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3 results on '"Raimann J"'

1. Unraveling the relationship between mortality, hyponatremia, inflammation and malnutrition in hemodialysis patients: results from the international MONDO initiative.

Author

Dekker MJ, Marcelli D, Canaud B, Konings CJ, Leunissen KM, Levin NW, Carioni P, Maheshwari V, Raimann JG, van der Sande FM, Usvyat LA, Kotanko P, and Kooman JP

Subjects
Aged, C-Reactive Protein metabolism, Cause of Death, Europe, Female, Humans, Hyponatremia blood, Hyponatremia mortality, Inflammation blood, Inflammation mortality, Logistic Models, Male, Malnutrition mortality, Middle Aged, Nutritional Status, Odds Ratio, Proportional Hazards Models, Prospective Studies, Renal Dialysis mortality, Renal Insufficiency therapy, Risk Factors, Serum Albumin metabolism, Hyponatremia etiology, Inflammation complications, Malnutrition complications, Renal Dialysis adverse effects, Sodium blood, Water-Electrolyte Imbalance
Abstract

Background/objectives: Hyponatremia is a risk factor for mortality in hemodialysis (HD) patients. It is not well known to which extent the comorbidities, malnutrition, fluid status imbalance and inflammation are related to hyponatremia and affect outcomes., Subjects/methods: We studied 8883 patients from the European subset of the international MONitoring Dialysis Outcomes initiative. Nutritional and fluid statuses were assessed by bioimpedance spectroscopy. Fluid depletion was defined as overhydration⩽-1.1 l and fluid overload as overhydration>+1.1 l, respectively. Malnutrition was defined as a lean tissue index below the 10th percentile of age- and gender-matched healthy controls. Hyponatremia and inflammation were defined as serum sodium levels <135 mEq/l and C-reactive protein levels>6.0 mg/l, respectively. We used logistic regression to test for predictors of hyponatremia and Cox proportional hazards analysis to assess the association with all-cause mortality., Results: Hyponatremia was predicted by the presence of malnutrition (odds ratio (OR)=1.49 (95% confidence interval (CI)=1.30-1.70), inflammation (OR=1.44 (95% CI=1.26-1.64)) and fluid overload ((>+1.1 l to +2.5 l) OR=0.73 (95% CI=0.62-0.85)) but not by fluid depletion (OR=1.34 (95% CI=0.92-1.96)). Malnutrition, inflammation, fluid overload, fluid depletion and hyponatremia (hazard ratio=1.70 (95% CI=1.46-1.99)) were independent predictors for all-cause mortality., Conclusions: In HD patients, hyponatremia is associated with malnutrition, inflammation and fluid overload. Hyponatremia maintained predictive for all-cause mortality after adjustment for malnutrition, inflammation and fluid status abnormalities. The presence of hyponatremia may assist in identifying HD patients at increased risk of death.

Published
2016
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2. Association between pre hemodialysis serum sodium concentration and blood pressure: results from a retrospective analysis from the international monitoring dialysis outcomes (MONDO) initiative.

Author

Raimann JG, Canaud B, Etter M, Kooman JP, Levin NW, Marcelli D, Marelli C, Power A, Duncan N, van der Sande FM, Carioni P, Thijssen S, Xu X, Usvyat LA, Wang Y, and Kotanko P

Subjects
Adult, Aged, Asia epidemiology, Biomarkers blood, Europe epidemiology, Female, Humans, Incidence, Kidney Failure, Chronic blood, Kidney Failure, Chronic epidemiology, Kidney Failure, Chronic physiopathology, Longitudinal Studies, Male, Middle Aged, North America epidemiology, Prevalence, Retrospective Studies, South America epidemiology, Time Factors, Treatment Outcome, Blood Pressure, Kidney Failure, Chronic therapy, Renal Dialysis, Sodium blood
Abstract

A recent study from the United Kingdom indicates an association between pre hemodialysis (HD) serum sodium (SNa(+)) and systolic and diastolic blood pressure (SBP and DBP) in chronic HD patients. We extend this analysis to an international cohort of incident HD patients. The Monitoring Dialysis Outcomes initiative encompasses patients from 41 countries. Over 2 years monthly pre-HD SNa(+) levels were used as predictors of pre-HD SBP and DBP in a linear mixed model (LMM) adjusted for age, gender, interdialytic weight gain, diabetes, serum albumin and calcium. Similar models were constructed with DBP as outcome. Analyses were carried out stratified by continent (North and South America; Europe and Asia). LMMs were also constructed for the entire observation period of 2 years, and separately the first and the second year after HD initiation. We studied 17 050 incident patients and found SNa(+) to have a significant slope estimate in the LMM predicting pre-HD SBP and DBP (ranging from 0.22 to 0.29 and 0.10 to 0.21 mm Hg per mEq l(-1), respectively, between the continents). The findings were similar in subsets of SBP and SNa(+) tertiles, and separately analyzed for the first and second year. Our analysis shows an independent association between SNa, SBP and DBP in a large intercontinental database, indicating that this relation is a profound biological phenomenon in incident and prevalent HD patients, generalizable to an international level and independent of SBP and DBP magnitude.

