Search

Federico Nalesso,1 Leda Cattarin,1 Laura Gobbi,1 Antonio Fragasso,1 Francesco Garzotto,2 Lorenzo Arcangelo Calò1 1Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Padova, Italy; 2Healthcare Directorate Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, ItalyCorrespondence: Federico NalessoDepartment of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova, Via Giustiniani, 2, Padova 35128, ItalyTel +39 049 8213128Email federico.nalesso@aopd.veneto.itAbstract: 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.Keywords: TIMP-2, IGFBP-7, NGAL, KIM-1, interleukin-18, L-FABP

Francesco Francini-Pesenti,1 Paolo Spinella,1 Lorenzo A Calò2 1Department of Medicine (DIMED), Nutrition Unit, University of Padova-Azienda Ospedaliera, Padova, Italy; 2Department of Medicine (DIMED), Nephrology, Dialysis and Transplantation Unit, University of Padova-Azienda Ospedaliera, Padova, ItalyCorrespondence: Lorenzo A Cal&#x00F2Department of Medicine, Nephrology, Dialysis and Transplantation Unit, University of Padova-Azienda Ospedaliera, Via Giustiniani 2, Padova 35128, ItalyTel +39 049 821 3071Fax +39 049 821 7921Email renzcalo@unipd.itAbstract: Metabolic syndrome (MetS) is a set of cardiovascular risk factors which severely increases the risk of type II diabetes, renal disease and cardiovascular disease. Over the last decades, the role of dietary bioactive substances in features of MetS has been extensively investigated. Due to their multiple properties, these plant-derived natural compounds have demonstrated to provide positive effects in obesity, diabetes, renal and in cardiovascular disease. Catechins of green tea and caffeine reduce body mass index and waist circumference. Catechins, anthocyanins and proanthocyanidins of cocoa reduce blood pressure and blood glucose. Curcumin and silymarin exert hepatoprotective effects. Monacolins of red yeast rice are effective cholesterol-lowering agents. However, inconsistent or conflicting results have been found in clinical trials when other promising compounds in vitro or in animal studies, such as policosanol, curcumin or silymarin, were used. Low oral bioavailability of substances, ineffective dosages, inadequate treatment duration and insufficient statistical approach may explain the lack of effectiveness observed in some human studies. Further clinical studies are needed to better understand the role of bioactive compounds in the prevention and management of MetS.Keywords: metabolic syndrome, bioactive substances, nutrition, cardiovascular risk

