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Renoprotecive Effect of Renin-Angiotensin System Inhibition in Chronic Kidney Disease: A Retrospective Analysis

血管張力素轉換酶抑制劑和血管張力素接受器阻斷劑在慢性腎臟疾病的保護角色

摘要


Irrespective of the primary causes, most patients with chronic kidney disease (CKD) eventually progress to end-stage renal disease (ESRD). The epidemiological data shows a rising incidence and prevalence rate of ESRD in Taiwan. To slow renal progression and prevent ESRD, multiple risk factor intervention therapies (MRFIT) can inhibit renal progression. One of the major therapeutic strategies is to inhibit rennin-angiotensin system by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin Ⅱ type I receptor blockers (ARBs). Both ACEIs and ARBs have similar effects on blood pressure (BP) control and lowering proteinuria. In addition, combination therapy may augment the individual’s benefit. Because most clinical data has been derived from a non-Asian population, we investigated clinical features and therapeutic responses of CKD patients in southern Taiwan. From October 2001 to January 2002, a total of 132 CKD patients, defined as serum creatinine (Scr) > 1.5 mg/dL (n=73), daily urinary protein loss (DPL) > 1g (n=40), or both (n=19), were enrolled in this study. Detailed medical records, including age, gender, smoking, underlying diseases, BP, antihypertensive medications, and blood biochemistry data, were collected. Primary endpoint (i.e. renal survival) was defined as a 50% increase in Scr or DPL from the baseline. Secondaly endpoints included BP control and the change of serum potassium. Kaplan-Meier survival analysis with log-rank test was performed to evaluate the impact of ACEIs/ARBs on renal progression, and the Cox proportional-hazards model was introduced to adjust for confounding variables. These patients were classified into the ACEIs/ARBs group (n=79), treated with ACEIs (n=45), ARBs (n=31) or ACEIs plus ARBs (n-3), and the control group (n=53), treated with other antihypertensive agents. There were no significant differences in the baseline characteristics between the two groups, except an older average age and a higher Scr in the control group. The results showed that the ACEIs/ARBs group had a better renal survival (P=0.047), which was not influenced by BP changes. Univariate analysis of sex, baseline Scr or DPL, and medication showed significant association with renal survival (hazard ratio=3.88, P=0.04). However, medication only, without ACEIs/ARBs, also had an impact on renal survival as determined by multivariate analysis. In comparison with the ARBs group, the ACEIs group was predominantly male and had a higher baseline level of serum potassium. After a mean follow-up of 31.1/24.6 months, diastolic BP and Scr in the ARBs group were significantly lower than in the ACEIs group, but there were no significant differences in renal survival and changes of serum potassium levels between the two groups. In conclusion, our study demonstrated that both ACEIs and ARBs did have renoprotective effects on Taiwanese with CKD. ARBs tended to be more renoprotective than ACEIs, but further prospective study is necessary for confirmation.

並列摘要


Irrespective of the primary causes, most patients with chronic kidney disease (CKD) eventually progress to end-stage renal disease (ESRD). The epidemiological data shows a rising incidence and prevalence rate of ESRD in Taiwan. To slow renal progression and prevent ESRD, multiple risk factor intervention therapies (MRFIT) can inhibit renal progression. One of the major therapeutic strategies is to inhibit rennin-angiotensin system by angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin Ⅱ type I receptor blockers (ARBs). Both ACEIs and ARBs have similar effects on blood pressure (BP) control and lowering proteinuria. In addition, combination therapy may augment the individual’s benefit. Because most clinical data has been derived from a non-Asian population, we investigated clinical features and therapeutic responses of CKD patients in southern Taiwan. From October 2001 to January 2002, a total of 132 CKD patients, defined as serum creatinine (Scr) > 1.5 mg/dL (n=73), daily urinary protein loss (DPL) > 1g (n=40), or both (n=19), were enrolled in this study. Detailed medical records, including age, gender, smoking, underlying diseases, BP, antihypertensive medications, and blood biochemistry data, were collected. Primary endpoint (i.e. renal survival) was defined as a 50% increase in Scr or DPL from the baseline. Secondaly endpoints included BP control and the change of serum potassium. Kaplan-Meier survival analysis with log-rank test was performed to evaluate the impact of ACEIs/ARBs on renal progression, and the Cox proportional-hazards model was introduced to adjust for confounding variables. These patients were classified into the ACEIs/ARBs group (n=79), treated with ACEIs (n=45), ARBs (n=31) or ACEIs plus ARBs (n-3), and the control group (n=53), treated with other antihypertensive agents. There were no significant differences in the baseline characteristics between the two groups, except an older average age and a higher Scr in the control group. The results showed that the ACEIs/ARBs group had a better renal survival (P=0.047), which was not influenced by BP changes. Univariate analysis of sex, baseline Scr or DPL, and medication showed significant association with renal survival (hazard ratio=3.88, P=0.04). However, medication only, without ACEIs/ARBs, also had an impact on renal survival as determined by multivariate analysis. In comparison with the ARBs group, the ACEIs group was predominantly male and had a higher baseline level of serum potassium. After a mean follow-up of 31.1/24.6 months, diastolic BP and Scr in the ARBs group were significantly lower than in the ACEIs group, but there were no significant differences in renal survival and changes of serum potassium levels between the two groups. In conclusion, our study demonstrated that both ACEIs and ARBs did have renoprotective effects on Taiwanese with CKD. ARBs tended to be more renoprotective than ACEIs, but further prospective study is necessary for confirmation.

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