Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD

Leigh Quarles, Daniel A. Yohay, Barbara A. Carroll, Charles E. Spritzer, Sharon A. Minda, Dorothy Bartholomay, Bruce A. Lobaugh

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

To examine the most effective route (intravenous vs. 'pulse' oral), dose (physiologic vs. pharmacologic) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease (ESRD), we randomized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo (pulse oral group; N = 9) or intravenous calcitriol and oral placebo (intravenous group; N = 10). Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 μg thrice weekly and increased as tolerated up to a maximum dose of 4 μg per treatment. All patients received similar daily calcium supplementation (2.5 g of elemental calcium) and low dialysate calcium (1.25 mmol/liter) throughout the study period. At the maximum tolerated calcitriol dose, serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous (389 pmol/liter) compared to oral administration (128 pmol/liter). In spite of the different pharmacologic profiles, intravenous and oral administered calcitriol resulted in similar reductions of serum PTH over the 36 week period of observation (P = 0.300), achieving an overall maximum average PTH reduction of 43% (P = 0.016). Long- term intensive calcitriol therapy (independent of administration route), however, failed to decrease parathyroid gland size as assessed by high resolution ultrasound and/or magnetic resonance imaging. Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading. Increases in serum calcium, but not calcitriol dose or parathyroid gland size, predicted decrements in serum PTH, whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy. Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered. These data indicate that intermittent intensive calcitriol therapy, regardless of administration route, is poorly tolerated, fails to correct parathyroid gland size and functional abnormalities, and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism.

Original languageEnglish (US)
Pages (from-to)1710-1721
Number of pages12
JournalKidney International
Volume45
Issue number6
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Fingerprint

Hyperparathyroidism
Calcitriol
Chronic Kidney Failure
Calcium
Parathyroid Glands
Therapeutics
Hyperphosphatemia
Serum
Placebos
Secondary Hyperparathyroidism
Maximum Tolerated Dose
Dialysis Solutions
Hypercalcemia
Oral Administration
Renal Dialysis
Magnetic Resonance Imaging
Observation

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Quarles, L., Yohay, D. A., Carroll, B. A., Spritzer, C. E., Minda, S. A., Bartholomay, D., & Lobaugh, B. A. (1994). Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney International, 45(6), 1710-1721. https://doi.org/10.1038/ki.1994.223

Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. / Quarles, Leigh; Yohay, Daniel A.; Carroll, Barbara A.; Spritzer, Charles E.; Minda, Sharon A.; Bartholomay, Dorothy; Lobaugh, Bruce A.

In: Kidney International, Vol. 45, No. 6, 01.01.1994, p. 1710-1721.

Research output: Contribution to journalArticle

Quarles, L, Yohay, DA, Carroll, BA, Spritzer, CE, Minda, SA, Bartholomay, D & Lobaugh, BA 1994, 'Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD', Kidney International, vol. 45, no. 6, pp. 1710-1721. https://doi.org/10.1038/ki.1994.223
Quarles, Leigh ; Yohay, Daniel A. ; Carroll, Barbara A. ; Spritzer, Charles E. ; Minda, Sharon A. ; Bartholomay, Dorothy ; Lobaugh, Bruce A. / Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. In: Kidney International. 1994 ; Vol. 45, No. 6. pp. 1710-1721.
@article{34d5571f0a2148768f006097fc4f3317,
title = "Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD",
abstract = "To examine the most effective route (intravenous vs. 'pulse' oral), dose (physiologic vs. pharmacologic) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease (ESRD), we randomized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo (pulse oral group; N = 9) or intravenous calcitriol and oral placebo (intravenous group; N = 10). Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 μg thrice weekly and increased as tolerated up to a maximum dose of 4 μg per treatment. All patients received similar daily calcium supplementation (2.5 g of elemental calcium) and low dialysate calcium (1.25 mmol/liter) throughout the study period. At the maximum tolerated calcitriol dose, serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous (389 pmol/liter) compared to oral administration (128 pmol/liter). In spite of the different pharmacologic profiles, intravenous and oral administered calcitriol resulted in similar reductions of serum PTH over the 36 week period of observation (P = 0.300), achieving an overall maximum average PTH reduction of 43{\%} (P = 0.016). Long- term intensive calcitriol therapy (independent of administration route), however, failed to decrease parathyroid gland size as assessed by high resolution ultrasound and/or magnetic resonance imaging. Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading. Increases in serum calcium, but not calcitriol dose or parathyroid gland size, predicted decrements in serum PTH, whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy. Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered. These data indicate that intermittent intensive calcitriol therapy, regardless of administration route, is poorly tolerated, fails to correct parathyroid gland size and functional abnormalities, and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism.",
author = "Leigh Quarles and Yohay, {Daniel A.} and Carroll, {Barbara A.} and Spritzer, {Charles E.} and Minda, {Sharon A.} and Dorothy Bartholomay and Lobaugh, {Bruce A.}",
year = "1994",
month = "1",
day = "1",
doi = "10.1038/ki.1994.223",
language = "English (US)",
volume = "45",
pages = "1710--1721",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD

AU - Quarles, Leigh

AU - Yohay, Daniel A.

