Clinical usefulness of novel prognostic biomarkers in patients on hemodialysis

Ortíz, Alberto; Massy, Ziad A.; Fliser, Danilo; Lindholm, Bengt; Wiȩcek, Andrzej; Martínez‐Castelao, Alberto; Covic, Adrian; Goldsmith, David; Suleymanlar, G.; London, Gérard M.; Zoccali, Carmine

doi:10.1038/nrneph.2011.170

Cited by 46 publications

(41 citation statements)

References 99 publications

(119 reference statements)

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“…2 TnT, BNP, and CRP levels individually reflect a unique pathophysiological pathway in cardiovascular disease, and may identify different subpopulations at increased risk of mortality. Thus, it is not surprising that simultaneous assessment of these 3 biomarkers yielded independent and complementary prognostic information.…”

Section: Multimarker Scorementioning

confidence: 99%

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Multimarker Approach to Risk Stratification for Long-Term Mortality in Patients on Chronic Hemodialysis

Ishii

Kitagawa

Kuno

et al. 2015

Circ J

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Section: Multimarker Scorementioning

confidence: 99%

“…40 However, echocardiography is often a limited resource and may not be routinely available. 2 Several studies have suggested that TnT (or TnI) and BNP (or…”

Section: Study Limitationsmentioning

confidence: 99%

Multimarker Approach to Risk Stratification for Long-Term Mortality in Patients on Chronic Hemodialysis

Ishii

Kitagawa

Kuno

et al. 2015

Circ J

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“…However, conventional risk stratification tools remain imprecise in establishing cardiovascular prognoses in this population [2]. Furthermore, traditional Framingham risk factors explain only a fraction of the high frequency of cardiovascular disease and death among hemodialysis patients [3].…”

Section: Introductionmentioning

confidence: 99%

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort

et al. 2017

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Background/Aims: Cardiovascular disease and protein-energy wasting are among the strongest predictors of the high mortality of dialysis patients. In the general population, the novel cardiovascular and wasting biomarker, growth differentiation factor 15 (GDF15), is associated with decreased survival. However, little is known about GDF15 in dialysis patients. Methods: Among prevalent hemodialysis patients participating in a prospective study (October 2011 to August 2015), we examined the association of baseline GDF15 levels with all-cause mortality using unadjusted and case mix-adjusted death hazard ratios (HRs) that controlled for age, sex, race, ethnicity, diabetes, and dialysis vintage. Results: The mean age ± SD of the 203 patients included in the study was 53.2 ± 14.5 years, and the cohort included 41% females, 34% African-Americans, and 48% Hispanics. GDF15 levels (mean ± SD 5.94 ± 3.90 ng/mL; range 1.58-39.8 ng/mL) were higher among older patients and were inversely associated with serum creatinine concentrations as a surrogate for muscle mass. Each 1.0 ng/mL increase in GDF15 was associated with an approximately 17-18% higher mortality risk in the unadjusted and case mix models (p < 0.05). Increments of about 1 SD (a 4.0 ng/mL increase in GDF15) were associated with a nearly 2-fold higher death risk. The highest GDF15 tertile was associated with higher mortality risk (reference: lowest tertile): the HRs (95% CI) were 3.19 (1.35-7.55) and 2.45 (1.00-6.00) in the unadjusted and the case mix-adjusted model, respectively. These incremental death trends were confirmed in cubic spline models. Conclusion: Higher circulating GDF15 levels are associated with higher mortality risk in hemodialysis patients. Future studies are needed to determine whether GDF15 may represent a novel therapeutic target for cardiovascular disease, wasting, and death in this population.

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“…IL-6 is a major proinflammatory mediator well characterized in the orchestration of the inflammatory response following acute renal insult 4,5 and has been shown to be a superior marker in renal patients compared with other proinflammatory candidates, such as the systemic inflammatory marker C-reactive protein. [6][7][8][9] On the other hand, IL-10, while not as established in kidney injury, is appreciated to be a prototypical anti-inflammatory cytokine that carries out the critical function of modulating inflammation. 10,11 Accordingly, IL-6 has been suggested to exacerbate renal injury, 12,13 while IL-10 has been shown to confer protective effects.…”

mentioning

confidence: 99%

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

Zhang

Garg

Coca

et al. 2015

Journal of the American Society of Nephrology

176

119

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Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n=960). AKI was defined as a $50% or $0.3-mg/dl increase in serum creatinine from baseline. Pre-and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P=0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes. AKI is a common complication of cardiac surgery, leading to increased morbidity and mortality. 1 Current paradigms of diagnosis and treatment are based on serum creatinine and are thus insensitive. These limitations have spurred the search for novel proteins that are involved in the process of kidney injury. 2,3 While AKI is traditionally recognized and diagnosed by renal functional impairment and structural damage, it is also an inflammatory condition. Understanding and measuring the processes of inflammation in AKI may provide unique tools for its assessment and prediction.To this end, we developed an ancillary study to our large, multicenter cohort study of adult patients

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Clinical usefulness of novel prognostic biomarkers in patients on hemodialysis

Cited by 46 publications

References 99 publications

Multimarker Approach to Risk Stratification for Long-Term Mortality in Patients on Chronic Hemodialysis

Multimarker Approach to Risk Stratification for Long-Term Mortality in Patients on Chronic Hemodialysis

Association of Growth Differentiation Factor 15 with Mortality in a Prospective Hemodialysis Cohort

Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery

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