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

Dekker, Marijke; Marcelli, Daniele; Canaud, Bernard; Konings, Constantijn; Leunissen, Karel M.L.; Levin, Nathan W.; Carioni, Paola; Maheshwari, Vaibhav; Raimann, Jochen G.; Sande, Frank M. van der; Usvyat, Len; Kotanko, Peter; Kooman, Jeroen P.

doi:10.1038/ejcn.2016.49

Cited by 61 publications

(74 citation statements)

References 43 publications

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“…This happens while lower levels are considered a reflection of adverse health conditions such as cardiovascular disease and inflammation. Our data confirm that hyponatremia is independently associated with all-cause mortality, which is consistent with previous findings [6].…”

Section: Discussionsupporting

confidence: 83%

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative

Kooman

Sande

et al. 2018

Am J Nephrol

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Background: Low serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative. Methods: All adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: –20≤ DR ≤ –6, Null DR: –6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group. Results: We included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results. Conclusion: Higher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.

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Section: Discussionsupporting

confidence: 83%

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative

Kooman

Sande

et al. 2018

Am J Nephrol

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“…Poulikakos et al reported that low serum sodium is associated with protein energy wasting and increased interdialytic weight gain in HD patients [24]. Dekker et al found that hyponatremia is associated with malnutrition, inflammation, and fluid overload [25]. Our study supports their findings because the low sodium group had significantly lower CGR, higher WBC count, and larger interdialytic weight gain (Table 4).…”

Section: Discussionsupporting

confidence: 82%

Low serum sodium concentration is a prognostic factor related to current blood glucose level in stable hemodialysis patients: an observational study

et al. 2017

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Background: A lot of risk factors for mortality have been proposed in hemodialysis patients. However, most of the findings were derived from the analyses using all of the hemodialysis patients. What we really want to know is the prognostic factor in stable hemodialysis patients who have good activities of daily living, because it is difficult to estimate their prognosis by physical appearance. Methods: This is a 7-year observational study. The study involved registering 631 patients who had undergone hemodialysis for more than 1 year at enrollment and were still alive more than 1 year after it. Demographic and clinical data were collected to analyze the relationship with mortality. Moreover, the patients were age-stratified to investigate age-dependent prognostic factors.

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“…However, this ratio is a combined marker of FO and/or malnutrition, given the fact that a loss of LTM may be reflected by a reduction of ICW. In another study in the same cohort, we found that inflammation, defined by CRP levels >6 mg/L, remained an independent predictor of survival after correction for FO, hyponatremia, and the presence of a LTM below the 10th percentile [12]. …”

Section: Combined Effects Of Fo and Inflammation On Outcomementioning

confidence: 99%

“…While FO in itself is an independent risk factor for mortality, after correction for other risk markers [12], the combined presence of FO and inflammation is also associated with an additive risk of mortality. For instance, the presence of mild FO (defined as OH >+1.1 to +2.5 L before dialysis) was associated with an hazard ratio (HR) of 1.67 (95% CI 1.19–2.33) for mortality in the absence of inflammation (defined as CRP levels >6 mg/L) but increased to an HR of 3.99 (95% CI 2.94–5.43) in the presence of inflammation.…”

Section: Combined Effects Of Fo and Inflammation On Outcomementioning

confidence: 99%

“…Traditionally, the relation between FO and outcome has been explained by its cardiovascular effects [3], such as left ventricular hypertrophy, systolic dysfunction, pulmonary hypertension, and increased aortic stiffness [4-7], but recent evidence suggests that noncardiovascular factors are also of importance in further explaining the relation between FO and mortality [8, 9]. One important factor appears to be systemic inflammation [10-12]. In this short review, the relevance of association between noncardiovascular risk factors and FO, with special emphasis on inflammation, is discussed.…”

Section: Introductionmentioning

confidence: 99%

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Fluid Overload and Inflammation Axis

et al. 2018

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Extracellular fluid overload (FO), which is assessed using bioimpedance technologies, is an important predictor of outcome in dialysis patients and in patients with early stages of chronic kidney disease. While traditional cardiovascular abnormalities are assumed to mediate this risk, recently also, the importance of noncardiovascular factors, such as systemic inflammation and malnutrition has been shown. While both FO and inflammation are independent risk factors for mortality, recent studies have shown that their combined presence can lead to a cumulative risk profile. From a pathophysiologic viewpoint, FO and inflammation can also be mutually reinforcing. Inflammation could contribute to FO by hypoalbuminemia, capillary leakage, and a (unnoticed) decline in lean and/or fat tissue mass resulting in incorrect estimation of dry weight. Reciprocally, FO could lead to inflammation by the translocation of endotoxins through a congested bowel wall or by a proinflammatory effect of tissue sodium. The relative importance of these putative factors is, however, not clear yet and epidemiological studies have shown no clear temporal direction regarding the relationship between FO and inflammation. FO and inflammation appear to be part of (dynamic) clusters of risk factors, including malnutrition and hyponatremia. Technology-guided fluid management of the often vulnerable dialysis patient with FO and inflammation cannot yet be based on evidence from randomized controlled trials, in which these specific patients were in general not included. In the absence of those trials, treatment should be based on identifying actionable causes of inflammation and on the judicious removal of excess volume based on frequent clinical reassessment.

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

Cited by 61 publications

References 43 publications

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative

Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative

Low serum sodium concentration is a prognostic factor related to current blood glucose level in stable hemodialysis patients: an observational study

Fluid Overload and Inflammation Axis

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