Skip to main content
Log in

The Pharmacological Role of the Kidney

  • Review Article
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Renal function can modify the relationship between drug dose and clinical effect in a variety of ways. Effects on absorption, distribution volume and elimination influence the concentration of drug attained in blood. Consequently, such effects can often be detected and/or prevented by monitoring of serum concentrations of drugs. However, such monitoring alone is insufficient for optimum therapeutic use of drugs and must be accompanied by clinical monitoring of endpoints of efficacy and toxicity, since the relationship between the concentration of drug in serum and response may also be changed.

Accumulation of active metabolites that are not measured by conventional drug assays makes interpretation of serum concentrations of drugs such as procainamide particularly hazardous. Effects of renal function on the relationship between amounts of drug in blood and response can only be detected by assessing endpoints of pharmacological effect.

Since renal function can affect drug disposition by such a wide variety of mechanisms, the astute clinician must be aware of these potential mechanisms to make best use of his clinical skills and laboratory armamentarium for the benefit of his patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Aherne, G.W.; Piall, E.; Marks, V.; Mould, G. and White, W.F.: Prolongation and enhancement of serum methotrexate concentrations by probenecid. British Medical Journal 1: 1097–1099 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Anderson, A.D.; Hodges, G.R. and Barnes, W.G.: Determination of serum gentamicin sulfate levels. Archives of Internal Medicine 126: 785–787 (1976a).

    Article  Google Scholar 

  • Anderson, E.T.; Young, L.S. and Hewitt, W.L.: Simultaneous antibiotic levels in “breakthrough” gram-negative rod bacteremia. American Journal of Medicine 61: 493–497 (1976b).

    Article  PubMed  CAS  Google Scholar 

  • Anderson, R.J.; Gambertoglio, J.G. and Schrier, R.W.: Clinical Use of Drugs in Renal Failure (Thomas, Springfield, Ill. 1976c).

    Google Scholar 

  • Azarnoff, D.L. and Huffman, D.H.: Therapeutic implications of bioavailability. Annual Review of Pharmacology and Toxicology 16: 53–66 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Bachmann, K.; Shapiro, R. and Mackiewicz, J.: Influence of renal dysfunction on warfarin plasma protein binding. Journal of Clinical Pharmacology 16: 468–472 (1976).

    PubMed  CAS  Google Scholar 

  • Barza, M. and Lauermann, M.: Why monitor serum levels of gentamicin? Clinical Pharmacokinetics 3: 202–215 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Bechtol, L.D. and Black, H.R.: Tobramycin in renal impairment. American Journal of the Medical Sciences 269: 317–321 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Beckett, A.H. and Rowland, M.: Urinary excretion kinetics of amphetamine in man. Journal of Pharmacy and Pharmacology 17: 628–639 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Belpaire, F.M.; Bogaert, M.D. and Mussche, M.D.: Influence of acute renal failure on the protein binding of drugs in animals and in man. European Journal of Clinical Pharmacology 11: 27–32 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Benet, L.Z.: Biopharmaceutics: Basis for design of drug products; in Arieus (Ed) Drug Design, pp. 1–35 (Academic Press, New York 1973).

    Google Scholar 

  • Bennett, W.M.: Principles of drug therapy in patients with renal disease. Western Journal of Medicine 123: 372–379 (1975).

    PubMed  CAS  Google Scholar 

  • Bennett, W.M.: Drug therapy in patients with chronic renal failure. Kidney 11: 5–9 (1978).

    Google Scholar 

  • Bennett, W.M.; Singer, I. and Coggins, C.H.: Guide to drug usage in adult patients with impaired renal function. A supplement. Journal of the American Medical Association 223: 991–997 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Bennett, W.M.; Singer, I. and Coggins, C.J.: A guide to drug therapy in renal failure. Journal of the American Medical Association 230: 1544–1553 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Bennett, W.M.; Singer, I.; Golper, T.; Peig, P. and Coggins, C.J.: Guidelines for drug therapy in renal failure. Annals of Internal Medicine 86: 754–783 (1977).

    PubMed  CAS  Google Scholar 

  • Beyer, K.H.; Russo, H.F.; Tillson, E.K.; Miller, A.K.; Verwey, W.F. and Gass, S.R.: “Benemid,” p-(di-n-Propylsulfamyl)-benzoic acid: Its renal affinity and its elimination. American Journal of Physiology 166: 625–639 (1951).

