Background The clearance of solutes removed by tubular secretion may be altered out of proportion to the glomerular filtration rate (GFR) in chronic kidney disease (CKD). Recent studies have described considerable variability in the secretory clearance of waste solutes relative to the GFR in patients with CKD. Methods To test the hypothesis that secretory clearance relative to GFR is reduced in patients approaching dialysis, we used metabolomic analysis to identify solutes in simultaneous urine and plasma samples from 16 CKD patients with an estimated GFR of 7±2 ml/min per 1.73m2 and 16 control participants. Fractional clearances were calculated as the ratios of urine to plasma levels of each solute relative to those of creatinine and urea in CKD patients and to those of creatinine in controls. Results Metabolomic analysis identified 39 secreted solutes with fractional clearance >3.0 in control participants. Fractional clearance values in CKD patients were reduced on average to 65%±27% of those in controls. These values were significantly lower for 18 of 39 individual solutes and significantly higher for only one. Assays of the secreted anions phenylacetyl glutamine, p-cresol sulfate, indoxyl sulfate, and hippurate confirmed variable impairment of secretory clearances in advanced CKD. Fractional clearances were markedly reduced for phenylacetylglutamine (4.2±0.6 for controls versus 2.3±0.6 for CKD patients, P<0.001), p-cresol sulfate (8.6±2.6 for controls versus 4.1±1.5 for CKD patients, P<0.001), and indoxyl sulfate (23.0±7.3 versus 7.5±2.8, P<0.001), but not for hippurate (10.2±3.8 versus 8.4±2.6, P=0.13). Conclusions Secretory clearances for many solutes are reduced more relative to the reduction in GFR in advanced CKD. Impaired secretion of these solutes might contribute to uremic symptoms as patients approach dialysis.

Background and objectivesAdsorption of uremic solutes to activated carbon provides a potential means to limit dialysate volumes required for new dialysis systems. The ability of activated carbon to take up uremic solutes has, however, not been adequately assessed.Design, setting, participants, & measurementsGraded volumes of waste dialysate collected from clinical hemodialysis treatments were passed through activated carbon blocks. Metabolomic analysis assessed the adsorption by activated carbon of a wide range of uremic solutes. Additional experiments tested the ability of the activated carbon to increase the clearance of selected solutes at low dialysate flow rates.ResultsActivated carbon initially adsorbed the majority, but not all, of 264 uremic solutes examined. Solute adsorption fell, however, as increasing volumes of dialysate were processed. Moreover, activated carbon added some uremic solutes to the dialysate, including methylguanidine. Activated carbon was particularly effective in adsorbing uremic solutes that bind to plasma proteins. In vitro dialysis experiments showed that introduction of activated carbon into the dialysate stream increased the clearance of the protein-bound solutes indoxyl sulfate and p-cresol sulfate by 77%±12% (mean±SD) and 73%±12%, respectively, at a dialysate flow rate of 200 ml/min, but had a much lesser effect on the clearance of the unbound solute phenylacetylglutamine.ConclusionsActivated carbon adsorbs many but not all uremic solutes. Introduction of activated carbon into the dialysate stream increased the clearance of those solutes that it does adsorb.

The adequacy of hemodialysis is now assessed by measuring the removal of the single solute urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and therefore cannot be increased much further. Other solutes which are less effectively cleared than urea may however contribute more to the residual uremic illness suffered by hemodialysis patients. We here review a variety of methods which could be employed to increase the clearance of such non-urea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients' health.