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Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial.

ABSTRACT: Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulating levels of interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), soluble TLR4 (sTLR4), and interferon-gamma (IFN-γ), were collected at diagnosis, and one and two weeks after. Compared with 14 non-infected HD patients, COVID-19 patients showed lymphopenia and higher ferritin and lactate dehydrogenase levels. Moreover, COVID-19 patients had higher levels of IL-10 (15.2 (12.5) vs. 1.2 (1.4) pg/mL, p = 0.02). Twenty-nine patients were randomized to HDx (n = 15) or PLD (n = 14). After a single treatment, IL-8 showed a significant reduction in both groups, whereas IL-10 decreased only in HDx. All over the study, there were no significant modifications in circulating cytokine levels between the two groups, except for a parallel increase of IL-8 and IL-10 at one week control in the HDx group. No correlations were found between cytokine levels and clinical outcomes. In maintenance HD patients, COVID-19 is not related to a sustained inflammatory response. Therefore, modulation of inflammation seems not to be a suitable therapeutic target in this specific population.

SUBMITTER: Esposito P

PROVIDER: S-EPMC8037035 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial.

Esposito Pasquale P Cipriani Leda L Verzola Daniela D Grignano Maria Antonietta MA De Amici Mara M Testa Giorgia G Grosjean Fabrizio F Russo Elisa E Garibotto Giacomo G Rampino Teresa T Viazzi Francesca F

Journal of clinical medicine 20210330 7

Uncontrolled inflammation plays a relevant role in the pathogenesis of coronavirus disease-19 (COVID-19). Here, we studied the time trend of inflammatory markers in a population of hemodialysis (HD) patients affected by COVID-19, undergoing two different dialysis approaches. In a prospective study, thirty-one maintenance HD patients with COVID-19 were randomized to expanded HD (HDx), performed using a medium cut-off membrane, or standard treatment using a protein-leaking dialyzer (PLD). Circulat ...[more]

PMID: 33808205

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Project description:ObjectiveThe goal of this investigation was to evaluate circulating and skeletal muscle inflammatory biomarkers between maintenance hemodialysis (MHD) and demographic-matched control subjects (CON) before and after ingestion of a protein-rich meal.Design and methodsCON (n = 8; 50 ± 2 years; 31 ± 1 kg/m2) and MHD patients (n = 8; 56 ± 5 years; 32 ± 2 kg/m2) underwent a basal blood draw and muscle biopsy and serial blood draws after the ingestion of a mixed meal on a nondialysis day. Plasma advanced glycation end products (AGEs) and markers of oxidation were assessed via liquid chromatography-tandem mass spectrometry before and after the meal (+240 min). Circulating inflammatory cytokines and soluble receptors for AGE (sRAGE) isoforms (endogenous secretory RAGEs and cleaved RAGEs) were determined before and after the meal (+240 min). Basal muscle was probed for inflammatory cytokines and protein expression of related signaling components (RAGE, Toll-like receptor 4, oligosaccharyltransferase subunit 48, TIR-domain-containing adapter-inducing interferon-β, total IκBα, and pIκBα).ResultsBasal circulating AGEs were 7- to 343-fold higher (P < .001) in MHD than those in CON, but only MG-H1 increased in CON after the meal (P < .001). There was a group effect (MHD > CON) for total sRAGEs (P = .02) and endogenous secretory RAGEs (P < .001) and a trend for cleaved RAGEs (P=.09), with no meal effect. In addition, there was a group effect (MHD < CON; P < .05) for circulating fractalkine, interleukin (IL)10, IL17A, and IL1β and a trend (P < .10) for IL6 and macrophage inflammatory protein 1 alpha, whereas tumor necrosis factor alpha was higher in MHD (P < .001). In muscle, Toll-like receptor 4 (P = .03), TIR-domain-containing adapter-inducing interferon-β (P = .002), and oligosaccharyltransferase subunit 48 (P = .02) expression was lower in MHD than that in CON, whereas IL6 was higher (P = .01) and IL8 (P = .08) tended to be higher in MHD.ConclusionOverall, MHD exhibited an exaggerated, circulating, and skeletal muscle inflammatory biomarker environment, and the meal did not appreciably affect the inflammatory status.

