Influence of nifedipine on interstitial fibrosis in renal transplant allografts treated with cyclosporin A.

McCulloch, Tom; Harper, Steven J.; Donnelly, P. K.; Moorhouse, Jennifer; Bell, P. R. F.; Walls, John; Feehally, John; Furness, Peter

doi:10.1136/jcp.47.9.839

Cited by 33 publications

(13 citation statements)

References 19 publications

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“…Recently, the degree of interstitial fibrosis in renal transplant biopsy specimens from immunosuppressed patients, receiving conventional doses of CsA, with and without calcium channel blockers was compared. 23 The renal interstitial volume from tissue specimens in the CsA plus NIF group was less than the CsA group at 6 and 12 months after transplantation. The histological results reflected the clinical findings, where the renal glomerular filtration rate was significantly lower in the CsA group than CsA plus NIF group at 6 and 12 months.…”

Section: Discussionmentioning

confidence: 97%

“…The authors suggested that NIF slowed the development of interstitial fibrosis in renal transplant recipients treated with CsA. 23 To evaluate whether NIF protects the small intestine from CsA-caused hemodynamic and functional impairments, isogeneic small intestinal transplantation was performed in rats which then received NIF or/and CsA therapy. 8 After CsA therapy, a marked elevation of vascular resistance and decreased blood flow and absorption were observed in both native and graft whole intestinal tissue.…”

Section: Discussionmentioning

confidence: 99%

“…[21][22][23] The animals were sacrificed by carbon dioxide inhalation at the end of experiment and gingival tissue sections were processed for histopathologic and histometric analysis. Following the dissection, the jaws were fixed in 10% formalin.…”

Section: Gingival Morphology and Histometric Analysismentioning

confidence: 99%

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Does Nifedipine Aggravate Cyclosporin‐ Induced Gingival Overgrowth? An Experiment in Rats

Chiu

Chiang

et al. 2001

Journal of Periodontology

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Does Nifedipine Aggravate Cyclosporin‐ Induced Gingival Overgrowth? An Experiment in Rats

Chiu

Chiang

et al. 2001

Journal of Periodontology

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“…Use of the calcium channel blocker nifedipine is one strategy that has shown a beneficial effect on renal dysfunction and interstitial fibrosis in patients treated with CsA for 6 and 12 mo after transplantation (35), suggesting that renal vasodilatation induced by nifedipine protects the kidney from detrimental CsA actions. Another strategy reported is dietary supplementation with fish oil.…”

Section: Invited Reviewmentioning

confidence: 99%

New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone

Bobadilla¹,

Gamba²

2007

American Journal of Physiology-Renal Physiology

116

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Cyclosporine A (CsA), a calcineurin inhibitor, has improved allograft survival in solid organ transplantation and has been increasingly applied in the management of autoimmune diseases. While marked progress has been made in patient and allograft survival rates, clinical use of CsA is often limited by its nephrotoxic effect, which can be presented as two distinct and well-characterized forms: acute and chronic nephrotoxicity. The acute form is characterized by renal vasoconstriction, induced by an imbalance of vasoactive substances release, which leads to renal dysfunction. This form is reversible. The chronic toxicity, in contrast, is characterized by the vasoconstriction plus the development of structural damage that includes arteriolopathy and tubulointerstitial fibrosis that are often not reversible. The exact mechanisms of these deleterious effects are not fully understood, but major advances have occurred over the last few years. Here we review the current literature regarding the pathogenesis and strategies that have been used to ameliorate renal injury in chronic CsA nephrotoxicity. Recent observations suggest that aldosterone plays a central role in the pathogenesis of CsA nephrotoxicity and that spironolactone could be a useful agent to prevent it. These studies and the use of mineralocorticoid receptor blockade are discussed.

