Observations on Phosphate Transport in Experimental Renal Disease*

100

The patterns of phosphate excretion in man with advancing chronic renal disease are well established. Although phosphate clearance decreases with time, it falls proportionately less than glomerular filtration rate, and the ratio of phosphate clearance to GFR increases as the disease advances (1). Thus the average rate of phosphate excretion per residual nephron increases as the nephron population diminishes, and the onset of hyperphosphatemia thereby is delayed. The explanation for this sequence is of considerable theoretical interest. The major possibilities are two: 1) The change could reflect the operation of a control system geared either to maintain external phosphate balance or to maintain plasma phosphate concentrations constant; 2) the relative phosphaturia per nephron could be a consequence of uremia or of the abnormalities in residual nephrons or both. These studies represent an attempt to distinguish between these two interpretations using the dog with intrinsic renal disease as the experimental model. The experiments also were designed to delineate the general characteristics of a control system, should one exist. phate intake of at least 0.5 g. A preliminary bladdersplitting operation was performed to permit the quantitative collection of urine from the individual kidneys without recourse to ureteral catheterization (2). Thereafter, unilateral pyelonephritis was induced by a technique described previously (3). In five dogs, the diseased kidney was studied in the presence of the control kidney, and the functions of the two organs were compared. These experiments were similar in design to those described in a previous publication (4) and were performed to verify the previous results in the present animals. In 27 dogs, the control kidneys were removed to permit investigation of the diseased kidneys under environmental conditions varying from moderate azotemia to severe uremia. Methods

supporting

confidence: 85%

The control of phosphate excretion in uremia.

Slatopolsky¹,

Gradowska²,

Kashemsant³

et al. 1966

100

“…It is well established that fractional reabsorption of filtered phosphate decreases progressively in the presence of advancing renal disease (1)(2)(3), and that this homeostatic process acts to maintain serum phosphorus concentrations within the normal range until the glomerular filtration rate (GFR)l falls to <20% of normal (4). Most evidence indicates that hyperparathyroidism secondary to the renal failure plays a key role in inhibiting tubular reabsorption of phosphate in this condition (2,3), although some observations suggest that phosphate adaptation can occur in the absence of parathyroid hormone (5,6).…”

Section: Introductionmentioning

confidence: 99%

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

Bank¹,

Su²,

Aynedjian³

1978

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

“…This finding has been the subject of numerous investigations both in humans and in animals with chronically diseased kidneys (2)(3)(4)(6)(7)(8). The information derived from above studies has established the importance of secondary hyperparathyroidism in maintaining the high fractional excretion of phosphorus (Cp/GFR)l in chronic renal failure.…”

Section: Introductionmentioning

confidence: 99%

“…The fractional tubular reabsorption of phosphorus is depressed in chronic renal insufficiency (1)(2)(3)(4)(5). This finding has been the subject of numerous investigations both in humans and in animals with chronically diseased kidneys (2)(3)(4)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Renal handling of phosphorus in oliguric and nonoliguric mercury-induced acute renal failure in rats

Popovtzer¹,

Massry²,

Villamil³

1971

A B S T R A C T The renal handling of phosphorus was evaluated in rats with acute renal failure (ARF) induced by injection of mercuric chloride (HgCls). Clearances of endogenous creatinine (Ccr) and of phosphorus (Cp) were measured in the following groups: 1. Intact animals (control); 2. Parathyroidectomized rats (PTX) with normal kidney function (PTX control) Received for publication 8 December 1970 and in revised form 7 June 1971. P < 0.0005. In the nonoliguric ARF animals of group 4 the Cp/GFR 0.27 ±0.08 did not differ from the clearance ratio in group 1, however it was higher than that in the PTX animals (group 2) P < 0.0005. Cp/GFR in the nonoliguric animals of group 5 was not different from that in the nonoliguric rats of group 3. In the animals with nonoliguric unilateral Hg-ARF Cp/GFR on the affected side 0.51 ±0.16 was higher than that on the control (contralateral) side, 0.23 --0.07, P <0.0005.These results indicate that the low Cp/GFR observed in the oliguric ARF animals was not related to the level of circulating parathyroid hormone nor to the presence or absence of azotemia but probably was due to a reduced renal cortical perfusion. The high Cp/GFR in the nonoliguric ARF animals could be explained by secondary hyperparathyroidism and impaired phosphorus reabsorption due to tubular injury.