In this open-label, prospective, pilot trial, we did not find that sucroferric oxyhydroxide independently improved serum albumin or appetite in patients with ESKD on PD. Consequently, nutrient intake did not appear to change over the course of the study. However, patients did significantly reduce their serum phosphorus levels and pill burden during the study. Additionally, study participants did have significant increases in phosphorus-attuned albumin. This suggested that participants may have maintained appetite or potentially attenuated any potential reductions in appetite. There were no changes in PTH at any study time-point. Sucroferric oxyhydroxide was well-tolerated without any significant adverse events. To our knowledge, this is the first study prospectively examining the effects of sucroferric oxyhydroxide therapy on albumin, appetite, and dietary changes among patients on PD.
While we didn’t find a significant increase in serum albumin, we did find an increase in phosphorus-attuned albumin. The increase in phosphorus-attuned albumin suggests an overall improvement in the nutritional status of the participants. Additionally, it suggests that the decreases in serum phosphorus were the result of SO, not decreases in protein intake. We confirmed this with the nutritional information collected which did not show a significant change in dietary protein intake. Our findings are similar to a recent retrospective database analysis . PD patients prescribed SO as part of routine care had significant reductions in serum phosphorus and pill burden. While the authors found a slight decrease in serum albumin over the 6 month follow-up period with SO, phosphorus-attuned albumin significantly increased similar to our findings. While this metric has not been used routinely in dialysis patient care, it is important that any rise in albumin should not be associated with a concurrent rise in phosphorus.
Similar results have also been found in patients with ESKD on hemodialysis. In a one-year cohort analysis, we found that HD patients who switched from non-sucroferric oxyhydroxide based binders to sucroferric oxyhydroxide also had significant reductions in serum phosphorus levels and pill burden , as observed in this current study of PD patients. We also found improvements in phosphorus-attuned albumin with no change in dietary intake comparable to previous studies [9, 10]. Kalantar-Zadeh et al.  found sucroferric oxyhydroxide therapy was associated with reductions in serum phosphorus levels and pill burden in both hypoalbuminemic and non-hypoalbuminemic HD patients. Serum albumin levels increased significantly in the hypoalbuminemic HD patients but serum albumin did not change in the non-hypoalbuminemic patients. These studies suggest that SO may improve the nutritional status of patients. However, these studies were retrospective and observational and to date, no prospective trials have been done in HD patients.
Previous studies have reported on the high prevalence of poor appetite in PD patients [13,14,15], which was also observed in our study. Reduced appetite predicts inadequate nutrition and malnutrition in PD patients . Both reduced appetite and malnutrition are associated with increased mortality among patients on PD . Low-albumin is also associated with mortality in patients on dialysis . However, hypoalbuminemia may be the result of both malnutrition and inflammation or other processes [17, 18]. Unfortunately, we were unable to obtain biochemical measures of inflammation (C-reactive protein and interleukin-6) and other markers (fibroblast growth factor 23 and prealbumin) in the majority of study participants at all time-points due to the COVID-19 pandemic. PD solution-induced hypophagia has been one proposed mechanism  that may have contributed to reported decreases in this study. However, studies have not widely quantified this effect and we did not account for this in the current study. Additionally, the presence of dialysate in the peritoneal cavity [13, 15] may have potentially contributed to delayed gastric emptying and reduced intestinal motility and subsequently decreased appetite. In our study, 8 participants had day dwells, but their prescription remained stable throughout the study. Other hypotheses for poor appetite include phosphate binder pill burden, pre-existing gastrointestinal symptoms, and gastrointestinal side effects as a result of phosphate binders.
In the current study, we found that participants’ appetite increased at 3 months and decreased at 6 months, while caloric and protein intake decreased at 3 months and increased at 6 months. However, the categorical and numerical trend was for poorer intake over the whole study duration. This indicates that patients self-reported appetite may not have been reflective of the nutrient intakes observed in this study. Notably, Wright et al.  reported that PD patients appear to normalize their self-reported appetite at lower levels than healthy controls. PD patients in the Wright et al.  study also report lower dietary nutrient intakes than healthy controls. Nutrient intakes observed in the current study were generally in-line with previous research studies, yet did not meet nutritional recommendations for PD.
We found that SO was well-tolerated even at the average final dose of 5 tablets per day. Previous trials in PD and hemodialysis patients found an average dose of 4 tablets per day of SO was well-tolerated and effective over a one-year time period . In this larger study, withdrawal from SO from adverse events occurred in only 8.2% of participants. Recent real-world studies of SO have also shown that it is effective and well-tolerated . We did not obtain information beyond the 6-month time period in our study, so we do not know if patients were able to continue on SO and thus do not have longer data regarding effectiveness or side effects.
Our study does have several limitations, including the lack of a control group and the small sample size. With the small sample size we were unable to examine subgroups including subgroups based on initial baseline phosphate binders (e.g. sevelamer vs. calcium acetate). The COVID-19 pandemic also significantly impacted our study. Due to the pandemic, we were unable to have serum phosphorus and albumin levels drawn at the same time of day in all participants. We recognize that phosphorus levels may change before or after meals. However, a recent study found that a high phosphorus meal only has a negligible effect on plasma phosphate compared to low phosphorus meal in PD patients . Additionally, we did not have information on D/P creatinine ratio at baseline and end of study in all participants. We acknowledge changes in D/P creatinine ratio may affect serum albumin and may change over an extended period of time, however given the short time frame of this study it is unlikely there were significant changes in D/P creatinine.