    PubMed  CAS  Google Scholar 

  • Bianchetti, G.; Graziani, G.; Brancaccio, D.; Morganti, A.; Leonetti, G.; Manfrin, M.; Sega, R.; Gomeni, R.; Ponticelli, C. and Morselli, P.L.: Pharmacokinetics and effects of propranolol in terminal uraemic patients and in patients undergoing regular dialysis treatment. Clinical Pharmacokinetics 1: 373 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Binnion, P.F.: Drug interactions with digitalis glycosides. Drugs 15: 369–380 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Bodey, G.P.; Hui-yen, C.; Rodriguez, V. and Stewart, D.: Feasibility of administering aminoglycoside antibiotics by continuous intravenous infusion. Antimicrobial Agents and Chemotherapy 8: 328–333 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Boobis, W.W.: Alteration of plasma albumin in relation to decreased drug binding in uremia. Clinical Pharmacology and Therapeutics 22: 147–153 (1977).

    PubMed  CAS  Google Scholar 

  • Brater, D.C. and Morrelli, H.F.; Cardiovascular drug interactions. Annual Review of Pharmacology and Toxicology 17: 293–309 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Brater, D.C. and Thier, S.O.: Renal disorders; in Melmon and Morrelli (Eds) Clinical Pharmacology, 2nd ed, pp.349–387 (Macmillan, New York 1978).

    Google Scholar 

  • Buchanan, N. and Rabinowitz, L.: Infantile salicylism a reappraisal. Journal of Pediatrics 84: 391–395 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Chan, R.A.; Benner, E.J. and Hoeprich, P.D.: Gentamicin therapy in renal failure: A nomogram for dosage. Annals of Internal Medicine 76: 773–778 (1972).

    PubMed  CAS  Google Scholar 

  • Cohen, M. and Pocelinko, R.: Renal transport mechanisms for the excretion of sulfisoxazole. Journal of Pharmacology and Experimental Therapeutics 185: 703–712 (1973).

    PubMed  CAS  Google Scholar 

  • Craig, W.A. and Kunin, C.M.: Significance of serum protein and tissue binding of antimicrobial agents. Annual Review of Medicine 27: 287–300 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Cross, R.J. and Taggart, J.V.: Renal tubular transport: accumulation of p-amminohippurate by rabbit kidney slices. Journal of Pharmacology and Experimental Therapeutics 161: 181–190 (1950).

    CAS  Google Scholar 

  • Cutler, R.E. and Orme, B.M.: Correlation of serum creatinine concentration and kanamycin half-life. Journal of the American Medical Association 209: 539–542 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Dahlgren, J.G.; Anderson, E.T. and Hewitt, W.L.: Gentamicin blood levels: a guide to nephrotoxicity. Antimicrobial Agents and Chemotherapy 8: 58–62 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Data, J.L. and Nies, A.S.: Dextran 40. Annals of Internal Medicine 81: 500–504 (1974).

    PubMed  CAS  Google Scholar 

  • Dayton, P.G.; Yu, T.F.; Chen, W.; Berger, L.; West, L.A.; and Gutman, A.B.: The physiological disposition of probenecid, including renal clearance, in man, studied by an improved method for its estimation in biological material. Journal of Pharmacology and Experimental Therapeutics 140: 278–286 (1963).

    PubMed  CAS  Google Scholar 

  • DeLuca, H.F.: Vitamin D metabolism and function. Archives of Internal Medicine 138: 836–847 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Dettli, L.: Drug dosage in patients with renal disease. Clinical Pharmacology and Therapeutics 16: 274–280 (1974).

    PubMed  CAS  Google Scholar 

  • Dettli, L: Drug dosage in renal disease. Clinical Pharmacokinetics 1: 126–134 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Dettli, L.: Elimination kinetics and dosage adjustment of drugs in patients with kidney disease. Progress in Pharmacology 1: 1–32 (1977).

