Going to war with COVID-19: Strategies for SARS-CoV-2 management in the Padua Nephrology and Dialysis Unit's hemodialysis facility.

BACKGROUND: The recent SARS-CoV-2 outbreak represents a global health emergency, and dialysis patients are a high-risk population. Patients with end-stage renal disease (ESRD) in hemodialysis facilities require specific protocols to be planned and promptly executed for the management of suspected/confirmed cases of COVID-19 with respect to prevention, protection, screening, and isolation. MATERIALS AND METHODS: In order to prevent the spread of SARS-CoV-2 in our Hemodialysis Unit, we adopted individual protection measures accompanied by measures to minimize contacts among hemodialysis patients with suspicious symptoms as well as other patients and medical staff. We provided our patients detailed instructions to be followed in the event of their having symptoms compatible with SARS-CoV-2 infection or having contacts with SARS-CoV-2-positive subjects. Ultimately, four possible scenarios and care paths were developed and implemented in collaboration with the Infectious Diseases and Emergency Units at the Padua University Hospital. RESULTS: The application of this strategy has resulted in the nearly 200 patients treated in our hemodialysis facilities while there were only 2 cases of COVID-19 (1% incidence rate) with no deaths. CONCLUSION: We attribute the low COVID-19 incidence noted so far for patients in our hemodialysis facilities to the early detection and prompt isolation of suspected patients per our specific plan along with the prompt application of preventive measures.

Evaluating Nephrocheck® as a Predictive Tool for Acute Kidney Injury.

Acute kidney injury (AKI) is a common complication in critically ill patients in the intensive settings with increased risks of short- and long-term complications and mortality. AKI is also associated with an increased length of stay in intensive care units (ICU) and worse kidney function recovery at hospital discharge. The management of AKI is one of the major challenges for nephrologists and intensivists overall for its early diagnosis. The current KDIGO criteria used to define AKI include the serum creatinine and urinary output that are neither sensitive nor specific markers of kidney function, since they can be altered only after hours from the kidney injury. In order to allow an early AKI detection, in the last years, several studies focused on the identification of new biomarkers. Among all these markers, urinary insulin-like growth factor-binding protein (IGFBP-7) and tissue inhibitor of metalloproteinase (TIMP-2) have been proven as the best-performing and have been proposed as a predictive tool for the AKI detection in the critical settings in order to perform an early diagnosis. Patients undergoing major surgery, cardiac surgery, those with hemodynamic instability or those with sepsis are believed to be the top priority patient populations for the biomarker test. In this view, the urinary [TIMP-2] x [IGFBP-7] becomes an important tool for the early detection of patients at high risk for AKI and its integration with the local ICU experience has to provide a multidisciplinary management of AKI with the institution of a rapid response team in order to assess patients and customize AKI management.

Angiotensin II and Cardiovascular-Renal Remodelling in Hypertension: Insights from a Human Model Opposite to Hypertension.

Insights into the Angiotensin II (Ang II) signalling pathways have been provided by extensive studies using Bartter's/Gitelman's syndromes patients. These syndromes are characterized by activation of the renin-angiotensin-aldosterone system but do not develop hypertension and cardiovascular remodelling, therefore represent a mirror image of hypertension and clinically manifest themselves as the opposite of hypertension. The short and the long-term signalling of Ang II remain an important matter of investigation to shed light on mechanisms responsible for the pathophysiology of hypertension and its long-term complications, such as cardiovascular remodelling and atherogenesis. In particular the long-term signalling of Ang II is involved in the pathophysiology of cardiovascular-renal remodelling, inflammatory and hypertrophic responses in which the relationship between RhoA/Rho kinase pathway and NO system plays a crucial role. This review reports the results of our studies in Bartter's and Gitelman's syndromes to get better insight these processes and the role of Ang II signaling. The information obtained from the studies in Bartter's/Gitelman's patients can, in fact, clarify, confirm or be used to gather more general data on the biochemical mechanisms responsible for the pathophysiology of hypertension and its long-term complications and could contribute to identify additional potential significant targets of therapy.

The blocking of angiotensin II type 1 receptor and RhoA/Rho kinase activity in hypertensive patients: Effect of olmesartan medoxomil and implication with cardiovascular-renal remodeling.

HYPOTHESIS/INTRODUCTION: The pathophysiological role of oxidative stress (OxSt) in hypertension and target organ damage is recognized. Angiotensin II (Ang II) induces OxSt via NAD(P)H oxidase activation and production of proinflammatory cytokines/growth factors leading to cardiovascular-renal remodeling. Ang II stimulates the RhoA/Rho kinase (ROCK) pathway, which is deeply involved in the development of cardiovascular-renal remodeling via OxSt induction. Olmesartan, an Ang II type 1 receptor blocker, possesses antioxidant and activating nitric oxide system-related effects, which we have shown in terms of p22(phox) reduction, heme oxygenase-1 and calcitonin gene-related peptide increase. This study evaluates in 15 untreated hypertensive patients the effect of olmesartan treatment on p63RhoGEF, key in Ang II-induced ROCK activation, and MYPT-1 phosphorylation, a marker of ROCK activity. MATERIALS AND METHODS: The p63RhoGEF protein level and MYPT-1 phosphorylation (Western blot) were evaluated at baseline, and after three and six months of olmesartan treatment. RESULTS: Olmesartan normalized systolic and diastolic BP (p < 0.001), reduced p63RhoGEF level: 1.3±0.25 d.u. (baseline) vs 1.0±0.29 (three months), p < 0.0001 vs 1.0±0.22, (six months), p < 0.0001 and MYPT-1 phosphorylation: 1.2 ±0.14 (baseline) vs 0.9±0.19 (three months), p = 0.008, vs 0.8±0.16 (six months), p = 0.001. CONCLUSIONS: These data added to our previous results further provide a mechanistic rationale for olmesartan's antioxidant/anti-inflammatory potential translation, in the long term, toward anti-atherosclerotic/anti-remodeling effects reported by clinical trials.