Autonomic nervous system dysfunction has a major role in the blood pressure (BP) decrease associated with orthostatic hypotension and syncope. The clinical picture of Bartter and Gitelman syndromes includes reduced extracellular fluid volume and normotension or hypotension, but no study has explored autonomic nervous system status in patients with hypotensive episodes associated with these diseases. We tested sympathetic and parasympathetic nervous system function in 4 patients with Bartter and Gitelman syndromes with chronic hypotension. Each patient underwent a battery of autonomic reflex tests, including BP and heart rate response to orthostatism, Valsalva maneuver, cold-pressor test, hand-grip test, and deep breathing. Plasma catecholamines also were measured. BP was monitored during tests by means of continuous noninvasive finger BP recording. Orthostatic hypotension was observed in 1 patient who experienced syncope episodes. Valsalva ratio ranged from 1.21 to 1.61. During the cold-pressor test, the range of systolic and diastolic BP increases were 8 to 31 and 6 to 24 mm Hg, respectively. During the hand-grip test, systolic and diastolic BP increases ranged from 10 to 39 and 8 to 32 mm Hg, respectively. During hyperventilation, the difference between the highest and lowest heart rates was 12 or more beats/min in all patients. Patients' plasma norepinephrine concentrations increased during standing. Our preliminary results suggest that chronic hypotension in patients with Bartter and Gitelman syndromes is not associated with sympathetic and parasympathetic nervous system dysfunction, even when orthostatic hypotension is present. This normal autonomic function suggests that other pathophysiological mechanisms, such as the characteristic vasoconstrictor abnormal cell signaling, may account for hypotension in patients with Bartter and Gitelman syndromes. Copyright © 2007 by the National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Bartter's and Gitelman's syndromes (BS/GS) are genetically determined kidney tubulopathies leading to electrolyte and neurohormonal abnormalities. Although considered benign entities, major adverse cardiovascular events may complicate both syndromes, in form of ventricular arrhythmias leading to palpitations, syncope or sudden cardiac death, microvascular cardiac dysfunction and exercise-induced myocardial contractile deficit. The mechanisms leading to cardiovascular complications are not only driven by chronic electrolyte abnormalities, i.e. chronic hypokalemia and hypomagnesemia, but also by neurohormonal alterations that can impair vascular tone and myocardial contractility. In presence of triggering factors, BS/GS patients may experience a spectrum of cardiac arrhythmias necessitating prompt diagnosis and treatment. The aim of this review is to explore the pathophysiological mechanisms of BS and GS, highlighting those responsible for cardiovascular involvement, and to analyze the spectrum of associated cardiovascular complications. This highlights the importance of an integrated shared management of GS/BS patients between Nephrologist and Cardiologist., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Oxidative stress (OxSt) and inflammation are common in end-stage renal disease and dialysis patients; they are known risk factors for cardiovascular disease and mortality. In peritoneal dialysis (PD), OxSt and inflammation are even further increased compared to the already increased oxidative stress of their pre-dialysis phase. This is due to the high glucose-based solutions currently used, whose continuous contact with the peritoneal membrane can induce significant long-term morphological and functional changes (mesothelial to mesenchymal transition, thickening, neo-angiogenesis and fibrosis) of the peritoneal membrane. Oxidative stress plays a very important role in these processes, which may compromise the peritoneal dialysis procedure. There is, therefore, the need for more biocompatible dialysis fluids with polymers other than glucose to prevent and treat OxSt and inflammation. The most known and used of such glucose-free and more biocompatible peritoneal dialysis solutions is icodextrin, which has shown a protective effect from oxidative stress. This has supported the consideration of the use of glucose-free-based peritoneal dialysis fluids in order to reduce oxidative stress and improve peritoneal membrane survival. Studies investigating peritoneal dialysis with the use of osmo-metabolic agents (L-carnitine, xylitol and their combination) in peritoneal fluids replacing glucose-based fluids are, in fact, ongoing. They represent a promising strategy to reduce OxSt, preserve the peritoneal membrane's integrity and improve patients' outcome.

Background/objectives: Comprehensive conservative management (CCM) is a viable treatment option for elderly patients with end-stage kidney disease (ESKD). However, it involves a significant change in dietary habits, such as adopting a low-protein diet. Therefore, it is crucial to understand its impact on the patient's quality of life (QoL), particularly when compared to hemodialysis (HD). The study aims to evaluate the differences in the QoL between patients undergoing CCM and HD., Methods: The study included 50 patients over 75 with ESKD, with 25 patients in the CCM group and 25 in the HD group. The CCM group followed a personalized low-protein diet, while the HD group did not have protein restrictions. Various parameters were assessed, including demographic data, urine output, blood tests, comorbidity index, Visual Analog Scale (VAS), and hospitalization. The SF-12 questionnaire assessed the QoL, and the Physical Composite Score (PCS) and Mental Composite Score (MCS) were calculated., Results: The study revealed no age and comorbidity index differences between CCM and HD patients. In contrast, CCM patients reported significantly better physical and mental well-being than HD patients. In univariate analysis, CCM (B 0.24, p = 0.001), protein intake (B -0.004, p = 0.008), hospitalization (B -0.18, p = 0.024), urine output (B 0.25, p = 0.001), and VAS (B -0.26, p < 0.001) influenced the PCS. At the same time, only the type of treatment (B = 0.15, p = 0.048), urine output (B 0.18, p = 0.02), and VAS (B -0.14, p = 0.048) influence the MCS. In contrast, in multivariate analysis, only CCM contributed to an improved PCS (B 0.19, p = 0.003) and MCS (B 0.16, p = 0.03), while a higher VAS worsened the PCS (B -0.24, p < 0.001) and MCS (B -0.157, p = 0.0024)., Conclusions: In elderly patients with similar basal conditions, health-related QoL perception is better in CCM than in HD patients.

