An acute fall in estimated glomerular filtration rate during treatment with
losartan predicts a slower decrease in long-term renal function.
Author(s): Holtkamp FA, de Zeeuw D, Thomas MC, Cooper ME, de Graeff PA, Hillege HJ, Parving
HH, Brenner BM, Shahinfar S, Lambers Heerspink HJ.
Affiliation(s): Department of Clinical Pharmacology, University Medical Center Groningen,
University of Groningen, Groningen, The Netherlands.
Publication date & source: 2011, Kidney Int. , 80(3):282-7
Intervention in the renin-angiotensin-aldosterone-system (RAAS) is associated
with slowing the progressive loss of renal function. During initiation of
therapy, however, there may be an acute fall in glomerular filtration rate (GFR).
We tested whether this initial fall in GFR reflects a renal hemodynamic effect
and whether this might result in a slower decline in long-term renal function. We
performed a post hoc analysis of the Reduction of Endpoints in
Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist
Losartan (RENAAL) trial. Patients assigned to losartan had a significantly
greater acute fall in estimated (eGFR) during the first 3 months compared to
patients assigned to placebo, but a significantly slower long-term mean decline
of eGFR thereafter. A large interindividual difference, however, was noticed in
the acute eGFR change. When patients were divided into tertiles of initial fall
in eGFR, the long-term eGFR slope calculated from baseline was significantly
higher in patients with an initial fall compared to those with an initial rise.
When eGFR decline was calculated from 3 months to the final visit, excluding the
initial effect, patients with a large initial fall in eGFR had a significant
lower long-term eGFR slope compared to those with a moderate fall or rise. This
relationship was independent of other risk markers or change in risk markers for
progression of renal disease such as blood pressure and albuminuria. Thus, the
greater the acute fall in eGFR, during losartan treatment, the slower the rate of
long-term eGFR decline. Hence, interpretation of trial results relying on
slope-based GFR outcomes should separate the initial drug-induced GFR change from
the subsequent long-term effect on GFR.
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