Middle molecule accumulation in uremia: an "extra uremic factor"

To evaluate middle molecule (MM) accumulation in relation with patients' well-being, plasma MM were analyzed in 115 uremic patients by using the two-step chromatographic technique described by Fürst et al. Unexpectedly, most of the patients exhibited small or undetectable subpeaks 7a, 7b, 7c, 7d. However, patients on regular dialysis treatment tend to present higher MM concentrations when a complication, such as infection, hyperparathyroidism, symptomatic neuropathy, or intercurrent disease occurs and peak 7d was very prominent after radio-contrast media administration. No correlation was found between plasma MM and small molecule accumulation (urea, creatinine, and uric acid) or residual renal function or hematocrit. An unexpected correlation was found between some MM fractions and serum PTH. These results indicate that MM do not accumulate in plasma only as a result of impaired renal function. This suggests considerable variations in their generation rates may be due to unknown misleading artifacts, PTH breakdown products, or other factors.