Background: The possibility of keeping liver grafts viable and functioning until transplantation has been explored since the 1950s. However, the current modalities of Normothermic Machine Perfusion (NMP) have shown several limitations, such as the inability to correct electrolytes and pH derangements efficiently. Combining NMP with continuous kidney replacement therapy (CKRT) might provide a promising new model to overcome these issues. Methods: An NMP that covers the organ perfusion, oxygenation, carbon dioxide removal, and thermal balance was connected to a CKRT circuit to ensure physiological hydro-electrolytes, acid-base balance, and catabolite removal from the perfusate. Results: The integration of NMP and CKRT maintains a neoplastic liver in a perfusion system with physiological perfusate for 100 h. CKRT re-established and maintained the hydro-electrolyte and acid-base status throughout the 100 h of perfusion. Significant limitations were the need for frequent monitoring of electrolytes and acid-base disorders and the loss of low molecular weight nutrients, which have to be replenished by manual infusion into the system. Conclusions: This novel CKRT-NMP integrated system may represent a practical and versatile model to support organs' perfusion and extend preservation times. Further experiments are needed to fix monitoring and adjusting processes.

Background: Oxidative stress (OxSt) and inflammation are common in CKD and are known CV and mortality risk factors. In peritoneal dialysis (PD) OxSt and Inflammation even increase due to the use of glucose-based solutions., Patients and Methods: This study analyzed in 15 PD patients the effect of 3 and 6 months of treatment with icodextrin-based glucose-free solutions on OxSt and inflammation, evaluating p22 phox protein expression (Western blot), NADPH oxidase subunit, essential for OxSt activation, MYPT-1 phosphorylation state, marker of RhoA/Rho kinase pathway (ROCK) activity, involved in the induction of OxSt (Western blot) and Malondialdehyde (MDA) production (fluorimetric assay). Interleukin (IL)-6 blood level (chemiluminescence assay) has been measured and used as a marker of inflammation., Results: p22 phox protein expression, MYPT 1 phosphorylation, and MDA were reduced after 3 months from the start of icodextrin (1.28 ± 0.18 d.u. vs. 1.50 ± 0.19, p = 0.049; 0.89 ± 0.03 vs. 0.98 ± 0.03, p = 0.004; 4.20 ± 0.18 nmol/mL vs. 4.84 ± 0.32 nmol/mL, p = 0.045, respectively). In a subgroup of 9 patients who continued the treatment up to 6 months, MYPT-1 phosphorylation was further reduced at 6 months compared to baseline (0.84 ± 0.06 vs. 0.99 ± 0.04, p = 0.043), while p22 phox protein expression was reduced only at 6 months versus baseline (1.03 ± 0.05 vs. 1.68 ± 0.22, p = 0.021). In this subgroup, MDA was reduced at 6 months versus baseline (4.03 ± 0.24 nmol/mL vs. 4.68 ± 0,32, p = 0.024) and also versus 3 months (4.03 ± 0.24 vs. 4.35 ± 0.21, p = 0.008). IL-6 level although reduced both at 3 and 6 months, did not reach statistical significance., Conclusions: The reduction of OxSt with icodextrin-based PD solutions, although obtained in a small patients cohort and in a limited time duration study, strongly supports the rationale of using osmo-metabolic agents-based fluids replacing glucose-based fluids. Ongoing studies with these agents will provide information regarding preservation of peritoneal membrane integrity, residual renal function, and reduction of CVD risk factors such as OxSt and inflammation., (© 2024 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.)

