- 期刊
- OpenAccess
Effects of Cyclosporine A in Renal Distal Tubule Calcium Handling
環孢靈對遠端腎小管鈣離子重吸收的影響
並列摘要
Cyclosporine A (CsA) is a well-established immunosuppressive agent in treating patients with autoimmune diseases and organ transplantation. Notably, CsA-associated nephropathy can cause impairment of renal function. In addition, tubulopathy with resulting hypercalciuria and hypermagnesiuria may also develop after CsA therapy. The underlying mechanism of CsA-induced tubulopathy remains to be determined. Distal tubule is the segment where active calcium reabsorption takes place under hormonal regulation. To investigate the effect of CsA treatment on calcium handling in this segment, mice were administered with CsA 20mg/kg/day intraperitoneally for one week. Urinary calcium/creatinine ratio and serum creatinine and calcium were measured before and after treatment. Alternation in expression of mRNA of renal calbindinD-28k and apical calcium channels, including epithelial calcium channel (ECaC), calcium transport 1 (CaT1), calcium transport 2 (CaT2), and voltage-gated calcium channel α1G subunit (VGCAC-A1G) were also evaluated by semiquantitative RT-PCR. Hypercalciuria developed after CsA therapy with significant increase in both urinary Ca/Cr ratio (0.078+0.03 vs 1.38+0.47,p＜0.05) and FECa (0.36+0.026 vs 3.41+1.87,p＜0.05). Serum creatinine and calcium levels were not affected after CsA treatment. There was a 60% reduction in mRNA and 50% reduction in protein levels of calbindin-D28k as determined by RT-PCR and Western blotting, respectively. None of the four calcium channels showed any alternation in mRNA expression after GsA therapy. Both hypercalciuria and reduction of calbindin D-28k were reversed 1 wk after discontinuing GsA. We conclude that CsA therapy can induce marked hypercalciuria without affecting serum calcim level. Down-regulation of renal calbindin-D28k may be associated with impaired distal tubule calcium reabsorption and renal calcium wasting. The distinct apical calcium channels, although co-localized with calbindin-D28k, were not influenced by CsA therapy in their expression.