    Google Scholar 

  • Dettli, L.; Spring, P. and Tyter, S.: Multiple dose kinetics and drug dosage in patients with kidney disease. Acta Pharmacologica et Toxicologica 29: 211–224 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Drayer, D.E.: Pharmacologically active drug metabolites: Therapeutic and toxic activities, plasma and urine data in man, accumulation in renal failure. Clinical Pharmacokinetics 1: 426–443 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Drayer, D.E.; Lowenthal, D.T.; Woosley, R.L.; Nies, A.S.; Schwartz, A. and Reidenberg, M.M.: Cumulation of N-acetylprocainamide, an active metabolite of procainamide, in patients with impaired renal function. Clinical Pharmacology and Therapeutics 22: 63–69 (1977).

    PubMed  CAS  Google Scholar 

  • Dundee, J.W. and Richards, R.K.: Effect of azotemia upon the action of intravenous barbiturate anesthesia. Anesthesiology 15: 333–346 (1954).

    Article  PubMed  CAS  Google Scholar 

  • Elion, G.B., Yu, T.; Gutman, A.B. and Hitchings, G.H.: Renal clearance of oxipurinol, the chief metabolite of allopurinol. American Journal of Medicine 45: 69–76 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Fabre, J. and Balant, L.: Renal failure, drug pharmacokinetics and drug action. Clinical Pharmacokinetics 1: 99–120 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Farah, A.; Rennick, B. and Frazer, M.: The influence of some basic substances on the transport of tetraethylammonium ion. Journal of Pharmacology and Experimental Therapeutics 119: 122–127 (1957).

    PubMed  CAS  Google Scholar 

  • Feuerstein, R.D.; Finberg, L. and Fleishman, E.: The use of acetazolamide in the therapy of salicylate poisoning. Pediatrics 25: 215–227 (1960).

    PubMed  CAS  Google Scholar 

  • Galeazzi, R.L.; Gugger, M. and Weidmann, P.: Beta blockade with pindolol. Differential cardiac and renal effects despite similar plasma kinetics in normal and uremic man. Kidney International 15: 661–668 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Galeazzi, R.L.; Sheiner, L.B.; Lockwood, T. and Benet, L.Z.: The renal elimination of procainamide. Clinical Pharmacology and Therapeutics 19: 55–62 (1976).

    PubMed  CAS  Google Scholar 

  • Garrett, E.R.: Pharmacokinetics and clearances related to renal processes. International Journal of Clinical Pharmacology and Biopharmacy 16: 155–172 (1978).

    PubMed  CAS  Google Scholar 

  • Gerhardt, R.E.; Knouss, R.F.; Thyrum, P.T.; Luchi, R.J. and Morris, J.J.: Quinidine excretion in aciduria and alkaluria. Annals of Internal Medicine 71: 927–933 (1969).

    PubMed  CAS  Google Scholar 

  • Gibson, T.P.; Atkinson, A.J.; Matusik, E.; Nelson, L.D. and Briggs, W.A.: Kinetics of procainamide and N-acetylprocainamide in renal failure. Kidney International 12: 422–429 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Gibson, T.P.; Matusik, E.J. and Briggs, W.A.: N-acetylprocainamide levels in patients with end-stage renal failure. Clinical Pharmacology and Therapeutics 19: 206–212 (1975).

    Google Scholar 

  • Gibson, T.P.; Matusik, E.; Nelson, L.D.; and Briggs, W.A.: Artificial kidneys and clearance calculations. Clinical Pharmacology and Therapeutics 20: 720–726 (1976).

    PubMed  CAS  Google Scholar 

  • Gibson, T.P. and Nelson, H.A.: Drug kinetics and artificial kidneys. Clinical Pharmacokinetics 2: 403–426 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Goldberg, M.A.; Barlow, C.F. and Roth, L.J.: The effects of carbon dioxide on the entry and accumulation in the central nervous system. Journal of Pharmacology and Experimental Therapeutics 121: 308–318 (1961).

    Google Scholar 

  • Goodman, E.L.; Van Gelder, J.; Holmes, R.; Hull, A.R. and Sanford, J.P.: Prospective comparative study of variable dosage and variable frequency regimens for administration of gentamicin. Antimicrobial Agents and Chemotherapy 8: 434–438 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Green, R.E.; Ricker, W.E.; Attwood, W.L.; Koh, Y.S. and Peters, L.: Studies of the renal tubular transport characteristics of N-methylnicotinamide and tetraalkylammonium compounds in the avian kidney. Journal of Pharmacology and Experimental Therapeutics 126: 195–201 (1959).

