Oxidative stress reduction by icodextrin-based glucose-free solutions in peritoneal dialysis: Support for new promising approaches.

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 p22phox 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: p22phox 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 p22phox 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.

"Every Cloud Has a Silver Lining": How Three Rare Diseases Defend Themselves from COVID-19 and What We Have Learnt from It.

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.

Oxidative stress and its role in Fabry disease.

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.

The Ultrasound Renal Stress Test for the Assessment of Functional Renal Reserve in Kidney Transplantation: A Pilot Study in Living Donors.

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 m2. 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.

Low-Protein Diet in Elderly Patients with Chronic Kidney Disease Stage 4 and 5 in Conservative Management: Focus on Sarcopenia Development.

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.

Conservative Management in End-Stage Kidney Disease between the Dialysis Myth and Neglected Evidence-Based Medicine.

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.

EBV Reactivation in Transplant Recipients following SARS-CoV-2 Infection: A Retrospective Study.

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.