Same therapy, same calcium mobilization? Exploring calcium exchange across body compartments using a patient-specific predictive model.

BACKGROUND: Comprehensive, patient-specific models are essential to study calcium deposition and mobilization during dialysis. We aim to develop tools to support clinical prescriptions with a more accurate approach for the prediction of calcium mobilization while also considering major electrolytes and catabolites. METHODS: We modified a multi-solute model predicting patient-specific dialysis response by incorporating a calcium buffer to represent bone exchanges. Data from four centers, involving 127 patients with six sessions each, were utilized. For each patient, three sessions were allocated for model training (ID123), while the remaining sessions were for validation (PRED456). The normalized root mean square error (nRMSE%) was used to evaluate both descriptive and predictive accuracy. Correlations between initial data and calcium exchanges were also assessed. RESULTS: The overall nRMSE% for ID123 was 3.92%. For PRED456, it was 3.46% (ranging from a minimum of 1.17% for [Na+] to a maximum of 6.62% for [urea]). The median nRMSE% for plasma calcium varied between 1.13 and 8.32 for SHD sessions, depending on whether Ca_dialysis fluid (Cad) was ≥ or <1.50 mmol/L, respectively. For HDF sessions, the range was between 2.90 and 5.89. A significant and moderate correlation was found between overall calcium removal and the buffer balance. The most robust correlation observed was between the amount of calcium administered via post-dilution fluid and the overall calcium removal in the dialysis filter. CONCLUSIONS: Identical therapy settings do not uniformly affect calcium mobilization, and our approach offers insight into calcium distribution across body compartments. This understanding will enhance clinical prescription practices.

Efficacy and safety of prophylactic anticoagulation in patients with primary nephrotic syndrome: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Nephrotic syndrome (NS) is associated with an increased incidence of venous thromboembolism (VTE), approximately 10%. We performed a systematic review to evaluate the efficacy and safety of prophylactic anticoagulation in patients with NS. METHODS: Studies evaluating prophylactic anticoagulation in NS were identified by an electronic search of MEDLINE and EMBASE databases until December 2021. Weighted mean proportion and 95% confidence intervals (CIs) of thromboembolic and haemorrhagic events were calculated using a fixed-effects and a random-effects model. The differences in the outcomes among groups were estimated as pooled odds ratio (OR) and corresponding 95% CI. Statistical heterogeneity was evaluated using the I2 statistic. RESULTS: Five cohort studies, for a total of 414 adult patients, were included. Only two studies had a control group. The weighted mean incidence of pulmonary embolism (PE) and deep vein thrombosis in patients who received VTE prophylaxis was 1.8% (95% CI: 0.6-3.5%; I2 : 4.4%) and 0.9% (95% CI: 0.2-2.2%; I2 : 43.4%) respectively. The weighted mean incidence of major bleeding in patients who received VTE prophylaxis was 2.3% (95% CI: 1-4.2%; I2 : 25.4%). Patients with NS that received VTE prophylaxis had a non-significant reduced risk of PE (OR: 0.63 (95% CI: 0.03-14.8; I2 : 64.4%)) and an increased risk of major bleeding (OR: 2.08 (95% CI: 0.41-10.45; I2 : 0%)) compared to patients with NS that did not receive VTE prophylaxis. CONCLUSIONS: Our findings suggest that prophylactic anticoagulation in adult patients with primary NS may reduce the risk of VTE, even if it may be associated with a not negligible bleeding risk.

Can the response to dialysis treatment be predicted by using patient-specific modeling of fluid and solute exchanges? A multicentric evaluation.

BACKGROUND: Parametric multipool kinetic models were used to describe the intradialytic trends of electrolytes, breakdown products, and body fluids volumes during hemodialysis. Therapy customization can be achieved by the identification of parameters, allowing patient-specific modulation of mass and fluid balance across dialyzer, capillary, and cell membranes. This study wants to evaluate the possibility to use this approach to predict the patient's intradialytic response. METHODS: 6 sessions of 68 patients (DialysIS© project) were considered. Data from the first three sessions were used to train the model, identifying the patient-specific parameters, that, together with the treatment settings and the patient's data at the session start, could be used for predicting the patient's specific time course of solutes and fluids along the sessions. Na+ , K+ , Cl- , Ca2+ , HCO3 - , and urea plasmatic concentrations and hematic volume deviations from clinical data were evaluated. RESULTS: nRMSE predictive error is on average equal to 4.76% when describing the training sessions, and only increases by 0.97 percentage points on average in independent sessions of the same patient. CONCLUSIONS: The proposed predictive approach represents a first step in the development of tools to support the clinician in tailoring the patient's prescription.