    PubMed  CAS  Google Scholar 

  • Greenblatt, D.J. and Koch-Weser, J.: Clinical pharmacokinetics. New England Journal of Medicine 293: 702–705 and 964-970 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt, D.J. and Koch-Weser, J.: Intra-muscular injection of drugs. New England Journal of Medicine 295: 542–546 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Greenblatt, D.J.; Shade, R.I.: MacLeod, S.M.; Sellers, K. F. and Giles, H.G.: Absorption of oral and intramuscular chlordiazepoxide. European Journal of Clinical Pharmacology 13: 267–274 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Gugler, R.; Shoeman, D.W.; Huffman, D.H.; Cohlmia, J.D. and Azarnoff, D.L.: Pharmacokinetics of drugs in patients with the nephrotic syndrome. Journal of Clinical Investigation 55: 1182–1189 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Gutman, A.B.; Dayton, P.G.; Yu, T.F.; Berger, L.; Chen, W.; Sican, L.E. and Burns, J.J.: A study of the inverse relationship between pKa and rate of renal excretion of phenylbutazone analogs in man and dog. American Journal of Medicine 28: 1017–1033 (1960).

    Article  Google Scholar 

  • Haag, H.B.; Larson, P.S. and Schwartz, J.J.: The effect of urinary pH on the elimination of quinine in man. Journal of Pharmacology and Experimental Therapeutics 79: 136–139 (1943).

    CAS  Google Scholar 

  • Hager, W.D.; Fenster, P.; Mayersohn, M.; Perrier, D.; Graves, P.; Marcus, F.I. and Goldman, S.: Digoxin-quinidine interaction: pharmacokinetic evaluation. New England Journal of Medicine 300: 1238–1241 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Halkin, H.; Sheiner, L.B.; Peck, C.C. and Melmon, K.L.: Determinants of the renal clearance of digoxin. Clinical Pharmacology and Therapeutics 17: 385–392 (1975).

    PubMed  CAS  Google Scholar 

  • Heel, R.C. and Avery, G.S.: Guide to drug dosage in renal failure; in Avery (Ed) Drug Treatment, 2nd ed, pp. 1290–1303 (ADIS Press, Sydney and New York; Churchill Livingstone, Edinburgh 1980).

    Google Scholar 

  • Hewitt, W.L.: Gentamicin: toxicity in perspective. Postgraduate Medical Journal 50: 55–59 (1974).

    PubMed  Google Scholar 

  • Hill, J.B.: Experimental salicylate poisoning observations on the effects of altering blood pH on tissue and plasma salicylate concentrations. Pediatrics 47: 658–665 (1971).

    PubMed  CAS  Google Scholar 

  • Hill, J.B.: Salicylate intoxication. New England Journal of Medicine 288: 1110–1113 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Hull, J.H. and Sarubbi, F.A., Jr.: Gentamicin serum concentrations: pharmacokinetic predictions. Annals of Internal Medicine 85: 183–189 (1976).

    PubMed  CAS  Google Scholar 

  • Iisalo, E.: Clinical pharmacokinetics of digoxin. Clinical Pharmacokinetics 2: 1–16 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Jackson, E.A. and McLeod, D.C.: Pharmacokinetics and dosing of antimicrobial agents in renal impairment. American Journal of Hospital Pharmacy 31: 36–52 and 137-148 (1974).

    PubMed  CAS  Google Scholar 

  • Jelliffe, R.W. and Brooker, G.: A nomogram for digoxin therapy. American Journal of Medicine 57: 63–68 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Jusko, W.J. and Gretch, M.: Plasma and tissue protein binding of drugs in pharmacokinetics. Drug Metabolism Reviews 5: 43–140 (1976).

    Article  CAS  Google Scholar 

  • Just, M.; Erdmann, G. and Habermann, E.: The renal handling of polybasic drugs. Archives of Pharmacology 399: 57–66 and 67-76 (1977).

    Article  Google Scholar 

  • Kampmann, J.; Hansen, J.M.; Siersbaek-Nielsen, K. and Laursen, H.: Effect of some drugs on penicillin half-life in blood. Clinical Pharmacology and Therapeutics 13: 516–519 (1972).

    PubMed  CAS  Google Scholar 

  • Kanto, J.: Plasma concentrations of diazepam and its metabolites after peroral, intramuscular and rectal administration. International Journal of Clinical Pharmacology 12: 427–432 (1975).