AU - Carroll, Barbara A.

AU - Spritzer, Charles E.

AU - Minda, Sharon A.

AU - Bartholomay, Dorothy

AU - Lobaugh, Bruce A.

PY - 1994/1/1

Y1 - 1994/1/1

N2 - To examine the most effective route (intravenous vs. 'pulse' oral), dose (physiologic vs. pharmacologic) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease (ESRD), we randomized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo (pulse oral group; N = 9) or intravenous calcitriol and oral placebo (intravenous group; N = 10). Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 μg thrice weekly and increased as tolerated up to a maximum dose of 4 μg per treatment. All patients received similar daily calcium supplementation (2.5 g of elemental calcium) and low dialysate calcium (1.25 mmol/liter) throughout the study period. At the maximum tolerated calcitriol dose, serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous (389 pmol/liter) compared to oral administration (128 pmol/liter). In spite of the different pharmacologic profiles, intravenous and oral administered calcitriol resulted in similar reductions of serum PTH over the 36 week period of observation (P = 0.300), achieving an overall maximum average PTH reduction of 43% (P = 0.016). Long- term intensive calcitriol therapy (independent of administration route), however, failed to decrease parathyroid gland size as assessed by high resolution ultrasound and/or magnetic resonance imaging. Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading. Increases in serum calcium, but not calcitriol dose or parathyroid gland size, predicted decrements in serum PTH, whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy. Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered. These data indicate that intermittent intensive calcitriol therapy, regardless of administration route, is poorly tolerated, fails to correct parathyroid gland size and functional abnormalities, and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism.

AB - To examine the most effective route (intravenous vs. 'pulse' oral), dose (physiologic vs. pharmacologic) and long-term efficacy of calcitriol therapy for secondary hyperparathyroidism in patients with end-stage renal disease (ESRD), we randomized 19 hemodialysis patients with severe hyperparathyroidism to receive over a 36-week study period either pulse orally administered calcitriol and intravenous placebo (pulse oral group; N = 9) or intravenous calcitriol and oral placebo (intravenous group; N = 10). Calcitriol was given intermittently in a double-blinded fashion at an initial dose of 2 μg thrice weekly and increased as tolerated up to a maximum dose of 4 μg per treatment. All patients received similar daily calcium supplementation (2.5 g of elemental calcium) and low dialysate calcium (1.25 mmol/liter) throughout the study period. At the maximum tolerated calcitriol dose, serum 1,25-dihydroxyvitamin D levels were significantly greater 60 minutes following intravenous (389 pmol/liter) compared to oral administration (128 pmol/liter). In spite of the different pharmacologic profiles, intravenous and oral administered calcitriol resulted in similar reductions of serum PTH over the 36 week period of observation (P = 0.300), achieving an overall maximum average PTH reduction of 43% (P = 0.016). Long- term intensive calcitriol therapy (independent of administration route), however, failed to decrease parathyroid gland size as assessed by high resolution ultrasound and/or magnetic resonance imaging. Calcitriol therapy also failed to alter the calcium sensitivity as assessed by serial PTH measurements in response to calcium loading. Increases in serum calcium, but not calcitriol dose or parathyroid gland size, predicted decrements in serum PTH, whereas hyperphosphatemia and the level of PTH suppression derived from the PTH/ionized calcium response curves predicted refractoriness to calcitriol therapy. Episodes of hypercalcemia and hyperphosphatemia were similar in both treatment groups and limited the dose of calcitriol that could be administered. These data indicate that intermittent intensive calcitriol therapy, regardless of administration route, is poorly tolerated, fails to correct parathyroid gland size and functional abnormalities, and has a limited ability to achieve sustained serum PTH reductions in end-stage renal failure patients with severe hyperparathyroidism.

UR - http://www.scopus.com/inward/record.url?scp=0028306074&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028306074&partnerID=8YFLogxK

U2 - 10.1038/ki.1994.223

DO - 10.1038/ki.1994.223

M3 - Article

VL - 45

SP - 1710

EP - 1721

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 6

ER -