Paricalcitol aggravates perivascular fibrosis in rats with renal insufficiency and low calcitriol

• Published in: Kidney international Vol. 72; no. 8; pp. 977 - 984
• Main Authors: Repo, J.M., Rantala, I.S., Honkanen, T.T., Mustonen, J.T., Kööbi, P., Tahvanainen, A.M., Niemelä, O.J., Tikkanen, I., Rysä, J.M., Ruskoaho, H.J., Pörsti, I.H.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.10.2007; Nature Publishing; Elsevier Limited
• Subjects: 1,25(OH)2D3; Animals; Atrial Natriuretic Factor - metabolism; Biological and medical sciences; Blood Pressure - drug effects; Calcitriol - deficiency; Calcitriol - metabolism; calcium; Calcium - metabolism; Calcium - pharmacology; Cardiovascular System - drug effects; Cardiovascular System - metabolism; Cardiovascular System - pathology; Chronic Disease; Creatinine - metabolism; Ergocalciferols - adverse effects; Ergocalciferols - pharmacology; Fibrosis; kidney failure; Kidneys; Male; Medical sciences; Nephrectomy; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; parathyroid hormone; Parathyroid Hormone - metabolism; Peptidyl-Dipeptidase A - metabolism; phosphate; Phosphorus - metabolism; Phosphorus - pharmacology; Rats; Rats, Sprague-Dawley; Renal failure; Renal Insufficiency - metabolism; Renal Insufficiency - pathology; Renin - blood; Urinary system involvement in other diseases. Miscellaneous; 1,25(OH)2D3; kidney failure; phosphate; parathyroid hormone; fibrosis; calcium; Phosphates; Agonist; Nephrology; Calcium; Rat; Renal fibrosis; Peptide hormone; Calcitriol; Inorganic element; Urology; Vitamin D; Paricalcitol; Kidney disease; Urinary system disease; Steroid hormone; Cholecalciferol(1,25-dihydroxy); Rodentia; Vertebrata; Mammalia; Low; Parathyroid hormone; Analog; Animal; Renal failure
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/sj.ki.5002458

Cardiovascular complications are a major problem in chronic renal failure. We examined the effects of plasma calcium, phosphate, parathyroid hormone (PTH), and calcitriol on cardiac morphology in 5/6 nephrectomized rats. Fifteen weeks after nephrectomy rats were given a control diet, high-calcium or -phosphorus diet, or given paricalcitol treatment for 12 weeks. Sham-operated rats were on a control diet. Blood pressure, plasma phosphate, and PTH were increased, while the creatinine clearance was reduced in remnant kidney rats. Phosphate and PTH were further elevated by the high-phosphate diet but suppressed by the high-calcium diet, while paricalcitol reduced PTH without influencing phosphate or calcium. The high-calcium diet increased, while the high-phosphate diet reduced plasma calcium. Plasma calcitriol was significantly reduced in other remnant kidney groups, but further decreased after paricalcitol. Cardiac perivascular fibrosis and connective tissue growth factor were significantly increased in the remnant kidney groups, and further increased in paricalcitol-treated rats. Hence, regardless of the calcium, phosphate, or PTH levels, cardiac perivascular fibrosis and connective tissue growth factor increase in rats with renal insufficiency in association with low calcitriol. Possible explanations are that aggravated perivascular fibrosis after paricalcitol in renal insufficiency may be due to further suppression of calcitriol, or to a direct effect of the vitamin D analog.