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

Background: Methylmalonic Aciduria (MA) without homocystinuria (or isolated MA) is a group of rare inherited metabolic disorders which leads to the accumulation of methylmalonic acid (MMA), a toxic molecule that accumulates in blood, urine, and cerebrospinal fluid, causing acute and chronic complications including metabolic crises, acute kidney injury (AKI), and chronic kidney disease (CKD). Detailed Case Description: Herein, we report a case of a 39-year-old male with MA and stage IV CKD who experienced acute metabolic decompensation secondary to gastrointestinal infection. The patient underwent a single hemodialysis (HD) session to correct severe metabolic acidosis unresponsive to medical therapy and to rapidly remove MMA. The HD session resulted in prompt clinical improvement and shortening of hospitalization., Discussion: MMA accumulation in MA patients causes acute and life-threatening complications, such as metabolic decompensations, and long-term complications such as CKD, eventually leading to renal replacement therapy (RRT). Data reported in the literature show that, overall, all dialytic treatments (intermittent HD, continuous HD, peritoneal dialysis) are effective in MMA removal. HD, in particular, can be useful in the emergency setting to control metabolic crises, even with GFR > 15 mL/min. Kidney and/or liver transplantations are often needed in MA patients. While a solitary transplanted kidney can be rapidly affected by MMA exposure, with a decline in renal function even in the first year of follow-up, the combined liver-kidney transplantation showed better long-term results due to a combination of reduced MMA production along with increased urinary excretion., Conclusions: Early diagnosis, multidisciplinary management and preventive measures are pivotal in MA patients to avoid recurrent AKI episodes and, consequently, to slow down CKD progression.

Fabry disease is a rare X-linked disease characterized by deficient expression and activity of alpha-galactosidase A with consequent lysosomal accumulation of glycosphingolipids, particularly globotriaosylceramide in various organs. Currently, enzyme replacement therapy with recombinant human α-galactosidase is the cornerstone of the treatment of Fabry patients, although in the long term enzyme replacement therapy fails to halt disease progression, in particular in case of late diagnosis. This suggests that the adverse outcomes cannot be justified by the lysosomal accumulation of glycosphingolipids alone, and that additional therapies targeted at further pathophysiologic mechanisms might contribute to halting the progression of cardiac, cerebrovascular and kidney disease in Fabry patients. Recent evidence points toward the involvement of oxidative stress, oxidative stress signaling and inflammation in the pathophysiology of cardio cerebrovascular and kidney damage in Fabry patients. This review reports the current knowledge of the involvement of oxidative stress in Fabry disease, which clearly points toward the involvement of oxidative stress in the pathophysiology of the medium to long-term cardio-cerebrovascular-kidney damage of Fabry patients and summarizes the antioxidant therapeutic approaches currently available in the literature. This important role played by oxidative stress suggests potential novel additional therapeutic interventions by either pharmacologic or nutritional measures, on top of enzyme replacement therapy, aimed at improving/halting the progression of cardio-cerebrovascular disease and nephropathy that occur in Fabry patients., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Introduction: Chronic kidney disease is a degenerative and increasingly prevalent condition that includes metabolic abnormalities and is associated with a higher risk of sarcopenia. The conservative approach points primarily to controlling metabolic issues and reducing the risk of malnutrition and sarcopenia, slowing the progression of kidney disease. The present study aims to evaluate the effect of a low-protein diet on malnutrition and sarcopenia., Methods: A total of 45 patients (33 male and 12 female) aged over 70 with chronic kidney disease stage 4-5 in conservative management were considered. All patients had a dietary assessment and prescription of personalized low-protein dietary plans (≤0.6 g protein/kg) and a follow-up control between 4 and 6 months. In preliminary and follow-up evaluations, anthropometric data, blood examinations, body composition results, muscle strength, physical performance, and a 3-day food diary were collected., Results: In the follow-up period, a significant weight loss ( p = 0.001) and a decrease in body mass index ( p = 0.002) were recorded. Food diaries revealed a significant reduction in protein, sodium, potassium, and phosphorus intake ( p < 0.001), with a significant reduction in urea ( p < 0.001) and proteinuria ( p = 0.01) without any impact on lean mass ( p = 0.66). Considerable variations in adherence between food diaries and the prescribed diet were also noted., Conclusions: Providing a personalized low-protein diet led to significant benefits in a short period without worsening the patient's nutritional status.