Published
2016
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3. Hypocalcemia-Induced Slowing of Human Sinus Node Pacemaking

Author

Yannick Lutz, Doris H. Fuertinger, Deborah Nairn, Jochen G. Raimann, Noémi Tóth, Norbert Nagy, Xiaoling Ye, Simonetta Genovesi, Peter Kotanko, Alan Fabbri, Stefano Severi, Axel Loewe, Loewe, A, Lutz, Y, Nairn, D, Fabbri, A, Nagy, N, Toth, N, Ye, X, Fuertinger, D, Genovesi, S, Kotanko, P, Raimann, J, Severi, S, Loewe, Axel, Lutz, Yannick, Nairn, Deborah, Fabbri, Alan, Nagy, Norbert, Toth, Noemi, Ye, Xiaoling, Fuertinger, Doris H., Genovesi, Simonetta, Kotanko, Peter, Raimann, Jochen G., and Severi, Stefano

Subjects
Bradycardia, Male, medicine.medical_specialty, Sodium, Biophysics, chemistry.chemical_element, Action Potentials, Calcium, sinus node, calcium, hemodialysis, cardiac arrest, electrolytes, 03 medical and health sciences, Electrolytes, 0302 clinical medicine, Biological Clocks, Diastole, Heart Rate, Renal Dialysis, Internal medicine, Heart rate, medicine, Extracellular, Humans, Computer Simulation, 030304 developmental biology, Aged, Sinoatrial Node, Calcium metabolism, 0303 health sciences, Hypocalcemia, Chemistry, Models, Cardiovascular, Depolarization, Articles, Middle Aged, CELL PHYSIOLOGY & BIOPHYSICS/4G - Cardiac, Smooth & Skeletal Muscle Electrophysiology, CHANNELS/5G - Ion Channels, Pharmacology & Disease, NEW DEVELOPMENTS IN BIOPHYSICAL TECHNIQUES /10E - Computational Methods & Bioinformatics, Kinetics, Cross-Sectional Studies, Cardiology, Female, medicine.symptom, 030217 neurology & neurosurgery, Intracellular
Abstract

Each heartbeat is initiated by cyclic spontaneous depolarization of cardiomyocytes in the sinus node forming the primary natural pacemaker. In patients with end-stage renal disease undergoing hemodialysis, it was recently shown that the heart rate drops to very low values before they suffer from sudden cardiac death with an unexplained high incidence. We hypothesize that the electrolyte changes commonly occurring in these patients affect sinus node beating rate and could be responsible for severe bradycardia. To test this hypothesis, we extended the Fabbri et al. computational model of human sinus node cells to account for the dynamic intracellular balance of ion concentrations. Using this model, we systematically tested the effect of altered extracellular potassium, calcium, and sodium concentrations. Although sodium changes had negligible (0.15 bpm/mM) and potassium changes mild effects (8 bpm/mM), calcium changes markedly affected the beating rate (46 bpm/mM ionized calcium without autonomic control). This pronounced bradycardic effect of hypocalcemia was mediated primarily by I(CaL) attenuation due to reduced driving force, particularly during late depolarization. This, in turn, caused secondary reduction of calcium concentration in the intracellular compartments and subsequent attenuation of inward I(NaCa) and reduction of intracellular sodium. Our in silico findings are complemented and substantiated by an empirical database study comprising 22,501 pairs of blood samples and in vivo heart rate measurements in hemodialysis patients and healthy individuals. A reduction of extracellular calcium was correlated with a decrease of heartrate by 9.9 bpm/mM total serum calcium (p < 0.001) with intact autonomic control in the cross-sectional population. In conclusion, we present mechanistic in silico and empirical in vivo data supporting the so far neglected but experimentally testable and potentially important mechanism of hypocalcemia-induced bradycardia and asystole, potentially responsible for the highly increased and so far unexplained risk of sudden cardiac death in the hemodialysis patient population.

Published
2019

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