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Methylxanthines and the Kidney

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Methylxanthines

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 200))

Abstract

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.

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References

  • Andersson KE, Johannesson N, Karlberg B, Persson CG (1984) Increase in plasma free fatty acids and natriuresis by xanthines may reflect adenosine antagonism. Eur J Clin Pharmacol 26:33–8

    Article  PubMed  CAS  Google Scholar 

  • Arakawa K, Suzuki H, Naitoh M, Matsumoto A, Hayashi K, Matsuda H, Ichihara A, Kubota E, Saruta T (1996) Role of adenosine in the renal responses to contrast medium. Kidney Int 49:1199–206

    Article  PubMed  CAS  Google Scholar 

  • Arend LJ, Bakris GL, Burnett JC Jr, Megerian C, Spielman WS (1987) Role for intrarenal adenosine in the renal hemodynamic response to contrast media. J Lab Clin Med 110:406–11

    PubMed  CAS  Google Scholar 

  • Armstrong LE (2002) Caffeine, body fluid-electrolyte balance, and exercise performance. Int J Sport Nutr Exerc Metab 12:189–206

    PubMed  CAS  Google Scholar 

  • Armstrong LE, Pumerantz AC, Roti MW, Judelson DA, Watson G, Dias JC, Sokmen B, Casa DJ, Maresh CM, Lieberman H, Kellogg M (2005) Fluid, electrolyte, and renal indices of hydration during 11 days of controlled caffeine consumption. Int J Sport Nutr Exerc Metab 15:252–65

    PubMed  CAS  Google Scholar 

  • Baer PG, Armstrong EL, Cagen LM (1983) Dissociation of effects of xanthine analogs on renal prostaglandins and renal excretory function in the awake rat. J Pharmacol Exp Ther 227:600–4

    PubMed  CAS  Google Scholar 

  • Bagshaw SM, Ghali WA (2005) Theophylline for prevention of contrast-induced nephropathy: a systematic review and meta-analysis. Arch Intern Med 165:1087–93

    Article  PubMed  Google Scholar 

  • Bailey MA (2004) Inhibition of bicarbonate reabsorption in the rat proximal tubule by activation of luminal P2Y1 receptors. Am J Physiol Renal Physiol 287:F789–96

    Article  PubMed  CAS  Google Scholar 

  • Bakr AF (2005) Prophylactic theophylline to prevent renal dysfunction in newborns exposed to perinatal asphyxia–a study in a developing country. Pediatr Nephrol 20:1249–52

    Article  PubMed  Google Scholar 

  • Balakrishnan VS, Coles GA, Williams JD (1993) A potential role for endogenous adenosine in control of human glomerular and tubular function. Am J Physiol 265:F504–10

    PubMed  CAS  Google Scholar 

  • Baranowski RL, Westenfelder C (1994) Estimation of renal interstitial adenosine and purine metabolites by microdialysis. Am J Physiol 267:F174–82

    PubMed  CAS  Google Scholar 

  • Belibi FA, Wallace DP, Yamaguchi T, Christensen M, Reif G, Grantham JJ (2002) The effect of caffeine on renal epithelial cells from patients with autosomal dominant polycystic kidney disease. J Am Soc Nephrol 13:2723–9

    Article  PubMed  CAS  Google Scholar 

  • Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT (2005) Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial. J Am Soc Nephrol 16:452–8

    Article  PubMed  CAS  Google Scholar 

  • Beutler JJ, Koomans HA, Bijlsma JA, Dorhout Mees EJ (1990) Renal actions of theophylline and atrial natriuretic peptide in humans: a comparison by means of clearance studies. J Pharmacol Exp Ther 255:1314–9

    PubMed  CAS  Google Scholar 

  • Bhat MA, Shah ZA, Makhdoomi MS, Mufti MH (2006) Theophylline for renal function in term neonates with perinatal asphyxia: a randomized, placebo-controlled trial. J Pediatr 149:180–4

    Article  PubMed  CAS  Google Scholar 

  • Bhat SG, Mishra S, Mei Y, Nie Z, Whitworth CA, Rybak LP, Ramkumar V (2002) Cisplatin up-regulates the adenosine A(1) receptor in the rat kidney. Eur J Pharmacol 442:251–64

    Article  PubMed  CAS  Google Scholar 

  • Bidani AK, Churchill PC (1983) Aminophylline ameliorates glycerol-induced acute renal failure in rats. Can J Physiol Pharmacol 61:567–71

    Article  PubMed  CAS  Google Scholar 

  • Bowmer CJ, Collis MG, Yates MS (1986) Effect of the adenosine antagonist 8-phenyltheophylline on glycerol-induced acute renal failure in the rat. Br J Pharmacol 88:205–12

    Article  PubMed  CAS  Google Scholar 

  • Bowmer CJ, Collis MG, Yates MS (1988) Amelioration of glycerol-induced acute renal failure in the rat with 8-phenyltheophylline: timing of intervention. J Pharm Pharmacol 40:733–5

    Article  PubMed  CAS  Google Scholar 

  • Brater DC, Kaojarern S, Chennavasin P (1983) Pharmacodynamics of the diuretic effects of aminophylline and acetazolamide alone and combined with furosemide in normal subjects. J Pharmacol Exp Ther 227:92–7

    PubMed  CAS  Google Scholar 

  • Brown NJ, Porter J, Ryder D, Branch RA (1991) Caffeine potentiates the renin response to diazoxide in man. Evidence for a regulatory role of endogenous adenosine. J Pharmacol Exp Ther 256:56–61

    PubMed  CAS  Google Scholar 

  • Brown NJ, Ryder D, Nadeau J (1993) Caffeine attenuates the renal vascular response to angiotensin II infusion. Hypertension 22:847–52

