Summary Anthracycline chemotherapy has a prominent role in treating many forms of cancer. Unfortunately, cardiotoxic side effects represent a serious limitation to their use, with doxorubicin being the leading drug of the group. Indeed, anthracycline‐induced cardiomyopathy is an important public health concern because it may not be detected for many years and remains a lifelong threat. Even after decades of investigation, neither the exact mode of action of anthracyclines nor the pathways leading to their side effect are fully understood. It is increasingly important to establish collaboration between oncologists and cardiologists to improve the management of cancer patient receiving anthracyclines. This article reviews the clinical course, pathogenesis, cardiac monitoring and new concepts in diagnosing and preventing anthracycline‐induced cardiotoxicity.

Over the past decades metformin has been the optimal first-line treatment for type 2 diabetes mellitus (T2DM). Only in the last few years, it has become increasingly clear that metformin exerts benign pleiotropic actions beyond its prescribed use and ongoing investigations focus on a putative beneficial impact of metformin on the kidney. Both acute kidney injury (AKI) and chronic kidney disease (CKD), two major renal health issues, often result in the need for renal replacement therapy (dialysis or transplantation) with a high socio-economic impact for the patients. Unfortunately, to date, effective treatment directly targeting the kidney is lacking. Metformin has been shown to exert beneficial effects on the kidney in various clinical trials and experimental studies performed in divergent rodent models representing different types of renal diseases going from AKI to CKD. Despite growing evidence on metformin as a candidate drug for renal diseases, in-depth research is imperative to unravel the molecular signaling pathways responsible for metformin’s renoprotective actions. This review will discuss the current state-of-the-art literature on clinical and preclinical data, and put forward potential cellular mechanisms and molecular pathways by which metformin ameliorates AKI/CKD.

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Abstract Introduction Sucroferric oxyhydroxide (PA21) is an efficacious, well-tolerated iron-based phosphate binder and a promising alternative to existing compounds. We compared the effects of PA21 with those of a conventional phosphate binder on renal function, mineral homeostasis and vascular calcification in a chronic kidney disease–mineral and bone disorder (CKD-MBD) rat model. Methods To induce stable renal failure, rats were administered a 0.25% adenine diet for 8 weeks. Concomitantly, rats were treated with vehicle, 2.5 g/kg/day PA21, 5.0 g/kg/day PA21 or 3.0 g/kg/day calcium carbonate (CaCO3). Renal function and calcium/phosphorus/iron metabolism were evaluated during the study course. Renal fibrosis, inflammation, vascular calcifications and bone histomorphometry were quantified. Results Rats treated with 2.5 or 5.0 g/kg/day PA21 showed significantly lower serum creatinine and phosphorus and higher ionized calcium levels after 8 weeks of treatment compared with vehicle-treated rats. The better preserved renal function with PA21 went along with less severe anaemia, which was not observed with CaCO3. Both PA21 doses, in contrast to CaCO3, prevented a dramatic increase in fibroblast growth factor (FGF)-23 and significantly reduced the vascular calcium content while both compounds ameliorated CKD-related hyperparathyroid bone. Conclusions PA21 treatment prevented an increase in serum FGF-23 and had, aside from its phosphate-lowering capacity, a beneficial impact on renal function decline (as assessed by the renal creatinine clearance) and related disorders. The protective effect of this iron-based phosphate binder on the kidney in rats, together with its low pill burden in humans, led us to investigate its use in patients with impaired renal function not yet on dialysis.

One of the most important risk factors for developing chronic kidney disease (CKD) is diabetes. To assess the safety and efficacy of potential drug candidates, reliable animal models that mimic human diseases are crucial. However, a suitable model of diabetic kidney disease (DKD) is currently not available. The aim of this study is to develop a rat model of DKD by combining streptozotocin and nicotinamide (STZ/NAD) with oral N(ω)-Nitro-L-Arginine Methyl Ester (L-NAME) administration. Diabetes was induced in male Wistar rats by intravenous injection of 65 mg/kg STZ, 15 min after intraperitoneal injection of 230 mg/kg NAD. Rats were assigned to different groups receiving L-NAME (100 mg/kg/day) (STZ/NAD/L-NAME) or vehicle (STZ/NAD) for a period of 9 or 12 weeks by daily oral gavage. All rats developed hyperglycemia. Hyperfiltration was observed at the start of the study, whereas increased serum creatinine, albumin-to-creatinine ratio, and evolving hypofiltration were detected at the end of the study. Daily L-NAME administration caused a rapid rise in blood pressure. Histopathological evaluation revealed heterogeneous renal injury patterns, which were most severe in the STZ/NAD/L-NAME rats. L-NAME-induced NO-deficiency in STZ/NAD-induced diabetic rats leads to multiple characteristic features of human DKD and may represent a novel rat model of DKD.