Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus

Campistol, Josep M.; Holt, David W.; Epstein, Solomon; M, Gioud-Paquet; Rutault, Karine; Burke, James T.

doi:10.1111/j.1432-2277.2005.00163.x

Cited by 58 publications

(32 citation statements)

References 38 publications

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“…Steroids directly worsen bone formation by impaired genesis and increased apoptosis of osteoblasts and enhanced osteoclastogenesis through an increased RANKL/OPG ratio [30] . Both cyclosporin and tacrolimus similarly promote bone loss via direct osteoclast activation [58] , but sirolimus is administered as a bone-sparing immunosuppressive agent due to its capability to inhibit osteoclast generation [57,59] .…”

Section: Ptbd: Epidemiology and Mechanismsmentioning

confidence: 99%

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Cianciolo¹,

Galassi

Capelli³

et al. 2016

Am J Nephrol

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Chronic kidney disease-mineral and bone disorder (CKD-MBD) is common in kidney transplant recipients (KTRs), where secondary hyperparathyroidism (HPTH) and post-transplantation bone disease (PTBD) are potential effectors of both graft and vascular aging. Reduced 25(OH)D levels are highly prevalent in KTRs. Experimental and clinical evidence support the direct involvement of deranged vitamin D metabolism in CKD-MBD among KTRs. This review analyzes the pathophysiology of vitamin D derangement in KTRs and its fall out on patient and graft outcome, highlighting the roles of both nutritional and active vitamin D compounds to treat PTBD, cardiovascular disease (CVD) and graft dysfunction. Fibroblast growth factor-23-parathyroid hormone (PTH)-vitamin D axis, immunosuppressive therapy and previous bone status have been associated with PTBD. Although several studies reported reduced PTH levels in KTRs receiving nutritional vitamin D, its effects on bone mineral density (BMD) remain controversial. Active vitamin D reduced PTH levels and increased BMD after transplantation, but paricalcitol treatment was not accompanied by benefits on osteopenia. Vitamin D is considered protective against CVD due to the widespread pleiotropic effects, but data among KTRs remain scanty. Although vitamin deficiency is associated with lower glomerular filtration rate (GFR) and faster estimated GFR decline and data on the anti-proteinuric effects of vitamin D receptor activation (VDRA) in KTRs sound encouraging, reports on related improvement on graft survival are still lacking. Clinical data support the efficacy of VDRA against HPTH and show promising evidence of VDRA's effect in counteracting post-transplant proteinuria. New insights are mandatory to establish if the improvement of surrogate outcomes will translate into better patient and graft outcome.

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Section: Ptbd: Epidemiology and Mechanismsmentioning

confidence: 99%

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Cianciolo¹,

Galassi

Capelli³

et al. 2016

Am J Nephrol

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“…Sirolimus does not cause bone loss in experimental animals [5]. In a recent study, sirolimus has been shown to cause less bone turnover when compared with CsA [6]. …”

Section: Introductionmentioning

confidence: 99%

Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism

Lee

Lien

et al. 2011

Am J Nephrol

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Background: Abnormalities in mineral metabolism are common complications of organ transplantation. The role of immunosuppressive agents in alteration of mineral metabolism is not clear. Methods: We conducted an animal study to investigate the effects of cyclosporine A (CsA), tacrolimus, and sirolimus on renal calcium, magnesium and vitamin D metabolism. Results: CsA and tacrolimus induced a 2- to 3-fold and 1.6- to 1.8-fold increase in urinary calcium and magnesium excretion, respectively, while rapamycin had no effects on calcium, but doubled the urinary magnesium excretion. CsA and tacrolimus, but not rapamycin, elevated serum 1,25(OH)₂ vitamin D without affecting the parathyroid hormone level. CsA and tacrolimus reduced mRNA abundance in TRPV5 (CsA: 64 ± 3% of control; tacrolimus: 50 ± 3%) calbindin-D28k (CsA: 62 ± 4%; tacrolimus: 43 ± 3%), and vitamin D receptor (CsA: 52 ± 3%; tacrolimus: 58 ± 2%, all p < 0.05). Rapamycin did not affect gene expression in any of studied proteins. The immunofluorescence staining study demonstrated a 50% reduction of TRPV5 and calbindin-D28k by CsA and tacrolimus. Conclusion: The suppression of VDR by calcineurin inhibitors is probably the underlying mechanism of renal calcium wasting. In spite of an increased 1,25(OH)₂ vitamin D level, the kidney is not able to reserve calcium, suggesting a role of vitamin D resistance that may be related to bone loss.

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“…However, some of the detrimental effects associated with cyclosporine A may actually be linked to a higher need for prednisolone [141]. Treatment with cyclosporine A in patients undergoing renal transplantation seemed associated with a higher bone turnover compared to sirolimus as evaluated by osteocalcin and urinary excretion of N-telopeptides [142]. In a histomorphometric study cyslosporine A was associated with an increased bone resorption and a decreased bone formation [143] when compared to azathiorpine and prednisolone [144].…”

Section: Disease Modifying Antirheumatic Drugs (Dmard)mentioning

confidence: 96%

Adverse Effects of Drugs on Bone and Calcium Metabolism/Physiology

Vestergaard

2007

Clinic Rev Bone Miner Metab

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Drugs may affect bone turnover and density in many ways. However, the disease for which the drugs are administered may also contribute to bone loss. Infection with human immunodeficiency virus leads to a loss of bone mineral, while treatment with highly active antiretroviral therapy does not seem to contribute to further bone loss. Type 1 diabetes is associated with a decrease in bone mineral, while type 2 diabetes is associated with an increase. The new class of thiazolidinediones (glitazones) has been associated with an increased loss of bone mineral. In breast cancer treatment, tamoxifen is associated with an increased bone mineral, while the newer class of aromatase inhibitors through a decrease in serum oestradiol are associated with an increased loss of bone mineral. Strong analgesics (opioids) may decrease bone mineral density through inhibition of gonadotrophins while weak analgesics such as the non-steroidal anti-inflammatory drugs may increase bone mineral through an effect on the prostaglandin system. However, possibly through an increased risk of falls, the weak analgesics are associated with an increased risk of fractures. Proton pump inhibitors may lead to a decreased calcium absorption and thus a decreased bone mineral and an increased risk of fractures.

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Bone metabolism in renal transplant patients treated with cyclosporine or sirolimus

Cited by 58 publications

References 38 publications

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Vitamin D in Kidney Transplant Recipients: Mechanisms and Therapy

Effects of Cyclosporine, Tacrolimus and Rapamycin on Renal Calcium Transport and Vitamin D Metabolism

Adverse Effects of Drugs on Bone and Calcium Metabolism/Physiology

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