Browsing by Author "Felsenfeld, AJ"

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    Effect of ammonium chloride and dietary phosphorus in the azotaemic rat.: I.: Renal function and biochemical changes
    (2004) Jara, A; Chacón, C; Ibaceta, M; Valdivieso, A; Felsenfeld, AJ
    Background. Both dietary phosphorus restriction and the ingestion of ammonium chloride (NH4Cl) given to rats on a high-phosphorus diet have been shown to preserve renal function in the azotaemic rat. Parathyroidectomy also has been reported to preserve renal function and, in addition, to prevent kidney hypertrophy in the remnant kidney model. Our goals were (i) to evaluate in azotaemic rats the effect of dietary phosphorus on renal function in a shorter time frame than previously studied and (ii) to determine whether NH4Cl administration (a) enhances the renoprotective effect of dietary phosphorus restriction and (b) improves renal function in the absence of parathyroid hormone (PTH).
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    Effect of ammonium chloride and dietary phosphorus in the azotaemic rat.: Part II -: kidney hypertrophy and calcium deposition
    (2004) Jara, A; Chacón, C; Ibaceta, M; Valdivieso, A; Felsenfeld, AJ
    Background. Kidney hypertrophy is stimulated by both partial nephrectomy and NH4Cl administration. Also, parathyroidectomy (PTX) has been reported to prevent kidney hypertrophy induced by a high protein diet. Our goal was to determine in the azotaemic rat: (i) the combined effects of NH4Cl administration and dietary phosphorus on the development of kidney hypertrophy and calcium deposition in the kidney and (11) whether the absence of parathyroid hormone (PTH) affected the development of kidney hypertrophy and calcium deposition.
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    Effect of calcitriol treatment and withdrawal on hyperparathyroidism in haemodialysis patients with hypocalcaemia
    (2001) Jara, A; Chacón, C; Valdivieso, A; Aris, L; Jalil, R; Felsenfeld, AJ
    Background. Calcitriol is used to treat secondary hyperparathyroidism in dialysis patients. For similarly elevated parathyroid hormone (PTH) levels, the PTH response to calcitriol treatment is believed to he better in hypocalcaemic dialysis patients than in dialysis patients with higher serum calcium values. Furthermore, few studies have evaluated the rapidity of the rebound in serum PTH values after prolonged treatment with calcitriol. Our goal was to evaluate (i) the PTH response to calcitriol treatment in hypocalcaemic haemodialysis patients, (ii) the rapidity of rebound in PTH after calcitriol treatment was stopped, and (iii) whether the effect of calcitriol treatment on PTH levels could be separated from those produced by changes in serum calcium and phosphate values.
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    Effect of endothelin receptor antagonist on parathyroid gland growth, PTH values and cell proliferation in azotemic rats
    (2006) Jara, A; von Höveling, A; Jara, X; Burgos, ME; Valdivieso, A; Mezzano, S; Felsenfeld, AJ
    Background. A variety of stimuli are involved in the pathogenesis of parathyroid gland hyperplasia in renal failure. Recently, it was shown that blocking the signal from the endothelin-1 (ET-1) receptor (ETAR/ETBR) by a non-selective receptor antagonist, bosentan, reduced parathyroid cell proliferation, parathyroid gland hyperplasia and parathyroid hormone (PTH) levels in normal rats on a calcium deficient diet. Our goal was to determine whether in 5/6 nephrectomized (NPX) rats with developing or established hyperparathyroidism, the endothelin receptor blocker, bosentan, reduced the increase in parathyroid cell proliferation, parathyroid gland hyperplasia and PTH values.
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    Failure of high doses of calcitriol and hypercalcaemia to induce apoptosis in hyperplastic parathyroid glands of azotaemic rats
    (2001) Jara, A; González, S; Felsenfeld, AJ; Chacón, C; Valdivieso, A; Jalil, R; Chuaqui, B
    Background. Whether calcitriol administration, which is used to treat secondary hyperparathyroidism in dialysis patients, induces regression of parathyroid-gland hyperplasia remains a subject of interest and debate. If regression of the parathyroid gland were to occur, the presumed mechanism would be apoptosis. However, information on whether high doses of calcitriol can induce apoptosis of parathyroid cells in hyperplastic parathyroid glands is lacking. Consequently, high doses of calcitriol were given to azotaemic rats and the parathyroid glands were evaluated for apoptosis.
