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Use of Serum Creatinine Concentrations to Determine Renal Function1

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Summary

Serum creatinine concentrations are widely used clinically as an index of renal function. In stable normal or reduced renal function they are determined by the rate of creatinine production and the endogenous creatinine clearance, and, during changing renal function, also by the apparent volume of distribution of creatinine. These determinants of serum creatinine concentrations, however, are affected by age, sex and body weight. The rate of creatinine production is proportional to body weight, and it decreases with age and is slower in females than in males. The endogenous creatinine clearance decreases with age and is lower in females than in males. The apparent volume of distribution of creatinine is equal to the total body water, which is proportional to body weight, and it decreases with age and is lower in females than in males. The individual relationships between the determinants of serum creatinine concentrations and age, sex, and body weight have been established using data from published reports. The effects of age, sex, and body weight on the relationship between normal and reduced renal function and serum creatinine concentrations are illustrated by simulations. Equations are derived to predict endogenous creatinine clearance from serum creatinine concentrations, and a nomogram is presented for determining relative renal function from serum creatinine concentrations, which take into account the age, sex and body weight of the individual patient. It is recommended for rapid clinical evaluation of stable normal or reduced renal function. When rapid changes are expected clinically, however, it is recommended to use a mid urine collection period serum creatinine sample for creatinine clearance determination.

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References

  • American Heart Association, Council on the Kidney in Cardiovascular Disease: Criteria for the evaluation of the severity of established renal disease. Annals of Internal Medicine 75: 251–252 (1971).

    Google Scholar 

  • Behnke, A.R.; Feen, B.G. and Welham, W.C.: The specific gravity of healthy men. Journal of the American Medical Association 118: 495–501 (1942).

    Article  Google Scholar 

  • Berger, E.Y.; Dunning, M.F.; Steele, J.M.; Jackenthal, R. and Brodie, B.B.: Estimation of intracellular water in man. American Journal of Physiology 162: 318–325 (1950).

    PubMed  CAS  Google Scholar 

  • Berlyne, G.M.; Varley, H.; Nilwarangkur, S. and Hoerni, M.: Endogenous creatinine clearance and glomerular filtration rate. Lancet 2: 874–875 (1964).

    Article  PubMed  CAS  Google Scholar 

  • Bianchi, C.: Measurement of the glomerular filtration rate. Progress in Nuclear Medicine 2: 21–53 (1972).

    PubMed  CAS  Google Scholar 

  • Bowden, R.E., Kimberley, R.P.; Gill, J.R.; Plotz, P.H. and Keiser, H.R.: Urinary prostaglandin E and renal function. Clinical Research 25: 427A (1977).

    Google Scholar 

  • Breckenridge, A. and Metcalfe-Gibson, A.: Methods for measuring glomerular filtration rate: A comparison of inulin, vitamin B-12, and creatinine clearances. Lancet 2: 265–267 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Brochner-Mortensen, J.; Jensen, S. and Rodbro, P.: Delimitation of plasma creatinine concentration values for assessment of relative renal function in adult patients. Scandinavian Journal of Urology and Nephrology 11: 257–262 (1977a).

    Article  PubMed  CAS  Google Scholar 

  • Brochner-Mortensen, J.; Jensen, S. and Rodbro. P.: Assessment of renal function from plasma creatinine in adult patients. Scandinavian Journal of Urology and Nephrology 11: 263–270 (1977b).

    Article  PubMed  CAS  Google Scholar 

  • Case Records of the Massachusetts General Hospital: Normal Reference Laboratory Values. New England Journal of Medicine 298: 34–45 (1978).

    Article  Google Scholar 

  • Chiou, W.L. and Hsu, F.H.: Pharmacokinetics of creatinine in man and its implications in the monitoring of renal function and in dosage regimen modifications in patients with renal insufficiency. Journal of Clinical Pharmacology 15: 427–434 (1975).

    PubMed  CAS  Google Scholar 

  • Chiou, W.L.; Gadalla, M.A.F. and Peng, G.W.: Simple, rapid and micro high-pressure liquid chromatographic determination of endogenous “true” creatinine in plasma, serum, and urine. Journal of Pharmaceutical Sciences 67: 182–187 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Cockcroft, D.W. and Gault, M.H.: Prediction of creatinine clearance from serum creatinine. Nephron 16: 31–41 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Davies, D.F. and Shock, N.W.: Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. Journal of Clinical Investigation 29: 496–507 (1950).

