Renal lipotoxicity: Insights from experimental models.

In recent decades, there has been a progressive increase in the prevalence of obesity and chronic kidney disease. Renal lipotoxicity has been associated with obesity. Although lipids play fundamental physiological roles, the accumulation of lipids in kidney cells may cause dysfunction and/or renal fibrosis. Adipose tissue that exceeds their lipid storage capacity begins to release triglycerides into the bloodstream that can get stored in several organs, including the kidneys. The mechanisms underlying renal lipotoxicity involve intracellular lipid accumulation and organelle dysfunction, which trigger oxidative stress and inflammation that consequently result in insulin resistance and albuminuria. However, the specific pathways involved in renal lipotoxicity have not yet been fully understood. We aimed to summarize the current knowledge on the mechanisms by which lipotoxicity affects the renal morphology and function in experimental models of obesity. The accumulation of fatty acids in tubular cells has been described as the main mechanism of lipotoxicity; however, lipids and their metabolism also affect the function and the survival of podocytes. In this review, we presented indication of mitochondrial, lysosomal and endoplasmic reticulum alterations involved in kidney damage caused by obesity. The kidney is vulnerable to lipotoxicity, and studies of the mechanisms underlying renal injury caused by obesity can help identify therapeutic targets to control renal dysfunction.

Adherence to antihypertensive medication after referral to secondary healthcare: A prospective cohort study.

BACKGROUND: Nonadherence (NAd) to antihypertensive medication is associated with lack of blood pressure control and worsened long-term outcomes. Increased access to a programme for high-risk cardiovascular patients has the potential to reduce NAd and improve clinical outcomes. We evaluated implementation NAd prevalence and risk factors among severely hypertensive patients after 12-month-long access to secondary healthcare centres. METHODS: The Morisky Green Levine Scale (MGLS) was used to analyse antihypertensive medication NAd in a prospective cohort of 485 patients. Logistic regression models evaluated the influence of ecological model factors on NAd. RESULTS: The majority of patients were female, had low health literacy, a low family income and a mean age of 61.8 ± 12.5 years. Prevalence of NAd fell from 57.1% at programme entry to 28.3% (P < .001) at the end of the study. After access to a secondary healthcare centre, we observed better blood pressure control, an increase in the number of pills/day and a higher number of antihypertensive medications. Predictive variables of NAd were age (OR 1.027; CI 1.003-1.051; P = .023), low health literacy (OR 1.987; CI 1.009-3.913; P = .047), systolic blood pressure (OR 1.010; CI 1.003-1.021; P = .049), dosages ≥ 2 times/day (OR 1.941; CI 1.091-3.451; P = .024) and patient satisfaction with the healthcare team (OR 0.711; IC 0.516-0.980; P = .037). CONCLUSIONS: Greater access to health services is associated with a reduction in NAd to antihypertensive medication and better blood pressure control. NAd was correlated with modifiable variables such as treatment complexity and, for the first time, team satisfaction, suggesting that implementation of similar programmes may limit NAd in similar patient groups.

Chronic kidney disease progression in kidney transplant recipients: A focus on traditional risk factors.

Kidney transplant recipients are a subset of patients with chronic kidney disease (CKD) that remain at high risk for progression to dialysis and mortality. Recent advances in immunosuppression have only partially improved long-term graft and patient survival. Discovery of new immunosuppressive regimens is a slow and resource-intensive process. Hence, recognition and management of modifiable allogeneic and non-allogeneic risk factors for progression to CKD among kidney transplant recipients is of major interest for improving long-term outcomes. Graft survival is mainly determined by the quality of the allograft and by the patient's alloimmune response, which is influenced by human leukocyte antigen matching and the presence of donor-specific antibodies. Alloimmune responses manifest as acute and chronic forms of cell- and antibody-mediated rejection, which can be worsened by patient non-adherence or under-immunosuppression. However, donor and patient ages, glomerular disease recurrence, time on dialysis, pre-existing cardiovascular burden, medication side-effects and traditional risk factors, such as hypertension, proteinuria, anaemia, dyslipidaemia, diabetes and bone mineral disorder, which can ultimately lead to severe endothelial derangement, also contribute to graft loss and mortality. These traditional risk factors, common to pre-dialysis patients, often are considered of secondary importance when compared to alloimmunity and immunosuppression concerns. In this review article, we focus on the epidemiological, pathophysiological and therapeutic features of non-allogeneic traditional risk factors for CKD. We also discuss the benefit of adopting a multidisciplinary approach to pursue the same therapeutic targets recommended for pre-dialysis patients.

