Multiple potential clinical benefits for 1α, 25-dihydroxyvitamin D3 analogs in kidney transplant recipients

MD Griffin, R Kumar - The Journal of steroid biochemistry and molecular …, 2005 - Elsevier
MD Griffin, R Kumar
The Journal of steroid biochemistry and molecular biology, 2005Elsevier
Therapeutic trials of 1α, 25 (OH) 2D3 and related synthetic analogs are merited in diverse
clinical fields, including treatment or prevention of bone disease, cancer, immune-mediated
diseases, cardiovascular diseases, and prostatic hypertrophy. Potential difficulties of
carrying out such trials successfully, include experimental data suggesting relatively modest
therapeutic effects of 1α, 25 (OH) 2D3 analogs as stand-alone intervention and the likely
requirement for large study group size and lengthy follow-up periods, if individual …
Therapeutic trials of 1α,25(OH)2D3 and related synthetic analogs are merited in diverse clinical fields, including treatment or prevention of bone disease, cancer, immune-mediated diseases, cardiovascular diseases, and prostatic hypertrophy. Potential difficulties of carrying out such trials successfully, include experimental data suggesting relatively modest therapeutic effects of 1α,25(OH)2D3 analogs as stand-alone intervention and the likely requirement for large study group size and lengthy follow-up periods, if individual prophylactic effects are to be proven. Thus, it may be wise to identify patient groups with multiple potential benefits, accelerated disease risks, and the possibility for exploring synergistic pharmacological effects, in whom to carry out clinical trials of 1α,25(OH)2D3 analogs. With this consideration in mind, the suitability of kidney transplant recipients for such studies is discussed. Although, highly effective in reversing end-stage renal disease, kidney transplantation continues to be limited by heightened risk of osteoporosis, persistent hyperparathyroidism, acute and chronic immunological injury, new cancer diagnosis, and cardiovascular events. In addition, kidney transplant recipients generally receive multiple immunosuppressants with a high prevalence of medication-related toxicities. Finally, it is pointed out that clinical trials carried out in organ transplant recipients provide a unique opportunity for longitudinal comparison of target tissue structural and gene expression profiles among treated and control patient groups. It is proposed that addition of a 1α,25(OH)2D3 analog to conventional post-kidney transplant medication regimens is likely to be associated with measurable effects to prevent or retard multiple important complications and that this patient group is especially suitable for carrying out clinical trials of these compounds.
Elsevier