    Article  PubMed  CAS  Google Scholar 

  • Cai H, Batuman V, Puschett DB, Puschett JB (1994) Effect of KW-3902, a novel adenosine A1 receptor antagonist, on sodium-dependent phosphate and glucose transport by the rat renal proximal tubular cell. Life Sci 55:839–45

    Article  PubMed  CAS  Google Scholar 

  • Cai H, Puschett DB, Guan S, Batuman V, Puschett JB (1995) Phosphate transport inhibition by KW-3902, an adenosine A1 receptor antagonist, is mediated by cyclic adenosine monophosphate. Am J Kidney Dis 26:825–30

    Article  PubMed  CAS  Google Scholar 

  • Chen YM, Lin SL, Chiang WC, Wu KD, Tsai TJ (2006) Pentoxifylline ameliorates proteinuria through suppression of renal monocyte chemoattractant protein-1 in patients with proteinuric primary glomerular diseases. Kidney Int 69:1410–5

    PubMed  CAS  Google Scholar 

  • Chen YM, Ng YY, Lin SL, Chiang WC, Lan HY, Tsai TJ (2004) Pentoxifylline suppresses renal tumour necrosis factor-alpha and ameliorates experimental crescentic glomerulonephritis in rats. Nephrol Dial Transplant 19:1106–15

    Article  PubMed  CAS  Google Scholar 

  • Choi KC, Lee J, Moon KH, Park KK, Kim SW, Kim NH (1993) Chronic caffeine ingestion exacerbates 2-kidney, 1-clip hypertension and ameliorates deoxycorticosterone acetate-salt hypertension in rats. Nephron 65:619–22

    Article  PubMed  CAS  Google Scholar 

  • Churchill PC, Rossi NF, Churchill MC, Bidani AK, McDonald FD (1990) Acute cyclosporine-induced renal vasoconstriction: lack of effect of theophylline. Am J Physiol 258:F41–5

    PubMed  CAS  Google Scholar 

  • Cirillo R, Grossi E, Franzone JS (1989) Doxofylline, an adenosine-nonblocking xanthine, does not induce cardiostimulant effects. Res Commun Chem Pathol Pharmacol 65:21–34

    PubMed  CAS  Google Scholar 

  • Coulson R, Johnson RA, Olsson RA, Cooper DR, Scheinman SJ (1991) Adenosine stimulates phosphate and glucose transport in opossum kidney epithelial cells. Am J Physiol 260:F921–8

    PubMed  CAS  Google Scholar 

  • Coulson R, Proch PS, Olsson RA, Chalfant CE, Cooper DR (1996) Upregulated renal adenosine A1 receptors augment PKC and glucose transport but inhibit proliferation. Am J Physiol 270:F263–74

    PubMed  CAS  Google Scholar 

  • Cox CD, Tsikouris JP (2004) Preventing contrast nephropathy: what is the best strategy? A review of the literature. J Clin Pharmacol 44:327–37

    Article  PubMed  Google Scholar 

  • Daly JW (2007) Caffeine analogs: biomedical impact. Cell Mol Life Sci 64:2153–69

    Article  PubMed  CAS  Google Scholar 

  • Davis JO, Shock NW (1949) The effect of theophylline ethylene diamine on renal function in control subjects and in patients with congestive heart failure. J Clin Invest 28:1459–68

    Article  PubMed  CAS  Google Scholar 

  • Day YJ, Huang L, McDuffie MJ, Rosin DL, Ye H, Chen JF, Schwarzschild MA, Fink JS, Linden J, Okusa MD (2003) Renal protection from ischemia mediated by A2A adenosine receptors on bone marrow-derived cells. J Clin Invest 112:883–91

    PubMed  CAS  Google Scholar 

  • Deray G, Martinez F, Cacoub P, Baumelou B, Baumelou A, Jacobs C (1990) A role for adenosine calcium and ischemia in radiocontrast-induced intrarenal vasoconstriction. Am J Nephrol 10:316–22

    Article  PubMed  CAS  Google Scholar 

  • Di Sole F (2008) Adenosine and renal tubular function. Curr Opin Nephrol Hypertens 17:399–407

    Article  PubMed  CAS  Google Scholar 

  • Di Sole F, Cerull R, Petzke S, Casavola V, Burckhardt G, Helmle-Kolb C (2003) Bimodal acute effects of A1 adenosine receptor activation on Na+/H+ exchanger 3 in opossum kidney cells. J Am Soc Nephrol 14:1720–30

    Article  PubMed  CAS  Google Scholar 

  • Dinour D, Brezis M (1991) Effects of adenosine on intrarenal oxygenation. Am J Physiol 261:F787–91

    PubMed  CAS  Google Scholar 

  • Edwards RM, Spielman WS (1994) Adenosine A1 receptor-mediated inhibition of vasopressin action in inner medullary collecting duct. Am J Physiol 266:F791–6

    PubMed  CAS  Google Scholar 

  • Efrati S, Berman S, Ilgiyeav I, Siman-Tov Y, Averbukh Z, Weissgarten J (2009) Differential effects of N-acetylcysteine, theophylline or bicarbonate on contrast-induced rat renal vasoconstriction. Am J Nephrol 29:181–91

    Article  PubMed  CAS  Google Scholar 

  • Eggertsen R, Andreasson A, Hedner T, Karlberg BE, Hansson L (1993) Effect of coffee on ambulatory blood pressure in patients with treated hypertension. J Intern Med 233:351–5

    Article  PubMed  CAS  Google Scholar 

  • Erley CM, Duda SH, Rehfuss D, Scholtes B, Bock J, Muller C, Osswald H, Risler T (1999) Prevention of radiocontrast-media-induced nephropathy in patients with pre-existing renal insufficiency by hydration in combination with the adenosine antagonist theophylline. Nephrol Dial Transplant 14:1146–9

