title: An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function.
abstract: 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.
authors: Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors: Frank A
authors: FA
authors: Holtkamp
authors: Dick
authors: D
authors: de Zeeuw
authors: Merlin C
authors: MC
authors: Thomas
authors: Mark E
authors: ME
authors: Cooper
authors: Pieter A
authors: PA
authors: de Graeff
authors: Hans J L
authors: HJ
authors: Hillege
authors: Hans-Henrik
authors: HH
authors: Parving
authors: Barry M
authors: BM
authors: Brenner
authors: Shahnaz
authors: S
authors: Shahinfar
authors: Hiddo J
authors: HJ
authors: Lambers Heerspink
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D015415:Biomarkers; D003404:Creatinine; D006442:Glycated Hemoglobin; D019808:Losartan; C517652:hemoglobin A1c protein, human