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“…28 In addition, it has been suggested that nifedipine prevents interstitial fibrosis in renal transplant allograft from patients treated with CsA. 30 In conclusion, our data suggest that the changes in the NOS isoform pattern of expression induced by CsA appears to be, at least in part, mediated by the hemodynamic alterations induced by this immunosuppressive agent.…”

Section: Sánchez-lozada Et Al Nos Mrna Expression In Csa Toxicity 645mentioning

confidence: 51%

Nifedipine Prevents Changes in Nitric Oxide Synthase mRNA Levels Induced by Cyclosporine

Sánchez‐Lozada

Gamba²,

Bolio³

et al. 2000

Hypertension

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Abstract-Cyclosporine toxicity mainly affects kidney and liver function. We have previously shown that cyclosporine nephrotoxicity alters kidney nitric oxide synthase mRNA pattern of expression. To determine if nitric oxide synthase expression changes are mediated directly by cyclosporine or by secondary hemodynamic alterations induced by cyclosporine, we evaluated if these effects are tissue specific and if nifedipine-induced vasodilation prevents these alterations. Uninephrectomized Wistar rats treated for 7 days with olive oil, cyclosporine (30 mg/kg), nifedipine (3 mg/kg), and nifedipineϩcyclosporine were studied. In vehicle and cyclosporine groups, the gene expression of the neuronal, inducible, and endothelial nitric oxide synthases in cerebellum, heart, intestine, liver, renal cortex, and medulla was evaluated. The administration of cyclosporine was associated with nephrotoxicity and hepatotoxicity, increased endothelial nitric oxide synthase mRNA levels in renal cortex and liver, and a decrease in inducible nitric oxide synthase and neuronal nitric oxide synthase in renal medulla. The mRNA levels of the 3 nitric oxide synthase isoforms were not affected in any other tissue. Nifedipine did not alter nitric oxide synthase expression in the control group but prevented changes associated with cyclosporine. These results suggest that cyclosporine-induced changes in the pattern of expression of the nitric oxide synthases may be secondary to its hemodynamic effects. (Hypertension. 2000;36:642-647.)Key Words: nitric oxide Ⅲ liver Ⅲ hypertension Ⅲ cyclosporine C yclosporine (CsA) is an immunosuppressor drug. Despite its beneficial effects, however, long-term use is frequently associated with hypertension, nephrotoxicity, and hepatotoxicity.Nephrotoxicity is the most common complication associated with CsA therapy. 1 It is characterized by renal vasoconstriction that induces a decrease in renal plasma flow and glomerular filtration rate. This side effect is usually reversible when CsA dose is reduced. However, even with normal blood levels or during long-term dosage, CsA can produce chronic hypertension and can be the cause of irreversible impairment of renal function. 2 The mechanism by which CsA induces hypertension remains unknown.Hepatotoxicity is a less common side effect, which is characterized by cholestasis and metabolic disturbances. 3,4 In isolated perfused rat liver, CsA administration produced a dose-dependent reduction of bile flow, increased the release of cytosolic and mitochondrial enzymes, and decreased oxygen consumption. 3 High blood levels of CsA in human allograft recipients have been associated with an increase in ␥-glutamyl transpeptidase, a liver enzyme that correlates with hepatotoxicity. 5 In one study, hepatic abnormalities developed in up to 32% of patients with endogenous uveitis treated with CsA. 6 CsA toxicity has been attributed to an imbalance of vasoactive substance release. 1 Recent studies have shown that nitric oxide (NO) is increased during CsA administration by a mechanism th...

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Influence of nifedipine on interstitial fibrosis in renal transplant allografts treated with cyclosporin A.

Cited by 33 publications

References 19 publications

Does Nifedipine Aggravate Cyclosporin‐ Induced Gingival Overgrowth? An Experiment in Rats

Does Nifedipine Aggravate Cyclosporin‐ Induced Gingival Overgrowth? An Experiment in Rats

New insights into the pathophysiology of cyclosporine nephrotoxicity: a role of aldosterone

Nifedipine Prevents Changes in Nitric Oxide Synthase mRNA Levels Induced by Cyclosporine

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