Effects of Late Conversion from Twice-Daily to Once-Daily Slow Release Tacrolimus on the Insulin Resistance Indexes in Kidney Transplant Patients

The use of tacrolimus (Tac) may be involved in the development of new-onset diabetes after transplantation (NODAT) in a dose-related manner. This study aimed to evaluate the effects of a standard twice-daily formulation of Tac (TacBID) vs. the once-daily slow-release formulation (TacOD) on the basal insulin resistance indexes (Homa and McAuley), and related metabolic parameters, in a cohort of kidney transplant patients. We retrospectively evaluated 20 stable renal transplant recipients who were switched from TacBID to TacOD. Blood levels of Tac were analyzed at one-month intervals from 6 months before to 8 months after conversion. Moreover, Homa and McAuley indexes, C-peptide, insulin, HbA1c, uric acid, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol serum levels and their associations with Tac levels were evaluated. We observed a significant decrease in Tac exposure (8.5 ± 2 ng/mL, CV 0.23 vs. 6.1 ± 1.9 ng/mL, CV 0.31, TacBID vs. TacOD periods, p 0.05) and McAuley indexes (7.12 ± 1 vs. 7.58 ± 1.4, p > 0.05). Similarly, blood levels of glucose, insulin, HbA1c, lipids, and uric acid were unchanged between the two periods, while C-peptide resulted significantly lower after conversion to TacOD. These data suggest that in kidney transplant recipients, reduced Tac exposure has no significant effects on basal insulin sensitivity indexes and metabolic parameters

The role of a data manager at a clinical trial center: the experience of the Alessandria hospital, Italy

Objectives: To define the Data Manager (DM) job description within the Clinical Trial Center (CTC) of the Alessandria Hospital (AO AL). To identify the number of authorized clinical studies after the implementation of three DMs in the CTC of the AO AL. Methods: The activities of the DM within the CTC of the AO AL take place in the activation, management and conclusion of clinical trials. The activities were monitored through specific indicators from June 01st, 2019 to May 31st, 2020. Results: During the reference period, an increased authorized studies were observed. Conclusion: The implementation of DMs in the CTC of AO AL has been demonstrated the importance of the figure itself, which, although it has not professionally recognized yet, is found to be fundamental in clinical research

Successful Extracorporeal Blood Purification Therapy using Double Haemoadsorption Device in Severe Endotoxin Septic Shock: A Case Report

Introduction:In patients admitted to the Intensive Care Unit (ICU), sepsis can lead to acute kidney injury (AKI), which may require the initiation of continuous renal replacement therapy (CRRT) in 15-20% of cases. There is no consensus about the best extracorporeal treatment to choose in septic patients with AKI. Case presentation We describe the case of a 70-year-old woman admitted to the ICU with a severe endotoxin septic shock due to Neisseria meningitidis serogroup C. Despite prompt medical intervention, including fluid resuscitation, high dose vasopressor, inotrope support, and broad-spectrum antimicrobial treatment, in a few hours patient's haemodynamic worsened and she developed multi-organ failure, including severe AKI, requiring CRRT. So, continuous veno-venous haemodiafiltration was started, using an oXiris (R) haemodiafilter set, in series with an adsorber device (CytoSorb (R)). After 48 hours of this combined extracorporeal treatment, haemodynamic parameters improved, allowing a significant reduction of the vasoactive therapy, with a concomitant decrease in endotoxin and inflammatory markers serum levels. In the following days patient's conditions still improved and renal function recovered. Conclusions Timely extracorporeal blood purification therapy, using a double haemoadsorption device, may be effective in the management of severe septic shock

Gli inibitori del segnale di proliferazione (inibitori di mTor) nel trapianto di rene [mTOR inhibitors in kidney transplantation]

A changing paradigm of treatment of kidney transplant recipients is a new, wider approach to immunosuppression, which should take into account both antiviral and anticancer effects, in addition to cardiovascular protection. Recent observations suggest that the early introduction of mammalian target of rapamycin inhibitors (mTORi) in association with low dose CNI may offer many of these effects. The present manuscript summarizes benefits and contraindications of combinations with mTORi in kidney transplant immunosuppressive strategies

Low Protein Diets and Plant-Based Low Protein Diets: Do They Meet Protein Requirements of Patients with Chronic Kidney Disease?