    Article  PubMed  CAS  Google Scholar 

  • Deane, N.: Intracellular water in man. Journal of Clinical Investigation 30: 1469–1470 (1951).

    Article  PubMed  CAS  Google Scholar 

  • Deane, N. and Smith, H.W.: The distribution of sodium and potassium in man. Journal of Clinical Investigation 31: 197–199 (1952).

    Article  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; in Progress in Pharmacology, vol. 1, No. 4, p. 9 (Gustav Fischer Verlag, Stuttgart 1977).

    Google Scholar 

  • Devine, B.J.: Clinical pharmacy case studies: Case number 25: Gentamicin therapy. Drug Intelligence and Clinical Pharmacology 8: 650–655 (1974).

    Google Scholar 

  • Dominguez, R.: Kinetics of elimination, absorption, and volume of distribution in the organism. Medical Physiology 2: 475–489 (1950).

    Google Scholar 

  • Dominguez, R. and Pomerene, E.: Recovery of creatinine after ingestion and after intravenous injection in man. Proceedings of the Society for Experimental Biology and Medicine 58: 26–28 (1945).

    CAS  Google Scholar 

  • Doolan, P.D.; Alpen, E.L. and Theil, G.B.: A clinical appraisal of the plasma concentrations and endogenous clearance of creatinine. American Journal of Medicine 32: 65–79 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Dubach, U.C.; Merz, I. and Schmid, P.: Serum creatinine values in 2258 employed subjects of various ages and sex. Klinische Wochenschrift 45: 621–629 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Edelman, I.S.; Haley, H.B.; Schloerb, P.R., Sheldon, D.B.; Friis-Hansen, B.J.; Stall, G. and Moore, F.D.: Further observations on total body water. I. Normal values throughout the life span. Surgery, Gynecology and Obstetrics 95: 1–12 (1952).

    CAS  Google Scholar 

  • Edelman, I.S.: Exchange of water between blood and tissues. Characteristics of dueterium oxide equilibrium in body water. American Journal of Physiology 171: 270–296 (1952).

    Google Scholar 

  • Edelman, L.S. and Leibman, J.: Anatomy of body water and electrolytes. American Journal of Medicine 27: 256–277 (1959).

    Article  PubMed  CAS  Google Scholar 

  • Edwards, K.D.G.: Creatinine space as a measure of total body water in anuric subjects, estimated after single injection and haemodialysis. Clinical Science 18: 455–464 (1959).

    PubMed  CAS  Google Scholar 

  • Edwards, O.M.; Bayliss, R.S. and Milien, S.: Urinary creatinine excretion as an index of the completeness of 24-hour urine collection. Lancet 2: 115–116 (1969).

    Google Scholar 

  • Effersoe, P.: Relationship between endogenous 24-hour creatinine clearance and serum creatinine concentration in patients with chronic renal disease. Acta Medica Scandinavica 156: 429–434 (1957).

    Article  PubMed  CAS  Google Scholar 

  • Enger, E. and Belgen, E.M.: The relationship between endogenous creatinine clearance and serum creatinine in renal failure. Scandinavian Journal of Clinical Laboratory Investigation 16: 273–280 (1964).

    Article  CAS  Google Scholar 

  • Forbes, G.B.: The adult decline in lean body mass. Human Biology 48: 161–173 (1976).

    PubMed  CAS  Google Scholar 

  • Friedman, S.A.; Raizner, A.E.; Rosen, H.; Solomon, N.A. and Sy, W.: Functional defects in the aging kidney. Annals of Internal Medicine 76: 41–45 (1972).

    PubMed  CAS  Google Scholar 

  • Friis-Hansen, B.: Body water compartments in children: Changes during growth and related changes in body composition. Pediatrics 28: 169–181 (1961).

    PubMed  CAS  Google Scholar 

  • George, C.R.P.: Non-specific enhancement of glomerular filtration by corticosteroids. Lancet 2: 728–729 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Gibaldi, M.: Biopharmaceutics and Clinical Pharmacokinetics. 2nd ed., p. 120 (Lea & Febiger, Philadelphia 1977).

    Google Scholar 

  • Gibaldi, M. and Perrier, D.: Pharmacokinetics, p. 28 (Marcel Dekker. New York 1975).

    Google Scholar 

  • Goldman, R.: Creatinine excretion in renal failure. Proceedings of the Society for Experimental Biology and Medicine 85: 446–448 (1954).

