베타 차단제(Beta blocker)가 신기능에 끼치는 영향

[1] The long-term effect of propranolol therapy on renal function.

베타차단제의 정맥 투여 ⇒ 10-20% GFR(glomerular filtration rate) & Renal plasma flow 감소

하지만 베타차단제의 경구 투여에 대한 데이터 값은 존재하지 않음.

METHOD

8명의 건강한 성인을 대상으로 0, 80, 160, 240, 320 mg/day 경구 복용 후 매주 creatinine clearance(CrCl), inulin clearance(Cin), para-amino hippurate clearance(CPAH)를 측정

복용 순응도 평가를 위해 plasma propranolol concentration monitoring 시행

RESULT

정상인에서 propranolol의 경구 사용 결과 Cin(27%) & CPAH(26%)의 감소됨이 관찰됨

(⇒ 수축기 혈압 감소 & 심장박동수 감소에 의한 심장 출력(cardiac output)의 감소로 인해 발생)

propranolol 중단 이후에도 지속적인 Cin의 감소가 관찰됨

CrCl은 GFR 감소를 반영하지 않음(CrCl technics did not reflect the magnitude of the reduction in glomerular filtration rate.)

The fractional excretion of creatinine demonstrated a significant inverse relationship to Cin, suggesting that creatinine secretion is increased with propranolol.

CONCLUSION :

We conclude that propranolol therapy results in prolonged changes in glomerular filtration rate, which may not revert to normal following its withdrawal.

[2] Renal effects of beta-adrenoceptor blockade.

three principal mechanisms by which the beta blockers could influence the kidney

1. by producing hemodynamic changes in the systemic circulation
2. by acting on the renin-angiotensin-aldosterone system
3. by possibly acting within the kidney to directly influence renal function

SUMMARY

Beta-adrenoceptor blockers do not substantially alter renal function as measured by blood urea nitrogen, serum creatinine, or endogenous creatinine clearance.

Thus, no significant changes in serum creatinine or blood urea nitrogen concentrations have been reported with propranolol, pindolol, acebutolol, or metoprolol when these agents have been given for the treatment of hypertension.
Recently, Bauer and Brooks[1] have reported the effects of administering propranolol to eight young normal volunteers during a 4-week period. As in most previous studies, these investigators also found that beta-blocker treatment did not significantly alter either regular or true creatinine clearance. Propranobol produced, however, significant decreases in GFR as measured by inulin clearance, and there was also a significant reduction in renal blood flow as measured by PAH clearance.
These findings emphasize that serum creatinine is not as reliable a measure of renal function as is creatinine clearance during betablocker treatment; and furthermore, they suggest that creatinine clearance is not as sensitive as is inulin clearance in quantifying changes in GFR

propranolol	pindolol	acebutolol	metoprolol
non-selective		β1-selective

• But there is evidence that inulin clearance may be decreased even when creatinine clearance is apparently normal, suggesting that the latter parameter may not dependably measure GFR during beta blockade, perhaps due to increased tubular creatinine secretion
• Unlike most other nondiuretic antihypertensive agents, beta blockers do not normally cause sodium and water retention.
• Thus, measurable increases in plasma volume do not occur even with long-term treatment, and body weight appears to increase only when the beta blockers are superimposed upon preexisting diuretic treatment.
• The most demonstrable intrarenal effect of the majority of beta blockers is their suppression of renin release, which in turn decreases production of All and aldosterone.
• Inhibition of the mineralocorticoid hormone aldosterone may be a key factor in minimizing volume retention during treatment, whereas decreases in the peripheral vasoconstrictor actions of All might play a part in the antihypertensive effects of these agents.

reference:

1) Bauer, John H., and Charles S. Brooks. "The long-term effect of propranolol therapy on renal function." The American journal of medicine 66.3 (1979): 405-410.

2) Weber, Michael A., and Jan IM Drayer. "Renal effects of beta-adrenoceptor blockade." Kidney international 18.5 (1980): 686-699.