A low protein diet (LPD) has historically been used to delay uremic symptoms and decrease nitrogen (N)-derived catabolic products in patients with chronic kidney disease (CKD). In recent years it has become evident that nutritional intervention is a necessary approach to prevent wasting and reduce CKD complications and disease progression. While a 0.6 g/kg, high biological value protein-based LPD has been used for years, recent observational studies suggest that plant-derived LPDs are a better approach to nutritional treatment of CKD. However, plant proteins are less anabolic than animal proteins and amino acids contained in plant proteins may be in part oxidized; thus, they may not completely be used for protein synthesis. In this review, we evaluate the role of LPDs and plant-based LPDs on maintaining skeletal muscle mass in patients with CKD and examine different nutritional approaches for improving the anabolic properties of plant proteins when used in protein-restricted diets

Everolimus for BKV nephropathy in kidney transplant recipients: a prospective, controlled study

There is no specific therapy for polyoma BK virus nephropathy (BKVN) in kidney transplant recipients, a condition associated with poor outcomes. Everolimus showed promising antiviral effects, but data from prospective studies are limited. Therefore, we converted ten consecutive kidney transplant recipients with biopsy-proven BKVN from standard exposure Calcineurin inhibitors and Mycophenolate to Everolimus and reduced exposure Calcineurin inhibitors. Ten patients not administered Everolimus, on reduced exposure Calcineurin inhibitor and halved MPA doses served as controls. All kidney transplant recipients continued steroid therapy. Each patient underwent kidney graft biopsy, BKV replication by PCR, and de novo DSA determination. During a 3-year follow-up no graft loss occurred in kidney transplant recipients on Everolimus but it was observed in 5/10 controls (P\u2009=\u20090.032). eGFR improved on Everolimus and worsened in controls (between group difference\u2009+\u200925.6 ml/min/1.73 m2, 95% CI 10.5-40.7, P\u2009=\u20090.002). BKV replication declined in the Everolimus group alone (from 6.4\u2009\ub1\u20090.8 to 3.6\u2009\ub1\u20091.6 Log 10 genomic copies, P\u2009=\u20090.0001), and we found a significant inverse relationship between eGFR and BKV genomic copy changes (P\u2009=\u20090.022). Average Calcineurin inhibitors trough levels did not differ between the two study groups during follow-up. By multivariable Cox regression analysis, Everolimus treatment resulted the only significant predictor of survival free of a combined endpoint of graft loss and 57% eGFR reduction (P\u2009=\u20090.02). Kidney transplant recipients on Everolimus had a higher survival free of adverse graft outcome (log-rank test, P\u2009=\u20090.009). In conclusion an Everolimus-based immunosuppressive protocol with minimization of Calcineurin inhibitors and antimetabolite discontinuation effectively treated BKVN in kidney transplant recipients

Baseline clinical characteristics and prognostic factors in hospitalized COVID-19 patients aged ≤ 65 years: A retrospective observational study.

BackgroundIndividual differences in susceptibility to SARS-CoV-2 infection, symptomatology and clinical manifestation of COVID-19 have thus far been observed but little is known about the prognostic factors of young patients.MethodsA retrospective observational study was conducted on 171 patients aged ≤ 65 years hospitalized in Alessandria's Hospital from 1st March to 30th April 2020 with laboratory confirmed COVID-19. Epidemiological data, symptoms at onset, clinical manifestations, Charlson Comorbidity Index, laboratory parameters, radiological findings and complications were considered. Patients were divided into two groups on the basis of COVID-19 severity. Multivariable logistic regression analysis was used to establish factors associated with the development of a moderate or severe disease.FindingsA total of 171 patients (89 with mild/moderate disease, 82 with severe/critical disease), of which 61% males and a mean age (± SD) of 53.6 (± 9.7) were included. The multivariable logistic model identified age (50-65 vs 18-49; OR = 3.23 CI95% 1.42-7.37), platelet count (per 100 units of increase OR = 0.61 CI95% 0.42-0.89), c-reactive protein (CPR) (per unit of increase OR = 1.12 CI95% 1.06-1.20) as risk factors for severe or critical disease. The multivariable logistic model showed a good discriminating capacity with a C-index value of 0.76.InterpretationPatients aged ≥ 50 years with low platelet count and high CRP are more likely to develop severe or critical illness. These findings might contribute to improved clinical management