A comparative study of the definitions of intradialytic hypotension correlated with increased mortality to identify universal predictors.

Intradialytic hypotension (IDH) is a common complication in patients undergoing hemodialysis therapy. No consensus on the definition of intradialytic hypotension has been established so far. As a result, coherent and consistent evaluation of its effects and causes is difficult. Some studies have highlighted existing correlations between certain definitions of IDH and the risk of mortality for the patients. This work is mainly focused on these definitions. Our aim is to understand if different IDH definitions, all correlated with increased mortality risk, catch the same onset mechanisms or dynamics. To check whether the dynamics captured by these definitions are similar, we performed analyses of the incidence, of the IDH event onset timing, and checked whether there were similarities between the definitions in those aspects. We evaluated how these definitions overlap with each other and we evaluated which common factors could allow identifying patients at risk of IDH at the beginning of a dialysis session. The definitions of IDH we analyzed through statistical and machine learning approaches, showed a variable incidence on the HD sessions and had different onset time. We found that the set of parameters relevant for the prediction of the IDH was not always the same for the definitions considered. However, it can be observed that some predictors, such as the presence of comorbidities such as diabetes or heart disease, and a low pre-dialysis diastolic blood pressure, have shown universal relevance in highlighting an increased risk of IDH during the treatment. Among those parameters, the one that showed a major importance is the diabetes status of the patients. Diabetes or heart disease presence are permanent risk factors pointing out an increased IDH risk during the treatments, while, pre-dialysis diastolic blood pressure is instead a parameter that can change at every session and should be used to evaluate the specific risk to develop IDH for each session. The identified parameters could be used in the future to train more complex prediction models.

Peritoneal videodialysis: first Italian audit.

Conceived and developed since 2001 at the Alba Center, Videodialysis (VD) was used initially to prevent dropout in prevalent PD patients by guiding them in performing dialysis (VD-Caregiver). Subsequently, its use was extended to the clinical follow-up of critical patients (VD-Clinical), problems relating to transport to the Center (VD-Transport), and since 2016 for training/retraining all patients (VD-Training). Since 2017 other Centers have employed VD using modalities analyzed in this paper. Methods: the paper reports the findings of an Audit (February 2021) of the Centers using VD on 31-12-2020. The Centers provided the following information: the characteristics of the patients using VD; the main and secondary reasons for using VD, considering nursing home (VD-NH) patients separately; VD outcomes: duration, drop-out, peritonitis, patient/caregiver satisfaction (minimum: 1 - maximum: 10). Results: VD, which began between 09-2017 and 12-2019, has been used in 6 Centers for 54 patients at 31-12-2020 (age:71.8±12.6 years - M:53.7% - CAPD:61.1% - Assisted PD:70.3%). The most frequent reason has been VD-Training (70.4%), followed by VD-Caregiver (16.7%), VD-NH (7.4%), VD-Clinical (3.7%), and VD-Transport (1.9%), with differences between Centers. VD-Training is used most with self-care patients (93.8% - p<0.05), while with patients on Assisted PD it is associated with secondary reasons (95.7% - p<0.02). VD-Training (duration: 1-4 weeks) has always been completed successfully. No peritonitis was reported; satisfaction was 8.4±1.4. Conclusion: videodialysis is a flexible, effective, safe, and valued tool that can be employed using various modalities depending on the choice of the Center and the complexity of the patient.

Low-Cost Biobased Coatings for AM60 Magnesium Alloys for Food Contact and Harsh Environment Applications.

Low-cost, environmentally friendly and easily applicable coating for Mg alloys, able to resist in real world conditions, are studied. Coatings already used for other metals (aluminum, steel) and never tested on Mg alloy for its different surface and reactivity were deposited on AM60 magnesium alloys to facilitate their technological applications, also in presence of chemically aggressive conditions. A biobased PA11 powder coating was compared to synthetic silicon-based and polyester coatings, producing lab scale samples, probed by drop deposition tests and dipping in increasingly aggressive, salty, basic and acid solutions, at RT and at higher temperatures. Coatings were analyzed by SEM/EDX to assess their morphology and compositions, by optical and IR-ATR microscopy analyses, before and after the drop tests. Migration analyses from the samples were performed by immersion tests using food simulants followed by ICP-OES analysis of the recovered simulant to explore applications also in the food contact field. A 30 µm thick white lacquer and a 120 µm PA11 coating resulted the best solutions. The thinner siliconic and lacquer coatings, appearing brittle and thin in the SEM analysis, failed some drop and/or dipping test, with damages especially at the edges. The larger thickness is thus the unique solution for edgy or pointy samples. Finally, coffee cups in AM60 alloy were produced, as real word prototypes, with the best performing coatings and tested for both migration by dipping, simulating also real world aging (2 h in acetic acid at 70° and 24 h in hot coffee at 60 °C): PA11 resulted stable in all the tests and no migration of toxic metals was observed, resulting a promising candidate for many real world application in chemically aggressive environments and also food and beverage related applications.

