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Introduction: The lack of specialized professionals potentially contributes to the inability to meet the demand for kidney transplantations. Moreover, there is no universal proposal for the training process of transplantation surgeons. We aimed to explore the characteristics of the training program and professional activities of kidney transplantation teams in the state of Minas Gerais, Brazil., Methods: We invited the surgeons of all 19 active kidney transplantation centers in Minas Gerais to participate in this cross-sectional study. Demographic and professional training data were compared using linear and logistic regression models., Results: The response rate among the centers was high (89%); half of the surgeons answered the survey (39/78). Most of the centers were public teaching institutions, under a production-based payment contract, with a mean of 6 ± 2.4 surgeons/team; 94.2% of the centers had urologists. The surgeons were 95% male (age of 46.3 ± 9.7 years) and 59% were urologists. Most were involved in organ procurement and transplantation; only one surgeon worked exclusively with transplantation. The mean period since training was 13 ± 9.4 years, with a mean of 10 ± 9.7 years as part of the transplantation team. Only 25.6% had specialized or formal training in transplantation, with only one completing a formal medical residency for kidney transplantation. The lack of training programs was the most frequently cited reason., Conclusion: Kidney transplantation surgeons are not exclusive and most have not completed a formal fellowship program in transplantation because they are not available. These data indicate the need to improve training programs and facilitate the formation of new kidney transplantation teams.

Introduction: The objective of this study was to investigate the role of fenofibrate, a peroxisome proliferator-activated receptor-α agonist, in obesity-induced kidney damage (lipotoxicity) in mice with uninephrectomy., Methods: C57BL/6 mice underwent uninephrectomy and sham surgeries and were fed normocaloric or high-fat diets. After 10 weeks, obese mice were administered 0.02% fenofibrate for 10 weeks. Kidney function and morphology were evaluated, as well as levels of inflammatory and fibrotic mediators and lipid metabolism markers., Results: High-fat diet-fed mice developed characteristic obesity and hyperlipidemia, with subsequent renal lipid accumulation and damage, including mesangial expansion, interstitial fibrosis, inflammation, and proteinuria. These changes were greater in obese uninephrectomy mice than in obese sham mice. Fenofibrate treatment prevented hyperlipidemia and glomerular lesions, lowered lipid accumulation, ameliorated renal dysfunction, and attenuated inflammation and renal fibrosis. Furthermore, fenofibrate treatment downregulated renal tissue expression of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and local expression of fibroblast growth factor-21., Conclusion: Peroxisome proliferator-activated receptor-α activation by fenofibrate, with subsequent lipolysis, attenuated glomerular and tubulointerstitial lesions induced by renal lipotoxicity, thus protecting the kidneys of uninephrectomy mice from obesity-induced lesions. The study findings suggest a pathway in the pharmacological action of fenofibrate, providing insight into the mechanisms involved in kidney damage caused by obesity in kidney donors.

Frailty, defined as an inappropriate response to stressful situations due to the loss of physiological reserve, was initially described in the elderly population, but is currently being identified in younger populations with chronic diseases, such as chronic kidney disease. It is estimated that about 20% of patients are frail at the time of kidney transplantation (KT), and there is great interest in its potential predictive value for unfavorable outcomes. A significant body of evidence has been generated; however, several areas still remain to be further explored. The pathogenesis is poorly understood and limited to the extrapolation of findings from other populations. Most studies are observational, involving patients on the waiting list or post-KT, and there is a scarcity of data on long-term evolution and possible interventions. We reviewed studies, including those with Brazilian populations, assessing frailty in the pre- and post-KT phases, exploring pathophysiology, associated factors, diagnostic challenges, and associated outcomes, in an attempt to provide a basis for future interventions.

