Immunosuppressive strategies and management

Advances in immunosuppressive therapy have significantly improved short-term allograft and patient survival.However,chronic allograft failure,antibody mediated rejection,recurrent diseases and immunosuppressive drug associated adverse effects remain serious barriers to long-term survival and quality of life.New immunosuppressive agents and protocols are being evaluated to combat these problems.Importantly,clinicians must work to manage post-transplant complications and avoid complex medication regimens,which will potentiate drug interactions and non.compliance.Different organs have different immunogenicities and each recipient has a unique clinical and immunologic profile.The clinician must recognize these variations and customize the immunosuppressive regimens and treatment protocols based on the individual condition.The general principles of an individualized immunosuppressive protocol should take the following factors into account:organ type,donor and recipient characteristics,quality of the donor organ,recipienVs medical history,recipient's undedying disease,immunologic risk for acute rejection,potential co-morbidity related to immunosuppression,significant druginteractions,medication costs and patient compliance.In addition,the combination of immunosuppressive drugs must have a pharmacologic rationale to achieve the desired goal of suppressing the individual's immune system to render the patient tolerant to the allograft while minimizing co-morbidities.For the past few years,many clinical strategies have been applied in an attempt to improve graft survival or to reduce immunsuppressants induced side-effects.Specific protocols include steroid or CNI avoidance,minimization or withdraw,desensitization,and treatment for antibody mediated rejection,disease specific,and pediatric specific.The short-term outcomes from these different strategies are promising but the long-term results remain to be determined.Unfortunately,current immunosuppressive agents or strategies have failed to adequately control chronic rejection in most of solid organ transplantation except liver transplantation.Eady post-transplant complications aye generally related to the operation,the severity of pre-operative illness,immunologic status,and the quality of the donor organ.Careful recipient and donor selection is paramount to minimize severity of disease and medical comorbidities.These early complications include allograft dysfunction,cardiovascular and hemodynamic instability,and immunosuppressive drug-induced adverse effects.Acute infection remains a common and serious early complication despite new and effective drug therapies,placing the responsibility on the clinician for early recognition and treatment.Emerging resistant bacteria and fungi require early and aggressive intervention.Unlike infection,early aUograft rejection is usually limited and manageable with the newer immunosuppressive agents.However,it must be distinguished from other causes of allograft dysfunction(ie.recurrent hepatitis C,ealcineurin induced nephrotoxicity,or infection).Recently approved Cylex@immune cell function assay allows clinicians to tailor and individualize immunosuppression to prevent organ rejection while minimizing infection and complications.Improved patient and allograft survival has enabled transplant recipients to reach milestones and return to productive lives provided they are compliant. It was also challenged the clinician to manage the long-term complications of immunosuppression therapy, adverse drug interaction, recurrent diseases and chronic allograft failure. Long-term immunosuppressive therapy places transplant recipients at risk for renal insufficiency, cardiovascular and metabolic diseases, de novo malignancies, and psychosocial challenges. The management of viral hepatitis C re-infection, chronic allograft nephropathy, vasculopathy, and obliterative bronchiolitis is currently the greatest challenges facing the transplant specialist. The management of immunosuppressants induced adverse effects/drug interactions, chronic allograft failure and recurrent disease is dependent on regular clinical follow-up, an accurate diagnosis and appropriate treatment.Our challenge for the future will be to develop strategies to determine the best, cost-effective regimens for an individual patient to prevent long-term graft loss. I believe the management of immunosuppression and posttransplant complications is best met with a multidisciplinary team approach. This presentation will discuss the current immunosuppressive strategies and the common post-transplant complications. It is designed to help the clinician recognize individual risk factors and provide appropriate management.