Figure 4. Integrative model of declining renal function.
In patients with ESRD receiving HD, we hypothesized phenyacetylglutamine, p-cresol sulfate, and ROS may increase vascular endothelial injury and subsequent release of RNASE1, which then degreades eRNA. Purines are degraded into uric acid. Since humans lack functional uricase, a free-radical, non-enzymatic oxidation converts uric acid to allantoin. Increased 4PY, a degradation product of NAD, inhibits PARP1, which along with allantoin may decrease leukocyte gene transcription. These interactions between 4PY, allantoin, renal function, and gene expression are hypothetical.