1. ¹Medical School, University of Tampere, Tampere, Finland
2. ²Department of Pathology, Tampere University Hospital, Tampere, Finland
3. ³Department of Internal Medicine, University of Tampere, Tampere, Finland
4. ⁴Department of Internal Medicine, Tampere University Hospital, Tampere, Finland
5. ⁵Department of Pharmacological Sciences, University of Tampere, Tampere, Finland
6. ⁶Department of Laboratory Medicine, Seinäjoki Central Hospital and University of Tampere, Tampere, Finland
7. ⁷Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
8. ⁸Minerva Institute for Medical Research, Biomedicum, Helsinki, Finland
9. ⁹Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Oulu, Finland

Correspondence: IH Pörsti, Department of Internal Medicine, Medical School, University of Tampere, Tampere FIN-33014, Finland. E-mail: ilkka.porsti@uta.fi

Received 11 October 2006; Revised 15 May 2007; Accepted 13 June 2007; Published online 1 August 2007.

Abstract

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.