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Cyclosporine, Hypertension, and the Kidney

  • D. Diederich
  • Dai Fu-Xiang
  • M. Jameson
Conference paper

Abstract

Cyclosporine has dramatically improved the success of organ transplantation [18, 19, 24]. The clinical usefulness of cyclosporine is compromised, however, by adverse effects of the agent, most important of which are reversible impairment in kidney function, hypertension, and nephrotoxicity [10, 11, 18, 19, 22, 28, 37, 70, 76, 80, 86]. The impairment in kidney function arises from direct effects of cyclosporine upon the renal vasculature and upon tubular cells. Cyclosporine induces renal vasoconstriction, which leads to a decrease in glomerular filtration rate in virtually every patient receiving the agent [5, 28]. The decrease in glomerular filtration rate is prompt and reversible. Injury to the tubular cells leads to magnesium wasting, renal hyperkalemia, and tubular acidosis [2, 7, 8. 100]. In addition, cyclosporine stimulates sodium and water reabsorption in the proximal tubules, leading to volume expansion. Renal and systemic vasoconstriction in the setting of volume expansion predispose to the development of hypertension. Indeed, hypertension is noted in the majority of patients treated with cyclosporine [10, 22, 31, 70]. Nephrotoxic effects of cyclosporine comprise a spectrum of abnormalities ranging from episodes of reversible and acute renal failure to chronic irreversible damage to the kidneys [38, 80, 86, 87, 106]. Recent studies which demonstrate alterations in vasoactive function of endothelial and mesangial cells induced by cyclosporine provide important new insight into mechanisms responsible for the major adverse effects of this agent. Indeed, endothelial dysfunction induced by cyclosporine provides a unifying, initiating mechanism to explain the impairment in kidney function and hypertension, as well as the acute nephrotoxicity related to the use of this agent. Chronic cyclosporine nephrotoxicity may also result in part from the same mechanism, but information is less clear in this regard.

Keywords

Glomerular Filtration Rate Acute Renal Failure Acute Rejection Renal Transplant Recipient Calcium Channel Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Verlag, Berlin Heidelberg 1992

Authors and Affiliations

  • D. Diederich
  • Dai Fu-Xiang
  • M. Jameson

There are no affiliations available

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