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108 | 2008
Annuaire du Collège de France 2007-2008
Résumé des cours et travaux 108e année
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Stroke, CV disease and chronic kidney disease

Résumé des conférences du Collège de France (2007-2008)
David Warnock
p. 929-931

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Stroke, CV disease and chronic kidney disease

1The incidence of end-stage renal disease (ESRD) is increasing in the United States (US) population USRDS, and the prevalence of chronic kidney disease also appears to be increasing, in parallel with increased surveillance, routine reporting of estimated glomerular filtration rates (eGFR) with the MDRD equation, as well as increasing prevalence of hypertension and diabetes in the general population. These same etiologic factors are also increasing at the global level; the increasing prevalence of CKD in the US population mirrors what is happening at the global level.

2There is an increasing realization that CKD is associated with cardiovascular outcome events, and that this association is more marked with more advanced CKD. This association has been described with short-term outcomes in patients with acute myocardial infarction, as well as longer term outcome measures, including mortality rates, hospitalization rates and cardiovascular event rates.

3Anemia is frequently associated with CKD, and when present, serves as an independent risk factor for cardiovascular morbidity and mortality associated.

4Abramson et al. reported that CKD and anemia (hemoglobin < 12 gm/dl in women, and < 13 gm/dl in men) were independent risk factors for stroke in a middle-aged community-based population in the Atherosclerosis Risk in the Community (ARIC) study, with a relative risk of 7.49 in those subjects who are anemic and had creatinine clearance < 60 ml/min compared to the non-anemic participants with creatinine clearances > 60 ml/min. Similarly, the combination of anemia and CKD has a significant impact on survival after acute myocardial infarction in a study of Medicare recipients in Georgia. There are 3 large samples of patients in the US that provide estimates of the prevalence of CKD, with stratification according to the degree of impairment of kidney function: a) the Renal REGARDS cohort is the focus of our current efforts at the University of Alabama at Birmingham ; b) the National Kidney Foundation Kidney Early Evaluation Program (KEEP) ; and c) the National Health and Nutrition Examination Survey (NHANES) 1999-2004. All three cohorts also provide prevalence estimates for co-morbidities such as cardiovascular and cerebrovascular disease.

5The REGARDS and KEEP cohorts are older than the NHANES cohort, and have slightly greater prevalence of more advanced CKD (Stage 3) than the NHANES cohort. These cohorts are the undergoing longitudinal evaluation to prospectively determine the incidence of cardiovascular disease (MI and CHF), cerebrovascular disease (strokes and TIAs), and progressive CKD and ESRD. Based on self-reported history of co-morbidities, there appears to be an association between CKD (eGFR < 60 ml/min/1.73 m2) and AMI and stroke, with an increased risk, adjusted for traditional (e.g., Framingham) risk factors of 35%. These prevalence estimates and associations will be converted to actual hazard ratios and detailed definition of the importance of traditional (i.e., systolic hypertension, diabetes, smoking, cholesterol, age, gender) and non-traditional (CKD stage, anemia, inflammation, ethnicity) risk factors for the occurrence of stroke, cardiovascular events and ESRD.

Proteinuria, Hypertension and Chronic Kidney Disease Progression

6Effective blood pressure control, especially of the systolic component, is of primary importance in both primary and secondary prevention of Cardiovascular and Cerebrovascular Events. Similarly, systolic blood pressure control is important in the primary and secondary prevention of chronic kidney disease (CKD), and in patients for whom kidney function is already affected, the focus is on preventing the worsening of their current condition, which is described as slowing the “progression” of CKD. Progression of CKD is usually quantified as the linear slope with time of changes in the glomerular filtration rate, expressed as ml/min/1.73 m2/year. In addition to systolic blood pressure, control of hyperlipidemia, anemia management, smoking cessation and dietary salt intake at the recommended daily allowance of 2.4 grams of sodium are part of the general approach to optimizing outcomes in patients with CKD.

7Proteinuria is an important biomarker is many forms of CKD, including type I, and type II diabetes mellitus. Even in forms of CKD not usually associated with proteinuria (e.g., autosomal dominant polycystic kidney disease), reduction of urine protein excretion with “anti-proteinuric” therapy can have a beneficial effect on the rate of progression CKD. Proteinuria is a biomarker of kidney damage, and may also directly contribute to the ongoing damage to the kidney in CKD associated with proteinuria. Angiotensin converting enzyme inhibitors (ACEIs), and angiotensin type 1-receptor blockers (ARBs), used either alone or in combination are the mainstays of antiproteinuric therapy. This effect is well described, and seems greater than that seen with other classes of antihypertensive therapy, giving rise to the feeling that these agents have beneficial effects above and beyond what can be achieved with blood pressure control alone.

8At present, there is a balancing act between the control of blood pressure and control of proteinuria. Even in the most well defined outcome studies of type I, and type II diabetes, the outcomes with respect to slowing the rate of progression of CKD, though significant, do not achieve the ultimate goal of reducing the progression rate to < 1 ml/min/1.73 m2/year.

9A new paradigm is emerging that focuses directly on the control of proteinuria to less than 0.5 grams/day with ACEI/ARB therapy and also other non-traditional forms of therapy including other forms of RAS blockers, vitamin D, and other agents.

10These issues will be put in focus for the case of Fabry nephropathy. Fabry disease is a rate multi-system disease caused by a mutation in the alpha-galactosidase A gene on the X-chromosome. It is a progressive form of proteinuric CKD, but in contrast to diabetes, the systolic blood pressure is not usually elevated, which makes the utilization of traditional anti-proteinuric therapy challenging.

11In conclusion, the importance of control of proteinuria in slowing the progression of CKD will be emphasized with the use of a combination of treatment approaches to achieve this goal. In this context, control of proteinuria, per se, rather than lowering the systolic blood pressure to an arbitrary, fixed goal becomes the primary outcome measure. While this approach clearly has merit, long-term outcome studies are need before reduction of urinary protein excretion can be accepted as a surrogate endpoint for slowing the progression of CKD.

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Référence papier

Cours et travaux du Collège de France. Annuaire 108e année, Collège de France, Paris, décembre 2008, p. 929-931. ISBN 978-2-7226-0082-9

Référence électronique

David Warnock, « Stroke, CV disease and chronic kidney disease », L’annuaire du Collège de France [En ligne], 108 | 2008, mis en ligne le , consulté le 25 mai 2018. URL :

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David Warnock

Professeur à l’Université d’Alabama, Birmingham (États-Unis)

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Droits d’auteur

Collège de France

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