    PubMed  CAS  Google Scholar 

  • Greenblatt, D.J.; Ransil, B.J.; Harmatz, J.S.; Smith, T.W.; Duhme, D.W. and Koch-Weser, J.: Variability of 24-hr urinary creatinine excretion by normal subjects. Journal of Clinical Pharmacology 16: 321–328 (1976).

    PubMed  CAS  Google Scholar 

  • Guyton, A.C.: Textbook of Medical Physiology, 5th ed., pp. 444, 946 (Saunders, Philadelphia 1976).

    Google Scholar 

  • Hamby, W.M.; Janknowski, G.J.; Pouget, J.M.; Dunea, G. and Gantt, C.L.: Intravenous use of diazoxide in the treatment of severe hypertension. Circulation 37: 169–174 (1968).

    Article  CAS  Google Scholar 

  • Harvey, A.M.; Johns, R.J.; Owens, A.H.; Ross, R.S. (Eds): The Principles and Practice of Medicine, 19th ed, pp. 72, 1807 (Appleton-Century-Crofts, New York 1976).

    Google Scholar 

  • Hoberman, H.D.; Sims, E.A.H. and Peters, J.H.: Creatinine and creatinine metabolism in the normal adult studied with the aid of isotopic nitrogen. Journal of Biological Chemistry 172: 45–58 (1948).

    PubMed  CAS  Google Scholar 

  • Hollenberg, N.K.; Adams, D.F.; Solomon, H.S.; Rashid, A.; Abrams, H.L. and Merrill, J.P.L.: Senescence and the renal vasculature in normal man. Circulation Research 34: 309–316 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Hook, J.B.; Blatt, A.H.; Brody, M.J. and Williamson, H.E.: Effects of several saluretic-diuretic agents on renal hemodynamics. Journal of Pharmacology and Experimental Therapeutics 154: 667–673 (1966).

    PubMed  CAS  Google Scholar 

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

    CAS  Google Scholar 

  • Jelliffe, R.W.: Creatinine clearance: Bedside estimate. Annals of Internal Medicine 79: 604–605 (1973).

    PubMed  CAS  Google Scholar 

  • Jelliffe, R.W. and Jelliffe, S.M.: A computer program for estimation of creatinine clearance from unstable serum creatinine levels by age, sex, and weight. Mathematical Biosciences 14: 17–24 (1972).

    Article  Google Scholar 

  • Johnson. B.F.: Diazoxide and renal function in man. Clinical Pharmacology and Therapeutics 12: 815–824 (1971).

    PubMed  CAS  Google Scholar 

  • Jones, J.D. and Burnett, P.C.: Creatinine metabolism in humans with decreased renal function: Creatinine deficit. Clinical Chemistry 20: 1204–1212 (1974).

    PubMed  CAS  Google Scholar 

  • Judson, W.E.; Hollander, W. and Wilkins, R.W.: The effects of intravenous Apresoline (hydralazine) on cardiovascular and renal function in patients with and without conjective heart failure. Circulation 13: 664–679 (1956).

    Article  PubMed  Google Scholar 

  • Kampman, J.; Siersbaek-Nielsen, K.; Kristensen, M. and Molholm Hansen, J.: Rapid evaluation of creatinine clearance. Acta Medica Scandinavica 196: 517–520 (1974).

    Article  Google Scholar 

  • Kassirer. J.P.: Clinical evaluation of kidney function-glomerular function. New England Journal of Medicine 285: 385–389 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Keys, A. and Brozek, J.: Body fat in adult man. Physiological Reviews 33: 245–325 (1953).

    PubMed  CAS  Google Scholar 

  • Kimberley, R.P. and Plotz, P.H.: Aspirin-induced depression of renal function. New England Journal of Medicine 296: 418–424 (1977).

    Article  Google Scholar 

  • Koch-Weser, J.: Diazoxide. New England Journal of Medicine 294: 1271–1274 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Koshy, M.C.; Mickley, D.; Bourgoignie, J. and Blaufox, M.D.: Physiologic evaluation of a new antihypertensive agent: Prazosin HCl. Circulation 55: 533–537 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Levy, G.: Pharmacokinetics in renal disease. American Journal of Medicine 62: 461–464 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Lim, C.K.; Richmond, W.; Robinson, D.P. and Brown, S.S.: Towards a definitive assay of creatinine in serum and in urine: Separation by high-performance liquid chromatography. Journal of Chromatography 145: 41–49 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Mawer, G.E.: Computer assisted prescribing of drugs. Clinical Pharmacokinetics 1: 67–78 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Mitch, W.E.; Collier, V.U. and Walser, M.: Creatinine metabolism in chronic renal failure. Clinical Research 26: 636A (1978).

