Exercise capacity is reduced in ESRD patients on maintenance peritoneal dialysis (PD) therapy, although the potential mechanisms and clinical implications of this remain unclear. In a recent AJKD article, Zuo et al discuss their findings of a study that evaluated the prevalence of and associations with reduced exercise capacity in PD patients. Authors Dr. Chun-Wah Siu (CS) and Dr. Wai-Kei Lo (WL) discuss this topic with Dr. Sean Kalloo (eAJKD), eAJKD Contributor.
eAJKD: Can you review the general findings of your study?
CS: It has been well recognized that patients with ESRD on maintenance hemodialysis have limited exercise capacity, which is a strong predictor of poor quality of life and higher mortality. Much less is known about patients on maintenance PD. In our study, we show an extremely high prevalence of reduced exercise capacity as measured by peak oxygen consumption (96%) amongst patients with ESRD on maintenance PD. Using quantitative echocardiographic technology and spectral bioelectrical impedance, we identified new parameters predicting reduced peak oxygen consumption. This includes the ratio of extracellular to intracellular fluid, which may be exploited as a treatment target in routine clinical practice to modify the outcomes of these patients.
eAJKD: Peritoneal dialysis allows patients to customize their renal replacement regimen. Your article mentions that all patients were typically undergoing 4 exchanges per day. Do you feel that one of the factors leading to a chronically volume “overloaded” state in the PD population may be not tailoring these regimens enough, and patients instead being managed on rather “generic” PD prescriptions?
WL: This study was not designed to study factors resulting in fluid overload. In our center, the primary determinant of PD fluid volume is clearance (Kt/V). Concentration adjustment and/or icodextrin PD fluid use are volume control. Yet, previous reports suggested that fluid overload in PD patients is quite common, and subclinical overload is easily underdiagnosed without the aid of bioelectrical impedance analysis (BIA). Our study is the first to identify the possible link of exercise peak oxygen consumption and fluid status as detected by BIA, suggesting that in the future BIA should be used more frequently for PD prescription adjustment to maintain a proper fluid status.
eAJKD: Can you discuss the measured parameters and the main outcomes in your study?
CS: As expected, several conventional clinical parameters such as increasing age, low serum albumin concentration, and low residual kidney function are associated with reduced peak oxygen consumption. In addition, we identify a few new parameters predicting reduced peak oxygen consumption. These include high ratio of extracellular to intracellular fluid, low lean tissue mass index, left ventricular diastolic dysfunction, and elevated echocardiographic-derived pulmonary capillary wedge pressure and pulmonary artery systolic pressure. Among these, extracellular-to-intracellular fluid volume ratio exhibited the strongest correlation.
eAJKD: Based on your data, does residual kidney function have any impact on your end points?
WL: Though residual kidney function has been reported to affect fluid status, we did not find a difference in residual kidney function between patients with higher and lower peak oxygen consumption. The sample of this cohort is too small for survival analysis, but in our center, residual kidney function at commencement of dialysis was not a significant risk factor for mortality.
eAJKD: Can you discuss the main clinical implications of your study?
CS: Our findings may have several important clinical implications. First, resembling their HD counterparts, patients on maintenance PD therapy have markedly reduced exercise capacity that may result in reduced quality of life and possibly poor survival. The goal of management for patients with ESRD should include optimizing their exercise capacity. Several potentially modifiable factors of exercise capacity identified in this study, and they may be exploited to improve outcomes in these patients. Because our data highlighted a strong correlation between the ratio of extracellular-to-intracellular fluid and exercise capacity in patients on peritoneal dialysis, the incorporation of bioimpedance-guided fluid management in clinical practice appears to be a promising intervention. It allows early identification of modifiable factors such as excess fluid and low muscle mass, and prompts implementation of therapeutic interventions. Nonetheless, the clinical benefits of this approach remain to be determined by randomized control trials.
eAJKD: What are the major limitations of your study?
CS: First, the study is limited by its cross-sectional, observational nature, so it is not possible to confirm causation. Second, we did not obtain echocardiographic measurements at peak exercise, thus limiting the exploration of pathophysiologic mechanisms during exercise. Third, the ratio of extracellular-to-intracellular fluid is not a pure index of volume status. Although in the present study the elevation of the ratio mostly reflected an expansion in extracellular fluid caused by hypervolemia, it could have indicated decreased intracellular fluid caused by malnutrition in a few patients.