Residual Function Effectively Controls Plasma Concentrations of Secreted Solutes in Patients on Twice Weekly Hemodialysis

Abstract

Most patients on hemodialysis are treated thrice weekly even if they have residual kidney function, in part because uncertainty remains as to how residual function should be valued and incorporated into the dialysis prescription. Recent guidelines, however, have increased the weight assigned to residual function and thus reduced the treatment time required when it is present. Increasing the weight assigned to residual function may be justified by knowledge that the native kidney performs functions not replicated by dialysis, including solute removal by secretion. This study tested whether plasma concentrations of secreted solutes are as well controlled in patients with residual function on twice weekly hemodialysis as in anuric patients on thrice weekly hemodialysis. We measured the plasma concentration and residual clearance, dialytic clearance, and removal rates for urea and the secreted solutes hippurate, phenylacetylglutamine, indoxyl sulfate, and -cresol sulfate in nine patients on twice weekly hemodialysis and nine patients on thrice weekly hemodialysis. Compared with anuric patients on thrice weekly dialysis with the same standard Kt/V, patients on twice weekly hemodialysis had lower hippurate and phenylacetylglutamine concentrations and similar indoxyl sulfate and -cresol sulfate concentrations. Mathematical modeling revealed that residual secretory function accounted for the observed pattern of solute concentrations. Plasma concentrations of secreted solutes can be well controlled by twice weekly hemodialysis in patients with residual kidney function. This result supports further study of residual kidney function value and the inclusion of this function in dialysis adequacy measures.

Gut-derived uremic toxin handling in vivo requires OAT-mediated tubular secretion in chronic kidney disease

“…Recently, there has been renewed interest in the relative importance of renal tubular secretory capacity in the setting of declining renal function in the context of the handling of drugs and organic solutes, including uremic solutes and uremic toxins (2)(3)(4). Growing evidence suggests the residual renal secretory capacity -especially via the organic anion transport (OAT) system -may be particularly important in the setting of CKD (2)(3)(4)(5)(6)(7)(8).…”

“…Recently, there has been renewed interest in the relative importance of renal tubular secretory capacity in the setting of declining renal function in the context of the handling of drugs and organic solutes, including uremic solutes and uremic toxins (2)(3)(4). Growing evidence suggests the residual renal secretory capacity -especially via the organic anion transport (OAT) system -may be particularly important in the setting of CKD (2)(3)(4)(5)(6)(7)(8). In fact, it is believed that residual function of the proximal tubule is likely to be central to the removal of compounds not generally cleared by hemodialysis, which include many of the protein-bound small-molecule uremic solutes and toxins (2,3,7,(9)(10)(11)(12)(13).…”

Individualized Hemodialysis Treatment: A Perspective on Residual Kidney Function and Precision Medicine in Nephrology

“…It should be noted that our ability to reduce solute concentrations by intensifying hemodialysis treatment is limited, probably due to the presence of nondialytic solute clearances and/or changes in solute production [55]. Native kidneys provide solute clearance equivalent to or more than that of hemodialysis treatment with the same urea clearance, especially for middle molecules (i.e., β 2 -microglobulin) and protein-bound uremic toxins (i.e., indoxyl sulfate and p-cresol sulfate) [2, 56]. RKF also provides other benefits than solute clearance, such as continuous fluid removal, and more preserved endocrine functions.…”

“…Due to its continuous nature, RKF has additional advantages over hemodialysis in mitigating dynamic changes in body fluid and facilitating the removal of middle molecules and protein-bound solutes [2-6]. RKF also plays a role in endocrine functions such as the production of erythropoietin and the activation of vitamin D [7].…”

“…Therefore, we believe it is time to reevaluate the clinical importance of RKF among hemodialysis patients and to incorporate RKF levels in the management of hemodialysis patients. Indeed, a recent study revealed that plasma concentrations of secreted solutes (i.e., hippurate, phenylacetylglutamine, indoxyl sulfate, and p-cresol sulfate) can be well controlled by twice-weekly hemodialysis in patients with RKF [2]. Given that patients with ESRD now tend to initiate maintenance hemodialysis therapy with higher RKF levels, there seem to be important opportunities for incremental hemodialysis by individualizing the dose and frequency according to their RKF levels.…”