Abstract
BackgroundAfter renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy.MethodsThe scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation.ResultsA total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse effects (p = 0.008) in renal transplant recipients receiving tacrolimus and mycophenolic acid compared to the cyclosporine regimen. This finding demonstrated construct validity. Intra-class correlation was 0.81 (95% confidence interval: 0.65-0.90) and Kappa statistic of 0.68 ± 0.25 for all 18 adverse effects and verified substantial inter-rater reliability.ConclusionsThis immunosuppressive adverse effects scoring system in stable renal transplant recipients was evaluated and substantiated face, content and construct validity with inter-rater reliability. The scoring system may facilitate prospective, standardized clinical monitoring of immunosuppressive adverse drug effects in stable renal transplant recipients and improve medication adherence.
Highlights
After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs
Maintenance immunosuppressive regimens consisted of either cyclosporine and mycophenolate mofetil (MMF) (n = 30 males) or tacrolimus plus enteric coated mycophenolate sodium (EC-MPS) (n = 28 females and males)
Post-transplant diabetes mellitus was observed in 30.0% of patients receiving cyclosporine and MMF compared to 32.1% of patient receiving tacrolimus (P = 0.860)
Summary
Many patients experience adverse effects from maintenance immunosuppressive drugs. Renal transplant recipients are treated with combination immunosuppression consisting of calcineurin inhibitors such as cyclosporine or tacrolimus and mycophenolic acid to prevent allograft rejection [4] These medications are associated with significant adverse effects which increase patient morbidity and decrease medication adherence [4,5,6,7,8,9,10,11,12,13,14]. Patient non-adherence with immunosuppressive medications has increased as a result of mild to moderate adverse effects which are not consistently documented during outpatient clinic appointments This may impact acute rejection and long-term allograft survival post-transplant [15,16,17]. Prospective clinical monitoring of immunosuppressive adverse effects is critical to prevent post-transplant complications and improve patient safety outcomes
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