Effect of the calcimimetic NPS R-467 on furosemide-induced nephrocalcinosis in the young rat

被引:21
|
作者
Pattaragarn, A
Fox, J
Alon, US
机构
[1] Univ Missouri, Childrens Mercy Hosp, Sect Pediat Nephrol, Kansas City, MO 64108 USA
[2] NPS Pharmaceut Inc, Salt Lake City, UT USA
关键词
calcimimetics; furosemide; nephrocalcinosis; parathyroid hormone;
D O I
10.1111/j.1523-1755.2004.00564.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. Furosemide induces nephrocalcinosis in both humans and animals. We showed previously that parathyroidectomy protected against the development of furosemide-induced nephrocalcinosis in young rats, indicating a possible role for parathyroid hormone (PTH) in its pathogenesis. Calcimimetic agents such as NPS R-467 are potent and selective agonists at the calcium-sensing receptor in parathyroid glands and inhibit PTH secretion. Methods. To determine whether NPS R-467 could, like parathyroidectomy, prevent furosemide-induced nephrocalcinosis, we studied 35 6-week-old male Sprague-Dawley rats, divided into five groups. Group A served as control, group B received intraperitoneally furosemide (40 mg/kg), groups C, D and E received furosemide and NPS R-467 intraperitoneally at doses of 10, 20, and 40 mumol/kg, respectively, daily for 8 days. During the last 3 days, animals were placed in metabolic cages for measurement of urine output, food, and water intake. Blood and kidneys were collected on day 8, 60 to 90 minutes after the last doses. Kidney calcium content was measured and nephrocalcinosis scoring (0 to 5) was assessed histologically. Results. Furosemide increased urine output and fluid intake, and decreased body weight gain similarly in all groups. Serum PTH levels (mean +/- SD) were significantly higher in furosemide-treated control animals (276 +/- 226 pg/mL vs. 64 +/- 21 pg/mL), NPS R-467 induced a dose-dependent decrease in PTH levels (52 +/- 51 pg/mL, 18 +/- 7 pg/mL, and 13 +/- 3 pg/mL in groups C, D, and E, respectively). Plasma Ca2+ was slightly but significantly lower in all three NPS R-467 treated groups (5.1 +/- 0.4 mg/dL, 4.8 +/- 0.3 mg/dL, and 4.5 +/- 0.3 mg/dL in groups C, D, and E. respectively) compared to 5.7 +/- 0.1 mg/dL and 5.5 +/- 0.2 mg/dL in groups A and B, respectively. Furosemide treatment induced a substantial increase in kidney calcium content (1819 +/- 664 mug/g dry weight vs. 126 +/- 26 mug/g dry weight) and nephrocalcinosis scoring (5.0 +/- 0.0 vs. 0.0 0.0). Treatment with NPS R-467 ameliorated the furosemide-induced increase in kidney calcium content (673 +/- 312 mug/g, 361 +/- 188 mug/g, and 563 +/- 291 mug/g) and nephrocalcinosis scoring (2.2 +/- 1.2, 0.7 +/- 0.8, and 9 1.0 +/- 1.2) in groups C, D, and E, respectively. Conclusion. The calcimimetic agent NPS R-467 prevents the development of hyperparathyroidism and attenuates nephrocalcinosis in the furosemide-treated young rat.
引用
收藏
页码:1684 / 1689
页数:6
相关论文
共 50 条
  • [1] Effect of the calcimimetic NPS R-467 on furosemide-induced nephrocalcinosis in the young rat.
    Pattaragarn, A
    Alon, MM
    Nichols, MA
    Alon, US
    [J]. JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2002, 13 : 579A - 579A
  • [2] Effect of thiazide on established furosemide-induced nephrocalcinosis in the young rat
    Knoll, S
    Alon, US
    [J]. PEDIATRIC NEPHROLOGY, 2000, 14 (01) : 32 - 35
  • [3] FUROSEMIDE-INDUCED NEPHROCALCINOSIS IN THE YOUNG-RAT - EFFECT OF AMILORIDE
    ALON, U
    HAHN, G
    HELLERSTEIN, S
    WARADY, BA
    [J]. CLINICAL RESEARCH, 1990, 38 (03): : A807 - A807
  • [4] Effect of thiazide on established furosemide-induced nephrocalcinosis in the young rat
    Sharon Knoll
    Uri S. Alon
    [J]. Pediatric Nephrology, 2000, 14 : 32 - 35
  • [5] Effect of age on furosemide-induced nephrocalcinosis in the rat
    Osorio, AV
    Alon, MM
    Nichols, MA
    Alon, US
    [J]. BIOLOGY OF THE NEONATE, 1998, 73 (05): : 306 - 312
  • [6] FUROSEMIDE-INDUCED NEPHROCALCINOSIS IN THE WEANLING RAT - EFFECT OF AMILORIDE
    ALON, US
    NICHOLS, M
    ALON, M
    [J]. PEDIATRIC RESEARCH, 1995, 37 (04) : A358 - A358
  • [7] EFFECT OF AMILORIDE ON FUROSEMIDE-INDUCED NEPHROCALCINOSIS
    ALON, U
    HAHN, G
    HELLERSTEIN, S
    WARADY, BA
    [J]. PEDIATRIC RESEARCH, 1991, 29 (04) : A337 - A337
  • [8] Effect of age on furosemide-induced nephrocalcinosis.
    Osorio, AV
    Alon, MM
    Nichols, MA
    Alon, US
    [J]. JOURNAL OF INVESTIGATIVE MEDICINE, 1996, 44 (07) : A344 - A344
  • [9] Critical role of parathyroid hormone in furosemide-induced nephrocalcinosis in the young rat.
    Alon, US
    Nichols, MA
    Alon, MM
    [J]. PEDIATRIC RESEARCH, 1996, 39 (04) : 2127 - 2127
  • [10] Histological long-term outcome of furosemide-induced nephrocalcinosis in the young rat
    Alon, US
    Kaplan, RA
    Gratny, LL
    Nichols, MA
    [J]. PEDIATRIC NEPHROLOGY, 1996, 10 (02) : 191 - 194