Prevalence and correlates of non-adherence to immunosuppressants and to health behaviours in patients after kidney transplantation in Brazil - the ADHERE BRAZIL multicentre study: a cross-sectional study protocol.

BACKGROUND: Non-adherence to immunosuppressive therapy is a prevalent risk factor for poor clinical and after kidney transplantation (KT), and has contributed to the lack of improvement in long-term graft survival over the past decade. Understanding the multilevel correlates and risk factors of non-adherence is crucial to determine the optimal level for planning interventions, namely at the patient, health care provider, KT centre, and health care system level. Brazil, having the largest public transplantation program in the world and with regional differences regarding access to health services and service implementation, is in a unique position to study this multilevel approach. Therefore, the Adhere Brazil Study (ADHERE BRAZIL) was designed to assess the prevalence and variability of non-adherence to immunosuppressants and to health behaviours among adult KT recipients in Brazil, and to assess the multilevel correlates of non-adherence to immunosuppressive medication. We describe the rationale, design, and methodology of the ADHERE BRAZIL study. METHODS/DESIGN: This is an observational, cross-sectional, multicentre study that includes 20 Brazilian KT centres. A stratified sampling approach is used, based on strata, with the following characteristics considered: geographical region and transplant activity (number of KTs per year). A random sample of patients (proportional to the size of the centre within each stratum) is selected from each centre. The prevalence of different health behaviours is assessed through self-report. The assessment of multilevel correlates of non-adherence is guided by the ecological model that considers factors at the level of the patient, health-care professional, and transplant centre, using established instruments or instruments developed for this study. Data will be collected over an 18-month period, with information obtained during the regular follow-up visits to the transplant outpatient clinic and directly entered into the Research Electronic Data Capture (RedCap) system. Data entry is performed by a trained professional who is part of the transplant team. The data collection began in December 2015. DISCUSSION: This multicentre study is the first to evaluate multilevel correlates of non-adherence in KT patients and will provide a reliable estimate of non-adherence in Brazilian KT patients. TRIAL REGISTRATION: ClinicalTrials.gov on 10/10/2013, NCT02066935 .

Self-efficacy beliefs, locus of control, religiosity and non-adherence to immunosuppressive medications in kidney transplant patients.

AIM: Adherence to immunosuppressive medication is essential for favourable kidney transplant outcomes. The present study aims to investigate how self-efficacy beliefs, health locus of control and religiosity are associated with adherence to immunosuppressives in post kidney transplant recipients. METHODS: This is a cross-sectional study with 88 recipients with more than 1 year after transplantation. Three methods were used to classify patients as adherent or non-adherent: Basel Assessment of Adherence Scale for Immunosuppressives - BAASIS, the collateral report and blood levels of immunosuppressive medications. Self-efficacy, health locus of control, and religiosity were evaluated applying General Perceived Self-Efficacy Scale, Multidimensional Health Locus of Control Scale and Duke University Religion Index, respectively. Non-adherence was modelled by uni- and multivariated analysis. RESULTS: Sixty-three percent of the patients were male, age 47.2 ± 12.9 years, and median post-transplant time 108.71 (49.0-266.0) months. We found 70.5% of patients were non-adherent through at least one method. Adherent patients presented higher self-efficacy scores (45.1 ± 4.9 vs 38.3 ± 8.6; P < 0.001) and higher intrinsic religiosity (14.0 ± 1.6 vs. 12.8 ± 2.5; P = 0.016) compared to the non-adherents. Organizational and non-organizational religiosity did not differ between these groups. By logistic regression, non-adherence was associated with lower self-efficacy (OR 0.81, IC 0.70-0.92, P = 0.002), chance locus of control (OR 1.23, IC 1.04-1.45, P = 0.016) and lower intrinsic religiosity (OR 0.56, IC 0.38-0.84, P = 0.006). CONCLUSION: Our study showed that self-efficacy, chance locus of control, and intrinsic religiosity were associated with non-adherence to immunosuppressives. A broader perception of the kidney transplant patient´s integrality can help health professionals to design strategies to promote adherence in this population.

