1. Clearance and micropuncture studies were performed in 27 dogs made uraemic by segmental infarction to examine the factors responsible for phosphate adaptation in chronic renal failure. 2. The animals were studied before and after extracellular volume expansion to 10% of body weight in the presence and absence of parathyroid glands. The results were compared with 19 normal dogs studied under similar experimental conditions. 3. In the dogs with a remnant kidney and intact parathyroids adaptation of phosphate transport was evident, with a high fractional excretion of phosphate. Thyroparathyroidectomy 3 days before study in the dogs with a remnant kidney and moderate renal failure reduced fractional excretion of phosphate to near normal values, indicating a major role of parathyroid hormone in phosphate adaptation. Extracellular volume expansion in these thyroparathyroidectomized uraemic dogs led to an exaggerated phosphaturic response with fractional excretion of phosphate returning towards the value in the uraemic dogs with intact parathyroid glands. Thus acute extracellular volume expansion could also contribute to the increase in fractional phosphate excretion, but extracellular volume probably plays a relatively minor role in the adaptation of phosphate excretion. 4. With more advanced renal failure fractional excretion of phosphate remained high, even after thyroparathyroidectomy, indicating that parathyroid hormone-independent factors become important for phosphate adaptation in the advanced stage of renal failure. The nature of parathyroid hormone-independent changes in fractional phosphate reabsorption in chronic renal failure remains unknown. 5. Proximal tubular fluid/plasma ultrafiltrate phosphate ratios were high in all groups of dogs with a remnant kidney regardless of thyroparathyroidectomy or the degree of renal failure. The non-specific nature of the proximal tubule pattern of phosphate transport indicates that phosphate adaptation is primarily determined by alterations in phosphate transport at a site distal to the proximal convoluted tubule. Alternatively, deep nephrons may play a greater role in determination of the overall phosphate adaptation in the chronically diseased kidney.
1. In order to study the relationship between sodium and glucose transport along the nephron, clearance and micropuncture experiments were performed in 16 dogs before and after administration of diuretics with different sites of action. 2. Administration of acetazolamide, 20 mg (90 μmol)/kg, in nine dogs significantly reduced proximal tubular reabsorption of sodium and glucose and slightly increased ‘distal’ delivery of glucose. Since no glycosuria developed despite significant natriuresis, the increased ‘distal’ load of glucose must have been reabsorbed. 3. The possible site of this ‘distal’ glucose reabsorption was further studied in seven dogs which had received extracellular volume expansion to 10% of body weight and acetazolamide, 10 mg (45 μmol)/kg, to suppress proximal tubule reabsorption. When frusemide, 10 mg (30 μmol)/kg, was added, fractional glucose excretion increased from 0·3 to 2% in the absence of additional proximal tubular effect. However, the frusemide effect on ‘distal’ glucose transport was far smaller than that on sodium since fractional sodium excretion reached 40%. 4. Our results indicate a good correlation between sodium and glucose transport in the proximal tubule since both are inhibited by acetazolamide. Administration of large doses of frusemide leads to a modest glycosuria, probably by inhibition of glucose reabsorption in the loop of Henle. However, frusemide effect on the proximal tubule of deep nephrons cannot be completely excluded. The large discrepancy in the magnitude of natriuresis and glycosuria suggests dissociation of ‘distal’ sodium and glucose transport. Alternative explanations for the frusemide-induced glycosuria are also discussed.