    Article  PubMed  CAS  Google Scholar 

  • Erley CM, Duda SH, Schlepckow S, Koehler J, Huppert PE, Strohmaier WL, Bohle A, Risler T, Osswald H (1994) Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. Kidney Int 45:1425–31

    Article  PubMed  CAS  Google Scholar 

  • Erley CM, Heyne N, Burgert K, Langanke J, Risler T, Osswald H (1997) Prevention of radiocontrast-induced nephropathy by adenosine antagonists in rats with chronic nitric oxide deficiency. J Am Soc Nephrol 8:1125–32

    PubMed  CAS  Google Scholar 

  • Eslami Z, Shajari A, Kheirandish M, Heidary A (2009) Theophylline for prevention of kidney dysfunction in neonates with severe asphyxia. Iran J Kidney Dis 3:222–6

    PubMed  Google Scholar 

  • Franco M, Bell PD, Navar LG (1989) Effect of adenosine A1 analogue on tubuloglomerular feedback mechanism. Am J Physiol Renal Physiol 257:F231–6

    CAS  Google Scholar 

  • Franzone JS, Cirillo R, Barone D (1988) Doxofylline and theophylline are xanthines with partly different mechanisms of action in animals. Drugs Exp Clin Res 14:479–89

    PubMed  CAS  Google Scholar 

  • Fulgraff G (1969) Xanthinderivate als diuretika. In: Herken H (ed) Handbuch der experimentellen Pharmakologie, vol XXIV. Springer, Berlin, pp 596–640

    Google Scholar 

  • Gerber JG, Nies AS (1986) Renal vasoconstrictor response to hypertonic saline in the dog: effects of prostaglandins, indomethacin and theophylline. J Physiol (Lond) 380:35–43

    CAS  Google Scholar 

  • Gerkens JF, Heidemann HT, Jackson EK, Branch RA (1983) Aminophylline inhibits renal vasoconstriction produced by intrarenal hypertonic saline. J Pharmacol Exp Ther 225:611–5

    PubMed  CAS  Google Scholar 

  • Gouyon JB, Guignard JP (1987) Renal effects of theophylline and caffeine in newborn rabbits. Pediatr Res 21:615–8

    Article  PubMed  CAS  Google Scholar 

  • Gouyon JB, Guignard JP (1988) Theophylline prevents the hypoxemia-induced renal hemodynamic changes in rabbits. Kidney Int 33:1078–83

    Article  PubMed  CAS  Google Scholar 

  • Grandjean AC, Reimers KJ, Bannick KE, Haven MC (2000) The effect of caffeinated, non-caffeinated, caloric and non-caloric beverages on hydration. J Am Coll Nutr 19:591–600

    PubMed  CAS  Google Scholar 

  • Grantham JJ, Orloff J (1968) Effect of prostaglandin E1 on the permeability response of the isolated collecting tubule to vasopressin, adenosine 3′,5′-monophosphate, and theophylline. J Clin Invest 47:1154–61

    Article  PubMed  CAS  Google Scholar 

  • Grenz A, Baier D, Petroktistis F, Wehrmann M, Kohle C, Schenk M, Sessler M, Gleiter CH, Fandrich F, Osswald H (2006) Theophylline improves early allograft function in rat kidney transplantation. J Pharmacol Exp Ther 317:473–9

    Article  PubMed  CAS  Google Scholar 

  • Handler JS, Butcher RW, Sutherland EW, Orloff J (1965) The effect of vasopressin and of theophylline on the concentration of adenosine 3′,5′-phosphate in the urinary bladder of the toad. J Biol Chem 240:4524–6

    PubMed  CAS  Google Scholar 

  • Hedqvist P, Fredholm BB (1976) Effects of adenosine on adrenergic neurotransmission; prejunctional inhibition and postjunctional enhancement. Naunyn Schmiedebergs Arch Pharmacol 293:217–23

    Article  PubMed  CAS  Google Scholar 

  • Hedqvist P, Fredholm BB, Olundh S (1978) Antagonistic effects of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney. Circ Res 43:592–8

    Article  PubMed  CAS  Google Scholar 

  • Heidemann HT, Muller S, Mertins L, Stepan G, Hoffmann K, Ohnhaus EE (1989) Effect of aminophylline on cisplatin nephrotoxicity in the rat. Br J Pharmacol 97:313–8

    Article  PubMed  CAS  Google Scholar 

  • Huber W, Jeschke B, Page M, Weiss W, Salmhofer H, Schweigart U, Ilgmann K, Reichenberger J, Neu B, Classen M (2001) Reduced incidence of radiocontrast-induced nephropathy in ICU patients under theophylline prophylaxis: a prospective comparison to series of patients at similar risk. Intensive Care Med 27:1200–9

    Article  PubMed  CAS  Google Scholar 

  • Huber W, Schipek C, Ilgmann K, Page M, Hennig M, Wacker A, Schweigart U, Lutilsky L, Valina C, Seyfarth M, Schomig A, Classen M (2003) Effectiveness of theophylline prophylaxis of renal impairment after coronary angiography in patients with chronic renal insufficiency. Am J Cardiol 91:1157–62

    Article  PubMed  CAS  Google Scholar 

  • Ibarrola AM, Inscho EW, Vari RC, Navar LG (1991) Influence of adenosine receptor blockade on renal function and renal autoregulation. J Am Soc Nephrol 2:991–9

    PubMed  CAS  Google Scholar 

  • Ishikawa I, Shikura N, Takada K (1993) Amelioration of glycerol-induced acute renal failure in rats by an adenosine A1 receptor antagonist (FR-113453). Ren Fail 15:1–5