Background: Quality of life (QoL) is a measure to evaluate kidney transplant (KT) results., Aim: To describe the QoL profile in a larger sample of Brazilian patients who underwent KT according to age, sex, and access to KT., Methods: We conducted a secondary data analysis of the ADHERE BRAZIL multicenter cross-sectional study including 1105 patients from 20 centers, considering KT access region and transplant activity. QoL was assessed by the WHOQOL-BREF. Data was compared using Generalized Estimating Equations., Results: Overall, 58.5 % of the patients were men, mean age of 47.6 ± 12.6 years. The general QoL score was 81 ± 15.1, 58.6 ± 11.6 for physical, 65.5 ± 11.4 for psychological, 68.3 ± 17.1 for social relationships, and 64.2 ± 13.3 for environmental domain. Higher QoL scores were observed in men compared to women in three WHOQOL-BREF domains: psychological (OR:2.62; CI, 1.29 ̶ 3.95, p < 0.0001), social relationships (OR:3.21; CI, 1.2 ̶ 5.23, p = 0.002) and environmental (OR:3.79; CI:2.23 ̶ 5.35, p < 0.0001). Younger patients (18-44 years) had higher scores in the psychological (OR:-2.69; CI, -4.13 ̶ -1.25; p < 0.001; OR:-3.52; CI, -5.39 ̶ -1.66; p < 0.001) and social (OR:-3.46; CI, -5.64 ̶ -1.27; p = 0.002; OR:-7.17; CI, -10 ̶ -4.35; p < 0.0001) domains than older ones (45-59 and > 60 years, respectively). Patients from higher KT access region had higher scores in environmental domain (OR:3.53; CI, 0.28 ̶ 6.78; p = 0.033)., Conclusions: Featuring the results of KT under patient view, the physical and social relationships domains were the most and least affected, respectively. Lower QoL subgroups (females and age > 45 years) should be targeted in future multi-professional interventions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Oral squamous cell carcinoma (OSCC) is one of the most-prevalent cancer types worldwide, and it poses a serious threat to public health due to its high mortality and morbidity rates. OSCC typically has a poor prognosis, significantly reducing the chances of patient survival. Therefore, early detection is crucial to achieving a favorable prognosis by providing prompt treatment and increasing the chances of remission. Salivary biomarkers have been established in numerous studies to be a trustworthy and non-invasive alternative for early cancer detection. In this sense, we propose an intelligent system that utilizes feed-forward artificial neural networks to classify carcinoma with salivary biomarkers extracted from control and OSCC patient samples. We conducted experiments using various salivary biomarkers, ranging from 1 to 51, to train the model, and we achieved excellent results with precision, sensitivity, and specificity values of 98.53%, 96.30%, and 97.56%, respectively. Our system effectively classified the initial cases of OSCC with different amounts of biomarkers, aiding medical professionals in decision-making and providing a more-accurate diagnosis. This could contribute to a higher chance of treatment success and patient survival. Furthermore, the minimalist configuration of our model presents the potential for incorporation into resource-limited devices or environments.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Erohildes Ferreira, Sanders-Pinheiro and Basile Colugnati.)

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.