Factors Associated With Physical Inactivity of Recipients of a Kidney Transplant: Results From the ADHERE BRAZIL Multicenter Study.

OBJECTIVE: Physical activity is recommended for recipients of a kidney transplant. However, ADHERE BRAZIL study found a high prevalence (69%) of physical inactivity in Brazilian recipients of a kidney transplant. To tackle this behavior, a broad analysis of barriers is needed. This study aimed to identify factors (patient and transplant center levels) associated with physical inactivity among recipients of a kidney transplant. METHODS: This was a subproject of the ADHERE BRAZIL study, a cross-sectional, multicenter study of 1105 recipients of a kidney transplant from 20 kidney transplant centers. Using a multistage sampling method, patients were proportionally and randomly selected. Applying the Brief Physical Activity Assessment questionnaire, patients were classified as physically active (≥150 min/wk) or physically inactive (<150 min/wk). On the basis of an ecological model, 34 factors associated with physical inactivity were analyzed by sequential logistic regression. RESULTS: At the patient level, physical inactivity was associated with smoking (odds ratio = 2.43; 95% CI = 0.97-6.06), obesity (odds ratio = 1.79; 95% CI = 1.26-2.55), peripheral vascular disease (odds ratio = 3.18; 95% CI = 1.20-8.42), >3 posttransplant hospitalizations (odds ratio = 1.58; 95% CI = 1.17-2.13), family income of >1 reference salary ($248.28 per month; odds ratio = 0.66; 95% CI = 0.48-0.90), and student status (odds ratio = 0.58; 95% CI = 0.37-0.92). At the center level, the correlates were having exercise physiologists in the clinical team (odds ratio = 0.54; 95% CI = 0.46-0.64) and being monitored in a teaching hospital (undergraduate students) (odds ratio = 1.47; 95% CI = 1.01-2.13). CONCLUSIONS: This study identified factors associated with physical inactivity after kidney transplantation that may guide future multilevel behavioral change interventions for physical activity. IMPACT: In a multicenter sample of recipients of a kidney transplant with a prevalence of physical inactivity of 69%, we found associations between this behavior and patient- and center-level factors. At the patient level, the chance of physical inactivity was positively associated with smoking, obesity, and patient morbidity (peripheral vascular disease and hospitalization events after kidney transplantation). Conversely, a high family income and a student status negatively correlated with physical inactivity. At the center level, the presence of a dedicated professional to motivate physical activity resulted in a reduced chance of physical inactivity. A broad knowledge of barriers associated with physical inactivity can allow us to identify patients at a high risk of not adhering to the recommended levels of physical activity.

Transcultural adaptation and initial validation of Brazilian-Portuguese version of the Basel assessment of adherence to immunosuppressive medications scale (BAASIS) in kidney transplants.