    Article  PubMed  CAS  Google Scholar 

  • Ishikawa SE, Okada K, Saito T (1992) Modulation by intracellular calcium pool of arginine vasopressin-induced cellular cyclic AMP production in rat renal papillary collecting tubule cells in culture. J Pharmacol Exp Ther 263:1050–5

    PubMed  CAS  Google Scholar 

  • Ix JH, McCulloch CE, Chertow GM (2004) Theophylline for the prevention of radiocontrast nephropathy: a meta-analysis. Nephrol Dial Transplant 19:2747–53

    Article  PubMed  CAS  Google Scholar 

  • Izzo JL Jr, Ghosal A, Kwong T, Freeman RB, Jaenike JR (1983) Age and prior caffeine use alter the cardiovascular and adrenomedullary responses to oral caffeine. Am J Cardiol 52:769–73

    Article  PubMed  CAS  Google Scholar 

  • Jackson EK, Mi Z, Gillespie DG, Dubey RK (1997) Metabolism of cAMP to adenosine in the renal vasculature. J Pharmacol Exp Ther 283:177–82

    PubMed  CAS  Google Scholar 

  • Jenik AG, Ceriani Cernadas JM, Gorenstein A, Ramirez JA, Vain N, Armadans M, Ferraris JR (2000) A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia. Pediatrics 105:E45

    Article  PubMed  CAS  Google Scholar 

  • Kapoor A, Kumar S, Gulati S, Gambhir S, Sethi RS, Sinha N (2002) The role of theophylline in contrast-induced nephropathy: a case-control study. Nephrol Dial Transplant 17:1936–41

    Article  PubMed  CAS  Google Scholar 

  • Katholi RE, Taylor GJ, McCann WP, Woods WT Jr, Womack KA, McCoy CD, Katholi CR, Moses HW, Mishkel GJ, Lucore CL et al (1995) Nephrotoxicity from contrast media: attenuation with theophylline. Radiology 195:17–22

    PubMed  CAS  Google Scholar 

  • Kawabata M, Ogawa T, Takabatake T (1998) Control of rat glomerular microcirculation by juxtaglomerular adenosine A1 receptors. Kidney Int Suppl 67:S228–30

    Article  PubMed  CAS  Google Scholar 

  • Kellett R, Bowmer CJ, Collis MG, Yates MS (1988) Effect of alkylxanthines on gentamicin-induced acute renal failure in the rat. J Pharm Pharmacol 40:849–54

    Article  PubMed  CAS  Google Scholar 

  • Kelly AM, Dwamena B, Cronin P, Bernstein SJ, Carlos RC (2008) Meta-analysis: effectiveness of drugs for preventing contrast-induced nephropathy. Ann Intern Med 148:284–94

    PubMed  Google Scholar 

  • Kim M, Chen SW, Park SW, Kim M, D'Agati VD, Yang J, Lee HT (2009) Kidney-specific reconstitution of the A1 adenosine receptor in A1 adenosine receptor knockout mice reduces renal ischemia-reperfusion injury. Kidney Int 75:809–23

    Article  PubMed  CAS  Google Scholar 

  • Knight RJ, Bowmer CJ, Yates MS (1993) The diuretic action of 8-cyclopentyl-1,3-dipropylxanthine, a selective A1 adenosine receptor antagonist. Br J Pharmacol 109:271–7

    Article  PubMed  CAS  Google Scholar 

  • Knight RJ, Collis MG, Yates MS, Bowmer CJ (1991) Amelioration of cisplatin-induced acute renal failure with 8-cyclopentyl-1,3-dipropylxanthine. Br J Pharmacol 104:1062–8

    Article  PubMed  CAS  Google Scholar 

  • Kolonko A, Wiecek A, Kokot F (1998) The nonselective adenosine antagonist theophylline does prevent renal dysfunction induced by radiographic contrast agents. J Nephrol 11:151–6

    PubMed  CAS  Google Scholar 

  • Koschlakoff DJ (1864) Beobachtungen ueber die Wirkung des citronensauren Coffeins. Virchows Arch Pathol Anat 31:436–445

    Article  Google Scholar 

  • Kost CK Jr, Herzer WA, Rominski BR, Mi Z, Jackson EK (2000) Diuretic response to adenosine A(1) receptor blockade in normotensive and spontaneously hypertensive rats: role of pertussis toxin-sensitive G-proteins. J Pharmacol Exp Ther 292:752–60

    PubMed  CAS  Google Scholar 

  • Kost CK Jr, Li P, Pfeifer CA, Jackson EK (1994) Telemetric blood pressure monitoring in benign 2-kidney, 1-clip renovascular hypertension: effect of chronic caffeine ingestion. J Pharmacol Exp Ther 270:1063–70

    PubMed  CAS  Google Scholar 

  • Kramer BK, Preuner J, Ebenburger A, Kaiser M, Bergner U, Eilles C, Kammerl MC, Riegger GA, Birnbaum DE (2002) Lack of renoprotective effect of theophylline during aortocoronary bypass surgery. Nephrol Dial Transplant 17:910–5

    Article  PubMed  CAS  Google Scholar 

  • Lancelot E, Idee JM, Lacledere C, Santus R, Corot C (2002) Effects of two dimeric iodinated contrast media on renal medullary blood perfusion and oxygenation in dogs. Invest Radiol 37:368–75

    Article  PubMed  Google Scholar 

  • Langard O, Holdaas H, Eide I, Kiil F (1983) Conditions for augmentation of renin release by theophylline. Scand J Clin Lab Invest 43:9–14

