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Nazareno Carullo,1 Maria Teresa Zicarelli,1 Alessandro Casarella,2 Ramona Nicotera,1 Alberto Castagna,2 Alessandra Urso,1 Pierangela Presta,1 Michele Andreucci,1 Emilio Russo,2 Davide Bolignano,1 Giuseppe Coppolino1 1Renal Unit, Department of Health Sciences, “Magna Graecia” University, Catanzaro, Italy; 2Department of Health Sciences, “Magna Graecia” University, Catanzaro, ItalyCorrespondence: Giuseppe CoppolinoRenal Unit, Department of Health Sciences, “Magna Graecia” University, Viale Europa - Germaneto, Catanzaro, 88100, ItalyTel +39 09613697170Email gcoppolino@unicz.itAbstract: Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent single-gene disorder leading to renal failure. Current therapies are aimed to treat renal and extrarenal complications of ADPKD, but improved knowledge of the pathophysiological mechanisms leading to the generation and growth of cysts has permitted the identification of new drug candidates for clinical trials. Among these, in this review, we will examine above all the role of metformin, hypothesized to be able to activate the AMP-activated protein kinase (AMPK) pathway and potentially modulate some mechanisms implicated in the onset and the growth of the cysts.Keywords: cystogenesis, renal cells, metformin, chronic renal disease, renal tubule

Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease-mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways. ADPKD is clinically characterized by the formation of many growing cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of end-stage renal disease (ESRD). The current aim of ADPKD therapy is the inhibition of cyst development and retardation of chronic kidney disease progression. Several drugs have been recently included as potential therapies for ADPKD including metformin, the drug of choice for the treatment of type 2 diabetes mellitus, according to its potential inhibitory effects on cystogenesis. In this review, we summarize preclinical and clinical evidence endorsing or rejecting metformin administration in ADPKD evolution and pathological mechanisms. We explored the biology of APDKD and the role of metformin in slowing down cystogenesis searching PubMed and Clinical Trials to identify relevant data from the database inception to December 2020. From our research analysis, evidence for metformin as emerging cure for ADPKD mainly arise from preclinical studies. In fact, clinical studies are still scanty and stronger evidence is awaited. Its effects are likely mediated by inhibition of the ERK pathway and increase of AMPK levels, which are both linked to ADPKD pathogenesis., (© 2021 Wiley Periodicals LLC.)

Diabetes Mellitus (DM) is a chronic and severe metabolic disease, characterized by chronic hyperglycemia due to insulin resistance and/or reduced insulin secretion. Concerning the non-insulin glucose-lowering therapy for diabetes, Dipeptidyl-peptidase-4 (DPP-4) inhibitors, members of the incretin family, represent new agents, capable of a glycemic control improvement with an advantageous safety profile, given the absence of weight gain, the low incidence of hypoglycemia and the good renal tolerance in patients suffering from chronic renal failure. In addition to demonstrating efficacy in glycemic control through inhibition of GLP-1 degradation, DPP-4 inhibitors (DPP-4is) seem to demonstrate pleiotropic effects, which also make them interesting in both diabetic and non-diabetic nephropathies, especially for their capacity of reducing proteinuria. Several studies about diabetic nephropathy on patients' cohorts and murine models have demonstrated a solid direct relationship between DPP-4 activity and urinary albumin excretion (UAE), thus confirming the capacity of DPP-4is to reduce proteinuria; the mechanism responsible for that effect was studied to assess if it was the result of a direct action on renal impairment or a secondary consequence of the better glycemic control related to these agents. As a result of these more in-depth studies, DPP-4is have demonstrated an improvement of renal inflammation markers and consequent proteinuria reduction, regardless of glucose