BACKGROUND: Transplant recipients are expected to adhere to a lifelong immunosuppressant therapeutic regimen. However, nonadherence to treatment is an underestimated problem for which no properly validated measurement tool is available for Portuguese-speaking patients. We aimed to initially validate the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS®) to accurately estimate immunosuppressant nonadherence in Brazilian transplant patients. METHODS: The BAASIS® (English version) was transculturally adapted and its psychometric properties were assessed. The transcultural adaptation was performed using the Guillemin protocol. Psychometric testing included reliability (intraobserver and interobserver reproducibility, agreement, Kappa coefficient, and the Cronbach's alpha) and validity (content, criterion, and construct validities). RESULTS: The final version of the transculturally adapted BAASIS® was pretested, and no difficulties in understanding its content were found. The intraobserver and interobserver reproducibility variances (0.007 and 0.003, respectively), the Cronbach's alpha (0.7), Kappa coefficient (0.88) and the agreement (95.2%) suggest accuracy, preciseness and reliability. For construct validity, exploratory factorial analysis demonstrated unidimensionality of the first three questions (r = 0.76, r = 0.80, and r = 0.68). For criterion validity, the adapted BAASIS® was correlated with another self-report instrument, the Measure of Adherence to Treatment, and showed good congruence (r = 0.65). CONCLUSIONS: The BAASIS® has adequate psychometric properties and may be employed in advance to measure adherence to posttransplant immunosuppressant treatments. This instrument will be the first one validated to use in this specific transplant population and in the Portuguese language.

A proposal to analyze the progression of non-dialytic chronic kidney disease by surrogate endpoints: introducing parametric survival models.

Introduction: Chronic kidney disease (CDK) progression studies increasingly use surrogate endpoints based on the estimated glomerular filtration rate. The clinical characteristics of these endpoints bring new challenges in comparing groups of patients, as traditional Cox models may lead to biased estimates mainly because they do not assume a hazard function. Objective: This study proposes the use of parametric survival analysis models with the three most commonly used endpoints in nephrology based on a case study. Estimated glomerular filtration rate (eGFR) decay > 5 mL/year, eGFR decline > 30%, and change in CKD stage were evaluated. Method: The case study is a 5-year retrospective cohort study that enrolled 778 patients in the predialysis stage. Exponential, Weibull, Gompertz, lognormal, and logistic models were compared, and proportional hazard and accelerated failure time (AFT) models were evaluated. Results: The endpoints had quite different hazard functions, demonstrating the importance of choosing appropriate models for each. AFT models were more suitable for the clinical interpretation of the effects of covariates on these endpoints. Conclusion: Surrogate endpoints have different hazard distributions over time, which is already recognized by nephrologists. More flexible analysis techniques that capture these relevant clinical characteristics in decision-making should be encouraged and disseminated in nephrology research.

Evaluation of the use of a Renal Health application by kidney transplant recipients.

OBJECTIVE: to evaluate the use of a renal health application by kidney transplant recipients. METHOD: a retrospective, observational study with a sample composed of individuals registered in the kidney transplant section of the application from July of 2018 to April of 2021. Demographic data, data entry, time of use, weight, blood pressure, blood glucose, creatinine, medication schedules, appointments, and tests were the variables collected. Descriptive analysis of the data was performed. RESULTS: eight hundred and twenty-three downloads of the application were identified, and 12.3% of those were registered as kidney transplant recipients, the majority from southeastern Brazil (44.9%), 36±11 years old, and female (59.1%). Of the sample, 35.1% entered information such as creatinine (62%), weight (58.2%), and blood pressure (51.8%). Most used the application for one day (63.3%) and 13.9% for more than one hundred days. Those who used it for more than one day (36.7%) recorded weight (69%), medication intake (65.5%) and creatinine (62%), and scheduled appointments (69%). CONCLUSION: the kidney transplant recipient section of the Renal Health application generated interest in the young population, but showed low adherence throughout the assessed months. These results offer a relevant perspective on the implementation of mHealth technologies in kidney transplantation.

Management strategies for implementing a multicenter cross-sectional study: lessons from the ADHERE Brazil study.