    Article  PubMed  CAS  Google Scholar 

  • Lee HT, Emala CW (2001) Systemic adenosine given after ischemia protects renal function via A(2a) adenosine receptor activation. Am J Kidney Dis 38:610–8

    Article  PubMed  CAS  Google Scholar 

  • Lee HT, Gallos G, Nasr SH, Emala CW (2004a) A1 adenosine receptor activation inhibits inflammation, necrosis, and apoptosis after renal ischemia-reperfusion injury in mice. J Am Soc Nephrol 15:102–11

    Article  PubMed  CAS  Google Scholar 

  • Lee HT, Jan M, Bae SC, Joo JD, Goubaeva FR, Yang J, Kim M (2006) A1 adenosine receptor knockout mice are protected against acute radiocontrast nephropathy in vivo. Am J Physiol Renal Physiol 290:F1367–75

    Article  PubMed  CAS  Google Scholar 

  • Lee HT, Xu H, Nasr SH, Schnermann J, Emala CW (2004b) A1 adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion. Am J Physiol Renal Physiol 286:F298–306

    Article  PubMed  CAS  Google Scholar 

  • Lee J, Ha JH, Kim S, Oh Y, Kim SW (2002) Caffeine decreases the expression of Na+/K+-ATPase and the type 3 Na+/H+ exchanger in rat kidney. Clin Exp Pharmacol Physiol 29:559–63

    Article  PubMed  CAS  Google Scholar 

  • Lin J, Bonventre JV (2005) Prevention of radiocontrast nephropathy. Curr Opin Nephrol Hypertens 14:105–10

    Article  PubMed  CAS  Google Scholar 

  • Lin JJ, Churchill PC, Bidani AK (1986) Effect of theophylline on the initiation phase of postischemic acute renal failure in rats. J Lab Clin Med 108:150–4

    PubMed  CAS  Google Scholar 

  • Lin JJ, Churchill PC, Bidani AK (1987) The effect of dipyridamole on the initiation phase of postischemic acute renal failure in rats. Can J Physiol Pharmacol 65:1491–5

    Article  PubMed  CAS  Google Scholar 

  • Lin JJ, Churchill PC, Bidani AK (1988) Theophylline in rats during maintenance phase of post-ischemic acute renal failure. Kidney Int 33:24–8

    Article  PubMed  CAS  Google Scholar 

  • Lin SL, Chen YM, Chiang WC, Wu KD, Tsai TJ (2008) Effect of pentoxifylline in addition to losartan on proteinuria and GFR in CKD: a 12-month randomized trial. Am J Kidney Dis 52:464–74

    Article  PubMed  CAS  Google Scholar 

  • Lin SL, Chen YM, Chien CT, Chiang WC, Tsai CC, Tsai TJ (2002) Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. J Am Soc Nephrol 13:2916–29

    Article  PubMed  CAS  Google Scholar 

  • Ludens JH, Willis LR, Williamson HE (1970) The effect of aminophylline on renal hemodynamics and sodium excretion. Arch Int Pharmacodyn Thér 185:274–86

    PubMed  CAS  Google Scholar 

  • Massey LK, Bergman EA, Wise KJ, Sherrard DJ (1994) Interactions between dietary caffeine and calcium on calcium and bone metabolism in older women. J Am Coll Nutr 13:592–6

    PubMed  CAS  Google Scholar 

  • Mazkereth R, Laufer J, Jordan S, Pomerance JJ, Boichis H, Reichman B (1997) Effects of theophylline on renal function in premature infants. Am J Perinatol 14:45–9

    Article  PubMed  CAS  Google Scholar 

  • McCormick BB, Sydor A, Akbari A, Fergusson D, Doucette S, Knoll G (2008) The effect of pentoxifylline on proteinuria in diabetic kidney disease: a meta-analysis. Am J Kidney Dis 52:454–63

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin GE, Abitbol CL (2005) Reversal of oliguric tacrolimus nephrotoxicity in children. Nephrol Dial Transplant 20:1471–5

    Article  PubMed  CAS  Google Scholar 

  • McLaughlin GE, Kashimawo LA, Steele BW, Kuluz JW (2003a) Reversal of acute tacrolimus-induced renal vasoconstriction by theophylline in rats. Pediatr Crit Care Med 4:358–62

    Article  PubMed  Google Scholar 

  • McLaughlin GE, Schober M, Perez M, Ruiz P, Steele BW, Abitbol C (2003b) Benefit of theophylline administration in tacrolimus-induced nephrotoxicity in rats. Pediatr Nephrol 18:860–4

    Article  PubMed  Google Scholar 

  • Mi Z, Herzer WA, Zhang Y, Jackson EK (1994) 3-Isobutyl-1-methylxanthine decreases renal cortical interstitial levels of adenosine and inosine. Life Sci 54:277–82

    Article  PubMed  CAS  Google Scholar 

  • Mizumoto H, Karasawa A (1993) Renal tubular site of action of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized rats. Jpn J Pharmacol 61:251–3

    Article  PubMed  CAS  Google Scholar 

  • Moosavi SM, Bayat G, Owji SM, Panjehshahin MR (2009) Early renal post-ischaemic tissue damage and dysfunction with contribution of A1-adenosine receptor activation in rat. Nephrology (Carlton) 14:179–88

    Article  CAS  Google Scholar 

  • Nagashima K, Kusaka H, Karasawa A (1995) Protective effects of KW-3902, an adenosine A1-receptor antagonist, against cisplatin-induced acute renal failure in rats. Jpn J Pharmacol 67:349–57

    Article  PubMed  CAS  Google Scholar 

  • Nauli SM, Alenghat FJ, Luo Y, Williams E, Vassilev P, Li X, Elia AE, Lu W, Brown EM, Quinn SJ, Ingber DE, Zhou J (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat Genet 33:129–37

