Impact of Intrapatient Immunosuppression Variability in Renal Transplantation Outcomes: A Systematic Review and Meta-analysis.

BACKGROUND

Intrapatient variability (IPV) is the changes of a drug's blood trough concentration in a patient. There is a lack of consensus on whether high IPV is associated with poor outcomes in transplantation.

METHODS

Several electronic databases, including MEDLINE/PubMed, Embase, Web of Science, Cochrane Reviews, and the Cochrane CENTRAL Register of Controlled Trials, served as sources for the literature search. Covidence facilitated the sorting and extraction of data. The meta-analysis was conducted using R Studio.

RESULTS

About 5210 studies were identified in initial database searches, with 41 articles ultimately included in this review. We reviewed outcomes, including acute rejection, chronic rejection, allograft survival, patient survival, and development of de novo donor-specific antibodies (dnDSA). Numerous papers supported the conjecture high IPV was associated with increased rejection rates and worse allograft survival rates, while for patient survival, chronic rejection, and dnDSA development results were equivocal regarding the effect of IPV. Meta-analysis showed that patients with low IPV had a 44% lower risk of acute rejection compared with patients with high IPV (RR = 0.56). Patients with high IPV had an increased risk of graft loss, HR = 2.42 (95% CI, 1.70-3.46).

CONCLUSIONS

Our analysis showed that acute rejection and allograft survival are impacted by high IPV. In conclusion, this study establishes high IPV as a significant modifiable risk factor for acute rejection and graft loss, warranting its integration into routine clinical monitoring.