Intradialytic Nutrition and Hemodialysis Prescriptions: A Personalized Stepwise Approach

Dialysis and nutrition are two sides of the same coin—dialysis depurates metabolic waste that is typically produced by food intake. Hence, dietetic restrictions are commonly imposed in order to limit potassium and phosphate and avoid fluid overload. Conversely, malnutrition is a major challenge and, albeit to differing degrees, all nutritional markers are associated with survival. Dialysis-related malnutrition has a multifactorial origin related to uremic syndrome and comorbidities but also to dialysis treatment. Both an insufficient dialysis dose and excessive removal are contributing factors. It is thus not surprising that dialysis alone, without proper nutritional management, often fails to be effective in combatting malnutrition. While composite indexes can be used to identify patients with poor prognosis, none is fully satisfactory, and the definitions of malnutrition and protein energy wasting are still controversial. Furthermore, most nutritional markers and interventions were assessed in hemodialysis patients, while hemodiafiltration and peritoneal dialysis have been less extensively studied. The significant loss of albumin in these two dialysis modalities makes it extremely difficult to interpret common markers and scores. Despite these problems, hemodialysis sessions represent a valuable opportunity to monitor nutritional status and prescribe nutritional interventions, and several approaches have been tried. In this concept paper, we review the current evidence on intradialytic nutrition and propose an algorithm for adapting nutritional interventions to individual patients

New intravenous calcimimetic agents: New options, new problems. an example on how clinical, economical and ethical considerations affect choice of treatment

Background. Dialysis treatment is improving, but several long-term problems remain unsolved, including metabolic bone disease linked to chronic kidney disease (CKD-MBD). The availability of new, efficacious but expensive drugs (intravenous calcimimetic agents) poses ethical problems, especially in the setting of budget limitations. Methods. Reasons of choice, side effects, biochemical trends were discussed in a cohort of 15 patients (13% of the dialysis population) who stared treatment with intravenous calcimimetics in a single center. All patients had previously been treated with oral calcimimetic agents; dialysis efficacy was at target in 14/15; hemodiafiltration was employed in 10/15. Median Charlson Comorbidity Index was 8. The indications were discussed according to the principlist ethics (beneficience, non maleficience, justice and autonomy). Biochemical results were analyzed to support the clinical-ethical choices. Results. In the context of a strict clinical and biochemical surveillance, the lack of side effects ensured “non-maleficence”; efficacy was at least similar to oral calcimimetic agents, but tolerance was better. Autonomy was respected through a shared decision-making model; all patients appreciated the reduction of the drug burden, and most acknowledged better control of their biochemical data. The ethical conflict resides in the balance between the clinical “beneficience, non-maleficience” advantage and “justice” (economic impact of treatment, potentially in attrition with other resources, since the drug is expensive and included in the dialysis bundle). The dilemma is more relevant when a patient’s life expectancy is short (economic impact without clear clinical advantages), or when non-compliance is an issue (unclear advantage if the whole treatment is not correctly taken). Conclusions. In a context of person-centered medicine, autonomy, beneficence and non-maleficence should weight more than economic justice. While ethical discussions are not aimed at finding “the right answer” but asking “the right questions”, this example can raise awareness of the importance of including an ethical analysis in the choice of “economically relevant” drugs

Risk of Preeclampsia and Adverse Pregnancy Outcomes after Heterologous Egg Donation: Hypothesizing a Role for Kidney Function and Comorbidity

