Impact of First Wave COVID-19 Crisis on Dialysis Parameters of COVID-Free Hemodialysis Patients: A NephoCare France Longitudinal Retrospective Cohort Study

<b><i>Background:</i></b> Chronic hemodialysis (HD) patients are at high risk of severe COVID-19 with a high risk of death. The organization of dialysis units to treat chronic HD patients with COVID-19 is demanding to prevent virus transmission both in COVID-free patients and the staff. These constraints may have an impact on the dialysis delivery to COVID-free HD patients. We report our experience in French NephroCare (NC) centers. <b><i>Methods:</i></b> We report retrospectively dialysis and nutritional indicators among COVID-free prevalent chronic HD patients’ cohort treated in French NC units from February 2020 to April 2020. The COVID-free HD patients were split into 2 subgroups for the analysis, Paris region and other regions because the incidence of COVID-19 was different according to the French regions. <b><i>Results:</i></b> The Paris region was the most impacted by COVID-19 with 73% of all the contaminations that occurred in French NC units (<i>n</i> = 118). The dialysis frequency was not reduced all over the NC regions. 2,110 COVID-free HD patients were split into 2 subgroups including Paris region (748 patients) and other regions (1,362 patients). The weekly treatment time decreased significantly in Paris region from February to April (723–696 min [<i>p</i> &#x3c; 0.00001]) but remained stable in the other regions. The processed blood volume, KT/V, and convective volume declined significantly in the Paris region subgroup but not in other regions. The 3-month weight loss significantly increased in the whole group of patients whatever the region from 0.0 to 0.2% between February 2020 and April 2020 (<i>p</i> &#x3c; 0.00001). Ultrafiltration rate (UFR) and the normalized proteic catabolic rate remained stable all along the period. The stepwise regression analysis identified February serum albumin level and April UFR as negatively associated with 3-month weight loss. <b><i>Conclusion:</i></b> HD delivery to COVID-free HD patients was negatively impacted in the Paris region because of the strong constraints on units’ organization related to the treatment of COVID-19+ HD patients and with a higher proportion of limited care/self-care units with less staff resources. The 3-month weight loss increase may be related to the suppression of intradialytic snack that impacted mostly the more malnourished patients or patients with lower interdialytic weight gain. These consequences of the COVID-19 crisis on COVID-free HD patients must be recognized and corrected to prevent further deleterious effects on patients’ outcomes.

MO849COVID-19 AT THE HEMODIALYSIS UNIT OF FELGUEIRAS, NORTH OF PORTUGAL

Background and Aims SARS-CoV-2 represents a challenge for hemodialysis (HD) patients due to their multiple comorbidities, disturbed immune defenses in the setting of kidney disease and increased age. Furthermore, sharing collective spaces during HD sessions increases the risk of contamination. In March 2020, the first COVID-19 cases in Portugal occurred in Felgueiras, a municipality belonging to the district of Porto. The HD unit that serves this population has 69 in-center patients and, from March 2020 until January 2021, has had 14 COVID-19 cases. We describe our experience concerning patient management and their clinical characteristics. Method Clinical and laboratory data were collected. We aimed at assessing the impact of the infection in hemoglobin, alanine transaminase, several electrolytes - potassium, phosphorus, sodium and calcium - as well as the normalized protein catabolic rate (nPCR) comparing results from the month before infection with those of the month after cure. Statistical analysis used SPSS® and variables were compared using paired-samples t-test. Results We used a dedicated room and staff for COVID-19 patients, disinfection protocols and specific routes. Transportation was done with a maximum of 3 patients in a 9-seater vehicle, all patients used masks, practiced social distancing, were asked for symptoms and had their temperature measured on each HD session. SARS-CoV-2 infection was established by reverse transcription polymerase chain reaction on nasal and oropharyngeal swabs. Of the 14 cases, 3 occurred in March, 5 from October until Christmas and 6 from then onwards, accounting for approximately 20% of the unit’s patients. Of these, 2 were asymptomatic, 6 had predominantly respiratory symptoms, 1 had fever and 1 had gastrointestinal symptoms. Three were hospitalized, 2 died due to COVID-19 and 1 died 1 month after cure due to advanced cancer. Mean age of these patients was 70±13.2; 5 were females and 6 had diabetic nephropathy. Only 7 patients had post-COVID-19 results for comparison. The mean hemoglobin value before COVID-19 was 10.5±1.7g/dL and did not change significantly after COVID-19. Although phosphorous dropped from a mean 3.8±0.9mg/dL to 3.2±1.3mg/dL, this difference did not reach significance (p=0.43). All other electrolytes remained stable. nPCR dropped from 1.23±0.47 to 0.95±0.37 although not a significant difference (p=0.24). Five patients were tested for IgG/IgM antibodies against SARS-CoV-2 one month after cure using Elecsys® qualitative immunoassay and 4 tested positive. Conclusion COVID-19 is a problem for HD patients where the percent of cases is larger than in the general population. Our 3 first cases and the 4 last cases shared the same HD shift and occurred in the same period confirming that, despite all protective measures, sharing the facilities in close proximity is a risk factor. Respiratory symptoms predominated but were only severe requiring hospital admission in 3 patients. Mortality represented 14% and the 2 patients whose death was attributable to COVID-19 had an increased burden of comorbidities and were old. Seroconversion was high 1 month after the disease. The only patient who tested negative for antibodies had been asymptomatic raising doubts about whether there could have been false test results or an undetectable immune response.

ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia

Objective: The mechanism by which evinacumab, a fully human monoclonal antibody directed against ANGPTL3 (angiopoietin-like 3 protein) lowers plasma LDL (low-density lipoprotein) cholesterol levels in patients with homozygous familial hypercholesterolemia is unknown. We investigated apoB (apolipoprotein B) containing lipoprotein kinetic parameters in patients with homozygous familial hypercholesterolemia, before and after treatment with evinacumab. Approach and Results: Four patients with homozygous familial hypercholesterolemia underwent apoB kinetic analyses in 2 centers as part of a substudy of a trial evaluating the efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia. The enrichment of apoB with the stable isotope (5,5,5- 2 H 3 )-Leucine was measured in VLDL (very LDL), IDL (intermediate-density lipoprotein), and LDL at different time points before and after intravenous administration of 15 mg/kg evinacumab. Evinacumab lowered LDL-cholesterol by 59±2% and increased IDL apoB and LDL apoB fractional catabolic rate in all 4 homozygous familial hypercholesterolemia subjects, by 616±504% and 113±14%, respectively. VLDL-apoB production rate decreased in 2 of the 4 subjects. Conclusions: In this small study, ANGPTL3 inhibition with evinacumab is associated with an increase in the fractional catabolic rate of IDL apoB and LDL apoB, suggesting that evinacumab lowers LDL-cholesterol predominantly by increasing apoB-containing lipoprotein clearance from the circulation. Additional studies are needed to unravel which factors are determinants in this biological pathway. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04722068.

The physiology of Venezillo arizonicus (Isopoda, Armadillidae): metabolism and thermal tolerance

Venezillo arizonicus (Mulaik & Mulaik, 1942) is the only oniscidean isopod native to the Southwest Desert Province of North America. In accordance with its desert habitat, we hypothesized that V. arizonicus would have a higher upper lethal temperature than mesic oniscideans. If oniscidean thermal tolerance is limited by an oxygen consumption-uptake mismatch (physiological hypoxia), as indicated by recent work with other land isopods, we further hypothesized that V. arizonicus would possess highly efficient pleopodal lungs, as defined by its capacity for metabolic regulation in reduced . Other adaptations to counter oxygen limitation at high temperatures could include reduced temperature sensitivity of metabolism (low ) and an overall reduction in metabolic rate. Thermal tolerance was measured using the progressive method of Cowles & Bogert and the catabolic rate of animals () was measured as a function of temperature and . The critical thermal maximum (CTmax) of winter-acclimatized animals was 43.0 ± 0.85°C, 1.6-2.6°C higher than published values for summer-acclimatized mesic oniscideans. The catabolic rate at 25°C was 1.50 ± 0.203 μl min−1 g−1, markedly lower than values determined for mesic Oniscidea (4-6 μl min−1 g−1) and was unaffected by hypoxia as low as 2% O2 (ca. 2 kPa). Catabolism was, however, quite sensitive to temperature, showing a mean of 2.58 over 25-42°C. The efficient pleopodal lungs and low metabolic rate of V. arizonicus will both tend to mitigate physiological hypoxia, consistent with the species’ high CTmax. A low catabolic rate may also be an adaptation to low habitat productivity and seasonally constrained activity patterns.