Background: Truncating pathogenic or likely pathogenic variants of CDH1 cause hereditary diffuse gastric cancer (HDGC), a tumour risk syndrome that predisposes carrier individuals to diffuse gastric and lobular breast cancer. Rare CDH1 missense variants are often classified as variants of unknown significance. We conducted a genotype-phenotype analysis in families carrying rare CDH1 variants, comparing cancer spectrum in carriers of pathogenic or likely pathogenic variants (PV/LPV; analysed jointly) or missense variants of unknown significance, assessing the frequency of families with lobular breast cancer among PV/LPV carrier families, and testing the performance of lobular breast cancer-expanded criteria for CDH1 testing., Methods: This genotype-first study used retrospective diagnostic and clinical data from 854 carriers of 398 rare CDH1 variants and 1021 relatives, irrespective of HDGC clinical criteria, from 29 institutions in ten member-countries of the European Reference Network on Tumour Risk Syndromes (ERN GENTURIS). Data were collected from Oct 1, 2018, to Sept 20, 2022. Variants were classified by molecular type and clinical actionability with the American College of Medical Genetics and Association for Molecular Pathology CDH1 guidelines (version 2). Families were categorised by whether they fulfilled the 2015 and 2020 HDGC clinical criteria. Genotype-phenotype associations were analysed by Student's t test, Kruskal-Wallis, χ 2 , and multivariable logistic regression models. Performance of HDGC clinical criteria sets were assessed with an equivalence test and Youden index, and the areas under the receiver operating characteristic curves were compared by Z test., Findings: From 1971 phenotypes (contributed by 854 probands and 1021 relatives aged 1-93 years), 460 had gastric and breast cancer histology available. CDH1 truncating PV/LPVs occurred in 176 (21%) of 854 families and missense variants of unknown significance in 169 (20%) families. Multivariable logistic regression comparing phenotypes occurring in families carrying PV/LPVs or missense variants of unknown significance showed that lobular breast cancer had the greatest positive association with the presence of PV/LPVs (odds ratio 12·39 [95% CI 2·66-57·74], p=0·0014), followed by diffuse gastric cancer (8·00 [2·18-29·39], p=0·0017) and gastric cancer (7·81 [2·03-29·96], p=0·0027). 136 (77%) of 176 families carrying PV/LPVs fulfilled the 2015 HDGC criteria. Of the remaining 40 (23%) families, who did not fulfil the 2015 criteria, 11 fulfilled the 2020 HDGC criteria, and 18 had lobular breast cancer only or lobular breast cancer and gastric cancer, but did not meet the 2020 criteria. No specific CDH1 variant was found to predispose individuals specifically to lobular breast cancer, although 12 (7%) of 176 PV/LPV carrier families had lobular breast cancer only. Addition of three new lobular breast cancer-centred criteria improved testing sensitivity while retaining high specificity. The probability of finding CDH1 PV/LPVs in patients fulfilling the lobular breast cancer-expanded criteria, compared with the 2020 criteria, increased significantly (AUC 0·92 vs 0·88; Z score 3·54; p=0·0004)., Interpretation: CDH1 PV/LPVs were positively associated with HDGC-related phenotypes (lobular breast cancer, diffuse gastric cancer, and gastric cancer), and no evidence for a positive association with these phenotypes was found for CDH1 missense variants of unknown significance. CDH1 PV/LPVs occurred often in families with lobular breast cancer who did not fulfil the 2020 HDGC criteria, supporting the expansion of lobular breast cancer-centred criteria., Funding: European Reference Network on Genetic Tumour Risk Syndromes, European Regional Development Fund, Fundação para a Ciência e a Tecnologia (Portugal), Cancer Research UK, and European Union's Horizon 2020 research and innovation programme., Competing Interests: Declaration of interests DGE declares fees from Astrazeneca and Recursion. ERW declares grants from International Alliance for Cancer Early Detection, for which they are codirector of the research domain. GNR declares receipt of funding for study materials, medical writing, and article processing charges from Italian Ministry of Education (GNR). MJLL declares consulting fees (via the Radboud University Medical Center) from Merck Sharp & Dohme (MSD), AstraZeneca, Lilly, Janssen-Cilag, Illumina, GlaxoSmithKline. PRB declares fees from AstraZeneca, MSD, and Bristol Myers Squibb; and is a scientific committee member for the Geneticancer patients association. JBa declares fees from AstraZeneca, Lilly, and Pfizer. SA is a member of APC subVCEP of the InSiGHT/ClinGen Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel; is an unpaid member of the German Gene Diagnostics Commission and speaker of the Centre for Hereditary Tumour Syndromes of the University of Bonn. RH declares grants from SLA Pharma and Janssen Pharmaceuticals; consulting fees from Janssen and One Two Therapeutics; equipment from Fujifilm; is the head of German Consortium for Familial Gastrointestinal Cancer; and is an unpaid advisory board member of the Lynch Syndrome advocacy Group and the Familial Polyposis Group. ES declares grants from NCT/DKTK Master. ES declares honoraria for presentations from AstraZeneca, Georg Thieme Verlag KG, and payment for expert testimony from Illumina; is a member of the board of directors of Deutsche Gesellschaft für HumanGenetik; an advisor for Dresden-concept Genome Center; and is board of directors president (paid) for LNS laboratoire National de Santé. RdP declares support for presentations (via his institution) from MSD and AstraZeneca. GC declares to receive funding for study materials, medical writing, article processing charges from the Spanish Ministry of Science and Innovation, the Instituto de Salud Carlos III CIBERONC, and the Government of Catalonia.; consulting fees from VCN Biosciences Synthetic Biologics; is the chair of the Council of the International Society of Hereditary Gastrointestinal Tumours and the FUREGA Fundació Recerca en Gastroenterologia; and stock in Synthetic Biologics. CLa declares consulting fees and honoraria from AstraZeneca and MSD, and is a paid advisory board member for Illumina., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