    CAS  Google Scholar 

  • Klotz, U.: Pathophysiological and disease-induced changes in drug distribution volume: pharmacokinetic implications. Clinical Pharmacokinetics 1: 204–218 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Koch-Weser, J.: Bioavailability of drugs. New England Journal of Medicine 291: 233–237 and 503-506 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Kostenbauder, H.B.; Portnoff, J.B. and Swintosky, J.V.: Control of urine pH and its effect on sulfaethidole excretion in humans. Journal of Pharmaceutical Sciences 51: 1084–1089 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Kunin, C.M.: A guide to use of antibiotics in patients with renal disease. Annals of Internal Medicine 67: 121–158 (1967).

    Google Scholar 

  • Kuntzman, R.G.; Tsai, I.; Brand, L. and Mark, L.C.: The influence of urinary pH on the plasma half-life of pseudoephedrine in man and dog and a sensitive assay for its determination in human plasma. Clinical Pharmacology and Therapeutics 12: 62–67 (1970).

    Google Scholar 

  • Lalka, D.; Meyer, M.B.; Duce, B.R. and Elvin, AT.: Kinetics of the oral antiarrhythmic lidocaine congener, tocainide. Clinical Pharmacology and Therapeutics 19: 757–766 (1976).

    PubMed  CAS  Google Scholar 

  • Lavene, D.; Weiss, Y.A.; Safar, M.E.; Loria, Y.; Agonis, N.; Georges, D. and Milliez, PL: Pharmacokinetics and hepatic extraction ratio of pindolol in hypertensive patients with normal and impaired renal function. Journal of Clinical Pharmacology 17: 501 (1977).

    PubMed  CAS  Google Scholar 

  • Leahey, E.B.; Reiffel, J.A.; Heissenbuttel, R.H.; Drusin, R.E.; Lovejoy, W.P. and Bigger, J.T., Jr.: Enhanced cardiac effect of digoxin during quinidine treatment. Archives of Internal Medicine 139: 519–521 (1979).

    Article  PubMed  Google Scholar 

  • Lee, C.S.; Gambertoglio, J.G.; Brater, D.C and Benet, L.Z.: Kinetics of oral ethambutol in the normal subject. Clinical Pharmacology and Therapeutics 22: 615–621 (1977).

    PubMed  CAS  Google Scholar 

  • Lee, W.; Strong, J.M.; Kehoe, R.R.; Dutcher, J.S. and Atkinson, A.J.: Antiarrhythmic efficacy of N-acetylprocainamide in patients with premature ventricular contractions. Clinical Pharmacology and Therapeutics 19: 508–514 (1975).

    Google Scholar 

  • LeSher, D.A.: Considerations in the use of drugs in patients with renal failure. Journal of Clinical Pharmacology 16: 570–576 (1976).

    Article  PubMed  Google Scholar 

  • Letteri, J.M.; Mellk, H.; Louis, S.; Kutt, H.; Durante, P. and Glazko, A.: Diphenylhydantoin metabolism in uremia. New England Journal of Medicine 285: 648–652 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Levine, S.D.; Franki, N.; Einhorn, R. and Hays, R.M.: Vasopressin-stimulated movement of drugs and uric acid across the toad urinary bladder. Kidney International 9: 30–35 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Levy, G.; Baliah, T. and Procknal, J.A.: Effect of renal transplantation on protein binding of drugs in serum of donor and recipient. Clinical Pharmacology and Therapeutics 20: 512–516 (1976).

    PubMed  CAS  Google Scholar 

  • Levy, G. and Koysooko, R.: Renal clearance of theophylline in man. Journal of Clinical Pharmacology 16: 329–332 (1976).

    PubMed  CAS  Google Scholar 

  • Levy, G.; Lampman, T.; Kamath, L. and Garrettson, L.K.: Decreased serum salicylate concentrations in children with antacid. New England Journal of Medicine 293: 323–325 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Levy, J. and Klastersky, J.: Correlation of serum creatinine concentration and amikacin half-life. Journal of Clinical Pharmacology 15: 705–707 (1975).

    PubMed  CAS  Google Scholar 

  • Liddell, N.E. and Maren, T.H.: CO2 retention as a basis for increased toxicity of salicylate with acetazolamide: avoidance of increased toxicity with benzolamide. Journal of Pharmacology and Experimental Therapeutics 195: 1–7 (1975).

