10.1586/ERC.12.124 1213 ISSN 1477-9072 © 2012 Expert Reviews Ltd www.expert-reviews.com
Key Paper Evaluation
Chronic kidney disease (CKD) increases the
risk of renal and cardiovascular (CV) complica-
tions, with major socioeconomic costs for the
patients, their families and health care systems
[1] . Projected increases in the prevalence of
CKD over the next two decades are explained
by population aging and the increasing bur-
den of obesity, hypertension and diabetes. In
such patients, blood pressure lowering is the
single most effective intervention in reducing
the risk of CV outcomes or end-stage renal
disease (ESRD) [2] , but appropriate control
is rarely reached, particularly in the presence
of advanced age, diabetes or proteinuria. The
study under evaluation [3] explored the associa-
tion between baseline estimated glomerular fil-
tration rate (eGFR), assessed by the simplified
Modification of Diet in Renal Disease and
the Chronic Kidney Disease Epidemiology
Collaboration equations [4] , and the long-term
risk of CV and renal outcomes in older high-risk
hypertensive patients.
Methods & results
In the original ALLHAT trial [5] , 33,357 high-
risk hypertensives, aged 55 years or older, were
randomly assigned (2:1:1 ratio) to diuretic
(chlorthalidone), angiotensin-converting enz-
yme inhibitor (lisinopril) or dihydropyridine
calcium-channel blocker (amlodipine). Newer
antihypertensives were not superior to diuretics
in preventing death, CV disease or ESRD, either
in the whole study population or in patients
stratified by baseline eGFR [6,7] . eGFR at the end
Giorgio Gentile*
1,2
and
Matias Trillini
1
1
Mario Negri Institute for
Pharmacological Research, Clinical
Research Center for Rare Diseases ‘Aldo
e Cele Daccò’, Villa Camozzi, Ranica,
Italy
2
Unit of Nephrology, Azienda
Ospedaliera ‘Ospedali Riuniti di
Bergamo’, Bergamo, Italy
*Author for correspondence:
Tel.: +39 035 45351
giorgio.gentile@marionegri.it
Evaluation of: Rahman M, Ford CE, Cutler JA et al.; ALLHAT Collaborative Research Group.
Long-term renal and cardiovascular outcomes in Antihypertensive and Lipid-Lowering Treatment
to Prevent Heart Attack Trial (ALLHAT) participants by baseline estimated GFR. Clin. J. Am. Soc.
Nephrol. 7(6), 989–1002 (2012).
Older individuals with a diagnosis of chronic kidney disease are at higher risk of all-cause
mortality, cardiovascular (CV) events and end-stage renal disease. In such patients, the
glomerular filtration rate may be estimated with different formulas, including the Modification
of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration equations.
The recently published post-hoc analysis of the long-term CV and renal outcomes of the ALLHAT
trial that enrolled older patients with hypertension and high CV risk, but very low risk of renal
disease progression, clearly highlights the interpretative pitfalls associated with this approach.
Until future studies better establish the boundaries of ‘normal’ glomerular filtration rate in
older people, physicians should not underestimate the importance of proteinuria and accurate
glomerular filtration rate measurement in choosing the most appropriate antihypertensive
combination in daily clinical practice, particularly in patients at high risk of progression to end-
stage renal disease.
Chronic kidney disease and risk
of mortality, cardiovascular
events or end-stage renal
disease in older patients with
hypertension
Expert Rev. Cardiovasc. Ther. 10(10), 1213–1216 (2012)
KEYWORDS:cardiovascularoutcomes•chronickidneydisease•elderly•estimatedGFR•hypertension
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