Renal function in patients receiving long-term cyclosporine therapy.
The site at which the vasomotor effects of cyclosporine are associated with acute nephrotoxicity appears to be the afferent arteriole. Proposed mechanisms mediating these effects include sympathetic nerve stimulation, disruption of the balance between vasodilating and vasoconstricting prostaglandins, hypersensitivity to vasoactive peptides, and endothelin release. These mechanisms mediate cyclosporine-associated intrarenal vasoconstriction, yet the causal relationship between these changes and the obliterative vasculopathy seen in association with chronic progressive renal allograft dysfunction is uncertain. Histologic findings seen in chronic progressive renal dysfunction are nonspecific and cannot be correlated solely with cyclosporine use. Retrospective studies analyzing both aggregate serial serum creatinine and reciprocal creatinine determinations did not report a pattern of progressive attrition consequent to toxic nephropathy. Prospective studies with serial GFR determinations with various reference substances found no progressive deterioration in allograft function. Both the retrospective and prospective studies indicate that the attrition of renal allograft function associated with cyclosporine use reflect the chronic effects of immunologic injury. Renal function in extrarenal transplant recipients immunosuppressed with cyclosporine can be characterized by an initial decline in native renal function followed by subsequent stabilization beyond the first 6 months. There does not appear to be an inordinate rate of progression to ESRD.
Van Buren
D H
DH
Renal Transplantation Division, Vanderbilt University Medical Center, Nashville, TN 37232-4750.
Burke
J F
JF
Lewis
R M
RM
D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D016027:Heart Transplantation / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000502:physiology; D016031:Liver Transplantation / Q000502:physiology; D016377:Organ Transplantation / Q000502:physiology*; D013997:Time Factors
D016572:Cyclosporine; D003404:Creatinine