The process of SARS-CoV-2 infection, responsible for the COVID-19 pandemic, is carried out through different steps, with the interaction between ACE2 and Spike protein (S) being crucial. Besides of that, the acidic environment of endosomes seems to play a relevant role in the virus uptake into cells and its intracellular replication. Patients affected by two rare genetic tubulopathies, Gitelman's and Bartter's Syndromes, and a rare genetic metabolic disease, Fabry Disease, have shown intrinsic protection from SARS-CoV-2 infection and COVID-19 on account of specific intrinsic features that interfere with the virus uptake into cells and its intracellular replication, which will be reported and discussed in this paper, providing interesting insights for present and future research.

In the evolving landscape of nephrology and kidney transplants, assessing renal functional reserve (RFR) in living kidney donors is essential for ensuring donor safety and successful transplantation. This study explores the use of the Intra-Parenchymal Renal Resistive Index Variation (IRRIV) test, a novel non-invasive method, to measure RFR in living donors. Our observational study included 11 participants undergoing living kidney donations, evaluated using the IRRIV-based Renal Stress Test (RST) before and 12 months post-nephrectomy. The study demonstrated significant changes in creatinine and eGFR CKD-EPI levels post-donation, with an average creatinine rise from 69 to 97 µmol/L and a reduction in eGFR from 104 to 66 mL/min/1.73 m 2 . These variations align with the expected halving of nephron mass post-nephrectomy and the consequent recruitment of RFR and hyperfiltration in the remaining nephrons. This pilot study suggests that the IRRIV-based RST is a practical, safe, and reproducible tool, potentially revolutionizing the assessment of RFR in living kidney donors, with implications for broader clinical practice in donor eligibility evaluation, even in borderline renal cases. Furthermore, it confirms the feasibility of RST in living kidney donors and allows us to assess the sample size in 48 donors for a future study.

In the last few decades, the aging of the general population has significantly increased the number of elderly patients with end-stage kidney disease (ESKD) who require renal replacement therapy. ESKD elders are often frail and highly comorbid with social issues and seem to not benefit from dialysis in terms of survival and quality of life. Conservative management (CM) could represent a valid treatment option, allowing them to live for months to years with a modest impact on their habits. Despite these possible advantages, CM remains underused due to the myth of dialysis as the only effective treatment option for all ESKD patients regardless of its impact on quality of life and survival. Both CM and dialysis remain valid alternatives in the management of ESKD. However, assessing comorbidities, disabilities, and social context should drive the choice of the best possible treatment for ESKD, while in elderly patients with short life expectancies, referring them to palliative care seems the most reasonable choice.

Reactivation and primary infection with a high Epstein Barr Virus (EBV) DNA level in kidney transplant patients could cause severe complications, including the development of Post-Transplantation Lymphoproliferative Disease (PTLD). While in the general population the reactivation of EBV after SARS-CoV-2 infection has been reported, very few data are available in transplant recipients. Our retrospective study aimed to evaluate a possible EBV reactivation in kidney transplant patients following SARS-CoV-2 infection and a possible impairment of the immune system. In addition, the effects of changes in immunosuppressive therapy on EBV DNA reactivation and vaccination were also evaluated. A total of 166 kidney transplant patients followed at the Kidney-Pancreas Transplant Ambulatory Nephrology Unit at Padova University Hospital were retrospectively considered for an observation period of 6 months from January 2020 to April 2023. EBV DNA level was measured by Rt-PCR and evaluated 6 months before and after SARS-CoV-2 infection. Patients' serological states were established via quantification of anti-VCA and anti-EBNA (chemiluminescence). Patients' immune systems were characterized by CD4 + /CD8 + lymphocyte ratio (flow cytometry). EBV DNA was reactivated in 50% of the 166 patients with COVID-19 who completed the study. Older patients with more severe forms of COVID-19 had higher EBV reactivation ( p < 0.05). EBV reactivation significantly increased in patients with severe SARS-CoV-2 infection requiring hospitalization compared to patients managed at home ( p < 0.001). CD4 + /CD8 + lymphocyte ratio was reduced in patients with a younger age of transplant ( p < 0.01) and on a higher dose of steroids ( p < 0.01). The results of our study confirm the role of immunodepression, especially in recent transplant patients and those on high steroids, in EBV reactivation. These results combined with the few available in the literature might contribute to providing an optimal management of immunosuppressive treatment for these patients in order to obtain an immune state unfavorable to the activation of latent viruses, including EBV.

