What Is the Adequate Dose for Peritoneal Dialysis in Acute Kidney Injury: Lower the Bar or Shift the Goalposts?

The persistently high mortality rate over the past 2 decades in patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT) has been of concern for the nephrology community. This has stimulated much interest in the dose of dialysis that should be provided, especially in the critically ill patient. Much of this has focused on extracorporeal techniques, with the publication of large randomized trials using continuous renal replacement therapies (CRRT) or intermittent hemodialysis (IHD) (1,2). These extracorporeal therapy studies have shown that there appears to be a threshold below which the dialysis dose impacts on survival but above which there does not appear to be increased benefit (1–3). There has been renewed interest in the use of peritoneal dialysis (PD) to treat patients with AKI, driven by the Saving Young Lives Program and the 0by25 campaign, as PD is the most cost-effective and logistically efficient method of dialysis in lowand middle-income countries (4). In high-income countries, there has been a proliferation of urgent-start PD for late-presenting chronic kidney disease (CKD), and this has expanded to include treatment of AKI in these units. It has been shown in randomized trials and meta-analyses that PD for AKI has similar outcomes to extracorporeal therapies in terms of mortality and allows more rapid recovery of renal function (5–7). The International Society for Peritoneal Dialysis’s (ISPD’s) recently published Guidelines for PD in AKI have attempted to address the issue of the optimal dose of dialysis when using PD to treat AKI (8). The guidelines committee appraised the available literature and recommended 2 different weekly Kt/V urea targets: the first was the optimal target of 3.5 based on studies from Brazil (outlined below) and the second was 2.1, extrapolated from the CRRT and IHD studies mentioned above. It was the feeling of many on the committee that the higher target, which requires high volumes of fluid, was unnecessary and, in lowand middle-income countries, would make it prohibitively expensive, resulting in many patients dying through lack of treatment. Unfortunately, at the time, the evidence for using the lower target was only sufficient to give a 2D GRADE recommendation (9). When prescribing dialysis in AKI, one aims to ensure adequate clearance of all solutes and uremic toxins that are going to impact on morbidity and survival. Unlike patients with CKD, these patients are often hypercatabolic, hypoalbuminemic, fluid overloaded, and acidemic. They also require high volumes of fluid removal to ensure a neutral balance due to the infusion of antibiotics, total parenteral nutrition, and other medications. There is much interest in whether dialysis is able to reduce the levels of cytokines produced in critically ill patients and thereby reduce the inflammatory cascade, which contributes significantly to the poor outcomes of these patients. There are therefore 3 targets which one needs to address: 1) fluid removal, 2) small solute clearance and correction of hyperkalemia and acidosis, and 3) middle molecule and cytokine clearance. Potassium, urea, bicarbonate, and water move rapidly across the peritoneal membrane and, as a result, reach equilibration rapidly. Thus, short dwell times and high volumes of fluid of the correct tonicity will ensure significant clearance of these molecules. It has been clearly demonstrated that rapid cycling in the first 24 to 48 hours in critically ill AKI patients will correct hyperkalemia, acidosis, and fluid overload to a significant degree, and this is ideal, as it is these toxins that may have an impact on short-term mortality (6,7,10). Larger molecule clearance however is different; it is dependent on the duration of contact between the dialysate and the peritoneal membrane (11). Therefore rapid cycling may limit clearance of these solutes by reducing dwell time lost to filling and draining. Certainly it has been shown in CKD patients that automated PD (APD), with its more rapid cycles than continuous ambulatory PD (CAPD), results in lower phosphate clearance in all but the high-transporter categories despite equivalent ultrafiltration (11). Tidal PD may theoretically overcome this issue as there is a relatively constant volume of fluid in contact with the peritoneal membrane throughout the 24-hour period; however, studies have produced conflicting results (12,13). Peritoneal weekly Kt/V urea has been used in many studies to assess the delivered dose of PD for AKI. This has inherent problems, as it represents the clearance of smaller molecules but does not give any indication of larger molecule clearance. As a result, it may under-estimate clearances of these toxins. Badve et al. showed that phosphate clearance in APD does not correlate with Kt/V urea and that there is a much better WHAT IS THE ADEQUATE DOSE FOR PERITONEAL DIALYSIS IN ACUTE KIDNEY INJURY: LOWER THE BAR OR SHIFT THE GOALPOSTS?