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This Article Full Text Full Text (PDF) All Versions of this Article: 294/4/F748    most recent 00220.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Piecha, G. Articles by Gross, M.-L. Search for Related Content PubMed PubMed Citation Articles by Piecha, G. Articles by Gross, M.-L.

Calcimimetic R-568 or calcitriol: equally beneficial on progression of renal damage in subtotally nephrectomized rats

¹Institute of Pathology, ²Division of Nephrology, Department of Internal Medicine, and ⁵University Children's Hospital, University of Heidelberg, Heidelberg, Germany; ³Department of Nephrology, Endocrinology, and Metabolic Diseases, Medical University of Silesia, Katowice, Poland; and ⁴Department of Pathophysiology, Semmelweis University, Budapest, Hungary

Submitted 4 May 2007 ; accepted in final form 9 January 2008

Patients with renal insufficiency develop secondary hyperparathyroidism. Monotherapy with active vitamin D or calcimimetics ameliorates secondary hyperparathyroidism. We compared kidney damage in subtotally nephrectomized (SNX) rats treated with active vitamin D (calcitriol) or the calcimimetic R-568. Male Sprague-Dawley SNX and sham-operated (sham-op) rats were randomized into the following treatment groups: SNX + R-568, SNX + calcitriol, SNX + vehicle, sham-op + R-568, sham-op + calcitriol, and sham-op + vehicle. Albuminuria and blood pressure were monitored and kidneys were examined using morphometry, immunohistochemistry, quantitative RT-PCR, and in situ hybridization. Parathyroid hormone concentrations were lowered to the same extent by the two interventions, although phosphorus and the calcium-phosphorus product were reduced only by R-568 treatment. SNX rats developed marked albuminuria, which was significantly reduced in ad libitum- and pair-fed animals treated with R-568 and animals treated with calcitriol. Mean glomerular volume (6.05 ± 1.46 vs. 2.70 ± 0.91 mm³), podocyte volume (831 ± 127 vs. 397 ± 67 µm³), the degree of foot process fusion (mean width of foot processes = 958 ± 364 vs. 272 ± 35 nm), and glomerular basement membrane thickness (244 ± 6 vs. 267 ± 23 nm), as well as desmin staining, were significantly higher in vehicle-treated SNX than sham-operated animals. These changes were ameliorated with R-568 and calcitriol. In SNX, as well as sham-operated, animals, expression of the calcium-sensing receptor (protein and mRNA) was upregulated by treatment with the calcimimetic, but not calcitriol. Calcitriol and R-568 were similarly effective in ameliorating kidney damage.

secondary hyperparathyroidism; chronic renal failure; nephroprotection; calcimimetics; calcitriol

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