Uremic neuropathy: evidence of middle molecule toxicity

Ten dialysis patients were followed in a prospective study to determine the neurotoxicity of metabolites in the middle molecule (MM) molecular weight (mol wt) range of 500-200 daltons/molecule. In the absence of readily available direct serum measurements of MM concentrations, a theoretically calculated dialysis index, D1(MM), which included the combined effects of dialysis and residual glomerular filtration rate (GFR) on MM removal was used to estimate changes in their predialysis concentrations. The ten patients were dialyzed on protocols which yielded a D1(MM) less than 1.0. Evidence of uremic neuropathy developed in six of these ten patients, and five of these six also developed a progression in their anemia. Two additional patients with no signs of neuropathy developed a progression in their anemia. One patient developed pericarditis with tamponade. A total of eight patients developed complications. One additional patient developed increased weakness, tiredness and general malaise without change in objective findings. When the dialysis therapy to reduce MM concentrations by increasing the D1(MM) above 1.0 was instituted, the complications were reversed. Our data support the findings of others, namely, that there are toxic substances in the MM mol wt range of 500-2000 daltons/molecule. However, a synergism between elevated concentrations of small molecules and MM cannot be ruled out.