Removal of Uremic Solutes from Dialysate by Activated Carbon.

Background And Objectives: Adsorption 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, & Measurements: Graded volumes of waste dialysate collected from clinical hemodialysis treatments were passed through activated carbon blocks.

Impaired Tubular Secretion of Organic Solutes in Advanced Chronic Kidney Disease.

Background: The clearance of solutes removed by tubular secretion may be altered out of proportion to the GFR in 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 patients with CKD and an eGFR of 7±2 ml/min per 1.

Association of Plasma Uremic Solute Levels with Residual Kidney Function in Children on Peritoneal Dialysis.

Background And Objectives: Residual native kidney function confers health benefits in patients on dialysis. It can facilitate control of extracellular volume and inorganic ion concentrations. Residual kidney function can also limit the accumulation of uremic solutes.

Impaired Tubular Secretion of Organic Solutes in Acute Kidney Injury.

Background: Impairment of kidney function is routinely assessed by measuring the accumulation of creatinine, an organic solute cleared largely by glomerular filtration. We tested whether the clearance of solutes that undergo tubular secretion is reduced in proportion to the clearance of creatinine in humans with AKI.

Methods: Four endogenously produced organic solutes (phenylacetylglutamine [PAG], hippurate [HIPP], indoxyl sulfate [IS], and p-cresol sulfate [PCS]) were measured in spot urine and plasma samples from ten patients with AKI and 17 controls.

Plasma pseudouridine levels reflect body size in children on hemodialysis.

Background: Dialysis in children as well as adults is prescribed to achieve a target spKt/V, where V is the volume of distribution of urea. Waste solute production may however be more closely correlated with body surface area (BSA) than V which rises in proportion with body weight. Plasma levels of waste solutes may thus be higher in smaller patients when targeting spKt/V since they have higher BSA relative to body weight.

Accumulation of uremic solutes in the cerebrospinal fluid in experimental acute renal failure.

The accumulation of uremic solutes in kidney failure may impair mental function. The present study profiled the accumulation of uremic solutes in the cerebrospinal fluid (CSF) in acute renal failure. CSF and plasma ultrafiltrate were obtained from rats at 48 h after sham operation (control; = 10) or bilateral nephrectomy ( = 10) and analyzed using an established metabolomic platform.

Contribution of 'clinically negligible' residual kidney function to clearance of uremic solutes.

Background: Residual kidney function (RKF) is thought to exert beneficial effects through clearance of uremic toxins. However, the level of native kidney function where clearance becomes negligible is not known.

Methods: We aimed to assess whether levels of nonurea solutes differed among patients with 'clinically negligible' RKF compared with those with no RKF.

Characteristics of Colon-Derived Uremic Solutes.

Background And Objectives: Colon microbial metabolism produces solutes that are normally excreted in the urine and accumulate in the plasma when the kidneys fail. This study sought to further identify and characterize human colon-derived uremic solutes.

Design, Setting, Participants, & Measurements: Colon-derived solutes normally excreted in the urine were identified by comparing urine from controls (=17) and patients with total colectomies (=12), using an established metabolomic platform.

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

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.

Untargeted mass spectrometry discloses plasma solute levels poorly controlled by hemodialysis.

Many solutes have been reported to remain at higher plasma levels relative to normal than the standard index solute urea in hemodialysis patients. Untargeted mass spectrometry was employed to compare solute levels in plasma and plasma ultrafiltrate of hemodialysis patients and normal subjects. Quantitative assays were employed to check the accuracy of untargeted results for selected solutes and additional measurements were made in dialysate and urine to estimate solute clearances and production.

Results of the HEMO Study suggest that p-cresol sulfate and indoxyl sulfate are not associated with cardiovascular outcomes.

Cardiovascular disease, the leading cause of mortality in hemodialysis patients, is not fully explained by traditional risk factors. To help define non-traditional risk factors, we determined the association of predialysis total p-cresol sulfate, indoxyl sulfate, phenylacetylglutamine, and hippurate with cardiac death, sudden cardiac death, and first cardiovascular event in the 1,273 participants of the HEMO Study. The results were adjusted for potential demographic, clinical, and laboratory confounders.

Limited reduction in uremic solute concentrations with increased dialysis frequency and time in the Frequent Hemodialysis Network Daily Trial.

The Frequent Hemodialysis Network Daily Trial compared conventional three-times weekly treatment to more frequent treatment with a longer weekly treatment time in patients receiving in-center hemodialysis. Evaluation at one year showed favorable effects of more intensive treatment on left ventricular mass, blood pressure, and phosphate control, but modest or no effects on physical or cognitive performance. The current study compared plasma concentrations of uremic solutes in stored samples from 53 trial patients who received three-times weekly in-center hemodialysis for an average weekly time of 10.

