A 65-year-old man is status post three-vessel coronary artery bypass graft

A 65-year-old man is status post three-vessel coronary artery bypass graft（冠状动脉搭桥术）. His medical history is significant for hypertension treated with lisinopril（赖诺普利）, congestive heart failure, for which he takes furosemide, 20 mg twice daily, and diabetes mellitus that is controlled with metformin（二甲双胍）. He is currently on continuous infusions of dopamine, 3 μg/kg/min, and nitroglycerine（硝酸甘油）, 20 μg/min.

Which of the following medications will lead to the greatest increase in glomerular filtration rate（肾小球滤过率） by its effects on renal plasma flow?

A. Furosemide B. Dopamine C. Lisinopril D. Metformin E. Metoprolol

解析：

Glomerular filtration rate (GFR) is the total amount of plasma filtered at the glomerulus（血浆）. Inulin（菊粉） is used to estimate GFR because it is freely filterable and not secreted or absorbed by the kidneys. Creatinine（肌酐） can be used as an approximation（近似） but is both filtered and secreted.

Renal plasma flow is the amount of plasma that flows through the kidneys per unit of time. This is difficult to measure and is instead estimated from the effective renal plasma flow (ERPF), which is the amount of plasma cleared of para-aminohippuric acid (PAH)（对氨基马尿酸） per unit time. PAH is primarily secreted rather than filtered, but can be used to estimate ERPF.

At a level of 3 μg/kg/min, dopamine theoretically（理论上） acts solely on the D1 receptor, causing dilation（扩张） of the afferent and efferent arterioles of the glomerulus, leading to increased renal plasma flow and glomerular filtration rate. Dose response studies demonstrated that the dopamine-induced increase in ERPF reaches its maximum at 3 mcg/kg/min. The increase in ERPF remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine（多巴酚丁胺） in doses producing similar increases in cardiac output showed that only dopamine increased ERPF. These findings indicate that indirect hemodynamic effects secondary to increases in cardiac contractility and cardiac output do not contribute significantly to the increase in renal perfusion caused by dopamine in doses lower than 3 mcg/kg/min. It is important to note that, despite this mechanism of action, dopamine has not been shown to prevent renal failure.

Furosemide is a loop diuretic that acts in the ascending limb（上升支） of the loop of Henle. It inhibits the cotransport（同向转运） of sodium, potassium and chloride out of the nephron, making the ultrafiltrate more tonic and leading to a less hypertonic interstitium. With a less hypertonic interstitium, free water is retained in the collecting duct and thus excreted. Furosemide does not affect filtration at the glomerulus by direct effects on renal plasma flow.

Lisinopril is an angiotensin-converting enzyme inhibitor (ACEI). Normally, in the setting of sympathetic stimulation（交感刺激） or decreased afferent blood flow, the renin-angiotensin-aldosterone system (RAAS) is activated, leading to increased release of angiotensin II, which acts both to increase aldosterone（醛固酮） secretion from the adrenal（肾上腺） cortex and directly causes constriction of the efferent arteriole to decrease ERPF and increase GFR. By inhibiting the formation of angiotensin II, ACEIs prevent efferent arteriolar constriction and therefore decrease GFR.

Metformin has no appreciable affects on ERPF or GFR.

References:

1. Olsen NV. Effects of dopamine on renal haemodynamics tubular function and sodiumexcretion in normal humans. Dan Med Bull. 1998 Jun;45(3):282-297.

2. Le T, Bhushan V. First Aid for the USMLE Step 1. New York, NY: McGraw-Hill; 2009: Page 30 of 336 438, 450-452.