concentrations. Considering the nephroprotective effects of DPP-4is might be glycemic independent, several studies were conducted to prove the validity of the same effects in non-diabetic nephropathies. Among these studies, DPP-4is demonstrated an improvement of various renal inflammatory markers on several models of non-diabetes dependent renal impairment, confirming their capacity to reduce proteinuria, independently from the action on glucose metabolism. The objective of this review is to present and discuss the so far demonstrated antiproteinuric effect of DPP-4is and their effects on diabetic and non-diabetic nephropathies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The mechanism of action of fibroblast growth factor-23 (FGF23) is becoming increasingly clearer as a result of studies that have defined its structure and pleiotropic effects. Furthermore, data are emerging on the effects exerted on this hormone by iron administration. Ten main iron formulations are recognized (with clear differences in composition and possible reactions of intolerance and anaphylaxis), which are indicated for iron deficiency anemia, including nephropathic subjects, as suggested by medical guidelines. With some types of iron formulation (especially iron carboxymaltose) a particular side effect has been observed: hypophosphatemia, mediated by FGF23. This review aims to draw attention to this correlation and the contradiction represented by the presence of both positive and negative modulation by FGF23, with the effects induced by its increase even after long-term treatment with iron formulation. However, more evidence is needed to understand the reasons for this differential stimulation., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Undergraduate nursing students have been documented to experience ethical distress during their clinical training and felt poorly supported in discussing the ethical issues they encountered., Research Aims: This study was aimed at exploring nursing students' perceived opportunity to discuss ethical issues that emerged during their clinical learning experience and associated factors., Research Design: An Italian national cross-sectional study design was performed in 2015-2016. Participants were invited to answer a questionnaire composed of four sections regarding: (1) socio-demographic data, (2) previous clinical learning experiences, (3) current clinical learning experience quality and outcomes, and (4) the opportunity to discuss ethical issues with nurses in the last clinical learning experience (from 0 - 'never' to 3 - 'very much')., Participants and Research Context: Participants were 9607 undergraduate nursing students who were attending 95 different three-year Italian baccalaureate nursing programmes, located at 27 universities in 15 Italian regions., Ethical Considerations: This study was conducted in accordance with the Human Subject Research Ethics Committee guidelines after the research protocol was approved by an ethics committee., Findings: Overall, 4707 (49%) perceived to have discussed ethical issues 'much' or 'very much'; among the remaining, 3683 (38.3%) and 1217 (12.7%) students reported the perception of having discussed, respectively, 'enough' or 'never' ethical issues emerged in the clinical practice. At the multivariate logistic regression analysis explaining 38.1% of the overall variance, the factors promoting ethical discussion were mainly set at the clinical learning environment levels (i.e. increased learning opportunities, self-directed learning, safety and nursing care quality, quality of the tutorial strategies, competences learned and supervision by a clinical nurse). In contrast, being male was associated with a perception of less opportunity to discuss ethical issues., Conclusion: Nursing faculties should assess the clinical environment prerequisites of the settings as a context of student experience before deciding on their accreditation. Moreover, the nursing faculty and nurse managers should also enhance competence with regard to discussing ethical issues with students among clinical nurses by identifying factors that hinder this learning opportunity in daily practice.

