.96). Test-retest reliability was adequate (intraclass correlation coefficient > 0.6) for all GIQLI subscales and all GSRS subscales except Diarrhea and Reflux syndrome. Correlations between the GSRS and PGWB were moderate (range: -0.21 to -0.53, all p < 0.001 except 6 correlations with p < 0.05); correlations between the GIQLI and PGWB were higher (range: 0.36 to 0.71 p < 0.001), indicating good construct validity. The GSRS and GIQLI demonstrated good discriminant validity, as they clinically and statistically distinguished between patients with and without GI complaints and among patients with varying GI complication severity. Patients with GI complaints reported higher GSRS scores than patients without complaints (all p < 0.001). GIQLI scores were lower in patients with GI complaints than patients without complaints (all p < 0.001). The GSRS and GIQLI differentiated among patients with four GI severity levels (overall Kruskall-Wallis test p < 0.001, except for one scale). The GSRS and GIQLI are acceptable for use in South American renal transplant patients. These two instruments demonstrate adequate reliability and validity. Patients with GI complaints reported poor HRQL and strategies are needed to improve patients' HRQL.