Renal cortical mitochondrial transport of calcium in chronic uremia

Renal cortical mitochondrial transport of calcium in chronic uremia. Calcium overload of tubular cells may occur in uremia, and may be the underlying functional abnormality in the continued deterioration of renal function in chronic renal failure. In order to study this question further, the effect of chronic uremia on the calcium transport properties and respiratory rates was examined in mitochondria (Mi) isolated from the cortex of the remnant kidneys of subtotally nephrectomized rats (SNX) and sham operated controls (C). Plasma calcium concentration was similar in both groups of rats, but a significant hyperphosphatemia was seen in SNX, 8.6 ± 0.6 mg%, as compared to 7.2 ± 0.2 mg% in C (P < 0.001). Mi calcium and phosphate concentrations (nmol/mg protein) were significantly elevated in SNX, 49.9 ± 7.9 and 35.1 ± 4.2, respectively, in SNX compared to C, 21.2 ± 4.2 and 21.4 ± 2.7, respectively (P < 0.01). Mi respiratory control ratio and ADP/O were similar in both experimental groups. Kinetic parameters for calcium uptake (Ca2+ concentrations in the medium of 1.25 to 16 µM) revealed initial velocities 1.5-fold higher in SNX Mi than in C. Mi retention of calcium in the presence of medium Ca2+ concentrations up to 500 µM was studied. Calcium retention was reduced in SNX: the Mi were unable to retain calcium at concentrations of 250 µM. The addition of ruthenium red to the medium substantially improved calcium retention by the uremic Mi. Chronic parathyroidectomy did not correct either the increased calcium uptake or the poor retention of uremic Mi. In conclusion: 1) Chronic uremia in rats is associated with a marked alteration in calcium transport of renal cortical Mi, which may result in Mi calcium overload. 2) The enhanced calcium uptake and poor calcium retention of uremic Mi is not PTH dependent. 3) Since Pi is known to cause a higher initial velocity of calcium uptake and to impair calcium retention of normal mitochondria, it seems that cellular accumulation of phosphate in chronic uremia may be involved in this abnormality