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. 2015 Apr;99(4):805-10.
doi: 10.1097/TP.0000000000000444.

Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients

Mara A McAdams-DeMarco  1 , Andrew Law, Jingwen Tan, Cassandra Delp, Elizabeth A King, Babak Orandi, Megan Salter, Nada Alachkar, Niraj Desai, Morgan Grams, Jeremy Walston, Dorry L Segev
Affiliations

Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients

Mara A McAdams-DeMarco et al. Transplantation. 2015 Apr.

Abstract

Background: Mycophenolate mofetil (MMF) side effects often prompt dose reduction or discontinuation, and this MMF dose reduction (MDR) can lead to rejection and possibly graft loss. Unfortunately, little is known about what factors might cause or contribute to MDR. Frailty, a measure of physiologic reserve, is emerging as an important, novel domain of risk in kidney transplantation recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR.

Methods: We measured frailty (shrinking, weakness, exhaustion, low physical activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 kidney transplantation recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model.

Results: By 2 years after transplantation, 54% of frail recipients and 45% of nonfrail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29 times (95% confidence interval [95% CI], 1.01-1.66; P = 0.04) more likely to experience MDR, as were deceased donor recipients (adjusted hazard ratio [aHR], 1.92; 95% CI, 1.44-2.54, P < 0.001) and older adults (age ≥ 65 vs <65; aHR, 1.47; 95% CI, 1.10-1.96, P = 0.01). Mycophenolate mofetil dose reduction was independently associated with a substantially increased risk of death-censored graft loss (aHR, 5.24; 95% CI, 1.97-13.98, P = 0.001).

Conclusion: A better understanding of risk factors for MMF intolerance might help in planning alternate strategies to maintain adequate immunosuppression and prolong allograft survival.

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Figures

Figure 1
Figure 1
Cumulative Incidence of MDR By Frailty Status. MDR was defined as a reduction in MMF immunosuppression to <2000 mg/day for Mycophenolate mofetil (Cellcept) and <1440 mg/day for mycophenolic acid (Myfortic). Frailty was defined as a score of ≥2 components. Log rank P=0.02.
Figure 2
Figure 2
Death-Censored Graft Loss, By MDR. MDR is defined as a reduction in MMF immunosuppression to <2000 mg/day for Mycophenolate mofetil (Cellcept) and <1440 mg/day for mycophenolic acid (Myfortic). MDR was treated as time-varying. Log rank P=0.003.
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References

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