BACKGROUND: Epidemiological studies involving large samples usually face financial and operational challenges. OBJECTIVES: To describe the planning and execution of ADHERE Brazil, an epidemiological study on 1,105 kidney transplant patients, and report on how the study was structured, difficulties faced and solutions found. DESIGN AND SETTING: Cross-sectional multicenter study in 20 Brazilian kidney transplantation centers. METHODS: Actions developed in each phase of implementation were described, with emphasis on innovations used within the logistics of this study, aimed at estimating the prevalence of nonadherence to treatment. RESULTS: Coordination of activities was divided into four areas: general, regulatory, data collection and statistics. Weekly meetings were held for action planning. The general coordination team was in charge of project elaboration, choice of participating centers, definition of publication policy and monitoring other coordination teams. The regulatory team provided support to centers for submitting the project to ethics committees. The data collection team prepared a manual on the electronic collection system, scheduled web meetings and was available to respond to queries. It also monitored the data quality and reported any inadequacies found. Communication with the centers was through monthly reports via e-mail and distribution of exclusive material. The statistical team acted in all phases of the study, especially in creating the data analysis plan and data bank, generation of randomization lists and data extraction. CONCLUSIONS: Through these logistics, we collected high-quality data and built a local research infrastructure for further studies. We present supporting alternatives for conducting similar studies. CLINICAL TRIAL ANNOTATION: http://clinicaltrials.gov/ on October 10, 2013; NCT02066935.

Iron-based phosphorus chelator: Risk of iron deposition and action on bone metabolism in uremic rats.

Phosphate chelators are frequently used in patients with chronic kidney disease (CKD). New iron-based chelators remain understudied and offer a promising therapeutic option for the control of bone and mineral disorders of chronic kidney disease (BMD-CKD). We assessed the effect of the phosphorus chelator, chitosan-iron III (CH-FeCl), compared to calcium carbonate (CaCO3) in BMD-CKD and the potential iron overload in uremic rats. Thirty-two animals were divided into four groups, namely the control, CKD, CKD/CH-FeCl, and CKD/CaCO3 groups. CKD was induced by adding 0.75% (4 weeks) and 0.1% (3 weeks) adenine to the diet. The chelators were administered from week 3 through week 7. The renal function, BMD-CKD markers, and histomorphometry of the femur were assessed at week 7. The CKD group showed a significant increase in creatinine (83.9 ± 18.6 vs. 41.5 ± 22.1 µmol/L; P = 0.001), phosphate (3.5 ± 0.8 vs. 2.2 ± 0.2 mmol/L; P = 0.001), fractional excretion of phosphorus (FEP) (0.71 ± 0.2 vs. 0.2 ± 0.17; P = 0.0001), and FGF23 (81.36 ± 37.16 pg/mL vs. 7.42 ± 1.96; P = 0.011) compared to the control group. There was no accumulation of serum or bone iron after the use of CH-FeCl. The use of chelators reduced the FEP (control: 0.71 ± 0.20; CKD/CH-FeCl: 0.40 ± 0.16; CKD/CaCO3 0.34 ± 0.15; P = 0.001), without changes in the serum FGF23 and parathyroid hormone levels. Histomorphometry revealed the presence of bone disease with high remodeling in the uremic animals without changes with the use of chelators. The CH-FeCl chelator was efficient in reducing the FEP without iron accumulation, thereby paving the way for the use of this class of chelators in clinical settings in the future.

Similar quality in chronic kidney disease multidisciplinary follow-up between kidney.

INTRODUCTION: Multidisciplinary clinics are the best approach towards Chronic Kidney Disease (CKD) patients in pre-dialysis phases. The few studies regarding kidney transplant recipients (KTR) compare multidisciplinary and non-multidisciplinary clinics. METHODS: In this study, we compared the quality of multidisciplinary CKD care between 101 KTR and 101 propensity score-matched non-transplant pre-dialysis patients (PDP). Prevalence of patients without specific treatment at any time and percent time without specific treatment for CKD complications were the main outcomes and patient and kidney function survival, glomerular filtration rate (GFR) decline, prevalence of CKD-related complications, and percent time within therapeutic goals were the exploratory ones. RESULTS: Time within most goals was similar between the groups, except for diastolic blood pressure (83.4 vs. 77.3%, RR 0.92, CI 0.88-0.97, p = 0.002) and hypertriglyceridemia (67.7 vs. 58.2%, OR 0.85, CI 0.78-0.93, p < 0.001), better in non-transplant PDP, and for proteinuria (92.7 vs. 83.5%, RR 1.1, CI 1.05-1.16, p < 0.001), better in KTR. Patient survival and GFR decline were similar between the groups, although non-transplant PDP tended to progress earlier to dialysis (9.9% vs. 6.9%, HR 0.39, p = 0.07, CI 0.14-1.08). DISCUSSION: The similar findings between non-transplant PDP and KTR suggests that good and comparable quality of multidisciplinary is a valid strategy for promoting optimal clinical management of CKD-related complications in KTR.

