The kidney provides a sensitive mechanism which aids in the maintenance of phosphorus equilibrium despite varying intakes and alterations in metabolic demand. Under normal conditions a large proportion of the phosphorus which is filtered at the glomerulus is reabsorbed by the tubules which thereby effect regulation of the urinary phosphorus (1). Few studies have been performed on patients or animals to determine how phosphorus homeostasis is maintained as renal function is progressively decreased (2, 3). It is well known that the concentration of serum inorganic phosphorus increases and of calcium decreases as renal failure becomes more pronounced (446), and that anatomical changes occur in the parathyroid glands which suggest hyperfunction of these organs (7). Since the parenteral administration of parathyroid hormone produces an increased phosphaturia, a decrease in the serum phosphorus, and an increase in the serum calcium, it is possible that the parathyroid hyperplasia represents a physiologic attempt to reverse these specific effects of renal failure (8). It seemed appropriate, therefore, to investigate the relationship of phosphate clearance to the general level of renal function and to test the response to exogenous parathyroid hormone at all gradations of renal impairment to determine whether a further response was possible or whether maximal effectiveness had been achieved by endogenous hormone activity.
MATERIALS AND METHODSA series of twenty males between the ages of 25 and 60 years was selected. Their glomerular filtration rates as measured by inulin clearance varied from 142 to 1.5 1 This work was supported in part by a grant-in-aid from the U. S. Public Health Service, Heart Institute, Grant No. H-1004 (C); and the Riker Laboratories, Inc., Los Angeles, California. ml. per minute, and covered the entire range of renal function from normal to advanced uremia. Those with reduced renal function had various diseases, chiefly chronic glomerulonephritis and chronic pyelonephritis. The patients with normal kidneys had been maintained on the regular hospital diet which provided 90 to 100 grams of protein and about 1.5 grams of phosphorus per day. Most of the patients with reduced renal function had ingested a diet in which the protein was restricted to about 40 grams and, the phosphorus intake to approximately 0.75 grams per day.Clearances were performed during the postabsorptive state and the glomerular filtration rate was measured by the use of inulin in all but four experiments in which the endogenous creatinine clearance was substituted. Three control periods of approximately 20 minutes each were obtained 30 minutes after the injection of the priming dose of inulin. Blood was drawn for the determination of serum inulin and phosphorus at the midpoint of each clearance period. During the fourth 20-minute period 500 units of parathyroid hormone 2 (Lilly) was given by slow intravenous injection. Three additional 20-minute clearance periods were obtained following the administration of the hormone. A satis...
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