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

BACKGROUND: 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. METHODS: 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. RESULTS: The Paris region was the most impacted by COVID-19 with 73% of all the contaminations that occurred in French NC units (n = 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 [p < 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 (p < 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. CONCLUSION: 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.

Long-term mortality risk associated with citric acid- and acetic acid-based bicarbonate haemodialysis: a historical cohort propensity score-matched study in a large, multicentre, population-based study.

BACKGROUND: Citric acid-based bicarbonate dialysate (CiD) is increasingly used in haemodialysis (HD) to improve haemodynamic tolerance and haemocompatibility associated with acetic acid-based bicarbonate dialysate. Safety concerns over CiD have been raised recently after a French ecological study reported higher mortality hazard in HD clinics with high CiD consumption. Therefore, we evaluated the mortality risk associated with various acidifiers (AcD, CiD) of bicarbonate dialysate. METHODS: In this multicentre, historical cohort study, we included adult incident HD patients (European, Middle-East and Africa Fresenius Medical Care network; 1 January 2014 to 31 October 2018). We recorded acidifiers of bicarbonate dialysis and dialysate composition for each dialysis session. In the primary intention-to-treat analysis, patients were assigned to the exposed group if they received CiD in >70% of sessions during the first 3 months (CiD70%), whereas the non-exposed group received no CiD at all. In the secondary analysis, exposure was assessed on a monthly basis for the whole duration of the follow-up. RESULTS: We enrolled 10 121 incident patients during the study period. Of them, 371 met the criteria for inclusion in CiD70%. After propensity score matching, mortality was 11.43 [95% confidence interval (CI) 8.86-14.75] and 12.04 (95% CI 9.44-15.35) deaths/100 person-years in the CiD0% and CiD70% groups, respectively (P = 0.80). A similar association trend was observed in the secondary analysis. CONCLUSIONS: We did not observe evidence of increased mortality among patients exposed to CiD in a large European cohort of dialysis patients despite the fact that physicians were more inclined to prescribe CiD to subjects with worse medical conditions.

Is high-volume post-dilution haemodiafiltration associated with risk of fluid volume imbalance? A national multicentre cross-sectional cohort study.

BACKGROUND: Fluid overload is frequent among hemodialysis (HD) patients. Dialysis therapy itself may favor sodium imbalance from sodium dialysate prescription. As on-line hemodiafiltration (OL-HDF) requires large amounts of dialysate infusion, this technique can expose to fluid accumulation in case of a positive sodium gradient between dialysate and plasma. To evaluate this risk, we have analyzed and compared the fluid status of patients treated with HD or OL-HDF in French NephroCare centers. METHOD: This is a cross-sectional and retrospective analysis of prevalent dialysis patients. Data were extracted from the EUCLID5 data base. Patients were split in 2 groups (HD and OL-HDF) and compared as whole group or matched patients for fluid status criteria including predialysis relative fluid overload (RelFO%) status from the BCM®. RESULTS: 2242 patients (age 71 years; female: 39%; vintage: 38 months; Charlson index: 6) were studied. 58% of the cohort were prescribed post-dilution OL-HDF. Comparing the HD and OL-HDF groups, there was no difference between HD and OL-HDF patients regarding the predialysis systolic BP, the interdialytic weight gain, the dialysate-plasma sodium gradient, and the predialysis RelFO%. The stepwise logistic regression did not find dialysis modality (HD or OL-HDF) associated with fluid overload or high predialysis systolic blood pressure. In OL-HDF patients, monthly average convective or weekly infusion volumes per session were not related with the presence of fluid overload. CONCLUSIONS: In this cross-sectional study we did not find association between the use of post-dilution OL-HDF and markers of fluid volume excess. Aligned dialysis fluid sodium concentrations to patient predialysis plasma sodium and regular monitoring of fluid volume status by bioimpedance spectroscopy may have been helpful to manage adequately the fluid status in both OL-HDF and HD patients.

Microbiota Quality and Mitochondrial Activity Link with Occurrence of Muscle Cramps in Hemodialysis Patients using Citrate Dialysate: A Pilot Study.

