Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

  • M Mazzali
  • R Kazamel
  • R Johnson
Keywords: chronic allograft dysfunction, cyclosporine, uric acid, hyperuricemia, vascular disease


Introduction: Chronic allograft dysfunction (CAD) is the primary cause of chronic graft failure after kidney transplantation. The pathogenesis of CAD involves both antigen-dependent and antigen-independent mechanisms. Serum uric acid could have a role in both mechanisms. Review: Hyperuricemia in subjects with renal transplantation is not usually viewed as clinically significant unless the subject develops gout. Drugs used in the treatment of hyperuricemia and gout are more likely to cause side effects in the kidney transplant reciepient. However, there are recent studies that raise the possibility that uric acid could have a role in CAD. Soluble uric acid has been shown to stimulate the proliferation of vascular smooth muscle, to inhibit endothelial cell proliferation and to reduce bioactive levels of endothelial NO. Studies in experimental models have found that hyperuricemia can cause hypertension associated with renal injury characterized by microvascular disease, tubulointerstitial disease, glomerular hypertrophy and glomerulosclerosis. Hyperuricemia was also found to worsen preexistent renal disease, and to be associated with the development of severe vascular lesions that are reminiscent of those observed in CAD. Furthermore, chronic cyclosporine nephropathy is very similar to what is observed in normal rats simply by raising uric acid levels. In addition, raising uric acid levels in rats receiving cyclosporine accelerates the nephropathy whereas lowering uric acid ameliorates the renal lesions. Conclusion: The pathogenic role of uric acid in CAD is still controversial. A controlled clinical trial would be the best approach to determine the effect of uric acid lowering treatment on the development of CAD and long term graft function. Keywords: chronic allograft dysfunction, cyclosporine, uric acid, hyperuricemia, vascular disease

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eISSN: 1858-554X
print ISSN: 1858-554X