Oxalate (dys)Metabolism: Person-to-Person Variability, Kidney and Cardiometabolic Toxicity.

Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.

Urinary Sediment Microscopy and Correlations with Kidney Biopsy: Red Flags Not To Be Missed.

BACKGROUND: Urinary sediment is a noninvasive laboratory test that can be performed by an automated analyzer or manually by trained personnel. Manual examination remains the diagnostic standard because it excels at differentiating isomorphic from dysmorphic red blood cells and identifying other urinary particles such as renal tubular epithelial cells (RTECs), lipids, crystals, and the composition of casts. This study aimed to investigate the prevalence of a complete profile of urinary sediment particles and its associations with histologic lesions on kidney biopsy, regardless of diagnosis. METHODS: This was a single-center, observational retrospective study of 131 patients who had contemporary manual urinary sediment evaluation and kidney biopsy. A comprehensive set of urinary particles and histologic lesions were quantified, and their associations were analyzed. RESULTS: In our samples, we found an elevated frequency of findings suggestive of proliferative kidney disease and a low frequency of particles evoking urologic damage. The association of histologic lesions and urinary particles was explored with a multivariate model. We identified urinary sediment characteristics that independently correlated with the presence of some histologic lesions: urinary lipids with mesangial expansion (OR=2.86; 95% confidence interval [95% CI], 1.3 to 6.3), mesangial hypercellularity (OR=2.44; 95% CI, 1.06 to 5.58), and wire loops and/or hyaline deposits (OR=2.89; 95% CI, 1.13 to 7.73); Urinary renal tubular epithelial cells with endocapillary hypercellularity (OR=3.17; 95% CI, 1.36 to 7.39), neutrophils and/or karyorrhexis (OR=4.51; 95% CI, 1.61 to 12.61), fibrinoid necrosis (OR=4.35; 95% CI, 1.48 to 12.74), cellular/fibrocellular crescents (OR=5.27; 95% CI, 1.95 to 14.26), and acute tubular necrosis (OR=2.31; 95% CI, 1.08 to 4.97). CONCLUSIONS: In a population of patients submitted to kidney biopsy, we found that the presence of some urinary particles (renal tubular epithelial cells, lipids, and dysmorphic erythrocytes), which are seldom reported by automated analyzers, is associated with active proliferative histologic lesions. In this regard, manual urinary sediment evaluation may help to shape the indications for performing a kidney biopsy.

Conflict of Interest Disclosure in a Top-Tier Portuguese Medical Journal.

INTRODUCTION: Scientific medical publications are considered to be a source of unbiased and independent information. Authors are required to disclose relationships with the pharmaceutical industry for transparency purposes. The aim of this work was to assess conflict of interest disclosure in a Portuguese top-tier medical journal by comparing authors' self-reported conflicts of interest with payments listed in the official database of Portuguese Ministry of Health. MATERIAL AND METHODS: All articles published in the Portuguese Journal of Cardiology from December 2015 to May 2016 were reviewed. Articles based on clinical images, with authors affiliated to foreign institutions, editorials, letters to the editor, or submitted before January 1st 2015 were excluded. Authors were categorized on concordance between self-reported disclosures and payments listed in the database. Authors who authored multiple articles were counted as new authors, since each paper offered a new opportunity for financial disclosure. RESULTS: Of the 155 authors surveyed, 82 (53%) were in perfect concordance with the sunshine database, while 73 authors (47%) had one or more undisclosed payments. Undisclosed payments totaled over € 210 000. Four (17%) articles mentioned a conflict of interest, 24 articles (96%) had at least one author with undisclosed payments. DISCUSSION: None of the payments listed in the database was acknowledged in self-reported conflicts of interest. This might indicate that authors do not consider their financial relationships with the industry to be relevant. CONCLUSION: The lack of concordance between self-reported conflicts of interest and payments found in the database raises concerns about incomplete disclosure.

Introdução: As publicações médicas são consideradas uma fonte de informação fidedigna e independente. Por motivos de transparência é exigido aos autores que divulguem as suas relações com a indústria farmacêutica. Os objectivos do presente estudo consistiram em avaliar a divulgação de conflitos de interesse numa publicação médica de referência, comparando os conflitos de interesse declarados pelos autores com os pagamentos listados na plataforma de transparência do Ministério da Saúde. Material e Métodos: Foram analisados todos os artigos publicados na Revista Portuguesa de Cardiologia entre dezembro de 2015 e maio de 2016. Critérios de exclusão: artigos baseados em imagens clínicas, artigos com autores afiliados a instituições estrangeiras, editoriais, cartas ao editor e trabalhos com data de submissão anterior a 1 de janeiro de 2015. Os autores foram classificados segundo a concordância entre os conflitos de interesse declarados e os pagamentos listados na plataforma de transparência. Os autores que publicaram mais do que artigo incluído na análise foram classificados como novo autor, uma vez que cada publicação permite uma nova oportunidade de divulgação de conflitos de interesse. Resultados: Dos 155 autores analisados, 82 (53%) estavam em plena concordância com os dados da plataforma, enquanto 73 autores (47%) apresentavam pelo menos um pagamento não divulgado. O total dos pagamentos não divulgados ascendia a € 210 000. Quatro (17%) artigos referiam conflitos de interesse, 24 artigos (96%) continham pelo menos um autor com pagamentos não divulgados. Discussão: Nenhum dos pagamentos listado na plataforma foi mencionado nos conflitos de interesse dos autores. Tal facto poderá indicar que os autores não consideram relevantes as suas relações financeiras com a indústria. Conclusão: A discordância encontrada entre conflitos de interesse declarados e os pagamentos suscita preocupação sobre divulgação insuficiente dos conflitos de interesse.