Nonadherence to immunosuppressives and treatment in kidney transplant: ADHERE BRAZIL Study.

OBJECTIVE: To estimate the prevalence and variability of nonadherence to immunosuppressives and nonpharmacological treatment across kidney transplantation centers and two health access-disparate regions in Brazil. METHODS: In a cross-sectional design, a random multistage sample of 1,105 patients was included, based on center transplantation activity (low/moderate/high) and region (R1: North/Northeast/Mid-West; and R2: South/Southeast). Nonadherence to immunosuppressives (implementation phase) was assessed using the Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS)©. Self-report questionnaires assessed nonadherence to physical activity, smoking cessation, alcohol intake, and appointment keeping. We compared regions using the adjusted-χ2 or t-test. RESULTS: Most patients were men (58.5%), white (51.4%), and had a mean age of 47.5 (SD = 12.6) years. Regarding kidney transplantation centers, 75.9% were from R2 and 38.2% had low activity. The patients in R2 were older, white-majority, had more frequently steady partners, and received peritoneal dialysis. Nonadherence to immunosuppressives ranged from 11-65.2%; 44.5-90% to physical activity; 0-23.7% to appointment keeping; and 0-14% to smoking cessation. The total prevalence of nonadherence and by region (R1 versus R2) were: for immunosuppressives, 39.7% (44.9% versus 38.1%, p = 0.18); for smoking, 3.9% (1% versus 5%, p < 0.001); for physical activity, 69.1% (71% versus 69%, p = 0.48); for appointment keeping, 13% (12.7% versus 12%, p = 0.77); and for alcohol consumption, 0%. CONCLUSION: Despite differences among centers and high variability, only the nonadherence to smoking cessation was higher in the region with greater access to kidney transplantation. We suppose that differences in healthcare access may have been overcome by other positive aspects of the post kidney transplantation treatment.

Multilevel Correlates of Immunosuppressive Nonadherence in Kidney Transplant Patients: The Multicenter ADHERE BRAZIL Study.

BACKGROUND: Immunosuppressive nonadherence is a risk factor for worse outcomes after kidney transplantation (KT). Brazil, having the world's largest public, fully covered transplantation system and the second-highest KT volume worldwide, provides a unique setting for studying multilevel correlates of nonadherence (patient, healthcare provider, transplant center, and healthcare system levels) independent of patients' financial burden. METHODS: By applying a multistage sampling approach, we included 1105 patients from 20 KT centers. Nonadherence to immunosuppressives (implementation phase) was defined as any deviation in taking or timing adherence and dose reduction assessed by the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Based on Bronfenbrenner's ecological model, we assessed multilevel factors using established instruments and measures specifically developed for this study and analyzed their independent contribution to nonadherence by performing sequential logistic regression analysis. RESULTS: The nonadherence prevalence rate was 39.7%. The following factors were independently associated with nonadherence: Patient level-having a stable partner (odds ratio [OR]: 0.75; confidence interval [CI]: 0.58-0.97), nonadherence to appointments (OR: 2.98; CI: 2.03-4.39), and nonadherence to physical activity recommendations (OR: 1.84; CI: 1.38-2.46); and transplant center level-satisfaction with the waiting room structure (OR: 0.54; CI: 0.42-0.71), consultation >30 minutes (OR: 1.60; CI: 1.19-2.14), adequacy of the consultation frequency (OR: 0.62; CI: 0.43-0.90), and centers with >500 beds (OR: 0.58; CI: 0.46-0.73). CONCLUSIONS: As the first multicenter study assessing multilevel correlates of nonadherence in KT, our findings point to the need for multilevel interventions beyond the patient level, targeting transplant center practice patterns as an approach to tackle nonadherence.

