A novel approach to the treatment of chronic allograft nephropathy

Transplantation. 1997 Dec 27;64(12):1706-10. doi: 10.1097/00007890-199712270-00013.

Abstract

Background: Progressive deterioration of renal function in kidney transplant recipients is the leading cause of graft failure. Both nonimmunologic and immunologic mechanisms contribute to this deterioration.

Methods: Twenty-eight cyclosporine (CsA)-treated renal transplant recipients (21 cadaveric, 5 living, 2 simultaneous kidney-pancreas) with progressive deterioration of renal function were prospectively enrolled in a clinical trial and had their immunosuppressive regimen changed 24.3+/-7.7 months after transplant. All patients had their CsA dose reduced by 50%, azathioprine was discontinued, and mycophenolate mofetil was added to the medical regimen. The mean creatinine of the patients at the initiation of the change in immunosuppression was 3.5+/-1.2 mg/dl (range 1.9 to 6.2 mg/dl).

Results: Before the change in immunosuppression, the mean loss in renal function as indicated by the least-squares slope of the reciprocal of creatinine versus time was -0.006+/-0.002 (mg/dl)-1 per month. The change in immunosuppression significantly decreased the rate of loss in renal function for most patients when compared with their pretreatment values with a mean slope of 0.007+/-0.003 (mg/dl)-1 per month (P=0.003). Renal function improved in 21 of 28 patients. Only one patient had continued deterioration of renal function. In a multivariate analysis adjusting for CsA dose, mean arterial blood pressure, and baseline creatinine, the change in immunosuppression was significantly associated with improved renal function (P=0.02). There were no acute rejections after the immunosuppression change.

Conclusions: We conclude that adding mycophenolate mofetil and reducing CsA in patients with chronic deterioration of graft function is well tolerated and results in a short-term improvement in renal function.

MeSH terms

  • Adult
  • Cadaver
  • Chronic Disease
  • Cyclosporine / administration & dosage*
  • Female
  • Graft Rejection / drug therapy
  • Humans
  • Immunosuppression Therapy / methods
  • Immunosuppressive Agents / administration & dosage*
  • Kidney Diseases / drug therapy*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Mycophenolic Acid / administration & dosage
  • Mycophenolic Acid / analogs & derivatives*
  • Prednisone / administration & dosage
  • Prospective Studies

Substances

  • Immunosuppressive Agents
  • Cyclosporine
  • Mycophenolic Acid
  • Prednisone