    Article  PubMed  CAS  Google Scholar 

  • Neuhauser B, Beine S, Verwied SC, Luhrmann PM (1997) Coffee consumption and total body water homeostasis as measured by fluid balance and bioelectrical impedance analysis. Ann Nutr Metab 41:29–36

    Article  Google Scholar 

  • Nishiyama A, Kimura S, He H, Miura K, Rahman M, Fujisawa Y, Fukui T, Abe Y (2001) Renal interstitial adenosine metabolism during ischemia in dogs. Am J Physiol Renal Physiol 280:F231–8

    PubMed  CAS  Google Scholar 

  • Nussberger J, Mooser V, Maridor G, Juillerat L, Waeber B, Brunner HR (1990) Caffeine-induced diuresis and atrial natriuretic peptides. J Cardiovasc Pharmacol 15:685–91

    Article  PubMed  CAS  Google Scholar 

  • Ohnishi A, Branch RA, Jackson K, Hamilton R, Biaggioni I, Deray G, Jackson EK (1986) Chronic caffeine administration exacerbates renovascular, but not genetic, hypertension in rats. J Clin Invest 78:1045–50

    Article  PubMed  CAS  Google Scholar 

  • Okusa MD, Linden J, Macdonald T, Huang L (1999) Selective A2A adenosine receptor activation reduces ischemia-reperfusion injury in rat kidney. Am J Physiol 277:F404–12

    PubMed  CAS  Google Scholar 

  • Oliw E, Anggard E, Fredholm BB (1977) Effect of indomethacin on the renal actions of theophylline. Eur J Pharmacol 43:9–16

    Article  PubMed  CAS  Google Scholar 

  • Onrot J, Goldberg MR, Biaggioni I, Hollister AS, Kingaid D, Robertson D (1985) Hemodynamic and humoral effects of caffeine in autonomic failure. Therapeutic implications for postprandial hypotension. N Engl J Med 313:549–54

    Article  PubMed  CAS  Google Scholar 

  • Orloff J, Handler JS (1962) The similarity of effects of vasopressin, adenosine-3′,5′-phosphate (cyclic AMP) and theophylline on the toad bladder. J Clin Invest 41:702–9

    Article  PubMed  CAS  Google Scholar 

  • Osswald H (1975) Renal effects of adenosine and their inhibition by theophylline in dogs. Naunyn Schmiedebergs Arch Pharmacol 288:79–86

    Article  PubMed  CAS  Google Scholar 

  • Osswald H, Helmlinger J, Jendralski A, Abrar B (1979) Improvement of renal function by theophylline in acute renal failure of the rat. Naunyn Schmiedebergs Arch Pharmacol 307(Suppl):R47 (abstract)

    Google Scholar 

  • Osswald H, Nabakowski G, Hermes H (1980) Adenosine as a possible mediator of metabolic control of glomerular filtration rate. Int J Biochem 12:263–7

    Article  PubMed  CAS  Google Scholar 

  • Osswald H, Schmitz HJ, Kemper R (1977) Tissue content of adenosine, inosine and hypoxanthine in the rat kidney after ischemia and postischemic recirculation. Pflugers Arch 371:45–9

    Article  PubMed  CAS  Google Scholar 

  • Palatini P, Canali C, Graniero GR, Rossi G, de Toni R, Santonastaso M, dal Follo M, Zanata G, Ferrarese E, Mormino P, Pessina AC (1996) Relationship of plasma renin activity with caffeine intake and physical training in mild hypertensive men. HARVEST Study Group. Eur J Epidemiol 12:485–91

    Article  PubMed  CAS  Google Scholar 

  • Panjehshahin MR, Munsey TS, Collis MG, Bowmer CJ, Yates MS (1992) Further characterization of the protective effect of 8-cyclopentyl-1,3-dipropylxanthine on glycerol-induced acute renal failure in the rat. J Pharm Pharmacol 44:109–13

    Article  PubMed  CAS  Google Scholar 

  • Passmore AP, Kondowe GB, Johnston GD (1987) Renal and cardiovascular effects of caffeine: a dose-response study. Clin Sci (Lond) 72:749–56

    CAS  Google Scholar 

  • Paul S, Jackson EK, Robertson D, Branch RA, Biaggioni I (1989) Caffeine potentiates the renin response to furosemide in rats. Evidence for a regulatory role of endogenous adenosine. J Pharmacol Exp Ther 251:183–7

    PubMed  CAS  Google Scholar 

  • Pawlowska D, Granger JP, Knox FG (1987) Effects of adenosine infusion into renal interstitium on renal hemodynamics. Am J Physiol 252:F678–82

    PubMed  CAS  Google Scholar 

  • Perkins RM, Aboudara MC, Uy AL, Olson SW, Cushner HM, Yuan CM (2009) Effect of pentoxifylline on GFR decline in CKD: a pilot, double-blind, randomized, placebo-controlled trial. Am J Kidney Dis 53:606–16

    Article  PubMed  CAS  Google Scholar 

  • Persson PB, Hansell P, Liss P (2005) Pathophysiology of contrast medium-induced nephropathy. Kidney Int 68:14–22

    Article  PubMed  CAS  Google Scholar 

  • Pfeifer CA, Suzuki F, Jackson EK (1995) Selective A1 adenosine receptor antagonism augments beta-adrenergic-induced renin release in vivo. Am J Physiol 269:F469–79

    PubMed  CAS  Google Scholar 

  • Pingle SC, Mishra S, Marcuzzi A, Bhat SG, Sekino Y, Rybak LP, Ramkumar V (2004) Osmotic diuretics induce adenosine A1 receptor expression and protect renal proximal tubular epithelial cells against cisplatin-mediated apoptosis. J Biol Chem 279:43157–67