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    How dietary phosphate, renal failure and calcitriol administration affect the serum calcium-phosphate relationship in the rat
    (2002) Jara, A; Chacón, C; Felsenfeld, AJ
    Background. The effect of hyperphosphataemia on serum calcium regulation in renal failure has not been well Studied in a setting in which hypercalcaemia is not parathyroid hormone (PTH) mediated. In azotemic rats with a normal serum calcium concentration, in increased dietary phosphate burden affects serum calcium regulation because of its effects on skeletal resistance to PTH, calcitriol production, and possibly intestinal calcium absorption. Our goal was to determine how hyperphosphataemia affected the development of hypercalcaemia during calcitriol-induced hypercalcaemia and PTH suppression in azotemic rats with established hyperparathyroidism.
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    Hyperphosphatemia modestly retards parathyroid hormone suppression during calcitriol-induced hypercalcemia in normal and azotemic rats
    (2002) Jara, A; Chacón, C; Felsenfeld, AJ
    Background/Aims: In in vitro studies, a high phosphate concentration has been shown to directly stimulate parathyroid hormone (PTH) secretion in a normal calcium concentration and to reduce PTH suppression in a high calcium concentration. In hemodialysis patients during dialysis-induced hypercalcemia, the effect of hyperphosphatemia on PTH secretion was less than in vitro studies. Our goal was to determine whether hyperphosphatemia retards PTH suppression during calcitriol-induced hypercalcemia in azotemic rats with hyperparathyroidism. Methods: Rats underwent a two-stage 5/6 nephrectomy or sham operations. After surgery, rats received a high phosphate diet (P 1.2%, Ca 0.6%) for 4 weeks to induce hyperparathyroidism and then were placed on a normal diet (P 0.6%, Ca 0.6%) for two additional weeks to normalize serum calcium values in azotemic rats. At week 7, rats were divided into five groups and before sacrifice received at 24-hour intervals, three doses of calcitriol (CTR) or its vehicle. The five groups and dietary phosphate content were: group 1 - normal renal function (NRF) + 0.6% P + vehicle; group 2 - NRF + 0.6% P + CTR; group 3 - renal failure (RF) + 0.6% P + vehicle; group 4 RF + 1.2% P + CTR; and group 5 - RF + 0.6% P + CTR. Results: In the two CTR-treated groups with marked hypercalcemia (groups 2 and 5), 15.52 +/- 0.26 and 15.12 +/- 0.13 mg/dl, respectively, stepwise regression showed that hyperphosphatemia retarded PTH suppression. When the two azotemic groups treated with CTR (groups 4 and 5) were combined to expand the range of serum calcium values, stepwise regression showed that hypercalcemia suppressed and hyperphosphatemia modestly retarded PTH suppression. Similarly, in groups 4 and 5 combined, correlations were present between PTH and both serum calcium (r = -0.70, p < 0.001) and serum phosphate (r = 0.64, p = 0.001). Conclusions: Hypercalcemia and high doses of calcitriol markedly reduced PTH secretion in azotemic rats despite severe hyperphosphatemia. Even though hyperphosphatemia did retard PTH suppression during hypercalcemia, its effect was small. Copyright (C) 2002 S. Karger AG, Basel.
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    Phosphate depletion in the rat: Effect of bisphosphonates and the calcemic response to PTH
    (1999) Jara, A; Lee, E; Stauber, D; Moatamed, F; Felsenfeld, AJ; Kleeman, CR
    Background. The removal of phosphate from the diet of the growing rat rapidly produces hypercalcemia, hypophosphatemia, hypercalciuria, and hypophosphaturia. Increased calcium efflux from bone has been shown to be the important cause of the hypercalcemia and hypercalciuria. It has been proposed that the increased calcium efflux from bone is osteoclast mediated. Because bisphosphonates have been shown to inhibit osteoclast-mediated bone resorption, this study was performed to determine whether bisphosphonate-induced inhibition of osteoclast function changed the biochemical and bone effects induced by phosphate depletion.