    PubMed  CAS  Google Scholar 

  • Manninen, V.; Melin, J.; Apajalahti, A. and Karesoja, M.: Altered absorption of digoxin in patients given propantheline and metoclopramide. Lancet 1: 398–400 (1973).

    Article  PubMed  CAS  Google Scholar 

  • McHenry, M.C.; Gavan, T.L.; Gifford, R.W., Jr.; Guerkink, N.A.; Van Ommen, R.A.; Town, M.A. and Wagner, J.G.: Gentamicin dosages for renal insufficiency. Annals of Internal Medicine 74: 192–197 (1971).

    PubMed  CAS  Google Scholar 

  • Milne, M.D.; Scribner, B.H. and Crawford, M.A.: Non-ionic diffusion and the excretion of weak acids and bases. American Journal of Medicine 24: 709–729 (1958).

    Article  PubMed  CAS  Google Scholar 

  • Morgan, A.G. and Polak, A.: Acetazolamide and sodium bicarbonate in treatment of salicylate poisoning in adults. British Medical Journal 1: 16–19 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Mudge, G.H.: Uricosuric action of cholecystographic agents. New England Journal of Medicine 284: 929–933 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Mudge, G.H.; Silva, P. and Stibitz, G.R.: Renal excretion by non-ionic diffusion (The nature of the disequilibrium). Medical Clinics of North America 59: 681–698 (1975).

    PubMed  CAS  Google Scholar 

  • Nash, C.W. and Heath, C.: Vascular responses to catecholamines during respiratory changes in pH. American Journal of Physiology 200: 755–782 (1961).

    PubMed  CAS  Google Scholar 

  • Nimmo, W.S.: Drugs, diseases and altered gastric emptying. Clinical Pharmacokinetics 1: 189–203 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Noone, P.; Beale, D.F.; Pollock, S.S.; Perera, M.R.; Amirak, I.D.; Fernando, O.N. and Moorhead, J.F.: Monitoring aminoglycoside use in patients with severely impaired renal function. British Medical Journal 2: 470–473 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Noone, P.; Parsons, T.M.C. and Pattison, J.R.: Experience in monitoring gentamicin therapy during treatment of serious gram-negative sepsis. Br. Med. J. 1: 477–481 (1974).

    Article  PubMed  CAS  Google Scholar 

  • O’Grady, F.: Antibiotics in renal failure. British Medical Journal 27: 142–417 (1971).

    Google Scholar 

  • Pagliaro, L.A. and Benet, L.Z.: Pharmacokinetic data: critical compilation of terminal half-life, per cent excreted unchanged, and changes in half-life in renal and hepatic failure for studies in humans, with references. Journal of Pharmacokinetics and Biopharmaceutics 3: 333–383 (1975).

    PubMed  CAS  Google Scholar 

  • Payne, J.P. and Rowe, G.G.: The effects of mecamylamine in the cat as modified by the administration of carbon dioxide. British Journal of Pharmacology 12: 457–460 (1957).

    CAS  Google Scholar 

  • Pearson, R.M.: Pharmacokinetics and response to diazoxide in renal failure. Clinical Pharmacokinetics 2: 198–204 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Pearson, R.M. and Breckenridge, A.M.: Renal function, protein binding and pharmacological response to diazoxide. British Journal of Clinical Pharmacology 3: 169–175 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Pechere, J.C. and Dugal, R.: Clinical pharmacokinetics of aminoglycoside antibiotics. Clinical Pharmacokinetics 4: 170–199 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Peters, L.: Renal tubular excretion of organic bases. Pharmacological Reviews 12: 1–35 (1960).

    PubMed  CAS  Google Scholar 

  • Prescott, L.F.: Limitations of haemodialysis and forced diuresis, in The Poisoned Patient: Role of the Laboratory. CIBA Foundation Symposium 26 (new series) p.269 (Associated Scientific Publishers, Oxford 1974).

    Google Scholar 

  • Prescott, L.F.: Mechanisms of renal excretion of drugs (with special reference to drugs used by anaesthetists). British Journal of Anaesthesia 44: 246–251 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F.: Drug overdosage and poisoning; in Avery (Ed) Drug Treatment, 2nd ed, pp.263–281 (ADIS Press, Sydney and New York; Churchill Livingstone, Edinburgh 1980).