Background: Parietal epithelial cells are a heterogeneous population of cells located on Bowman's capsule. These cells are known to internalize albumin with a still undetermined mechanism, although albumin has been shown to induce phenotypic changes in parietal epithelial cells. Proximal tubular cells are the main actors in albumin handling via the macromolecular complex composed by ClC-5, megalin, and cubilin. This study investigated the role of ClC-5, megalin, and cubilin in the parietal epithelial cells of kidney biopsies from proteinuric lupus nephritis patients and control subjects and identified phenotypical changes occurring in the pathological milieu., Methods: Immunohistochemistry and immunofluorescence analyses for ClC-5, megalin, cubilin, ANXA3, podocalyxin, CD24, CD44, HSA, and LTA marker were performed on 23 kidney biopsies from patients with Lupus Nephritis and 9 control biopsies (obtained from nephrectomies for renal cancer)., Results: Two sub-populations of hypertrophic parietal epithelial cells ANXA3 + /Podocalyxin - /CD44 - , both expressing ClC-5, megalin, and cubilin and located at the tubular pole, were identified and characterized: the first one, CD24 + /HSA - /LTA -  had characteristics of human adult parietal epithelial multipotent progenitors, the second one, CD24 - /LTA + /HSA + committed to become phenotypically proximal tubular cells. The number of glomeruli presenting hypertrophic parietal epithelial cells positive for ClC-5, megalin, and cubilin were significantly higher in lupus nephritis patients than in controls., Conclusions: Our results may provide further insight into the role of hypertrophic parietal epithelial cells located at the tubular pole and their possible involvement in protein endocytosis in lupus nephritis patients. These data also suggest that the presence of hypertrophic parietal epithelial cells in Bowman's capsule represents a potential resource for responding to protein overload observed in other glomerulonephritis., (© 2023. The Author(s).)

In the last two decades, the study of the renin-angiotensin-aldosterone system (RAAS) has revealed a counterregulatory protective axis. This protective arm is characterized by ACE2/Ang 1-7/MasR and Ang 1-9 that largely counteracts the classic arm of the RAAS mediated by ACE/Ang II/AT1R/aldosterone and plays an important role in the prevention of inflammation, oxidative stress, hypertension, and cardiovascular remodeling. A growing body of evidence suggests that enhancement of this counterregulatory arm of RAAS represents an important therapeutic approach to facing cardiovascular comorbidities. In this review, we provide an overview of the beneficial effects of ACE2, Ang 1-7/MasR, and Ang 1-9 in the context of oxidative stress, vascular dysfunction, and organ damage.

Regional Citrate Anticoagulation (RCA) is considered the first-line anticoagulation for Continuous Kidney Replacement Therapy (CKRT). The RCA requires strict protocols and trained staff to avoid unsafe use and ensure its benefit. We have analyzed all our CKRT prescriptions from December 2020 to April 2022 anonymously, collecting data on CKRT, lab tests, clinical conditions, and complications of RCA. In addition, in order to better detect citrate accumulation, we have performed an RCA protocol by reducing the Ca Tot /Ca 2+ ratio cut-off from 2.50 to 2.40 and increasing the number of calcium checks according to its trend. Among the 374 patients in CKRT, 104 received RCA prescriptions, of which 11 (10.6%) were discontinued: 4 for the suspicion of citrate accumulation, 1 for the development of metabolic alkalosis, 1 for the shift to a different CKRT procedure due to the need for a higher bicarbonate dose, 4 for the elevation of hepatocytolysis indexes, and 1 due to a preemptive discontinuation following massive post-surgery bleeding. None of the patients have had citrate toxicity as indicated by a Ca Tot /Ca 2+ greater than 2.50, and our protocol has allowed the early identification of patients who might develop clinical citrate toxicity.