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 (KT) recipients. We hypothesized that frailty, an inflammatory phenotype, might be associated with MDR. Methods: We measured frailty (shrinking, weakness, exhaustion, low activity, and slowed walking speed), other patient and donor characteristics, longitudinal MMF doses, and graft loss in 525 KT recipients. Time-to-MDR was quantified using an adjusted Cox proportional hazards model. Results: By 2 years post-transplant, 54% of frail recipients and 45% of non-frail recipients experienced MDR; by 4 years, incidence was 67% and 51%. Frail recipients were 1.29-times (95%CI:1.01-1.66; P=0.04) more likely to experience MDR, as were deceased donor recipients (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). MDR 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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The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction or stillbirth. Animal studies have identified reflected pressure waves traveling counter to the direction of blood flow as an important factor in the shape of these waveforms. In the present study, we establish a method to measure reflected waves in the human umbilical artery and assess their influence on blood velocity pulsation. Ninety-five pregnant women were recruited from a general obstetrics clinic between 26 and 37 wk of gestation and examined by Doppler ultrasound. Blood velocity waveforms were recorded for each umbilical artery at three locations along the umbilical cord. With the use of a computational procedure, a pair of forward and reverse propagating waves was identified to explain the variation in observed Doppler ultrasound waveforms along the cord. Among the data sets that met data quality requirements, waveforms in 93 of the 130 arteries examined agreed with the wave reflection model to within 1.5% and showed reflections ranging in magnitude from 3 to 52% of the forward wave amplitude. Strong reflections were associated with large differences in pulsatility between the fetal and placental ends of the cord. As reflections arise from transitions in the biomechanical properties of blood vessels, these observations provide a plausible mechanism for the link between abnormal waveforms and clinically significant placental pathology and could lead to more precise screening methods for detecting pregnancies complicated by placental disease. NEW & NOTEWORTHY The pulsatile pattern of blood motion measured by Doppler ultrasound within the umbilical artery is known to contain useful diagnostic information and is widely used to monitor pregnancies at risk of fetal growth restriction. We demonstrate based on a study of 95 pregnant women that the shape of these umbilical artery waveforms is explained by the presence of a reflected pressure wave traveling counter to the direction of blood flow.