Correction to: Practical indications for the prevention and management of SARS-CoV-2 in ambulatory dialysis patients: lessons from the first phase of the epidemics in Lombardy.

The originally published article the co-author name Marco Heidempergher incorrectly spelled as Marco Hedemperger. The correct name given below.

Practical indications for the prevention and management of SARS-CoV-2 in ambulatory dialysis patients: lessons from the first phase of the epidemics in Lombardy.

Confronting the SARS-CoV-2 outbreak has allowed us to appreciate how efficiently highly-resourced settings can respond to crises. However even such settings are not prepared to deal with the situation, and lessons are only slowly being learnt. There is still an urgent need to accelerate protocols that lead to the implementation of rapid point-of-care diagnostic testing and effective antiviral therapies. In some high-risk populations, such as dialysis patients, where several individuals are treated at the same time in a limited space and overcrowded areas, our objective must be to ensure protection to patients, the healthcare team and the dialysis ward. The difficult Italian experience may help other countries to face the challenges. The experience of the Lombardy underlines the need for gathering and sharing our data to increase our knowledge and support common, initially experience-based, and as soon as possible evidence-based position to face this overwhelming crisis.

The Use of POSS-Based Nanoadditives for Cable-Grade PVC: Effects on its Thermal Stability.

Plasticized-Poly(vinyl chloride) (P-PVC) for cables and insulation requires performances related to outdoor, indoor and submarine contexts and reduction of noxious release of HCl-containing fumes in case of thermal degradation or fire. Introducing suitable nanomaterials in polymer-based nanocomposites can be an answer to this clue. In this work, an industry-compliant cable-grade P-PVC formulation was added with nanostructured materials belonging to the family of Polyhedral Oligomeric Silsesquioxane (POSS). The effects of the nanomaterials, alone and in synergy with HCl scavenging agents as zeolites and hydrotalcites, on the thermal stability and HCl evolution of P-PVC were deeply investigated by thermogravimetric analysis and reference ASTM methods. Moreover, hardness and mechanical properties were studied in order to highlight the effects of these additives in the perspective of final industrial uses. The data demonstrated relevant improvements in the thermal stability of the samples added with nanomaterials, already with concentrations of POSS down to 0.31 phr and interesting additive effects of POSS with zeolites and hydrotalcites for HCl release reduction without losing mechanical performances.

Assessment of intradialysis calcium mass balance by a single pool variable-volume calcium kinetic model.

INTRODUCTION: A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single-pool variable-volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. METHODS: Thirty-four patients on thrice-weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end-dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. FINDINGS: The difference between predicted and measured values was 0.02 mmol/L (range -0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD -0.84 ± 1.33 mmol, range -5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. DISCUSSION: The proposed single pool variable-volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.

Patient-specific modeling of multicompartmental fluid and mass exchange during dialysis.

BACKGROUND: Dialysis is associated with a non-negligible rate of morbidity, requiring treatment customization. Many mathematical models have been developed describing solute kinetics during hemodialysis (HD) for an average uremic patient. The clinical need can be more adequately addressed by developing a patient-specific, multicompartmental model. MATERIALS AND METHODS: The data from 148 sessions (20 patients), recorded at the Regional Hospital of Lugano, Switzerland, were used to develop and validate the mathematical model. Diffusive and convective interactions among patient, dialysate and substitution fluid were considered. Three parameters, related to mass transfer efficiency at the cell membrane, at the dialyzer and at the capillary wall, were used to tune the model. The ability of the model to describe the clinical evolution of a specific HD session was evaluated by comparing model outputs with clinically acquired data on solutes and catabolite concentrations. RESULTS: The model developed in this study allows electrolyte and catabolite concentration trends during each HD session to be described. The errors obtained before the estimation of the patient-specific parameters drastically decrease after their identification. With the optimized model, plasmatic concentration trends can be described with an average percent error lower than 2.1% for Na+, Cl-, Ca2+ and HCO3-, lower than 5% for K+ and lower than 8% for urea. CONCLUSIONS: The peculiarity of the proposed model is the possibility it offers to perform a real-time simulation enabling quantitative appraisal of hematochemical quantities whose direct measurement is prohibitive. These will be beneficial to dialysis therapy planning, reducing intradialysis complications and improving patients' quality of life.

