Management and prevention of cyclosporine nephrotoxicity after renal transplantation: Use of low doses of cyclosporine, azathioprine and prednisone

This article represents an attempt to fine-tune clinical immunosuppressive transplant protocols. The basic idea is to use the profound immunosuppressive yet infection-sparring properties of CsA while avoiding the nephrotoxicity. Other attempts to monitor CsA kinetics have not been successful and dosage reduction, while frequently successful, cannot be relied upon to provide adequate immunosuppression based on current knowledge. In our randomized prospective stratified study, CsA toxicity is clear. It is particularly severe in cadaver recipients with ATN, and CsA toxicity may well mask or confound low grade or chronic rejection. Our clinical manipulations reported here and our laboratory experience has led us to try lower doses of CsA in combination with modified doses of Aza, ALG, and P. Clearly, this is an excellent protocol for mismatched related transplants, permitting early discharge after transplantion, a reduction in our previous prednisone dose, and virtual elimination of early nephrotoxicity. The combination of ALG/Aza/CsA/P (with CsA administration delayed until Cr clearance is normal) for cadaver transplants has also been successful in reducing CsA toxicity, but the infection potentiating effect of ALG remains and further modifications will be necessary. The reader should clearly recognize that study II represents an attempt to document a satisfactory clinical experience and that study III represents such an attempt in progress. Once apparently satisfactory protocols have evolved, their relative efficacy will require testing using the scientific methods of clinical experimental design in study I.