Blog entry by Meguid El Nahas

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by Meguid El Nahas - Thursday, 12 December 2013, 9:48 AM
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Kidney Int. 2013 Dec 4. doi: 10.1038/ki.2013.470. [Epub ahead of print]

Subclinical cardiovascular disease is associated with a high glomerular filtration rate in the nondiabetic general population.


1] Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway [2] Section of Nephrology, University Hospital of North Norway, Tromsø, Norway [3] Department of Clinical Research, University Hospital of North Norway, Tromsø, Norway.


A reduced glomerular filtration rate (GFR) in chronic kidney disease is a risk factor for cardiovascular disease. However, evidence indicates that a high GFR may also be a cardiovascular risk factor. This issue remains unresolved due to a lack of longitudinal studies of manifest cardiovascular disease with precise GFR measurements. Here, we performed a cross-sectional study of the relationship between high GFR measured as iohexol clearance and subclinical cardiovascular disease in the Renal Iohexol Clearance Survey in Tromsø 6 (RENIS-T6), a representative sample of the middle-aged general population. A total of 1521 persons without cardiovascular disease, chronic kidney disease, diabetes, or micro- or macroalbuminuria were examined with carotid ultrasonography and electrocardiography. The GFR in the highest quartile was associated with an increased odds ratio of having total carotid plaque area greater than the median of non-zero values (odds ratio 1.56, 95% confidence interval 1.02-2.39) or electrocardiographic signs of left ventricular hypertrophy (odds ratio 1.62, 95% confidence interval 1.10-2.38) compared to the lowest quartile. The analyses were adjusted for cardiovascular risk factors, urinary albumin excretion, and fasting serum glucose. Thus, high GFR is associated with carotid atherosclerosis and left ventricular hypertrophy and should be investigated as a possible risk factor for manifest cardiovascular disease in longitudinal studies.Kidney International advance online publication, 4 December 2013; doi:10.1038/ki.2013.470.


Interesting study showing an association between high measured GFR (iohexol clearance) and subclinical CVD. It is remarkable as it did MEASURE GFR, but also measured 24h Ambulatory Blood pressure measurements (ABPM) as well as undertook measurements of atherosclerosis (Carotid intima media thickness) and LVH by ECG (would have been better by echocardiography).

Adjustment were also made for obesity and BMI.

But pre-diabetes, metabolic syndrome or insulin resistance cannot be excluded as an underlying cause for both raised GFR and increased atherosclerosis. Multivariate analysis adjusted for fasting blood glucose but not for HbA1c.

Insulin resistance and suboptimal hyperglycemia may impact on both GFR, LVH as well as ATS by altering autoregulation thus increasing glomerular blood flow and GFR. Insulin resistance is also known to be associated with atherosclerosis and LVH. Additionally, the study being cross-sectional and measured once, ABPM may underestimate the overall rise in BP over a longer period of time in those affected.

The authors also put forward the possibility of sympathetic overactivity.

Having said all that, this is a very interesting observation that ties up nicely with the so-called hyperfiltration of early diabetes mellitus. It associates such early hyperfiltration with sub-clinical CVD. This may in itself also explain the strong link between subclinical CVD and CKD in the community;

Perhaps starting with hyperfiltration and progressing to hypofiltration and CKD.

As with many previous publications, this paper highlights the close association between underlying CVD and renal abnormalities, be it hyperfiltration, incident CKD or even progressive CKD.

CKD in the community (cCKD) is a manifestation of underlying subclinical or over CVD and atherosclerosis.


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