    Google Scholar 

  • Reidenberg, M.M.; Odar-Cederlof, I.; von Bahr, C.; Borga, O. and Sjoqvist, F.: Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function. New England Journal of Medicine 285: 264–267 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Reimold, E.W.; Worthen, H.G. and Reilly, T.P.: Salicylate poisoning; comparison of acetazolamide administration and alkaline diuresis in the treatment of experimental salicylate intoxication in puppies. American Journal of Diseases of Children 125: 668–674 (1973).

    PubMed  CAS  Google Scholar 

  • Rennick, B.R.: Renal excretion of drugs; tubular transport and metabolism. Annual Review of Pharmacology and Toxicology 12: 121–156 (1972).

    Google Scholar 

  • Rennick, B.R.; Moe, G.K.; Lyons, R.H.; Hoobler, S.W. and Neligh, R.: Absorption and renal excretion of the tetraethylammonium ion. Journal of Pharmacology and Experimental Therapeutics 91: 210–217 (1947).

    PubMed  CAS  Google Scholar 

  • Reuning, R.H.; Sams, R.A. and Notari, R.E.: Role of pharmacokinetics in drug dosage adjustment. Journal of Clinical Pharmacology 13: 127–141 (1973).

    CAS  Google Scholar 

  • Roman, R.J. and Kauker, M.L.: Renal tubular transport of H-digoxin in saline diuresis in rats. Circulation Research 38: 185–191 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Rosenbaum, J.L.; Kramer, M.S. and Raja, R.: Resin hemoperfusion for acute drug intoxication. Archives of Internal Medicine 136: 263–266 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Ross, C.R.; Diezi-Chomety, F. and Roch-Ramel, F.: Renal excretion of N-methylnicotinamide in the rat. American Journal of Physiology 228: 1641–1645 (1975).

    PubMed  CAS  Google Scholar 

  • Sawchuk, R.J. and Zaske, D.E.: Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients. Journal of Pharmacokinetics and Biopharmaceutics 4: 183–195 (1976).

    PubMed  CAS  Google Scholar 

  • Schuck, O.; Grafnetterova, J.; Nadvornikove, H. and Prat, V.: Urinary excretion of drugs in chronic renal impairment with respect to changes in their tubular handling by residual nephrons. International Journal of Clinical Pharmacology and Biopharmacy 14: 149–154 (1976).

    PubMed  CAS  Google Scholar 

  • Schumacher, G.E.: Pharmacokinetic analysis of gentamicin dosage regimens recommended for renal impairment. Journal of Clinical Pharmacology 15: 656–665 (1975).

    PubMed  CAS  Google Scholar 

  • Scribner, B.H.; Crawford, M.A. and Dempster, W.J.: Urinary excretion by nonionic diffusion. American Journal of Physiology 196: 1135–1140 (1959).

    PubMed  CAS  Google Scholar 

  • Serrano, E.E.; Roye, D.B.; Hammer, R.H. and Wilder, B.J.: Plasma diphenylhydantoin values after oral and intramuscular administration of diphenylhydantoin. Neurology 23: 311–317 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Sheiner, L.B.; Halkin, H.; Peck, C. et al.: Improved computer-assisted digoxin therapy. A method using feedback of measured serum digoxin concentrations. Annals of Internal Medicine 82: 619–627 (1975).

    PubMed  CAS  Google Scholar 

  • Shen, S. and Bressler, R.: Clinical pharmacology of oral antidiabetic agents. New England Journal of Medicine 296: 493–496 and 787-793 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Shoeman, D.W. and Azarnoff, D.L.: Diphenylhydantoin potency and plasma protein binding. Journal of Pharmacology and Experimental Therapeutics 195: 84–86 (1975).

    PubMed  CAS  Google Scholar 

  • Silverblatt, F.J. and Kuehn, C.: Autoradiography of gentamicin uptake by the rat proximal tubule cell. Kidney International 15: 335–345 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Sjoqvist, F.; Borga, O. and Orme, M.L’E.: Fundamentals of clinical pharmacology; in Avery (Ed) Drug Treatment, 2nd ed, pp. 1–61 (ADIS Press, Sydney and New York; Churchill Livingstone, Edinburgh 1980).

