Can protocol biopsy better inform our choices in renal transplantation?

The use of protocol biopsies has provided insights into the pathogenesis of many renal allograft diseases. It is now widely accepted that acute and chronic immune injury, as well as other pathologies associated with eventual graft loss, may occur initially in the absence of graft dysfunction. Indeed, renal transplant biopsies performed at the time of graft dysfunction may disclose advanced stages of renal injury that may not be amenable to treatment. However, protocol biopsies have several limitations that include their morbidity, cost, and potential for sampling error. Furthermore, the prevalence of early subclinical rejection is decreasing in the modern era of immunosuppression, which argues against their use in patients of low immunological risk. Conversely, the transplantation community has, perhaps unadvisedly, embarked upon protocols of immunosuppressive drug minimization. The consequences of these practices may result in late inflammation in the graft that could prove deleterious to its function in the long term. It is hoped that in the future "systems biology" techniques (eg, genomics, proteomics, and metabolomics) may guide clinicians regarding the safety of drug minimization protocols, inform them as to when a renal transplant biopsy should be procured, and perhaps one day replace the renal transplant biopsy altogether. Until such time, however, the renal biopsy remains an indispensable tool in the management of renal transplant recipients.