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Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: a meta-analysis.

Mafham M, Emberson J, Landray MJ, Wen CP, Baigent C - PLoS ONE (2011)

Bottom Line: We used a novel method to summarise the published results.While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design.If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment.

View Article: PubMed Central - PubMed

Affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom.

ABSTRACT

Background: Lower estimated glomerular filtration rate (eGFR) has been associated with an increased risk of major vascular events (MVEs) and death, but differences in methodology make between-study comparisons difficult. We used a novel method to summarise the published results.

Methods and findings: Studies assessing the relationship between baseline eGFR and subsequent MVEs or all cause mortality were identified using Pubmed. Those which involved at least 500 individuals, planned at least 1 year of follow-up, reported age and sex adjusted relative risks, and provided the mean eGFR in each category (or sufficient information to allow its estimation) were included. To take account of differences in underlying risk between studies, proportional within-study differences in eGFR (rather than absolute eGFR values) were related to risk. Fifty studies (2 million participants) assessing MVEs and 67 studies (5 million participants) assessing all cause mortality were eligible. There was an inverse relationship between lower eGFR and the risk of MVEs and of death. In studies among people without prior vascular disease, a 30% lower eGFR level was on average associated with a 29% (SE 0.2%) increase in the risk of a MVE and a 31% (SE 0.2%) increase in the risk of death from any cause. In studies among people with prior vascular disease, these estimates were 26% (SE 1.0%) and 23% (SE 0.2%) respectively. While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design.

Conclusions: Lower eGFR was consistently associated with a moderate increase in the risk of death and MVEs. If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment.

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Related in: MedlinePlus

Hypothetical age-specific estimates of the population attributable risk fraction for major vascular events associated with reduced eGFR.
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pone-0025920-g005: Hypothetical age-specific estimates of the population attributable risk fraction for major vascular events associated with reduced eGFR.

Mentions: The present study cannot determine whether any of the observed associations are causal, although an association between reduced GFR and vascular disease is suggested by studies indicating that minor degrees of renal impairment following kidney donation result in permanent increases in blood pressure [33]; [34]. If it is assumed that the relationships are causal, how large might the contribution of reduced renal function to the risk of vascular disease in the general population be? In order to assess this hypothetically, prevalence data from the National Health and Nutrition Estimation Survey [3] were used to calculate population attributable risk fractions (PARFs) of MVEs for three categories of reduced eGFR (60–89 ml/min/1.73 m2, 30–59 ml/min/1.73 m2 and 15–29 ml/min/1.73 m2) in both middle and old age (ie the proportion of vascular events that would have been avoided if the risk among those with reduced eGFR was the same as among those with an eGFR ≥90 ml/min/1.73 m2). Figure 5 indicates that if each category of reduced eGFR was causally associated with about a 25% increase in the risk of a MVE, the combined PARF associated with an eGFR <90 ml/min/1.73 m2 would be about 10% among those aged 40–59 years rising to over 20% among those aged over 70 years. Since the incidence of vascular events is much higher among older people, the absolute number of excess vascular events potentially attributable to renal impairment would be substantially higher at older ages. Based on US death rates in 2005, we might expect 10 excess vascular deaths per 100,000 people per year among those aged 45–54 years compared to 400 excess vascular deaths per 100,000 people per year among those aged 75–84 years.


Estimated glomerular filtration rate and the risk of major vascular events and all-cause mortality: a meta-analysis.

Mafham M, Emberson J, Landray MJ, Wen CP, Baigent C - PLoS ONE (2011)

Hypothetical age-specific estimates of the population attributable risk fraction for major vascular events associated with reduced eGFR.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3198450&req=5

pone-0025920-g005: Hypothetical age-specific estimates of the population attributable risk fraction for major vascular events associated with reduced eGFR.
Mentions: The present study cannot determine whether any of the observed associations are causal, although an association between reduced GFR and vascular disease is suggested by studies indicating that minor degrees of renal impairment following kidney donation result in permanent increases in blood pressure [33]; [34]. If it is assumed that the relationships are causal, how large might the contribution of reduced renal function to the risk of vascular disease in the general population be? In order to assess this hypothetically, prevalence data from the National Health and Nutrition Estimation Survey [3] were used to calculate population attributable risk fractions (PARFs) of MVEs for three categories of reduced eGFR (60–89 ml/min/1.73 m2, 30–59 ml/min/1.73 m2 and 15–29 ml/min/1.73 m2) in both middle and old age (ie the proportion of vascular events that would have been avoided if the risk among those with reduced eGFR was the same as among those with an eGFR ≥90 ml/min/1.73 m2). Figure 5 indicates that if each category of reduced eGFR was causally associated with about a 25% increase in the risk of a MVE, the combined PARF associated with an eGFR <90 ml/min/1.73 m2 would be about 10% among those aged 40–59 years rising to over 20% among those aged over 70 years. Since the incidence of vascular events is much higher among older people, the absolute number of excess vascular events potentially attributable to renal impairment would be substantially higher at older ages. Based on US death rates in 2005, we might expect 10 excess vascular deaths per 100,000 people per year among those aged 45–54 years compared to 400 excess vascular deaths per 100,000 people per year among those aged 75–84 years.

Bottom Line: We used a novel method to summarise the published results.While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design.If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment.

View Article: PubMed Central - PubMed

Affiliation: Clinical Trial Service Unit, University of Oxford, Oxford, United Kingdom.

ABSTRACT

Background: Lower estimated glomerular filtration rate (eGFR) has been associated with an increased risk of major vascular events (MVEs) and death, but differences in methodology make between-study comparisons difficult. We used a novel method to summarise the published results.

Methods and findings: Studies assessing the relationship between baseline eGFR and subsequent MVEs or all cause mortality were identified using Pubmed. Those which involved at least 500 individuals, planned at least 1 year of follow-up, reported age and sex adjusted relative risks, and provided the mean eGFR in each category (or sufficient information to allow its estimation) were included. To take account of differences in underlying risk between studies, proportional within-study differences in eGFR (rather than absolute eGFR values) were related to risk. Fifty studies (2 million participants) assessing MVEs and 67 studies (5 million participants) assessing all cause mortality were eligible. There was an inverse relationship between lower eGFR and the risk of MVEs and of death. In studies among people without prior vascular disease, a 30% lower eGFR level was on average associated with a 29% (SE 0.2%) increase in the risk of a MVE and a 31% (SE 0.2%) increase in the risk of death from any cause. In studies among people with prior vascular disease, these estimates were 26% (SE 1.0%) and 23% (SE 0.2%) respectively. While there was substantial statistical heterogeneity between the results of individual studies, a 30% lower eGFR was consistently associated with a 20-30% higher risk of both outcomes, irrespective of prior history of vascular disease or study design.

Conclusions: Lower eGFR was consistently associated with a moderate increase in the risk of death and MVEs. If these relationships are causal and continuous, then around one fifth of vascular events among those over 70 years might be attributable to renal impairment.

Show MeSH
Related in: MedlinePlus