BACKGROUND/AIMS: Hemodialysis-associated muscle cramp (HAMC) is a common complication under citrate dialysate (CD) occurring in 30% of cases. Our objectives were to assess the gut microbiota quality, mitochondrial activity, and to investigate their possible relationship with HAMC. METHODS: Ten end-stage renal disease patients (78.9 ± 2.1 years) treated by hemodialysis (HD) with CD were enrolled and then classified according to the frequency of HAMCs: "frequent HAMCs group" (n = 5) and "absence of HAMCs group" (n = 5). Gut microbiota quality, mitochondrial activity, and some markers of oxidative stress (OS) were investigated. RESULTS: In patients with cramps, gut microbiota diversity seemed lower and some genera including Helicobacter, Lachnospira, Roseburia, and Haemophilus seemed over-expressed, a significant increase of citratemia and significant lowering mitochondrial function were observed. No difference was observed on the OS markers. CONCLUSION: This first clinical study revealed a possible dysbiosis of microbiota and a mitochondrial dysfunction into HD patients with cramps under CD compared to patients without cramp.

Long-term impact of COVID-19 among maintenance haemodialysis patients.

BACKGROUND: Maintenance haemodialysis (MHD) patients have a high risk of initial mortality from coronavirus disease 2019 (COVID-19). However, long-term consequences of this disease in the MHD population are poorly described. We report the clinical presentation, outcome and long-term follow-up of MHD patients affected by COVID-19 in a multicentric cohort from the Paris, France area. METHODS: We conducted a retrospective analysis of clinical presentation and long-term follow-up of MHD patients affected by COVID-19 in 19 MHD centres in the Paris, France area. RESULTS: In this cohort of 248 patients with an initial mortality rate of 18%, age, comorbidities, dyspnoea and previous immunosuppressive treatment were associated with death at <30 days. Among the 203 surviving patients following the acute phase, long-term follow-up (median 180 days) was available for 189 (93%) patients. Major adverse events occurred in 30 (16%) patients during follow-up, including 12 deaths (6%) after a median of 78 days from onset of symptoms. Overall, cardiovascular events, infections and gastrointestinal bleeding were the main major adverse events. Post-COVID-19 cachexia was observed in 25/189 (13%) patients. Lower initial albuminaemia was significantly associated with this cachexia. No reinfection with severe acute respiratory syndrome coronavirus 2 was observed. CONCLUSIONS: This work demonstrates the long-term consequences of COVID-19 in MHD patients, highlighting both initial and long-term severity of the disease, including severe cachexia.

Arterial Versus Venous Port Site Administration of Nadroparin for Preventing Thrombosis of Extracorporeal Blood Circuits in Patients Receiving Hemodiafiltration Treatment.

INTRODUCTION: Administration of low-molecular-weight heparins (LMWHs) is necessary for preventing extracorporeal circuit thrombosis during hemodialysis. A substantial amount of LMWH is removed with online hemodiafiltration (OL-HDF) when administered through the inlet site of the extracorporeal circuit. Consequently, administration of LMWH at the outlet site appears to be more efficient. In this study we aimed to compare the effects of nadroparin calcium (NAD) administered through the outlet versus the inlet port site in postdilution OL-HDF and assess the NAD dose reduction. METHODS: Forty-nine hemodialysis patients were included in 3 consecutive 6-week studies as follows: phase I, inlet port line; phase II, outlet port line; and phase III, outlet port line with reduced dose. We evaluated clotting in the hemodialyzer and venous bubble trap, the dialysis dose (K t/V), and substitution volume. RESULTS: Thirty four percent, 63%, and 66% were categorized as "white" during phases I, II, and III, respectively. During phases I, II, and III, 75%, 93%, and 95% of the venous bubble traps were "clean," and 9%, 0.6%, and 0.4% of the dialyzers clotted, respectively. Average NAD dose was 0.43 ml during phase I and 0.3 ml during phase II. During phase III, the LMWH dose was reduced by 33% to 50% in 15 patients. In phase III, Kt/V improved from 1.64 to 1.75 and substitution volume increased from 20.18 to 21.96 L. CONCLUSIONS: When using OL-HDF, a single administration of NAD at the outlet port line allows for a significant dose reduction and was associated with improved dialysis performance.

[Cinacalcet impact on calcium homeostasis and bone remodeling in 13 renal transplanted patients with hyperparathyroidism and hypercalcaemia]. / Effet du cinacalcet sur l'homéostasie calcique et le remodelage osseux chez 13 transplantés rénaux présentant une hyperparathyroïdie avec hypercalcémie.