    Article  PubMed  CAS  Google Scholar 

  • Potier M, Aparicio M, Cambar J (1997) Protective effect of three xanthine derivatives (theophylline, caffeine and pentoxifylline) against the cyclosporin A-induced glomerular contraction in isolated glomeruli and cultured mesangial cells. Nephron 77:427–34

    Article  PubMed  CAS  Google Scholar 

  • Premen AJ, Hall JE, Mizelle HL, Cornell JE (1985) Maintenance of renal autoregulation during infusion of aminophylline or adenosine. Am J Physiol 248:F366–73

    PubMed  CAS  Google Scholar 

  • Prevot A, Liet JM, Semama DS, Justrabo E, Guignard JP, Gouyon JB (2002) Disparate effects of chronic and acute theophylline on cyclosporine A nephrotoxicity. Pediatr Nephrol 17:418–24

    Article  PubMed  CAS  Google Scholar 

  • Rachima-Maoz C, Peleg E, Rosenthal T (1998) The effect of caffeine on ambulatory blood pressure in hypertensive patients. Am J Hypertens 11:1426–32

    Article  PubMed  CAS  Google Scholar 

  • Rakic V, Burke V, Beilin LJ (1999) Effects of coffee on ambulatory blood pressure in older men and women: a randomized controlled trial. Hypertension 33:869–73

    Article  PubMed  CAS  Google Scholar 

  • Reid IA, Stockigt JR, Goldfien A, Ganong WF (1972) Stimulation of renin secretion in dogs by theophylline. Eur J Pharmacol 17:325–32

    Article  PubMed  CAS  Google Scholar 

  • Ren Y, Arima S, Carretero OA, Ito S (2002) Possible role of adenosine in macula densa control of glomerular hemodynamics. Kidney Int 61:169–76

    Article  PubMed  CAS  Google Scholar 

  • Rieg T, Steigele H, Schnermann J, Richter K, Osswald H, Vallon V (2005) Requirement of intact adenosine A1 receptors for the diuretic and natriuretic action of the methylxanthines theophylline and caffeine. J Pharmacol Exp Ther 313:403–9

    Article  PubMed  CAS  Google Scholar 

  • Riesenhuber A, Boehm M, Posch M, Aufricht C (2006) Diuretic potential of energy drinks. Amino Acids 31:81–3

    Article  PubMed  CAS  Google Scholar 

  • Robertson D, Frolich JC, Carr RK, Watson JT, Hollifield JW, Shand DG, Oates JA (1978) Effects of caffeine on plasma renin activity, catecholamines and blood pressure. N Engl J Med 298:181–6

    Article  PubMed  CAS  Google Scholar 

  • Robertson D, Hollister AS, Kincaid D, Workman R, Goldberg MR, Tung CS, Smith B (1984) Caffeine and hypertension. Am J Med 77:54–60

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez-Moran M, Guerrero-Romero F (2005) Pentoxifylline is as effective as captopril in the reduction of microalbuminuria in non-hypertensive type 2 diabetic patients–a randomized, equivalent trial. Clin Nephrol 64:91–7

    PubMed  CAS  Google Scholar 

  • Rossi N, Ellis V, Kontry T, Gunther S, Churchill P, Bidani A (1990) The role of adenosine in HgCl2-induced acute renal failure in rats. Am J Physiol 258:F1554–60

    PubMed  CAS  Google Scholar 

  • Saad SY, Najjar TA, Alashari M (2004) Role of non-selective adenosine receptor blockade and phosphodiesterase inhibition in cisplatin-induced nephrogonadal toxicity in rats. Clin Exp Pharmacol Physiol 31:862–7

    Article  PubMed  CAS  Google Scholar 

  • Schnermann J, Osswald H, Hermle M (1977) Inhibitory effect of methylxanthines on feedback control of glomerular filtration rate in the rat. Pflugers Arch 369:39–48

    Article  PubMed  CAS  Google Scholar 

  • Schnermann J, Weihprecht H, Briggs JP (1990) Inhibition of tubuloglomerular feedback during adenosine1 receptor blockade. Am J Physiol Renal Physiol 258:F553–61

    CAS  Google Scholar 

  • Scott D, Rycroft JA, Aspen J, Chapman C, Brown B (2004) The effect of drinking tea at high altitude on hydration status and mood. Eur J Appl Physiol 91:493–8

    Article  PubMed  Google Scholar 

  • Seideman P, Sollevi A, Fredholm BB (1987) Additive renal effects of indomethacin and dipyridamole in man. Br J Clin Pharmacol 23:323–30

    Article  PubMed  CAS  Google Scholar 

  • Shirley DG, Walter SJ, Noormohamed FH (2002) Natriuretic effect of caffeine: assessment of segmental sodium reabsorption in humans. Clin Sci (Lond) 103:461–6

    Article  CAS  Google Scholar 

  • Siragy HM, Linden J (1996) Sodium intake markedly alters renal interstitial fluid adenosine. Hypertension 27:404–7

    Article  PubMed  CAS  Google Scholar 

  • Smits P, Hoffmann H, Thien T, Houben H, Van’t Laar A (1983) Hemodynamic and humoral effects of coffee after beta 1-selective and nonselective beta-blockade. Clin Pharmacol Ther 34:153–8

    Article  PubMed  CAS  Google Scholar 

  • Spielman WS (1984) Antagonistic effect of theophylline on the adenosine-induced decreased in renin release. Am J Physiol 247:F246–51

