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Frailty, mycophenolate reduction, and graft loss in kidney transplant recipients
Mara A McAdams-DeMarco1, Andrew Law, Jingwen Tan
11 Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD. 2 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 3 Division of Nephrology, Johns Hopkins University School of Medicine, Baltimore, MD. 4 Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Baltimore, MD.
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.
Insights
Frailty increases the risk of mycophenolate mofetil dose reduction (MMF-DR) in kidney transplant recipients. MMF-DR is linked to a higher risk of graft loss, highlighting the need for strategies to manage MMF intolerance.
Area of Science:
- Nephrology
- Transplantation immunology
- Geriatrics
Background:
- Mycophenolate mofetil (MMF) side effects can lead to dose reduction or discontinuation, potentially causing graft rejection and loss.
- Frailty, a state of reduced physiological reserve, is an emerging risk factor in kidney transplant recipients.
- The relationship between frailty and MMF dose reduction (MDR) is not well understood.
Purpose of the Study:
- To investigate the association between frailty and MMF dose reduction in kidney transplant recipients.
- To identify risk factors contributing to MMF dose reduction.
- To explore the impact of MMF dose reduction on graft survival.
Main Methods:
- A cohort of 525 kidney transplant recipients was studied.
- Frailty was assessed using measures of shrinking, weakness, exhaustion, low physical activity, and slow walking speed.
- Cox proportional hazards models were used to analyze time-to-MMF dose reduction and its association with graft loss.
Main Results:
- Frail recipients had a higher likelihood of MMF dose reduction compared to non-frail recipients (1.29 times more likely).
- Deceased donor recipients and older adults (≥65 years) were also more prone to MMF dose reduction.
- MMF dose reduction was significantly associated with an increased risk of death-censored graft loss (5.24 times higher risk).
Conclusions:
- Frailty is a significant risk factor for MMF dose reduction in kidney transplant recipients.
- Identifying patients at risk for MMF intolerance is crucial for developing alternative immunosuppression strategies.
- Effective management of MMF intolerance may improve long-term allograft survival.
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