The purpose of the study is to assess the impact of cinacalcet on calcium and bone remodeling, in post-renal transplanted patients with persistent hypercalcaemia secondary to hyperparathyroidism. Thirteen renal-transplanted adult recipients with a glomerular filtration rate over 30 ml/min/1.73 m(2), a total serum calcium>2.60 mmol/l with ionized calcium>1.31 mmol/l and a parathyroid hormone serum level over 70 pg/ml, were treated with cinacalcet for 4 months followed by a 15-day wash out. The results show that cinacalcet lowers significantly total and ionized calcium respectively from 2,73 (2,67-2,86) to 2,31 (2,26-2,37) mmol/l (P<0.05) and from 1,39 (1,37-1,47) to 1,21 (1,15-1,22) mmol/l (P<0.05) with no alteration of the 24-hour urine calcium/creatinine ratio and no significant expected PTH serum level suppression (153 [115-214,9] and 166 [122-174] pg/ml). On the other hand, fasting urine calcium was significantly decreased from 0,61 (0,27-1,02) to 0,22 (0,15-0,37) (P<0.05) and bone-specific alkaline phosphatases increased from 20,5 (13-46,6) to 33,8 (12-58,9) ng/ml, upon cinacalcet treatment. After its discontinuation, all these effects were reversible. In conclusion, cinacalcet normalizes total and ionized calcium in renal-transplanted recipients with hypercalcemia secondary to hyperparathyroidism through a mechanism that could be independent of PTH serum level suppression. The increase in bone-specific alkaline phosphatases, biochemical markers of bone accretion and the significant decrease in fasting urine calcium suggest the possibility of a beneficial impact of cinacalcet on bone remodeling.

[Secondary hyperparathyroidism and anemia. Effects of a calcimimetic on the control of anemia in chronic hemodialysed patients. Pilot Study]. / Hyperparathyroïdie secondaire et anémie. Effets d'un calcimimétique sur le contrôle de l'anémie des hémodialysés chroniques. Étude pilote.

UNLABELLED: The main cause of resistance to erythropoiesis-stimulating agents (ESA) used for treatment of anemia in chronic hemodialysed patients (CHP) is the iron deficiency, absolute or functional. Secondary hyperparathyroidism (SHPT) is a secondary factor of resistance. Indeed, it has been reported in the literature an improvement of anemia parameters after surgical parathyroidectomy (PTX). The objective of this study is to assess in CHP, the impact of the correction of SHPT by a calcimimetic, cinacalcet (CI), (which is considered as a pharmacological PTX) on the response to ESA, measured by the erythropoietin resistance index (ERI). Twenty-two CHP with severe SHPT documented by an intact parathyroid hormone (iPTH) above 800pg/mL were included in this prospective pilot study. Mineral bone metabolism, anemia and nutritional parameters were measured baseline and after 6 months of treatment by CI. The effect on anemia was assessed at the end of study by the ERI, the change in Hb concentration, and the proportion of patients with Hb levels above 11g/dL. RESULTS: At the end of study there was a significant decrease (M6 vs M0) in iPTH (1302 vs 674pg/mL or -48%, p=0.006), serum calcium (2.39 vs 2.15mmol/L or -10%), serum phosphate (2 vs 1.7mmol/L or -15%), serum calcium-phosphorus product (CaxP) (4.8 vs 3.8mmol(2)/L(2) or - 20% (p<0.05), and the number of patients with CaxP>4.4mmol(2)/L(2) (64 vs 32%, p<0.05). The level of bone alkaline phosphatase remained stable during the study (28 vs 27 IU/L). The Hb levels increased from 11 to 11.4g/dL, as did the proportion of patients whose Hb concentration reached 11g/dL or higher (50 vs 70%, p<0.05) without important change of the median weekly ESA dosis in the majority of patients, 18 cases (81%) vs four (19%). Two subgroups were identified from the median decreases in iPTH (delta iPTH) between M0 and M6, Group 1 (delta iPTH≥400pg/mL, n=10) and group 2 (delta iPTH<400pg/mL, n=12): in group 1, we found a correlation between the decrease in iPTH by CI and the stability or decrease in ERI (group 1), at comparable dose of dialysis, nutritional and iron intakes and inflammatory profiles; in group 2 without a significant effect of CI on PTH reduction the levels of ERI and ESA dosis were more elevated. CONCLUSION: A treatment by calcimimetic improves the control of anemia by ESA in CHP and interferes positively on a cause of secondary resistance to ESA represented by SHPT. The mechanism of these effects could be linked to the decreased of bone marrow fibrosis and inflammation and to the triptych formed by the reduction in iPTH, CaxP and phosphate.