Does the Adequacy Parameter Kt/Vurea Reflect Uremic Toxin Concentrations in Hemodialysis Patients?

Abstract

Hemodialysis aims at removing uremic toxins thus decreasing their concentrations. The present study investigated whether Kt/Vurea, used as marker of dialysis adequacy, is correlated with these concentrations. Predialysis blood samples were taken before a midweek session in 71 chronic HD patients. Samples were analyzed by colorimetry, HPLC, or ELISA for a broad range of uremic solutes. Solute concentrations were divided into four groups according to quartiles of Kt/Vurea, and also of different other parameters with potential impact, such as age, body weight (BW), Protein equivalent of Nitrogen Appearance (PNA), Residual Renal Function (RRF), and dialysis vintage. Dichotomic concentration comparisons were performed for gender and Diabetes Mellitus (DM). Analysis of Variance in quartiles of Kt/Vurea did not show significant differences for any of the solute concentrations. For PNA, however, concentrations showed significant differences for urea (P<0.001), uric acid (UA), p-cresylsulfate (PCS), and free PCS (all P<0.01), and for creatinine (Crea) and hippuric acid (HA) (both P<0.05). For RRF, concentrations varied for β2-microglobulin (P<0.001), HA, free HA, free indoxyl sulfate, and free indole acetic acid (all P<0.01), and for p-cresylglucuronide (PCG), 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), free PCS, and free PCG (all P<0.05). Gender and body weight only showed differences for Crea and UA, while age, vintage, and diabetes mellitus only showed differences for one solute concentration (UA, UA, and free PCS, respectively). Multifactor analyses indicated a predominant association of concentration with protein intake and residual renal function. In conclusion, predialysis concentrations of uremic toxins seem to be dependent on protein equivalent of nitrogen appearance and residual renal function, and not on dialysis adequacy as assessed by Kt/Vurea. Efforts to control intestinal load of uremic toxin precursors by dietary or other interventions, and preserving RRF seem important approaches to decrease uremic solute concentration and by extension their toxicity.

The Uremic Toxicity of Indoxyl Sulfate and p-Cresyl Sulfate

“…74 Because our knowledge regarding this issue is extending, alternative options may arise in the nearby future. Anyway, the fact that dietary components and residual renal function seem to affect proteinbound solute concentration more than dialysis adequacy, as assessed by Kt/V, 75 may suggest that alternative methods focusing on preserving kidney function or affecting intestinal toxin generation For animal experiments, we presumed that serum albumin was present at the same concentrations as usually in these animals; all solute concentrations were measured in serum, except for the study by Ito et al 30 (plasma), and steady state at the end of exposure on euthanasia of the animals, except for the study by Koppe et al 44 (peak after i.p. injection).…”

The Cardiovascular Effect of the Uremic Solute Indole-3 Acetic Acid

“…However, in patients undergoing hemodialysis, IAA levels are not related to protein equivalent of total nitrogen appearance, a reliable estimate of dietary protein intake. 20 IAA is bound to albumin with a high affinity, 21 and the protein binding of IAA is about 80%. 22 IAA is party removed during hemodialysis, with a reduction rate of about 45% during the dialysis session.…”

“…However, predialysis concentrations of IAA seem to depend on residual renal function rather than on dialysis adequacy, assessed by Kt/V urea . 20 This observational clinical study has some limits. First, the relation to outcomes is only observational.…”

Once upon a time in dialysis: the last days of Kt/V?

“…35,36 One up till now largely neglected alternative factor is the generation of uremic toxins by the intestinal microbiota. 37 The concentration of several compounds, among which indoxyl sulfate and p-cresyl sulfate, was 50-to 100-fold lower in hemodialysis patients without colon than in patients with a colon 38 in spite of similar Kt/V urea .…”