The prevalence and associated factors of nonadherence to antihypertensive medication in secondary healthcare.

PURPOSE: Non-adherence (NA) to medication is a major contributor to treatment failure in hypertensive patients. Factors of the ecological model, at family/healthcare professional, service, and system levels, are rarely evaluated as correlates of NA in hypertensive patients. METHODS: This crossectional study assessed the prevalence of and associated factors of NA to antihypertensive medication among 485 hypertensive patients upon receiving secondary healthcare. The Morisky Green Levine Scale (MGLS) measured the implementation phase of adherence, and the Short Assessment of Health Literacy for Portuguese-speaking Adults (SAHLPA) instrument, health literacy. Multivariate analysis to NA included variables according to the levels of the ecological model. RESULTS: Most patients were female (56.3%), white (53.2%), mean age of 62.0 ± 12.6 years, illiterate (61.6%), with low health literacy (70.9%), and low income (65.4%). Uncontrolled BP was frequent (75.2%); 57.1% of patients were nonadherent. In multivariate analysis based on the ecological model, adjusted for micro, meso- and macro-level correlates, NA was associated only with variables of patient-level: low health literacy (OR 1.62, CI 1.07-2.44, p = 0.020), income ≥ two reference wages (OR 0.46, CI 0.22-0.93, p = 0.031), lack of homeownership (OR 1.99, CI 1.13-3.51, p = 0.017), sedentarism (OR 1.78, CI 1.12-2.83, p = 0.014), and complexity of treatment (number of medications taken ≥ two times/day) (OR 1.56, CI 1.01-2.41, p = 0.042). CONCLUSION: In this group of severely hypertensive patients with high cardiovascular risk, only patient-related characteristics were associated with NA. Our findings highlight the need for effective actions to optimize clinical outcomes in similar healthcare programs.

Nonadherence to Immunosuppressive Medications Following Pediatric Kidney Transplantation Within Full Cost Coverage Health System: Prevalence and Correlates.

OBJECTIVES: Pediatric patients are at higher risk of nonadherence to immunosuppressive medication after kidney transplant and the resulting adverse outcomes. Factors associated with nonadherence vary, which follow an epidemiological framework and according to health system patterns. The Brazilian public health system covers all costs of kidney transplant, including immunosuppressive medications. We aimed to assess the prevalence and correlates of nonadherence to immunosuppressive medications in a pediatric kidney transplant population who received free access to immunosuppressive medications within the health care system. MATERIALS AND METHODS: In this single-center crosssectional study, we studied a convenience sample of 156 outpatients (< 18 years old) who were a minimum of 4 weeks posttransplant. Implementation nonadherence to immunosuppressive medications was measured by the 4 questions of the Basel Assessment of Adherence to Immunosuppressive Medications Scale. Multilevel correlates to non - adherence (patient, micro, and macro levels) were assessed. RESULTS: In our patient population, 61% were males, mean age was 13.6 ± 3.1 years, 77% were adolescents, and 84% received organs from deceased donors. We found that 33% were nonadherent to immuno - suppressive medications, mainly in timing (25%) and taking (10.9%) dimensions. Being an adolescent (odds ratio: 2.66; CI, 1.02-6.96), religion other than Catholic or Protestant (odds ratio: 4.33; CI, 1.13-16.67), and family income higher than 4 reference wages (odds ratio: 3.50; CI, 1.14-10.75) were factors associated with nonadherence. CONCLUSIONS: In our patient population of mostly adolescents, one-third displayed nonadherence to immunosuppressants. Unexpectedly, a higher economic profile, potentially representing better previous access to health care, was independently associated with nonadherence. This result highlights the need for identifying specific correlates to non - adherence before designing interventions.

Public Knowledge and Attitudes Toward Organ Donation and Transplantation: A Survey From a Medium-Sized Brazilian City.

