The Proximal Tubule Secretes Organic Ions
The proximal tubule secretes a wide variety of organic ions into the tubule fluid. Many organic ions4 including both endogenous waste products and exogenous drugs or toxins, are protein bound in the plasma and thus are poorly filtered by the glomerulus.
However, the proximal tubule takes up these substances from the blood and extrudes them into the tubule fluid by a carrier-mediated process, thus clearing them from the plasma. Endogenous organic compounds secreted by the proximal tubule include bile salts, oxalate, urate, creatinine, prostaglandins, epinephrine, and hippurates. Drugs and toxinssecreted by the proximal tubule include antibiotics (e.g., penicillin G, trimethoprim)» diuretics (e.g., chlorothiazide, furosemide), the analgesic morphine and many of its derivatives, and the potent herbicide paraquat.
This aspect of proximal tubule function has broad practical applications. Tubule secretion of endogenous organic ions, drugs, and toxins provides the basis for urine testing for hormones and foreign substances as a reflection of blood levels that may be only transiently elevated. Tubule secretion of exogenous p-aminohippurate is used to estimate renal plasma flow. Tubule secretion of certain antibiotics is important in determining which antibiotics can reach high concentrations in the urine for more effective treatment of urinary tract infections. Similarly, secretion of diuretics such as furosemide enhances delivery of these drugs to their site of action in the thick ascending limb of Henles loop. Finally, tubule secretion of certain drugs determines in part their excretion rate and affects appropriate dosing, which can be particularly important in patients with compromised renal function.
Tubule secretion plays a larger role in birds than in mammals. The end product of protein metabolism in mammals is ιιreay which is excreted primarily through glomerular filtration. In birds the end product of protein metabolism is uric acid. Uric acid is produced by the liver and the kidney in birds and is excreted primarily by tubule secretion. In fact, in starlings the total amount of uric acid excreted by the kidney is more than five times the amount filtered. The principal site of uric acid secretion in the avian kidney is believed to be the proximal portion of reptilian-type nephrons.