Background: Effective performance of clinical handovers should be one of the priorities of nursing education to promote efficient communication skills and ensure patient safety. However, to date, no studies have explored to what extent nursing students are involved in handovers., Objective: To explore nursing students' handover involvement during their clinical rotations and associated factors., Method: This was a secondary analysis of a large national cross-sectional study that involved 9607 undergraduate nursing students in 27 universities across 95 three-year Italian baccalaureate nursing programs. The involvement in the clinical handovers was the end point (from 0, never, to 3, always). A path analysis was performed to identify variables directly and indirectly affecting students' handover involvement., Results: Handover involvement was reported as 'only a little', 'to some extent', and 'always' by 1739 (18.1%), 2939 (30.6%), and 4180 (43.5%) students, respectively; only 749 (7.8%) of students reported never being involved. At the path analysis explaining the 19.1% of variance of nursing students' involvement, some variables emerged that directly increased the likelihood of being involved in handovers. These were being female (β = 0.115, p < 0.001); having children (β = 0.107, p = 0.011); being a 3rd-year student (β = 0.142, p < 0.001) and being a 2nd-year student as compared to a 1st-year student (β = 0.050, p = 0.036); and having a longer clinical rotation (β = 0.015, p < 0.001) in units with high 'quality of the learning environment' (β = 0.279, p < 0.001). Moreover, students who were supervised by the nurse teacher (β = -0.279, p < 0.001), or by a nurse on a daily basis (β = -0.253, p = 0.004), or by the staff (β = -0.190, p < 0.001) reported being less involved in handovers as compared to those students supervised by a clinical nurse. Variables with indirect effects also emerged (model of student's supervision adopted at the unit level, and number of previous clinical rotations attended by students). Moreover, handover involvement explained 11.5% of students self-reported degree of competences learned during the clinical experience., Conclusions: Limiting students' opportunity to be involved in handover can prevent the development of communication skills and the professional socialization processes. Strategies at different levels are needed to promote handover among undergraduate nursing students., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: The early suspension of Altitude trial in recent years has induced most nephrologists and cardiologists to abandon Aliskiren use. Consequently, the potential usefulness of the direct renin inhibition in IgA glomerulonephritis remained an under-investigated therapeutic option., Case Report: We report the case of a 53 years old IgA GMN patient unresponsive to all conventional anti-angiotensin-2 agents, steroids and immunosuppressants, in which the administration of Aliskiren permitted to achieve and maintain a complete proteinuria remission in the absence of any adverse event., Conclusion: Aliskiren might represent a valid and safe therapeutic option in IgA GMN, although further investigations would be needed to confirm this conclusion., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Easy-to-access tools have been demonstrated to improve evidence-based practice (EBP) competences among nursing students. However, students' perception of access to EBP tools (e.g., clinical practice guidelines [CPGs], protocols) is unknown., Aims: To explore: (1) nursing students' opportunity to access EBP tools during their education, and (2) associated factors., Methods: A national cross-sectional study including all Italian nursing programs. Nursing students were deemed eligible according to the following inclusion criteria: Those who (1) were attending or just ended their practical rotation lasting at least 2 weeks at the time of the survey, and (2) expressed through written informed consent their willingness to take part in the study. Participants were asked about their perceived opportunity to access EBP tools during their most recent clinical learning experience (from 0 - not at all to 3 - always). A set of explanatory variables was collected at the individual, nursing program, and regional levels by using a questionnaire., Results: Nine thousand six hundred and seven (91.6%) out of 10,480 nursing students took part in the study. Overall, 4,376 (45.6%) students perceived not at all or only a small opportunity to access EBP tools during their most recent clinical rotation. In the multilevel analysis, factors promoting access were mainly set at the clinical learning environment level (high safety and nursing care quality, high self-directed learning opportunities, high quality of the learning environment, and being supervised by a clinical nurse). In contrast, male gender and lower academic class were associated with a lower perception of accessibility to EBP tools. A consistent variability in the perceived opportunity to access EBP tools emerged across regions., Linking Evidence to Action: Evidence-based decision-making is increasingly expected from nurses. Therefore, nursing faculties should safeguard and continuously improve students' competence regarding EBP, by implementing strategies mainly at the nursing program and regional levels., (© 2018 Sigma Theta Tau International.)

Non-diabetic glomerulonephritis is a frequent cause of end-stage renal disease. The use of renin-angiotensin-aldosterone system blockers is a fundamental therapeutic approach. However, converting enzyme inhibitors (ACE-is) and angiotensin receptor blockers do not always achieve the desired target of proteinuria. The induction of the prorenin and renin up-regulation is a possible explanation. Aliskiren is the first drug acting as direct inhibitor of plasmatic renin activity, also able to interfere with the prorenin and renin profibrotic escape. We aimed at reviewing the literature for the assessment of potential efficacy and safety of aliskiren in the treatment of non-diabetic glomerulonephritis. The data on this topic are limited; however, we concluded for a possible usefulness of aliskiren. The renal safety profile appears potentially acceptable in non-diabetic patients although extreme carefulness, particularly with respect to long-term renal and cardiovascular tolerability, is recommended.