Estimated Glomerular Filtration Rate Is a Poor Predictor of Concentration for a Broad Range of Uremic Toxins

Abstract

SummaryBackground and objectives The degree of chronic kidney disease (CKD) is currently expressed in terms of GFR, which can be determined directly or estimated according to different formulas on the basis of serum creatinine and/or cystatin C measurements (estimated GFR [eGFR]). The purpose of this study was to investigate whether eGFR values are representative for uremic toxin concentrations in patients with different degrees of CKD. Design, setting, participants, & measurementsAssociations between eGFR based on serum cystatin C and different uremic solutes (mol wt range 113 to 240 D; determined by colorimetry, HPLC, or ELISA) were evaluated in 95 CKD patients not on dialysis (CKD stage 2 to 5). The same analysis was also applied for six other eGFR formulas.Results There was a substantial disparity in fits among solutes. In linear regression, explained variance of eGFR was extremely low for most solutes, with eGFR Ͼ 0.4 only for creatinine. The other eGFR formulations gave comparably disappointing results with regard to their association to uremic solutes. Relative similarity in R 2 values per solute for the different eGFR values and the strong disparity in values between solutes suggest that the differences in R 2 are mainly due to discrepancies in solute handling apart from GFR.Conclusions eGFR is poorly associated with concentrations of all studied uremic toxins in patients with different degrees of CKD, correlates differently with each individual solute, and can thus not be considered representative for evaluating the accumulation of solutes in the course of CKD.

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

“…Note that serum IAA level increases with CKD stage but is poorly associated with eGFR in patients with CKD not on dialysis. 24 In our study, when adjusted with eGFR, IAA was not predictive of mortality and cardiovascular events. This was probably because analysis was limited to the 47 patients with CKD who were not undergoing dialysis, who were the only patients with laboratory values available for eGFR calculations.…”

Role of Uremic Compounds in Organ Injury

“…The evidence so far collected confirms that the eGFR values show a very weak and diverse correlation with other proven uremic toxins. Hence, the current criteria based exclusively on eGFR seem inadequate to justify the decision to start dialysis [1][2][3][4][5][6][7][8][9].…”

Role of Uremic Compounds in Organ Injury

“…The suggested approaches include the use of probiotics (products containing Bifidobacteria), prebiotics (resistant starch, oligofructose-enriched inulin) and antibiotics influencing the growth and metabolism of intestinal bacteria. Reducing dietary protein intake and increasing the amount of dietary fiber may be an easy way to decrease the production of colon-derived uremic solutes such as IS and p-CS generated by intestinal bacteria [7,9]. Additionally, intestinal protein absorption is disturbed in renal failure with the resulting increase in the number of intestinal substrates derived from dietary amino acids (phenylalanine, tryptophan) for colon microbes.…”

“…The cardiorenal syndrome is classified into five types in which acute or chronic dysfunction of the heart or kidneys can induce acute or chronic dysfunction of the other organ. Better understanding of the so far unclear pathomechanism of the relationship between renal disease and cardiovascular disease is needed for developing effective treatment strategies and the activity of endogenous uremic toxins is considered by many researchers to be a likely factor [2,3,5,9,13,14,[24][25][26].…”

“…The evidence so far collected confirms that the eGFR values show a very weak and diverse correlation with other proven uremic toxins. Hence, the current criteria based exclusively on eGFR seem inadequate to justify the decision to start dialysis [1][2][3][4][5][6][7][8][9].…”