A micropuncture study of renal phosphate transport in rats with chronic renal failure and secondary hyperparathyroidism.

Abstract

A B S T R A C T Micropuncture studies were carried out in rats to determine changes in tubular transport of phosphate which occur in chronic renal failure and secondary hyperparathyroidism. Rats underwent subtotal nephrectomy (NX) and were fed a low calcium, high phosphorus diet for 3-4 wk. Other groups consisted of normal control animals, normal rats infused with sodium phosphate to raise filtered load of phosphate, subtotal NX rats parathyroidectomized (PTX) on the day of experiment, and normal PTX rats infused with sodium phosphate. It was found that filtered phosphate/nephron is markedly increased in subtotal NX rats due to high single nephron filtration rates, proximal tubular fluid plasma phosphate ratios are >1.0, and fractional reabsorption of phosphate is decreased in the proximal tubule. More phosphate was present in the final urine than in surface distal convoluted tubules. Acute PTX in subtotal NX rats resulted in a striking increase in proximal phosphate reabsorption, and urinary phosphate became approximately equal to that remaining in surface distal tubules. Phosphate loading in normal rats reduced fractional reabsorption in the proximal tubule, but urinary phosphate was not greater than that at the end of surface distal tubules. Acute PTX in normal phosphate-loaded animals had no significant effect on proximal tubular phosphate reabsorption. These observations suggest that phosphate homeostasis in chronic renal failure is achieved by inhibition of proximal phosphate reabsorption, counteracting a greatly enhanced intrinsic capacity for reabsorption. In addition, the large amount of urinary phosphate is consistent either with secretion by the collecting ducts or with a disproportionately high contribution by deep nephrons. The changes in phosphate transport are mediated by

Parathyroid Hormone, Fibroblast Growth Factor 23, and Parameters of Phosphate Reabsorption

“…Previously, we provided an algebraic argument (reproduced in SOM) that E P /C cr is proportional to [P] CDN , which is increased in CKD [4, 12]. We showed that normal calcium reabsorption accompanied high [PTH] in patients with CKD, and we documented significant linear regressions of [PTH] and [FGF23] on E P /C cr [4, 9, 10].…”

Relationship between Proximal Tubule Total CO₂ and Phosphate Reabsorption in Acute and Chronic PTX Rats

“…The trachea was cannulated, and tubing was inserted into a jugular vein and carotid artery as previously described [3,4]. An initial arterial blood sample was collected for measurement of calcium, phos phorus, sodium, potassium, and blood gases.…”

“…The left kidney was exposed through a lateral abdominal incision and prepared for micropuncture as described previously [3,4]. The urinary bladder was externalized through a suprapubic incision and flanged PE tubing was inserted into the lumen and ligated.…”

“…Proximal tubular fluid and urine collections were started 90 min after TPTX and 60 min after equil ibration of isotopes. The tubular fluid collections were obtained proximal to an oil block, as describ ed previously [3,4], and were timed with a stop watch. Transit time of pulse-injected FD and C green dye was measured as previously described [3,4].…”

“…The tubular fluid collections were obtained proximal to an oil block, as describ ed previously [3,4], and were timed with a stop watch. Transit time of pulse-injected FD and C green dye was measured as previously described [3,4]. Small arterial blood samples were collected immediately after each tubular fluid collection for determination of *H-inulin and 32po4 concentra tions.…”