Project description:Background and objectivesPulse pressure has been shown as a risk factor for mortality in patients on maintenance hemodialysis (MHD). However, the effect of change in pulse pressure during hemodialysis on survival in a large cohort of patients on MHD has not been sufficiently investigated.Design, setting, participants, & measurementsThis study examined the association between time-varying Δ pulse pressure (postdialysis minus predialysis pulse pressure) and mortality in a cohort of 98,577 patients on MHD (July 2001-June 2006) using Cox proportional hazard models with restricted cubic splines.ResultsThe average patient age was 62 years old; among the patients, 33% were black and 59% had diabetes. During 134,814 patient-years of at-risk time, 16,054 (16%) patients died, with 6827 (43%) of the deaths caused by cardiovascular causes. In the models including adjustment for either predialysis systolic BP or mean arterial BP, there was a U-shaped association between change in pulse pressure during hemodialysis and all-cause mortality. In the systolic BP plus case mix plus malnutrition-inflammation complex syndrome-adjusted model, large declines in pulse pressure (>-25 mmHg) and increases in pulse pressure >5 mmHg were associated with higher all-cause mortality (reference: ≥-5 to <5 mmHg): hazard ratios (95% confidence intervals [95% CIs]) for change pulse pressures of <-25, ≥-25 to <-15, ≥-15 to <-5, 5 to <15, 15 to <25, and ≥25 mmHg were 1.21 (95% CI, 1.14 to 1.29), 1.03 (95% CI, 0.97 to 1.10), 1.01 (95% CI, 0.96 to 1.06), 1.06 (95% CI, 1.01 to 1.11), 1.17 (95% CI, 1.11 to 1.24), and 1.15 (95% CI, 1.08 to 1.23), respectively. The U-shaped association was observed with cardiovascular death.ConclusionsModest reductions in pulse pressure after hemodialysis are associated with the greatest survival, whereas large declines or rises in pulse pressure are related to higher mortality. Trials determining how to modify pulse pressure response to improve survival in the hemodialysis population are indicated.

Project description:BackgroundPeople with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared with similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized, controlled trial of intravenous iron treatment strategies in HD.MethodsWe analyzed data from the Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial, focusing on variables associated with risk of stroke. The trial randomized 2141 adults who had started HD <12 months earlier and who were receiving an erythropoiesis-stimulating agent (ESA) to high-dose IV iron administered proactively or low-dose IV iron administered reactively in a 1:1 ratio. Possible stroke events were independently adjudicated. We performed analyses to identify variables associated with stroke during follow-up and assessed survival following stroke.ResultsDuring a median 2.1 years of follow-up, 69 (3.2%) patients experienced a first postrandomization stroke. Fifty-seven (82.6%) were ischemic strokes, and 12 (17.4%) were hemorrhagic strokes. There were 34 postrandomization strokes in the proactive arm and 35 postrandomization strokes in the reactive arm (hazard ratio, 0.90; 95% confidence interval, 0.56 to 1.44; P=0.66). In multivariable models, women, diabetes, history of prior stroke at baseline, higher baseline systolic BP, lower serum albumin, and higher C-reactive protein were independently associated with stroke events during follow-up. Hemoglobin, total iron, and ESA dose were not associated with risk of stroke. Fifty-eight percent of patients with a stroke event died during follow-up compared with 23% without a stroke.ConclusionsIn patients on HD, stroke risk is broadly associated with risk factors previously described to increase cardiovascular risk in this population. Proactive intravenous iron does not increase stroke risk.Clinical Trial registry name and registration number: Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL), 2013-002267-25.

Project description:Rationale & objectiveThe incidence of arrhythmia varies by time of day. How this affects individuals on maintenance dialysis is uncertain. Our objective was to quantify the relationship of arrhythmia with the time of day and timing of dialysis.Study designSecondary analysis of the Monitoring in Dialysis study, a multicenter prospective cohort study.Settings & participantsLoop recorders were implanted for continuous cardiac monitoring in 66 participants on maintenance dialysis with a follow up of 6 months.ExposureTime of day based on 6-hour intervals.OutcomesEvent rates of clinically significant arrhythmia.Analytical approachNegative binomial mixed effects regression models for repeated measures were used to evaluate data from the Monitoring in Dialysis study for differences in diurnal patterns of clinically significant arrhythmia among those with end-stage kidney disease with heart failure and end-stage kidney disease alone. We additionally analyzed rates according to presence of heart failure, time of dialysis shift, and dialysis versus nondialysis day.ResultsRates of clinically significant arrhythmia peaked between 12:00 AM and 5:59 AM and were more than 1.5-fold as frequent during this interval than the rest of the day. In contrast, variations in atrial fibrillation peaked between 6:00 AM and 11:59 AM, but variations across the day were qualitatively small. Clinically significant arrhythmia occurred at numerically higher rate in individuals with end-stage kidney disease and heart failure (5.9 events/mo; 95% CI, 1.3-26.8) than those without heart failure (4.0 events/mo; 95% CI, 0.9-17.9). Although differences in overall rate were not significant, their periodicity was significantly different (P < 0.001), with a peak between 12:00 AM and 6:00 AM with kidney failure alone and between 6:00 AM and 11:59 AM in those with heart failure. Although the overall clinically significant arrhythmia rate was similar in morning compared with evening dialysis shifts (P = 0.43), their periodicity differed with a peak between 12:00 AM and 5:59 AM in those with AM dialysis and a later peak between 6:00 AM and 11:59 AM in those with PM shifts.LimitationsPost hoc analysis, unable to account for unmeasured confounders.ConclusionClinically significant arrhythmias showed strong diurnal patterns with a maximal peak between 12:00 AM and 5:59 AM and noon. Although overall arrhythmia rates were similar, the peak rate occurred overnight in individuals without heart failure and during the morning in individuals with heart failure. Further exploration of the influence of circadian rhythm on arrhythmia in the setting of hemodialysis is needed.

Dataset Information

Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial.

Publications

Effects of Different Dialysis Strategies on Inflammatory Cytokine Profile in Maintenance Hemodialysis Patients with COVID-19: A Randomized Trial.

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