Hypothesis: CYP3A5-guided tacrolimus dosing plus the first trough trajectory will outperform weight-only dosing for early exposure control in autoimmune nephritis

Testable hypothesis: in lupus nephritis and related autoimmune nephritis cohorts, a prespecified model that combines CYP3A5 phenotype, starting dose normalized to weight, early tacrolimus trough trajectory, and CYP3A inhibitor/inducer exposure will identify patients who fail to reach target exposure by day 7 better than weight-based dosing alone. Primary endpoint: failure to reach at least 80% of the prespecified target trough by day 7 or protocol-defined need for major dose escalation. Secondary endpoints: calibration slope, AUC, Brier score, and decision-curve net benefit. Mechanistic basis: CYP3A5 expressers generally need higher dose intensity to achieve similar troughs, while renal/hepatic context and interacting drugs modify the real-world expression of that genotype effect. References: Birdwell KA et al., Clin Pharmacol Ther 2015, DOI 10.1002/cpt.113; Niioka T et al., Clin Exp Nephrol 2015, DOI 10.3109/00498254.2015.1045571; Wei L et al. 2025, DOI 10.12182/20250560509.