Background and objectives: Preeclampsia (PE) is a risk factor for kidney diseases; egg-donation (ED) increasingly used for overcoming fertility reduction, is a risk factor for PE. CKD is also a risk factor for PE. However, kidney function is not routinely assessed in ED pregnancies. Objective of the study is seeking to assess the importance of kidney function and maternal comorbidity in ED pregnancies. Design, setting, participants and measurements. Design: retrospective observational study from clinical charts. Setting: Sant'Anna Hospital, Turin, Italy (over 7000 deliveries per year). Selection: cases: 296 singleton pregnancies from ED (gestation > 24 weeks), who delivered January 2008-February 2019. Controls were selected from the TOrino Cagliari Observational Study (1407 low-risk singleton pregnancies 2009-2016). Measurements: Standard descriptive analysis. Logistic multiple regression analysis tested: PE; pregnancy-induced hypertension; preterm delivery; small for gestational age; explicatory variables: age; BMI; parity; comorbidity (kidney diseases; immunologic diseases; thyroid diseases; other). Delivery over time was analyzed according to Kaplan Meier; ROC (Relative Operating Characteristic) curves were tested for PE and pre-term delivery, employing serum creatinine and e-GFR as continuous variables. The analysis was performed with SPSS v.14.0 and MedCalc v.18. Results: In keeping with ED indications, maternal age was high (44 years). Comorbidity was common: at least one potential comorbid factor was found in about 40% of the cases (kidney disease: 3.7%, immunologic 6.4%, thyroid disease 18.9%, other-including hypertension, previous neoplasia and all other relevant diseases-10.8%). No difference in age, parity and BMI is observed in ED women with and without comorbidity. Patients with baseline renal disease or "other" comorbidity had a higher risk of developing PE or preterm delivery after ED. PE was recorded in 23% vs. 9%, OR: 2.513 (CI 1.066-5.923; p = 0.039); preterm delivery: 30.2% vs. 14%, OR 2.565 (CI: 1.198-5.488; p = 0.044). Limiting the analysis to 124 cases (41.9%) with available serum creatinine measurement, higher serum creatinine (dichotomised at the median: 0.67 mg/dL) was correlated with risk of PE (multivariate OR 17.277 (CI: 5.125-58.238)) and preterm delivery (multivariate OR 2.545 (CI: 1.100-5.892). Conclusions: Within the limits of a retrospective analysis, this study suggests that the risk of PE after ED is modulated by comorbidity. While the cause effect relationship is difficult to ascertain, the relationship between serum creatinine and outcomes suggests that more attention is needed to baseline kidney function and comorbidity

Multidisciplinary analysis of cancer-related fatigue at the time of diagnosis: preliminary results of the BIOCARE FActory cohort

International audiencePurpose. Cancer-related fatigue (CRF) is a common side effect of cancer and cancer treatment that significantly impairs thequality of life and can persist for years after treatment completion. Although fatigue is often associated with cancer treatment,it is also a result of the disease itself, even before intervention. CRF at the time of diagnosis may affect treatmenttiming or completion and is a consistent predictor of post-treatment fatigue at any time. The mechanisms underlying CRFare multidimensional and not well understood, particularly at the time of diagnosis.Methods. Sixty-five breast cancer patients at the time of diagnosis were included. The participants completed self-assessmentquestionnaires about CRF, sleep disturbances, and emotional symptoms and wore an accelerometer to assess levelsof spontaneous physical activity and sleep quality. During the experimental session, the participants underwent cognitive,neuromuscular, and exercise metabolism evaluations.Results. Using augmented backward elimination regression, this study found that emotional symptoms and perceived sleepdisturbances were the strongest predictors of CRF (adjusted r2 = 0.51). Neuromuscular fatigability and sleep disturbancewere also associated with physical dimensions, whereas cognitive performance was associated with cognitive dimensions.Conclusion. At the time of diagnosis, emotional and cognitive dimensions are over-represented compared to the generalpopulation, and specific subdimensions have specific predictors that support the idea of distinct mechanisms. EvaluatingCRF subdimensions and their potential mechanisms at the time of diagnosis would be particularly relevant for identifyinghigh-risk patients and offering them appropriate interventions.Trial registration This study was registered at ClinicalTrials.gov (NCT04391543) in May, 2020

Protection against Leptospira interrogans Sensu Lato Challenge by DNA Immunization with the Gene Encoding Hemolysin-Associated Protein 1

The use of DNA constructs encoding leptospiral proteins is a promising new approach for vaccination against leptospirosis. In previous work we determined that immunization with hemolysis-associated protein 1 (Hap1) (LipL32) expressed by adenovirus induced significant protection against a virulent Leptospira challenge in gerbils. To avoid the use of the adenovirus vector, we checked for clinical protection against lethal challenge by DNA vaccination. A DNA vaccine expressing Hap1 was designed to enhance the direct gene transfer of this protein into gerbils. A challenge was performed 3 weeks after the last immunization with a virulent strain of serovar canicola. Our results show that the cross-protective effect with pathogenic strains of Leptospira, shared by Hap1, could be mediated by the DNA plasmid vector. This finding should facilitate the design and development of a new generation of vaccines against bacteria, particularly Leptospira interrogans sensu lato