An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in...

Area of Science:

• Nephrology
• Pharmacology
• Cardiovascular Medicine

Background:

• Renin-angiotensin-aldosterone-system (RAAS) blockade slows chronic kidney disease progression.
• Initiating RAAS inhibitor therapy can cause an acute, temporary drop in glomerular filtration rate (GFR).

Purpose of the Study:

• To investigate if the initial acute fall in estimated GFR (eGFR) during RAAS blockade is a hemodynamic effect.
• To determine if this acute eGFR fall predicts long-term renal function decline.

Main Methods:

• Post hoc analysis of the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial.
• Comparison of acute eGFR changes and long-term eGFR slopes between losartan and placebo groups.
• Stratification of patients based on tertiles of initial eGFR fall to assess long-term outcomes.

Main Results:

• Patients on losartan experienced a greater acute eGFR fall in the first 3 months versus placebo.
• Despite the initial fall, losartan-treated patients showed a slower long-term mean eGFR decline.
• A larger initial eGFR fall correlated with a significantly slower long-term eGFR decline, independent of other risk markers.

Conclusions:

• The acute fall in eGFR during losartan treatment is a hemodynamic effect.
• This initial eGFR reduction is associated with slower long-term renal function decline.
• Trial interpretations using slope-based GFR outcomes should distinguish initial drug effects from long-term impacts.