An Obituary for GFR as the Main Marker for Kidney Function?

Abstract

This publication comments on the recently published findings of a study by Eloot et al. (cJASN, 6: 1266-1273, 2011) that evaluated the correlation between several formulae for calculating estimated GFR (eGFR) and different low molecular weight uremic toxins; eGFRs were based on serum creatinine (SCrea), cystatin C (Cys C), or a combination of both. Unexpectedly, the correlations for the different solutes were highly inconsistent, irrespective of the eGFR formula. On the other hand, the different eGFR formulae gave consistent results per solute. Correlation coefficients for some solutes were low (hippuric acid, p-cresylsulfate, indole acetic acid, uric acid, asymmetric dimethylarginine) to nonsignificant (carboxy-methyl-propyl-furanpropionic acid). These data point to the fact that eGFR is a deceiving predictor of uremic solute concentration and their biological action; this inconsistency is very likely the result of the impact of other factors affecting concentration, such as tubular secretion, generation by intestinal flora and metabolism.

Estimated Glomerular Filtration Rate Is a Poor Predictor of the Concentration of Middle Molecular Weight Uremic Solutes in Chronic Kidney Disease

“…These data suggest another reason for the sometimes deceiving associations than a discrepancy among mGFR and eGFR, namely that uremic solute concentration depends on other factors than GFR as well. In this way, our study corroborates findings in an earlier study with small water-soluble and protein-bound compounds [15], [46].…”

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

“…However, if urinary urea excretion is determined at all, this is not necessarily a predictor of urinary removal pattern of other uremic solutes. Indeed, urinary urea removal is likely to overlook the complex relation between glomerular filtration and tubular secretion/ reabsorption in the urinary excretion of other components, which is hardly predictable because of differences among solutes, 35,40,41 among patients, and probably also as renal failure progresses. Therefore, serious doubts can be casted on whether including urinary urea excretion into Kt/V urea would enable to figure out the complex but essential interaction between kidney function and individual toxins.…”

“…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 .…”

Uremic Solutes in Chronic Kidney Disease and Their Role in Progression

“…In a follow-up article the authors argued that this might mean that, indices of tubular function become more important as renal failure progresses. [30] This view is corroborated by the results of the IDEAL study, in which three quarters of all patients randomized to a late start of hemodialysis, initiated dialysis prior to achieving the target eGFR due to uremic symptoms. [31] GFR, and its decline, may not be the only important outcome parameter in progressive CKD.…”