(A and B) Box-and-whisker plots illustrating the effects of probenecid treatment on GFR (A) and tubular secretion (B). After treating the animals with probenecid, there was little to no effect on GFR in either the sham-operated animals or STN animals (A). Probenecid (PBD) treatment, however, had a significant (*P ≤ 0.05) effect on tubular secretion (B), such that, in both the sham-operated and the STN animals after probenecid treatment, there was a dramatic reduction in PAH clearance (PBD, probenecid; gray boxes, untreated sham-operated controls and untreated STN animals; white boxes, probenecid-treated sham-operated controls and STN animals). As in Figure 1, black cross in each box represents the mean; solid black center lines indicate the median; open circles represent the individual data points; box limits indicate the 25th and 75th percentiles, as determined by R software; whiskers extend 1.5 times the interquartile range from the 25th and 75th percentiles, outliers are represented by dots (92) (5 animals were used for each of the experimental groups; a 2-tailed Student t test was used to determine statistical significance; a P value less than 0.05 was considered significant.) (C) Partial least squares discrimination analysis of the metabolomic profiling data reveals clear separations between serum/plasma metabolites obtained from untreated sham-operated animals (control; red), untreated STN animals (STN; purple), and probenecid-treated STN animals (STN+PROB; green). (D) A Z score plot of metabolite intensities for the 58 uremic solutes affected by treatment of the STN animals with probenecid. The greater the distance of each dot (individual measurements for each metabolite) from the x axis, the greater the magnitude of change in plasma concentration for each metabolite (black circles, sham-treated control; green circles, STN rats; red circles, STN rats treated with probenecid). In this case, the distance of the green dot (STN alone) from the x axis is the average score of the STN animal above the sham-treated control (black dot), while the distance of the red dot (STN with probenecid) from the x axis is the average score of the probenecid-treated STN animal above the untreated STN animal. Plasma increases in metabolite concentration (positive Z scores) are seen above the x axis, while decreases in plasma concentration are represented by those dots below the x axis. As can be seen, many metabolites belonging to the amino acid metabolic superpathway show significant accumulation in the plasma of the STN animal following probenecid treatment.