    PubMed  CAS  Google Scholar 

  • Suzuki F, Shimada J, Mizumoto H, Karasawa A, Kubo K, Nonaka H, Ishii A, Kawakita T (1992) Adenosine A1 antagonists. 2. Structure-activity relationships on diuretic activities and protective effects against acute renal failure. J Med Chem 35:3066–75

    Article  PubMed  CAS  Google Scholar 

  • Takeda M, Yoshitomi K, Imai M (1993) Regulation of Na(+)-3HCO3- cotransport in rabbit proximal convoluted tubule via adenosine A1 receptor. Am J Physiol 265:F511–9

    PubMed  CAS  Google Scholar 

  • Tanner GA, Tanner JA (2001) Chronic caffeine consumption exacerbates hypertension in rats with polycystic kidney disease. Am J Kidney Dis 38:1089–95

    Article  PubMed  CAS  Google Scholar 

  • Thomson S, Bao D, Deng A, Vallon V (2000) Adenosine formed by 5′-nucleotidase mediates tubuloglomerular feedback. J Clin Invest 106:289–98

    Article  PubMed  CAS  Google Scholar 

  • Tofovic SP, Branch KR, Oliver RD, Magee WD, Jackson EK (1991) Caffeine potentiates vasodilator-induced renin release. J Pharmacol Exp Ther 256:850–60

    PubMed  CAS  Google Scholar 

  • Tofovic SP, Jackson EK (1999) Effects of long-term caffeine consumption on renal function in spontaneously hypertensive heart failure prone rats. J Cardiovasc Pharmacol 33:360–6

    Article  PubMed  CAS  Google Scholar 

  • Tofovic SP, Kost CK Jr, Jackson EK, Bastacky SI (2002) Long-term caffeine consumption exacerbates renal failure in obese, diabetic, ZSF1 (fa-fa(cp)) rats. Kidney Int 61:1433–44

    Article  PubMed  CAS  Google Scholar 

  • Tofovic SP, Kusaka H, Rominski B, Jackson EK (1999) Caffeine increases renal renin secretion in a rat model of genetic heart failure. J Cardiovasc Pharmacol 33:440–50

    Article  PubMed  CAS  Google Scholar 

  • Tofovic SP, Rominski BR, Bastacky S, Jackso EK, Kost CK Jr (2000) Caffeine augments proteinuria in puromycin-aminonucleoside nephrotic rats. Ren Fail 22:159–79

    Article  PubMed  CAS  Google Scholar 

  • Tofovic SP, Salah EM, Jackson EK, Melhem M (2007) Early renal injury induced by caffeine consumption in obese, diabetic ZSF1 rats. Ren Fail 29:891–902

    Article  PubMed  CAS  Google Scholar 

  • Tseng CJ, Kuan CJ, Chu H, Tung CS (1993) Effect of caffeine treatment on plasma renin activity and angiotensin I concentrations in rats on a low sodium diet. Life Sci 52:883–90

    Article  PubMed  CAS  Google Scholar 

  • Wang W, Zolty E, Falk S, Basava V, Reznikov L, Schrier R (2006) Pentoxifylline protects against endotoxin-induced acute renal failure in mice. Am J Physiol Renal Physiol 291:F1090–5

    Article  PubMed  CAS  Google Scholar 

  • Weihprecht H, Lorenz JN, Schnermann J, Skott O, Briggs JP (1990) Effect of adenosine1-receptor blockade on renin release from rabbit isolated perfused juxtaglomerular apparatus. J Clin Invest 85:1622–8

    Article  PubMed  CAS  Google Scholar 

  • Wemple RD, Lamb DR, McKeever KH (1997) Caffeine vs caffeine-free sports drinks: effects on urine production at rest and during prolonged exercise. Int J Sports Med 18:40–6

    Article  PubMed  CAS  Google Scholar 

  • Wilcox CS, Welch WJ, Schreiner GF, Belardinelli L (1999) Natriuretic and diuretic actions of a highly selective adenosine A1 receptor antagonist. J Am Soc Nephrol 10:714–720

    PubMed  CAS  Google Scholar 

  • Wise KJ, Bergman EA, Sherrard DJ, Massey LK (1996) Interactions between dietary calcium and caffeine consumption on calcium metabolism in hypertensive humans. Am J Hypertens 9:223–9

    Article  PubMed  CAS  Google Scholar 

  • Yagil Y (1990) Interaction of adenosine with vasopressin in the inner medullary collecting duct. Am J Physiol 259:F679–87

    PubMed  CAS  Google Scholar 

  • Yao K, Heyne N, Erley CM, Risler T, Osswald H (2001) The selective adenosine A1 receptor antagonist KW-3902 prevents radiocontrast media-induced nephropathy in rats with chronic nitric oxide deficiency. Eur J Pharmacol 414:99–104

    Article  PubMed  CAS  Google Scholar 

  • Yoneda H, Hisa H, Satoh S (1990) Effects of adenosine on adrenergically induced renal vasoconstriction in dogs. Eur J Pharmacol 176:109–16

    Article  PubMed  CAS  Google Scholar 

  • Zou AP, Wu F, Li PL, Cowley AW Jr (1999) Effect of chronic salt loading on adenosine metabolism and receptor expression in renal cortex and medulla in rats. Hypertension 33:511–6

    Article  PubMed  CAS  Google Scholar 

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  1. National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 4D51, 10 Center Drive MSC 1370, Bethesda, MD, 20892, USA

    Jürgen Schnermann

  2. Department of Pharmacology and Toxicology, University of Tübingen, Wilhelmstrasse 56, 72074, Tübingen, Germany

    Hartmut Osswald

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Osswald, H., Schnermann, J. (2011). Methylxanthines and the Kidney. In: Methylxanthines. Handbook of Experimental Pharmacology, vol 200. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-13443-2_15

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