Klotho in pregnancy and intrauterine development-potential clinical implications: a review from the European Renal Association CKD-MBD Working Group.

Intrauterine development is crucial for life-long health; therefore, elucidation of its key regulators is of interest for their potential prognostic and therapeutic implications. Originally described as a membrane-bound anti-aging protein, Klotho has evolved as a regulator of numerous functions in different organ systems. Circulating Klotho is generated by alternative splicing or active shedding from cell membranes. Recently, Klotho was identified as a regulator of placental function, and while Klotho does not cross the placental barrier, increased levels of circulating α-Klotho have been identified in umbilical cord blood compared with maternal blood, indicating that Klotho may also play a role in intrauterine development. In this narrative review, we discuss novel insights into the specific functions of the Klotho proteins in the placenta and in intrauterine development, while summarizing up-to-date knowledge about their structures and functions. Klotho plays a role in stem cell functioning, organogenesis and haematopoiesis. Low circulating maternal and foetal levels of Klotho are associated with preeclampsia, intrauterine growth restriction, and an increased perinatal risk for newborns, indicating a potential use of Klotho as biomarker and therapeutic target. Experimental administration of Klotho protein indicates a neuro- and nephroprotective potential, suggesting a possible future role of Klotho as a therapeutic agent. However, the use of Klotho as intervention during pregnancy is as yet unproven. Here, we summarize novel evidence, suggesting Klotho as a key regulator for healthy pregnancies and intrauterine development with promising potential for clinical use.

Pancreatic steatosis is an independent risk factor for post-transplant diabetes mellitus in kidney transplant patients.

BACKGROUND AND AIM: Post-transplant diabetes mellitus (PTDM) is associated with an increased risk of post-transplant cardiovascular diseases, and several risk factors of PTDM have been shown in the literature. Yet, the relationship between hepatic and pancreatic steatosis with post-transplant diabetes mellitus remains vague. We aimed to evaluate pancreatic steatosis, a novel component of metabolic syndrome, and hepatic steatosis association with post-transplant diabetes mellitus in a single-center retrospective cohort study conducted on kidney transplant recipients. METHOD: We have performed a single-center retrospective cohort study involving all kidney transplant recipients. We have utilized pretransplant Fibrosis-4, nonalcoholic fatty liver disease fibrosis score, and abdominal computed tomography for the assessment of visceral steatosis status. RESULTS: We have included 373 kidney transplant recipients with a mean follow-up period of 32 months in our final analysis. Post-transplant diabetes mellitus risk is associated with older age (p < .001), higher body-mass index (p < .001), nonalcoholic fatty liver disease-fibrosis score (p = .002), hepatic (p < .001) or pancreatic (p < .001) steatosis on imaging and higher pre-transplant serum triglyceride (p = .003) and glucose levels (p = .001) after multivariate analysis. CONCLUSION: Our study illustrates that recipients' pancreatic steatosis is an independent predictive factor for post-transplant diabetes mellitus including in kidney transplant patients.

Social isolation and loneliness: Undervalued risk factors for disease states and mortality.

Social isolation and loneliness are two common but undervalued conditions associated with a poor quality of life, decreased overall health and mortality. In this review, we aim to discuss the health consequences of social isolation and loneliness. We first provide the potential causes of these two conditions. Then, we explain the pathophysiological processes underlying the effects of social isolation and loneliness in disease states. Afterwards, we explain the important associations between these conditions and different non-communicable diseases, as well as the impact of social isolation and loneliness on health-related behaviours. Finally, we discuss the current and novel potential management strategies for these conditions. Healthcare professionals who attend to socially isolated and/or lonely patients should be fully competent in these conditions and assess their patients thoroughly to detect and properly understand the effects of isolation and loneliness. Patients should be offered education and treatment alternatives through shared decision-making. Future studies are needed to understand the underlying mechanisms better and to improve the treatment strategies for both social isolation and loneliness.

A new immune disease: systemic hypertension.

Systemic hypertension is the most common medical comorbidity affecting the adult population globally, with multiple associated outcomes including cerebrovascular diseases, cardiovascular diseases, vascular calcification, chronic kidney disease, metabolic syndrome and mortality. Despite advancements in the therapeutic field approximately one in every five adult patients with hypertension is classified as having treatment-resistant hypertension, indicating the need for studies to provide better understanding of the underlying pathophysiology and the need for more therapeutic targets. Recent pre-clinical studies have demonstrated the role of the innate and adaptive immune system including various cell types and cytokines in the pathophysiology of hypertension. Moreover, pre-clinical studies have indicated the potential beneficial effects of immunosuppressant medications in the control of hypertension. Nevertheless, it is unclear whether such pathophysiological mechanisms and therapeutic alternatives are applicable to human subjects, while this area of research is undoubtedly a rapidly growing field.