Estimated glomerular filtration rate is a poor predictor of the concentration of middle molecular weight uremic solutes in chronic kidney disease

Background

Uremic solute concentration increases as Glomerular Filtration Rate (GFR) declines. Weak associations were demonstrated between estimated GFR (eGFR) and the concentrations of several small water-soluble and protein-bound uremic solutes (MW<500Da). Since also middle molecular weight proteins have been associated with mortality and cardiovascular damage in Chronic Kidney Disease (CKD), we investigated the association between several eGFR formulae and the concentration of Low Molecular Weight Proteins (LMWP) (MW>500Da).

Materials and Methods

In 95 CKD-patients (CKD-stage 2–5 not on dialysis), associations between different eGFR-formulae (creatinine, CystatinC-based or both) and the natural logarithm of the concentration of several LMWP’s were analyzed: i.e. parathyroid hormone (PTH), Cystatin C (CystC), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), leptin, retinol binding protein (RbP), immunoglobin light chains kappa and lambda (Ig-κ and Ig-λ), beta-2-microglobulin (β₂M), myoglobin and fibroblast growth factor-23 (FGF-23)).

Results

The regression coefficients (R²) between eGFR, based on the CKD-EPI-Crea-CystC-formula as reference, and the examined LMWP’s could be divided into three groups. Most of the LMWP’s associated weakly (R² <0.2) (FGF-23, leptin, IL-6, TNF-α, Ig-κ, Ig-λ) or intermediately (R² 0.2–0.7) (RbP, myoglobin, PTH). Only β₂M and CystC showed a strong association (R² >0.7). Almost identical R²-values were found per LMWP for all eGFR-formulae, with exception of CystC and β₂M which showed weaker associations with creatinine-based than with CystC-based eGFR.

Conclusion

The association between eGFR and the concentration of several LMWP’s is inconsistent, with in general low R²-values. Thus, the use of eGFR to evaluate kidney function does not reflect the concentration of several LMWP’s with proven toxic impact in CKD.