Figure 5. CF kidney exhibits defective amino acid reabsorption.

(A) Schematic of renal filtration and reabsorption. Most metabolites are first filtered, and selected metabolites are then actively reabsorbed back into the systemic circulation. (B) Heatmap showing 28 metabolite abundance ratios of the renal vein relative to the artery and urine relative to the artery. Blue color in urine/artery indicates reabsorption, and red color indicates loss into urine. *P < 0.05, **P < 0.01, and ***P < 0.001 of CF urine/artery relative to WT, by 2-tailed Student’s t test or Mann-Whitney U test (see Supplemental Table 2). Urine data were normalized to urine creatinine levels. (C) Correlation between WT urine/artery and CF urine/artery for each circulating metabolite (color coded by categories). Examples of amino acids that are poorly reabsorbed in CF are labeled. (D) Schematic of stable isotope tracing in pigs. Pigs were intravenously infused with four ¹³C-labeled amino acid tracers. (E) ¹³C-labeled amino acid abundance in WT and CF urine samples. The ion counts of ¹³C-labeled amino acids in urine (normalized to urine creatinine) were normalized to the labeled amino acids in arterial blood. Data are individual points with the mean shown by a blue line. n = 2 WT and n = 2 CF littermates. (F) Fold difference in urine amino acids, normalized by urine osmolality, from 12-month-old children with CF (n = 22) relative to non-CF controls (n = 22). P values by Welch’s 2-sample t test. Data were adapted from BONUS (12).