Pemetrexed induced acute kidney injury in patients with non-small cell lung cancer: reversible and chronic renal damage.

BACKGROUND: Pemetrexed (Alimta(®)) (PEM) is an antifolate antineoplastic agent effective in several tumor types, such as non-small-cell lung cancer (NSCLC) and mesothelioma, among others. It is almost exclusively excreted by the kidney and an eGFR lower 45 mL/min is a contraindication for its use: above this level PEM administration is considered safe and dose adjustment is not required. Although there are some reported cases of PEM-induced renal injury, its incidence and the negative effects on patients' outcome has not been systematically evaluated. METHODS: We report a retrospective evaluation on the incidence of PEM-induced renal injury in patients affected by NSCLC. Between June 2010 and March 2012 a total of 38 NSCLC patients were treated at our hospital. In 29 of them other possible cause of renal injury were excluded and thus they were eligible to be analysed. RESULTS: Although by protocol all of them had eGFR >45 mL/min at baseline, six patients (average eGFR 56.2 ± 11.5 mL/min/1.73 m(2)) developed AKI (21 %). In these six patients PEM-induced myelosuppression was more severe and hospitalization was longer. Kidney function completely recovered in four patients whereas in the other two deterioration of renal function was irreversible. The number of patients with baseline eGFR <60 mL/min/1.73 m(2) was higher (4/6) in the group that developed AKI as compared to those who did not (6/23) (p < 0.05). CONCLUSIONS: There is no clear cut eGFR above which PEM may be used without potential risks of renal toxicity. If PEM has to be used, all the coexisting risk factors for AKI should be possibly corrected.

Post-procedural hemodiafiltration in acute coronary syndrome patients with associated renal and cardiac dysfunction undergoing urgent and emergency coronary angiography.

OBJECTIVES: We investigated the use of a 3-hr treatment with hemodiafiltration, initiated soon after emergency or urgent coronary angiography in acute coronary syndrome (ACS) patients with associated severe renal and cardiac dysfunction. BACKGROUND: Patients with ACS and severe combined renal and cardiac dysfunction have a particularly high mortality risk. In them, the ideal strategy to both optimize treatment of coronary disease and minimize renal injury risk is currently unknown. METHODS: This was an interventional study. ACS patients (STEMI and NSTEMI) with associated severe renal (eGFR ≤30 ml/min/1.73 m(2) ) and cardiac (LVEF ≤40%) dysfunction, admitted at La Spezia Hospital <24 hr from symptoms onset, underwent a prophylactic 3-hr hemodiafiltration treatment, which was started soon after urgent or emergency coronary procedure. Controls were patients matched for age, gender, Mehran's risk score, and kind of ACS, admitted at the Centro Cardiologico Monzino Milan. In-hospital and 1-year outcomes were evaluated. RESULTS: Sixty patients (30% STEMI), 30 hemodiafiltration-treated patients and 30 controls, with similar baseline characteristics, were included. In-hospital and cumulative 1-year mortality rates were significantly lower in hemodiafiltration-treated patients than in controls (3% vs. 23%; P = 0.05, and 10% vs. 53%; P < 0.001, respectively). Moreover, they had a lower incidence of severe AKI (10% vs. 40%; P = 0.015) and lower need for rescue renal replacement therapy during hospitalization (7% vs. 27%; P = 0.04). CONCLUSIONS: Our pilot study suggests that, in ACS patients with severe renal and cardiac insufficiency, treatment with an aggressive prophylactic hemodiafiltration session after urgent or emergency coronary angiography seems to be associated with a relevant improvement in survival.

Rosuvastatin-induced acute interstitial nephritis.

We report a case of acute interstitial nephritis (AIN), most likely induced by rosuvastatin, in an 83-year-old male patient. The patient underwent angioplasty of the left internal carotid artery, after which he began a regimen of rosuvastatin (20 mg/day). After 3 weeks the patient was admitted to our unit for acute renal failure with mild proteinuria with negligible urinary sediment. A left kidney biopsy showed dense interstitial infiltrates, mainly composed of lymphocytes with evident tubulitis. Rosuvastatin withdrawal plus prednisolone (1 mg/kg/day) treatment, which was slowly tapered over a period of 4 weeks, allowed for a complete recovery of renal function. To our knowledge, this is the first case report of rosuvastatin-induced AIN. Acute renal failure is associated with a clear increase in morbidity, length of hospital stay and mortality. Moreover, since statins are among the most widely prescribed drugs in Western countries, we think that the risk of AIN should be taken into account as a possible side effect of rosuvastatin.