Uremic Neuropathy: Evidence of Middle Molecule Toxicity

Abstract

Ten dialysis patients were followed in a prospective study to determine the neurotoxicity of metabolites in the middle molecule (MM) MW range of 500-2000 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 10 patients were dialyzed on protocols which yielded a D1(MM) < 1.0. Evidence of uremic neuropathy developed in 6 of these 10 patients, and 5 of these 6 also developed a progression in their anemia. Additional patients (2) with no signs of neuropathy developed a progression in their anemia. One patient developed pericarditis with tamponade. A total of 8 patients developed complications. One additional patient developed increased weakness, tiredness and general malaise without change in objective findings. When dialysis therapy to reduce MM concentrations by increasing the D1 (MM) above 1.0 was instituted, the complications were reversed. There are toxic substances in the MM MW range of 500-2000 daltons/molecule. A synergism between elevated concentrations of small molecules and MM cannot be ruled out.