INTRODUCTION: In Brazil, where organ donation occurs after brain death (BD) and needs family consent, notification of potential donors increased in the last decade, although family refusal is still around 40%. Among modifiable factors, there is a lack of knowledge by the population regarding BD and the process of organ donation. Our goal was to evaluate the knowledge of the population about these topics in a medium-sized Brazilian city with a high family refusal rate. METHODS: In a cross-sectional study, we randomly recruited 868 individuals in public places in January through March 2017. We collected data about demographics and concepts related to organ donation by interview. Groups were compared by χ2 test. RESULTS: Most of the subjects were women (57.3%), 54.6% of whom were white, and the mean age was 37.1 ±15.8 years; 58.8% had at least 11 years of schooling, and 55.8% had a monthly familiar income of < 3 reference wages. Individuals who declared to be donors (67.5%) were younger (36.0 ± 14.9 vs 39.6 ± 17.4 years, P = .007) and had higher schooling (47.3 vs 28.7% with > 11 years of schooling, P < .001). Among donors, 41% did not inform their families, 38% believed that donation could occur regardless of the kind of death, and 26.8% believed in the reversibility of BD. At least 90% of individuals, however, independent from donation status, would authorize organ donation of a relative if they previously knew the donation status of that relative. CONCLUSION: We observed, despite a high prevalence of potential donors, conflictive concepts regarding BD. This information suggests directions for the design of educative measures.

Digital radiography as an alternative method in the evaluation of bone density in uremic rats.

INTRODUCTION: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. METHODS: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. RESULTS: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). CONCLUSION: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

Fibroblast growth factor 21 in chronic kidney disease.

Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF family that acts as a metabolic regulator of both glucose and lipid metabolism. Similar to fibroblast growth factor 23 (FGF23), serum FGF21 levels rise progressively with the loss of renal function, reaching 20 times normal values in end-stage renal disease. In patients with chronic kidney disease (CKD), higher serum FGF21 levels correlate with poorer metabolic profile, higher inflammatory markers, more comorbidities, and higher mortality. The high serum FGF21 levels are above and beyond what can be explained by the loss of FGF21 renal clearance, suggesting increased production and/or impaired non-renal clearance. In diabetic nephropathy, serum FGF21 levels correlate with the severity of albuminuria and faster loss of glomerular filtrate rate and can potentially be a biomarker of poor prognostic. The observational and associative human data contrast sharply with in vitro and in vivo preclinical experimental data, which is more in line with a protective role of FGF21 in chronic nephropathies. We here review the physiology of FGF21, and the literature regarding its behavior in CKD with particular focus on diabetic nephropathy. Finally, we speculate on the role of FGF21 in CKD.

Uremic Cardiomyopathy: A New Piece in the Chronic Kidney Disease-Mineral and Bone Disorder Puzzle.

Cardiovascular diseases are the main cause of death in chronic kidney disease (CKD) patients. In dialysis patients, sudden cardiac death accounts for 40% of all deaths. In these patients, sudden cardiac death is usually secondary to an underlying cardiomyopathy, which is clinically identified by the high prevalence of left ventricular hypertrophy and the resultant mechanical and electrical dysfunction. CKD-related cardiomyopathy has a multifactorial pathophysiology. Recent evidence has highlighted the central pathophysiological role of chronic kidney disease-mineral and bone disorder (CKD-MBD) with hyperphosphatemia and high fibroblast growth factor 23 (FGF23) levels in these patients. Further, since CKD is known to be an αKlotho deficiency state, experimental studies have demonstrated that the deleterious effects of FGF23 can be minimized by reestablishing adequate soluble Klotho levels. Herein, we present a review that addresses not only the development of the understanding of CKD-related cardiomyopathy pathophysiology, but also explores the recent data that identify the triad of hyperphosphatemia, high FGF23 levels and αKlotho deficiency as playing a central role on it. Taken together, the data suggest that the uremic cardiomyopathy can be considered a new piece in the CKD-DMO puzzle.