    Google Scholar 

  • Stamey, T.A.; Fair, W.R.; Timothy, M.M.; Mihara, G. and Lowery, Y.C.: Serum versus urinary antimicrobial concentrations in cure of urinary tract infections. New England Journal of Medicine 291: 1159–1163 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Storstein, L.: Studies on digitalis. Clinical Pharmacology and Therapeutics 20: 158–166 (1976).

    PubMed  CAS  Google Scholar 

  • Stowers, J.M. and Borthwick, L.J.: Oral hypoglycaemic drugs; clinical pharmacology and therapeutic use. Drugs 14: 41–56 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Szeto, H.H.; Inturrisi, C.E.; Houde, R.; Saal, S.; Cheigh, J. and Reidenberg, M.M.: Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure or cancer. Annals of Internal Medicine 86: 738–741 (1977).

    PubMed  CAS  Google Scholar 

  • Torretti, J.; Weiner, I.M. and Mudge, G.H.: Renal tubular secretion and reabsorption of organic bases in the dog. Journal of Clinical Investigation 41: 793–804 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Trafford, J.A.P.; Jones, R.H.; Evans, R.; Sharp, P.; Sharpstone, P. and Cook, J.: Haemoperfusion with R-004 amberlite resin for treating acute poisoning. British Medical Journal 2: 1435–1496 (1977).

    Article  Google Scholar 

  • Vallner, J.J.: Binding of drugs by albumin and plasma protein. Journal of Pharmaceutical Sciences 66: 447–465 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Van Gemert, A.G.M. and Duyff, J.W.: Optimal dosage of drugs. Acta Physiologica et Pharmacologica Neerlandica 1: 256–278 (1950).

    PubMed  Google Scholar 

  • Van Scoy, R.E. and Wilson, W.R.: Antimicrobial agents in patients with renal insufficiency. Mayo Clinic Proceedings 52: 704–706 (1977).

    PubMed  Google Scholar 

  • Wadell, W.J. and Butler, T.C.: The distribution and excretion of phenobarbital. Journal of Clinical Investigation 36: 1217–1226 (1957).

    Article  Google Scholar 

  • Waldorff, S.; Andersen, J.D.; Heeboll-Nielsen, N.; Nielsen, O.G.; Moltke, E.; Sorensen, U. and Steiness, E.: Spironolactone-induced changes in digoxin kinetics. Clinical Pharmacology and Therapeutics 24: 162–167 (1978).

    PubMed  CAS  Google Scholar 

  • Weily, H.S. and Genton, E.: Pharmacokinetics of procainamide. Archives of Internal Medicine 120: 366–369 (1972).

    Article  Google Scholar 

  • Weiner, I.M. and Mudge, G.H.: Renal tubular mechanisms for excretion of organic acids and bases. American Journal of Medicine 36: 743–762 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Welling, P.G.; Craig, W.A. and Kunin, C.M.: Prediction of drug dosage in patients with renal failure using data derived from normal subjects. Clinical Pharmacology and Therapeutics 18: 45–52 (1975).

    PubMed  CAS  Google Scholar 

  • Wilensky, A.J. and Lowden, J.A.: Inadequate serum levels after intramuscular administration of diphenylhydantoin. Neurology 23: 318–324 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson, G.R. and Beckett, A.H.: Absorption, metabolism and excretion of the ephedrïnes in man. I. The influence of urinary pH and urine volume output. Journal of Pharmacology and Experimental Therapeutics 162: 139–147 (1968).

    PubMed  CAS  Google Scholar 

  • Woodhall, P.B.; Tisher, C.C.; Simonton, C.A. and Robinson, R.R.: Relationship between para-aminohippurate secretion and cellular morphology in rabbit proximal tubules. Journal of Clinical Investigation 61: 1320–1329 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Yacobi, A.; Lampman, T. and Levy, G.: Frequency distribution of free warfarin and free Phenytoin fraction values in serum of healthy human adults. Clinical Pharmacology and Therapeutics 21: 283–286 (1976).

    Google Scholar 

  • Young, J.L.; Boswell, R.B. and Nies, A.S.: Severe allopurinol hypersensitivity. Archives of Internal Medicine 134: 553–558 (1974).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brater, D.C. The Pharmacological Role of the Kidney. Drugs 19, 31–48 (1980). https://doi.org/10.2165/00003495-198019010-00003

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-198019010-00003

Keywords

Navigation