Kt/Vurea and Nonurea Small Solute Levels in the Hemodialysis Study.

The Hemodialysis (HEMO) Study showed that high-dose hemodialysis providing a single-pool Kt/V of 1.71 provided no benefit over a standard treatment providing a single-pool Kt/V of 1.32.

Effect of a sustained difference in hemodialytic clearance on the plasma levels of p-cresol sulfate and indoxyl sulfate.

Background: The protein-bound solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) accumulate to high plasma levels in renal failure and have been associated with adverse events. The clearance of these bound solutes can be altered independently of the urea clearance by changing the dialysate flow and dialyzer size. This study tested whether a sustained difference in clearance would change the plasma levels of PCS and IS.

An Enlarged Profile of Uremic Solutes.

Better knowledge of the uremic solutes that accumulate when the kidneys fail could lead to improved renal replacement therapy. This study employed the largest widely available metabolomic platform to identify such solutes. Plasma and plasma ultrafiltrate from 6 maintenance hemodialysis (HD) patients and 6 normal controls were first compared using a platform combining gas and liquid chromatography with mass spectrometry.

Effect of increasing dietary fiber on plasma levels of colon-derived solutes in hemodialysis patients.

Background And Objectives: Numerous uremic solutes are derived from the action of colon microbes. Two such solutes, indoxyl sulfate and p-cresol sulfate, have been associated with adverse outcomes in renal failure. This study tested whether increasing dietary fiber in the form of resistant starch would lower the plasma levels of these solutes in patients on hemodialysis.

Prominent accumulation in hemodialysis patients of solutes normally cleared by tubular secretion.

Dialytic clearance of urea is efficient, but other small solutes normally secreted by the kidney may be cleared less efficiently. This study tested whether the high concentrations of these solutes in hemodialysis patients reflect a failure of passive diffusion methods to duplicate the efficacy of clearance by tubular secretion. We compared the plasma concentrations and clearance rates of four solutes normally cleared by tubular secretion with the plasma concentrations and clearance rates of urea and creatinine in patients receiving maintenance hemodialysis and normal subjects.

Numerous protein-bound solutes are cleared by the kidney with high efficiency.

The kidney clears numerous solutes from the plasma; however, retention of these solutes causes uremic illness when the kidneys fail. We know remarkably little about which retained solutes are toxic and this limits our ability to improve dialysis therapies. To explore this, we employed untargeted mass spectrometry to identify solutes that are efficiently cleared by the kidney.

The production of p-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores.

Background And Objectives: The uremic solutes p-cresol sulfate (PCS) and indoxyl sulfate (IS) are generated by colon bacteria acting on food components that escape absorption in the small bowel. The production of these potentially toxic compounds may thus be influenced by diet. This study examined whether production of PCS and IS is different in vegetarians and omnivores.

Selectively increasing the clearance of protein-bound uremic solutes.

Background: The toxicity of bound solutes could be better evaluated if we could adjust the clearance of such solutes independent of unbound solutes. This study assessed whether bound solute clearances can be increased while maintaining urea clearance constant during the extended hours of nocturnal dialysis.

Methods: Nine patients on thrice-weekly nocturnal dialysis underwent two experimental dialysis treatments 1 week apart.

Colonic contribution to uremic solutes.

Microbes in the colon produce compounds, normally excreted by the kidneys, which are potential uremic toxins. Although p-cresol sulfate and indoxyl sulfate are well studied examples, few other compounds are known. Here, we compared plasma from hemodialysis patients with and without colons to identify and further characterize colon-derived uremic solutes.

Contribution of residual function to removal of protein-bound solutes in hemodialysis.

Background And Objectives: This study evaluated the contribution of residual function to the removal of solutes for which protein binding limits clearance by hemdialysis.

Design, Setting, Participants, & Measurements: Solute concentrations were measured in 25 hemodialysis patients with residual urea clearances ranging from 0.1 to 6.

Effect of increasing dialyzer mass transfer area coefficient and dialysate flow on clearance of protein-bound solutes: a pilot crossover trial.

Background: Protein-bound solutes are poorly cleared by means of conventional hemodialysis because protein binding limits the "free" solute concentration driving diffusion. This study tested the modeled prediction that clearances of bound solutes could be increased by increasing the dialyzer mass transfer area coefficient (K(o)A) and dialysate flow (Q(d)) to greater than the levels used in conventional practice.

Study Design: Pilot crossover trial.