RENAL AMINO-ACID-TRANSPORT IN ADULTS WITH OXIDATIVE-PHOSPHORYLATION DISEASES

The clinical manifestations of mitochondrial DNA (mtDNA) mutations dep end on a variety of factors including ratios of normal to abnormal mtD NA and tissue-specific differences in ATP production by oxidative phos phorylation (OXPHOS). In order to investigate the effects of OXPHOS de fects on renal tubule function, we characterized sodium-coupled transp ort processes in six individuals with OXPHOS diseases. Pathogenic mtDN A mutations were identified in five of these individuals. Sodium coupl ed transport processes were evaluated by determining fractional excret ions of amino acids, glucose, lactate, urate, and phosphate in patient s and controls. Four of the six individuals had high fractional excret ions of neutral amino acids, indicating abnormal renal tubule reabsorb tion of these amino acids. Abnormalities in fractional excretions of l actate, glucose, urate, and phosphate were less pronounced. These resu lts demonstrate that sodium-coupled transport processes in the kidney are sensitive to OXPHOS impairment. When abnormalities in these proces ses are encountered, an OXPHOS disease should be included in the diffe rential diagnosis.