The regulation of calcitriol by parathyroid hormone and absorbed dietary phosphorus in subjects with moderate chronic renal failure.

The two best-recognized stimuli for calcitriol production are parathyroid hormone (PTH) and dietary phosphorus deprivation. We studied the relative importance of these two stimuli in subjects with moderate chronic renal failure (MCRF). We recruited 10 subjects with MCRF aged 49 +/- 13 years (mean +/- SD) and having a creatinine clearance rate of 31 +/- 24 mL/min. After an overnight fast, they received 400 IU human PTH 1-34 subcutaneously, and blood and urine samples were collected over the subsequent 24 hours. They then took aluminum hydroxide 30 mmol/d for 2 months to reduce gut phosphorus absorption, at the end of which the PTH stimulation test was repeated. Responses were compared with those obtained in 11 normal subjects aged 44 +/- 16 years and having a creatinine clearance rate of 102 +/- 37 mL/min who were only studied while on their normal diet. Following PTH stimulation in the normal subjects but not the MCRF subjects, there was a significant increase in plasma calcium and calcitriol levels, with a significant decrease in renal phosphorus threshold. In both groups there was a similar and significant increase in urine cyclic adenosine monophosphate (cAMP) levels. Following restriction of absorption of dietary phosphorus in MCRF subjects, plasma calcitriol levels increased compared with baseline values. This study shows that these MCRF subjects were unable to respond with an increase in calcitriol to a PTH stimulus that produced a similar urine cAMP response in normal subjects. However, they were capable of responding to a reduction in phosphorus absorption with an increase in calcitriol.(ABSTRACT TRUNCATED AT 250 WORDS)