RENAL TUBULAR SITES OF ALTERED CALCIUM-TRANSPORT IN PHOSPHATE-DEPLETED RATS

Increased calcium (Ca) excretion is characteristic of chronic phosphate (PO4) depletion (PD). To study the changes in tubular transport and the site of the hypocalciuric effect of PO4 administration, clearance and micropuncture experiments were performed in intact rats pair fed either a control diet (0.5% PO4) or a PO4-depleted (PD) diet (0.01% PO4) plus Al(OH3) and in parathyroidectomized (PTX) PD rats, infused either with saline or with neutral sodium PO4. Intact PD rats, compared with intact rats on a control diet, exhibited a lower plasma ultrafiltrate (UF) PO4 (5.8±0.5 vs. 7.8±0.3 mg/dl), higher fractional excretion (FE) of Ca (4.1±1.2 vs 0.6±0.1%), and reduced FE PO4 (0.1±0.01 vs. 10.2±1.8%). Tubular fluid/plasma inulin was lower in the late proximal tubule of PD rats, associated with increases in fractional delivery (FD) from the proximal tubule of Na and Ca. The %FD of Ca to the early distal tubule of PD rats was increased (20±3 vs. 11±2%), but this difference was abolished by the late distal tubule (5.1±1.2 vs. 3.3±0.9%). In PTX-PD rats, PO4 infusion increased plasma UF PO4 (13.8±0.7 vs. 7.8±0.7 mg/dl). FE of Ca was reduced (1.08±0.35 vs 4.59±1.57%) without correcting the increased Ca delivery to the late distal tubule. These data indicate that PD impairs Ca reabsorption in tubular segments before but not within the distal convoluted tubule, so that hypercalciuria is ultimately a result of decreased Ca transport either in the terminal nephron or in deeper nephrons where PO4 infusion stimulates Ca transport independent of parathyroid hormone or changes in the filtered load of Ca.