Methylxanthines and the Kidney

  • Hartmut Osswald
  • Jürgen SchnermannEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 200)


This chapter describes the effects of the natural methylxanthines caffeine and theophylline on kidney function. Theophylline in particular was used traditionally to increase urine out put until more potent diuretics became available in the middle of the last century. The mildly diuretic actions of both methylxanthines are mainly the result of inhibition of tubular fluid reabsorption along the renal proximal tubule. Based upon the use of specific adenosine receptor antagonists and the observation of a complete loss of diuresis in mice with targeted deletion of the A1AR gene, transport inhibition by methylxanthines is mediated mainly by antagonism of adenosine A1 receptors (A1AR) in the proximal tubule. Methylxanthines are weak renal vasodilators, and they act as competitive antagonists against adenosine-induced preglomerular vasoconstriction. Caffeine and theophylline stimulate the secretion of renin by inhibition of adenosine receptors and removal of the general inhibitory brake function of endogenous adenosine. Since enhanced intrarenal adenosine levels lead to reduced glomerular filtration rate in several pathological conditions theophylline has been tested for its therapeutic potential in the renal impairment following administration of nephrotoxic substances such as radiocontrast media, cisplatin, calcineurin inhibitors or following ischemia-reperfusion injury. In experimental animals functional improvements have been observed in all of these conditions, but available clinical data in humans are insufficient to affirm a definite therapeutic efficacy of methylxanthines in the prevention of nephrotoxic or postischemic renal injury.


Adenosine Caffeine Diuresis Natriuresis Nephropathy Renin Theophylline 


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© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.National Institute of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.Department of Pharmacology and ToxicologyUniversity of TübingenTübingenGermany

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