South Korea
South Korea (대한민국)
Many of us focus on hyperphosphatemia and stress about which phosphate binder works the best. The Reds (the South Korean national team) remind us that we have an equally, if not greater, concern with hypophosphatemia. On one side of the spectrum we have traditional/conventional hemodialysis in which little phosphorous is removed. On the other side is continuous renal replacement therapy (CRRT) in which phosphorous is effectively removed and hypophosphatemia results in serious medical consequences (Carousel 1).
Carousel 1: Hypophosphatemia in a nutshell | Courtesy of Drs. Gregory Romero-Gonzalez and Javier Neyra
Among all the negative consequences of hypophosphatemia, perhaps the most known is the deleterious effect on ATP. As early as 1971 scientists have observed a decrease in ATP or its by-products in patients with persistently low levels of phosphorous (Figure 1). These changes simply add to the stress that kidney patients receiving CRRT face -- an additional burden that should be avoided whenever possible. And that's where this year's South Korean NephroWorldCup team comes in.
FIGURE 1: Reduction in ATP in red blood cells due to hypophosphatemia | Presented at the 2019 AKI CRRT conference | Courtesy of Dr. Tulun Sokit (zoom in for details)
This year's South Korean team focuses on mitigating hypophosphatemia using a phosphate-containing dialysate solution. Known as Phoxillum, this dialysate (or replacement) solution is increasingly used in CRRT (Figure 2). Rather than look at how Phoxillum use alters a hard outcome like mortality, the South Korean researchers decided to compare/contrast those predictor variables that are known to prognosticate mortality. Does Phoxillum use over a 48-hour CRRT period alter the variables that predict mortality compared to standard CRRT solution use?
Figure 2: Commercially available phoshate-containing dialysis solutions | Presented at the 2019 CRRT Academy | Courtesy of Dr. Francesco Iannuzzella
In this single-center analysis, 272 patients were split into two groups: those receiving Phoxillum (N = 176) and those receiving a non-phosphate containing CRRT solution (N = 96). Since the study is retrospective, the decision to use Phoxillum was based on individual physician decision after considering baseline potassium and phosphorous values (Figure 3).
Figure 3: Choice of CRRT solution based on entry potassium and phosphorous levels (zoom in for details)
Interestingly, the researchers chose not to study how phosphate-containing solutions affect renal recovery and/or mortality. Instead, the researchers ran models to identify variables that predicted all-cause mortality in patients with AKI receiving 30-35 ml/kg/hr of CRRT. What did their analyses reveal (Figure 4)? More predictor variables identified in the Phoxillum group.
Figure 4: Predictor variables for all-cause mortality based on Phoxillum exposure
FIGURE 5: Example of a hypophosphatemia treatment protocol | Presented at the 2020 Kidney Week annual meeting | Courtesy of Drs. Nathanial Reisinger and Anitha Vijayan
Figure 6: Cost differential of Phoxillum and a common non-phosphate-containing CRRT solution | Courtesy Baxter
Where does this lead us? The Reds have played it safe in this year's NephroWorldCup. Rather than look at a traditionally hard outcome, they *improved* the all-cause mortality prediction model by using Phoxillum. Given the cost of Phoxillum (minor increase) and the numerous alternative options for combating hypophosphatemia in CRRT patients, it's unclear if this study can move the needle in the way we treat CRRT-induced hypophosphatemia (Figures 5 and 6).