    Google Scholar 

  • Moss, G.A.; Bondar, R.J. and Buzzelli, D.M.: Kinetic enzymatic method for determining serum creatinine. Clinical Chemistry 21: 1422–1426 (1975).

    PubMed  CAS  Google Scholar 

  • Mudge, G.H.: Diuretics and other agents employed in the mobilization of edema fluid; in Goodman and Oilman (Eds). The Pharmacologic Basis of Therapeutics, 5th ed., pp. 831, 834 (Macmillan. New York 1975).

    Google Scholar 

  • Nickerson, M. and Ruedy, J.: Antihypertensive agents and the drug therapy of hypertension; in Goodman and Gilman (Eds) The Pharmacologic Basis of Therapeutics, 5th ed., p. 711 (Macmillan. New York 1975).

    Google Scholar 

  • Onesti, G.; Schwartz, A.B.; Kim, K.E.; Swartz, G. and Brest, A.N.: Pharmacodynamic effects of a new antihypertensive drug, Catapres (5T-155). Circulation 39: 219–228 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Onesti, G.: Systemic hemodynamic effect of α-methyldopa in man; in Onesti, Fernandes and Kim (Eds) Regulation of Blood Pressure by the Central Nervous System, p. 387 (Grune & Stratton, New York 1976).

    Google Scholar 

  • Osserman, E.F.; Pitts, G.C.; Welham, W.C. and Behnke, A.R.: In vivo measurement of body fat and body water in a group of normal men. Journal of Applied Physiology 2: 633–639 (1950).

    PubMed  CAS  Google Scholar 

  • Page, I.H.; Corcoran, A.C.; Dustan, H.P. and Koppanyi, T.: Cardiovascular actions of sodium nitroprusside in animals and hypertensive patients. Circulation 11: 188–198 (1955).

    Article  PubMed  CAS  Google Scholar 

  • Page, I.H.; Hurley, R.E. and Dustan, H.P.: The prolonged treatment of hypertension with guanethidine. Journal of the American Medical Association 175: 543–549 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Pasternack, A. and Kuhlback, B.: Diurnal variations of serum and urine creatine and creatinine. Scandinavian Journal of Clinical and Laboratory Investigation 27: 1–7 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Pettinger, W.A.: Clonidine, a new antihypertensive drug. New England Journal of Medicine 293: 1179–1180 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Prentice, T.C.; Siri, W.; Berlin, N.I.; Hyde. G.M.; Parsons, R.J.; Joiner, E.E. and Lawrence, J.H.: Studies of total body water with tritium. Journal of Clinical Investigation 31: 412–418 (1952).

    Article  PubMed  CAS  Google Scholar 

  • Rapoport, A. and Husdan, H.: Endogenous creatinine clearance and serum creatinine in the clinical assessment of kidney function. Canadian Medical Association Journal 99: 149–156 (1968).

    PubMed  CAS  Google Scholar 

  • Reubi, F.C.: Clinical use of furosemide. Annals of the New York Academy of Sciences 139: 433–442 (1966).

    Article  PubMed  CAS  Google Scholar 

  • Reusen, C.S.: The cardiorenal hemodynamic effects of antihypertensive therapy with reserpine. American Heart Journal 6: 643–649 (1962).

    Google Scholar 

  • Richards. R.K.; Bjornsson, T.D. and Waterbury. L.D.: Rise in serum and urine creatinine after phenacemide. Clinical Pharmacology and Therapeutics 23: 430–437 (1978).

    PubMed  CAS  Google Scholar 

  • Rowe, J.W.; Andres, R.; Tobin, J.D.; Norris, A.H. and Shock, N.W.: The effect of age on creatinine clearance in men: A cross-sectional and longitudinal study. Journal of Gerontology 31: 155–163 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Sannerstedt, R. and Conway, J.: Hemodynamic and vascular responses to antihypertensive treatment with adrenergic blocking agents: A review. American Heart Journal 79: 122–127 (1970).

    Article  PubMed  CAS  Google Scholar 

  • Schentag, J.; Jusko, W.J.; Vance, J.W.; Cumbo, T.J.; Abrutyn, E.; DeLattre, M. and Gerbracht, L.M.: Gentamicin disposition and tissue accumulation on multiple dosing. Journal of Pharmacokinetics and Biopharmaceutics 5: 559–577 (1977).

