C/D Ratio in Long-Term Renal Function

Area of Science:

• Pharmacology
• Nephrology
• Immunosuppression

Background:

• Tacrolimus is an immunosuppressive drug crucial for preventing organ rejection.
• Therapeutic drug monitoring of tacrolimus often relies on C0 concentrations, which may not fully reflect its pharmacologic effect.
• The C/D ratio, an indicator of tacrolimus metabolism rate, was previously developed by Thölking et al.

Purpose of the Study:

• To evaluate the utility of the C/D ratio for classifying tacrolimus metabolism rates in patients undergoing long-term follow-up after renal transplantation (RTx).
• To determine if established C/D ratio cutoffs for fast, intermediate, and slow metabolizers are applicable in the context of long-term RTx outcomes.

Main Methods:

• The C/D ratio was analyzed in 571 patients at least one year post-RTx (mean follow-up: 84 months).
• Kidney function, including creatinine and estimated glomerular filtration rate (eGFR), was assessed at the most recent appointment and early after RTx.
• Correlation analyses were performed between the C/D ratio and kidney function parameters.

Main Results:

• A median C/D ratio of 1.68 was observed in the study cohort.
• The C/D ratio showed a negative correlation with creatinine and a positive correlation with eGFR in the long term post-RTx.
• A cutoff C/D ratio of 1.53 was identified, differentiating patients with eGFR < 60 mL/min/1.73 m² from those with eGFR ≥ 60 mL/min/1.73 m².
• Significant differences in creatinine and eGFR levels, as well as their longitudinal changes, were noted between groups defined by the 1.53 C/D ratio cutoff.

Conclusions:

• The C/D ratio serves as a valuable tool for assessing the impact of tacrolimus metabolism on long-term renal function post-transplantation.
• A C/D ratio of 1.53 is proposed as a critical threshold, with values below this point suggesting a negative prognosis for long-term renal function.