Normalized Protein Catabolic Rate Is a Superior Nutritional Marker Associated With Dialysis Adequacy in Continuous Ambulatory Peritoneal Dialysis Patients

Introduction: Current knowledge of the relationship between normalized protein catabolic rate (nPCR) and dialysis adequacy is limited. Our study aimed to explore the potential relationship between nPCR and dialysis adequacy.Methods: In this cross-sectional study, we analyzed the association of nPCR with peritoneal dialysis adequacy in 266 continuous ambulatory peritoneal dialysis (CAPD) patients (mean age 48.6 ± 13.1 years; 50.8% male). The patients were divided into two groups: a dialysis inadequacy group (total weekly Kt/V urea &lt; 1.70) and a dialysis adequacy group (total weekly Kt/V urea≥1.70). We then analyzed the correlation between dialysis adequacy and the patients' primary cause of end-stage renal disease, nutritional and inflammatory markers, and biochemical parameters. Multivariable logistic regression analysis was also used to identify risk factors for inadequate dialysis.Results: We observed a significantly higher level of nPCR (0.98 ± 0.22 vs. 0.79 ± 0.18 g/kg/day, p &lt; 0.001) in the dialysis adequacy group, whereas we observed no significant differences among other nutritional markers such as albumin, prealbumin, and transferrin. Correlation analyses revealed that dialysis adequacy was positively associated with residual glomerular filtration rate (rGFR), hemoglobin, serum calcium, and body mass index (BMI), while dialysis adequacy was negatively associated with leak-protein, uric acid, high-sensitivity C-reactive protein, interleukin-6, and serum phosphorus. Furthermore, a logistic regression analysis revealed that gender (male), nPCR &lt;0.815 g/kg/day, higher weight, and rGFR &lt;2.43 mL/min/1.73 m2 were independent risk factors for inadequate dialysis.Conclusion: Nutritional status is closely associated with dialysis adequacy. Among common nutritional markers, nPCR may be superior for predicting CAPD dialysis adequacy. Gender (male), nPCR &lt;0.815 g/kg/day, higher weight, and rGFR &lt;2.43 mL/min/1.73 m2 are independent risk factors for dialysis inadequacy in CAPD patients.

Longitudinal Causal Effects of Normalized Protein Catabolic Rate on All-Cause Mortality in Patients with End-Stage Renal Disease: Adjusting for Time-varying Confounders Using G-estimation Method

This study aimed to estimate causal effect of normalized protein catabolic rate (nPCR) on mortality among end stage renal disease (ESRD) patients in the presence of time-varying confounding affected by prior exposure using g-estimation. Information about 553 ESRD patients was retrospectively collected over 8 years, from 2011 to 2019, from hemodialysis facilities at Kerman, southeast of Iran. nPCR was dichotomized to &lt; 1.2 versus ≥ 1.2 g/kg per day. Then standard time-varying accelerated failure time (AFT) Weibull model was built, and results were compared with those generated by g-estimation. After appropriately adjusting for time-varying confounders, weighted g-estimation yielded 78% shorter survival time (95% confidence interval [95% CI]: -81% to -73%) in patients under continuous nPCR &lt; 1.2 than those who had nPCR ≥ 1.2 g/kg per day during the follow-up, though it was 18% (95% CI: -57% to +54%) in Weibull model. Moreover, the hazard ratio estimates of 4.56 (95% CI: 3.69 to 5.37), and 1.20 (95% CI: 0.66 to 2.17) were obtained by weighted g-estimation and Weibull model, respectively. G-estimation indicated that inadequate dietary protein intake characterized by nPCR increases all-cause mortality among ESRD patients, but the Weibull model provided a substantially biased effect estimate towards the null.

Evolution of body composition and wasting indicators by time of day of haemodialysis

Background It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates. Methods We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011–16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient). Results Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of −0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators. Conclusions This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.