Key result
ACE inhibitor treatment is linked to ~22-fold higher plasma AcSDKP in chronic renal failure.
Why the study?
Does ACE inhibitor treatment alter the plasma concentration and urinary excretion of AcSDKP in subjects with normal and impaired renal function?
Observational (n=140)
Does ACE inhibitor treatment alter the plasma concentration and urinary excretion of AcSDKP in subjects with normal and impaired renal function?
Intermittent reactivation of ACE between doses prevents major AcSDKP accumulation during chronic ACE inhibition in patients with normal renal function, but significant accumulation occurs in those with chronic renal failure.
Answers are grounded in this paper and cite their sources.
ACE inhibitors may cause substantial AcSDKP accumulation in chronic renal failure; leaves open clinical consequences and need for prospective outcome studies.
We investigated the contributions of angiotensin-converting enzyme (ACE) and glomerular filtration to creating the new metabolic balance of the hemoregulatory peptide N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) that occurs during acute and chronic ACE inhibition in healthy subjects. We also studied the effect of chronic renal failure on the plasma concentration of AcSDKP during long-term ACE inhibitor (ACEI) treatment or in its absence. In healthy subjects, a single oral dose of 50 mg captopril (n=32) and a 7-day administration of 50 mg captopril BID (n=10) resulted in a respective 42-fold (range, 18- to 265-fold) and 34-fold (range, 24-fold to 45-fold) increase in the ratio of urinary AcSDKP to creatinine accompanied by a 4-fold (range, 2- to 6.8-fold) and 4.8-fold (range, 2.6- to 11.8-fold) increase in plasma AcSDKP levels. Changes in plasma AcSDKP and in vitro ACE activity over time showed an intermittent reactivation of ACE between each captopril dose. In subjects with chronic renal failure (creatinine clearance<60 mL/min per 1.73 m2), plasma AcSDKP levels were 22 times higher (95% confidence interval, 15 to 33) in the ACEI group (n=35) than the control group (n=23); in subjects with normal renal function, they were only 4.1 times higher (95% confidence interval, 3.2 to 5.3) in the ACEI group (n=19) than the non-ACEI group (n=21). Renal failure itself led to a slight increase in plasma AcSDKP concentration. In conclusion, intermittent reactivation of ACE between doses of an ACEI is the major mechanism accounting for the lack of major AcSDKP accumulation during chronic ACE inhibition in subjects with normal renal function.
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Azizi et al. (1999) conducted an observational in Chronic renal failure and normal renal function (n=140). ACE inhibitor (captopril) vs. No ACE inhibitor treatment was evaluated on Plasma AcSDKP levels (22 times higher, 95% CI 15-33). In subjects with chronic renal failure, plasma AcSDKP levels were 22 times higher (95% CI, 15-33) during ACE inhibitor treatment compared to controls.
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