E-cadherin, a CDH1 gene product, is a calcium-dependent cell-cell adhesion molecule playing a critical role in the establishment of epithelial architecture, maintenance of cell polarity, and differentiation. Germline pathogenic variants in the CDH1 gene are associated with hereditary diffuse gastric cancer (HDGC), and large rearrangements in the CDH1 gene are now being reported as well. Because CDH1 pathogenic variants could be associated with breast cancer (BC) susceptibility, CDH1 rearrangements could also impact it. The aim of our study is to identify rearrangements in the CDH1 gene in 148 BC cases with no BRCA1 and BRCA2 pathogenic variants. To do so, a zoom-in CGH array, covering the exonic, intronic, and flanking regions of the CDH1 gene, was used to screen our cohort. Intron 2 of the CDH1 gene was specifically targeted because it is largely reported to include several regulatory regions. As results, we detected one large rearrangement causing a premature stop in exon 3 of the CDH1 gene in a proband with a bilateral lobular breast carcinoma and a gastric carcinoma (GC). Two large rearrangements in the intron 2, a deletion and a duplication, were also reported only with BC cases without any familial history of GC. No germline rearrangements in the CDH1 coding region were detected in those families without GC and with a broad range of BC susceptibility. This study confirms the diversity of large rearrangements in the CDH1 gene. The rearrangements identified in intron 2 highlight the putative role of this intron in CDH1 regulation and alternative transcripts. Recurrent duplication copy number variations (CNV) are found in this region, and the deletion encompasses an alternative CDH1 transcript. Screening for large rearrangements in the CDH1 gene could be important for genetic testing of BC.

Monkeypox, a neglected and re-emergent zoonotic disease caused by monkeypox virus (MPXV) infection, has been endemic in Central and Western Africa for decades. More recently, an outbreak has spread to a global level, occurring in sites with no previous reported cases and being clustered among men who have sex with men, suggesting new modes of transmission. There is an urgent need for research for a better understanding of the genomic evolution and changing epidemiology of the Orthopoxvirus group. Our work aimed to characterize the clinical and epidemiological features of a cohort of patients with MPXV infection in a Portuguese hospital, admitted between 5 May and 26 July 2022. In this retrospective observational study, aggregate data of a case series on the presentation, clinical course, and outcomes of confirmed MPXV infections are reported. The study included 40 men and 1 woman, with a mean age of 37.2 years old; 92.7% identified as men who have sex with men, 90.2% had unprotected sex or sex with multiple or anonymous partners in the previous month, and 39.0% reported to have had sex with an MPXV-confirmed case; 59.5% had previously known human immunodeficiency virus (HIV) infection, all of whom were under antiretroviral therapy, and no patients had acquired immunodeficiency syndrome (AIDS) criteria. About a quarter of patients were observed only a week after symptom onset. All patients had skin or mucosal lesions and the anogenital region was the most frequent lesion site. There were no statistically significant clinical differences between HIV-positive and negative individuals. Four patients were admitted to the inpatient clinic, two of whom had proctitis with difficult-to-manage anal pain. There were no reported deaths. Our findings suggest the sexual route as a relevant mode of transmission of MPXV and confirm the mostly benign presentation of this disease.

Objectives: The aim of this study was to com-pare the risk of International Society of Urological Pathology (ISUP) score upgrading between magnetic resonance imaging targeted fusion biopsy (MRI-TB) and tran-srectal ultrasound-guided biopsy (TRUS-B) in the final radical prostatectomy (RP) specimen pathological report., Materials and Methods: This retrospective single center study included 51 patients with prostate cancer (PCa) diagnosed with MRI-TB and 83 patients diagnosed with TRUS-B between October/2019 and July/2021. We compared the rates of ISUP score upgrading between both groups after robotic-assisted radi-cal prostatectomy (RARP) and the specific transition of each ISUP score based on biopsy modality. The rate of ISUP score concordance and downgrading were also assessed. To define the intra and interobserver concordance for each ISUP score in biopsy and RP specimen for each biopsy modality, the Cohen's Kappa coefficient was calculated. ISUP scores and biopsy modal-ity were selected for multivariate analysis and a logistic regres-sion model was built to provide independent risk factors of ISUP score upgrading., Results: The difference of the rate of upgrading between MRI-TB group and TRUS-B group was statistically significant (p = 0.007) with 42.2% of patients of TRUS-B group experiencing an upgrade in their ISUP score while only 19.6% in MRI-TB group. Concordance and downgrading rates did not statistically differ between the two groups. Strength of concordance using Cohen's Kappa coefficient was fair in both groups but higher in MRI-TB group (TRUS-B group k = 0.230; p < 0.001; concordance: 47%vs. MRI/TB group k = 0.438; p < 0.001; concordance: 62.7%). Biopsy modality and ISUP 1 on biopsy were independent predic-tors of ISUP upgrading after RP., Conclusions: MRI-TB is highly accurate with lower risk of PCa upgrading after RP than TRUS-B. Patients with ISUP 1 on biopsy have greater susceptibility to upgrading their ISUP score.

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.

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 (CaCO 3 ) 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/CaCO 3 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/CaCO 3 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.

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., (© 2021 John Wiley & Sons Australia, Ltd.)