    PubMed  CAS  Google Scholar 

  • Schloerb, P.R.; Friis-Hansen, B.J.; Edelman, I.S.; Sheldon, D.B. and Moore, F.D.: The measurement of total body water in the human subject by dueterium oxide dilution: with consideration of the dynamics of deuterium distribution. Journal of Clinical Investigation 29: 1296–1310 (1950).

    Article  PubMed  CAS  Google Scholar 

  • Siersbaek-Nielseri, K.; Hansen, J.M.; Kampmann, J. and Kristensen, M.: Rapid evaluation of creatinine clearance. Lancet 1: 1133 (1971).

    Article  Google Scholar 

  • Soberman, R.J.; Brodie, B.B.; Levy, B.B.; Axelrod, J.; Hollander, V. and Steele, J.M.: The use of antipyrine in the measurement of total body water in man. Journal of Biological Chemistry 179: 31–42 (1949).

    PubMed  CAS  Google Scholar 

  • Steele, J.M.; Berger, E.Y.; Dunning, M.F. and Brodie, B.B.: Total body water in man. American Journal of Physiology 162: 313–317 (1950).

    PubMed  CAS  Google Scholar 

  • Tobias, G.J.; McLaughlin, R.F. and Hopper, J.: Endogenous creatinine clearance: A valuable clinical test of glomerular filtration and a prognostic guide in chronic renal failure. New England Journal of Medicine 266: 317–323 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Turner, W.J. and Cohn, S.: Total body potassium and 24-hour creatinine excretion in healthy males. Clinical Pharmacology and Therapeutics 18: 405–412 (1975).

    PubMed  CAS  Google Scholar 

  • van Rossum, J.M.: Pharmacokinetics of accumulation. Journal of Pharmaceutical Sciences 57: 2162–2164 (1968).

    Article  PubMed  Google Scholar 

  • Vestal, R.E.; Norris, A.H.; Tobin, J.D.; Cohen, B.H.; Shock, N.W. and Andres, R.: Antipyrine metabolism in man: Influence of age, alcohol, caffeine, and smoking. Clinical Pharmacology and Therapeutics 18: 425–432 (1975).

    PubMed  CAS  Google Scholar 

  • Villarreal, H.; Revollo, A.; Exaire, E. and Larrondo, F.: Effect of chlorothiazide on renal hemodynamics. Comparative study of acute administration in normotensive and hypertensive subjects. Circulation 26: 409–412 (1962).

    CAS  Google Scholar 

  • Wagner, J.G.: Fundamentals of Clinical Pharmacokinetics, p. 162 (Drug Intelligence Publications, Hamilton, Illinois 1975).

    Google Scholar 

  • Warren, D.J.: Beta-adrenergic receptor blockade and renal function. American Heart Journal 91: 265–266 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Weatherburn, M.W.; Trotman, R.B.B. and Jackson, S.H.: Specific method for serum creatinine determination based on ion exchange chromatography and an automated alkaline picrate reaction — A proposed reference method. Clinical Biochemistry 11: 159–166 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Wesson, L.G., Jr.: Electrolyte excretion in relation to diurnal cycles of renal function. Medicine (Balt.) 43: 547–592 (1964).

    Article  Google Scholar 

  • Wesson, L.G., Jr.: Renal hemodynamics in physiological states: in Wesson (Ed) Physiology of the Human Kidney, p. 96 (Grune & Stratton, New York 1969).

    Google Scholar 

  • Wilkinson, E.L.; Backman, H. and Hecht, H.H.: Cardiovascular and renal adjustments to a hypotensive agent (l-hydrazinophthalazine: Ciba BA-5968, Apresoline). Journal of Clinical Investigation 31: 872–879 (1952).

    Article  PubMed  CAS  Google Scholar 

  • Woosley. R.L. and Nies, A.S.: Guanethidine. New England Journal of Medicine 295: 1053–1056 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Young, D.S.; Pestaner, L.C. and Gibberman. V.: Effects of drugs on clinical laboratory tests. Clinical Chemistry 21: 286D–287D (1975).

    Google Scholar 

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  1. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, Amherst, New York, USA

    Thorir D. Bjornsson

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Bjornsson, T.D. Use of Serum Creatinine Concentrations to Determine Renal Function1. Clin Pharmacokinet 4, 200–222 (1979). https://doi.org/10.2165/00003088-197904030-00003

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