Increase in Urinary Thromboxane B2 in Rats Caused by Cyclosporine

Kawaguchi, Akira T.; Goldman, Mitchell H.; Shapiro, Ron; Foegh, Marie L.; Ramwell, Peter W.; Lower, Richard R.

doi:10.1097/00007890-198508000-00022

Cited by 77 publications

(21 citation statements)

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“…Recently, there has been considerable interest in ciclosporin-induced renal hemodynamic changes as probable factors contributing to the observed alterations in renal function and morphology [13,[40][41][42][43]. Several mechanisms have been proposed to explain the decreased renal blood flow associated with ciclosporin administration including in creased sympathetic nervous activity [38,44], activation of the renin-angiotensin system [45][46][47], increased renal thromboxane A2 production [48][49][50], and altered produc tion of prostacyclin-stimulating factor [51]. The morpho logic alterations of renal arterioles may be the conse quence of endothelial injury caused by ischemia or a direct toxic effect of ciclosporin [52,53], Widespread endothe lial cell swelling and subintimai edema have been noted in our patients.…”

Section: Discussionmentioning

confidence: 99%

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Austin¹,

Palestine²,

Sabnis³

et al. 1989

Am J Nephrol

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Among 73 patients treated with ciclosporin (CS) for autoimmune uveitis, a 50% elevation of serum creatinine was observed in 37% within 3 months of starting CS and in 25% after more than 6 months of relatively uncomplicated therapy. Sequential renal function and histologic evaluations were performed in 17 patients to further characterize the nephrotoxic effects of long-term CS therapy. Inulin clearance remained essentially unchanged in 12 patients despite CS dosage reductions in the majority. In 2 such patients, repeat renal biopsy specimens revealed evidence of progressive irreversible kidney injury even though renal function was stable. Inulin clearance decreased substantially in 3 patients; in 1 case a follow-up renal biopsy showed increased severity of chronic histologic change. For 2 patients, the inulin clearance more than doubled after CS dosage reduction; and in 1 of those cases, repeat renal biopsy showed no evidence of progressive renal scarring. Overall, the morphologic attributes of irreversible kidney injury (designated by a chronicity index including glomerular sclerosis, tubular atrophy and interstitial fibrosis) were increased in 3 of 6 follow-up renal biopsy specimens. Histologic alterations of renal arterioles, including hyaline change, were observed in all CS-treated patients. The hyaline change of arterioles was either extensive in the first renal biopsy specimen or became extensive in the second biopsy in the 3 cases manifesting an increased chronicity index on the follow-up renal biopsy. Thus, parenchymal injury can progress in some cases despite CS dosage reduction and stable renal function; renal arteriolar histologic change is a prominent finding in these patients. Patients that exhibit a substantial improvement in renal function after dosage reduction may experience a more favorable course.

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Section: Discussionmentioning

confidence: 99%

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Austin¹,

Palestine²,

Sabnis³

et al. 1989

Am J Nephrol

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“…It has also been proposed that CSA alters the balance of the vasodilator prostacyclin and the vasoconstrictor thromboxane in renal cortical tissue (1 1-1 3 ) , leading to renal toxicity. An increase in urinary TXB, produced by renal cells and an increase in the 2,3-dinor TXB, produced, for example, by macrophages and platelets have been noted in rats treated with CSA (14). The purpose of this study was to determine the effects of CSA on renal prostaglandin excretion and to determine whether CSA, when admi'nistered without NSAIDs, would produce nephrotoxicity .…”

mentioning

confidence: 99%

The effects of cyclosporin a on eicosanoid excretion in patients with rheumatoid arthritis

Weinblatt

Helfgott

Coblyn

et al. 1991

Arthritis & Rheumatism

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Alterations in renal eicosanoid levels have been postulated as a factor in cyclosporin A (CSA) nephrotoxicity. The effects of CSA on renal eicosanoid excretion in rheumatoid arthritis were studied over a 24-week period, during which treatment with nonsteroidal antiinflammatory drugs was discontinued. The initial dosage of CSA was 4 mglkglday; at week 24, the mean dosage of CSA was 3.9 mglkglday. At week 24, the mean (2SD) serum creatinine level (1.04 2 0.24 mg/dl) was 32% above the baseline value; renal blood flow had decreased by 21% (P < 0.03) and the glomerular filtration rate had decreased by 16%. There was a significant increase (P < 0.03) in the 2,3-dinor thromboxane B, level at week 2, but there was no significant change in the levels of the other eicosanoids. This study demonstrates that after CSA treatment, there is a selective increase in a thromboxane metabolite that parallels an increase in renal vascular resistance, even in the absence of nonsteroidal antiinflammatory drugs,

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“…The first report demonstrating that CS alters renal arachidonate metabolism is due to Kawaguchi et al [32] who showed that administration of 15 mg/kg CS for 14 days to nonoperated Fischer rats as well as to rats receiving a heterotopic cardiac isograft induced an increase in urinary excretion of thromboxane B2 (TxB2). It is generally accepted that urinary excretion of TxB2 largely reflects the renal synthesis of the vasoac tive parent compound [33].…”

Section: Cs Nephrotoxicity and Arachidonate Metabolitesmentioning

confidence: 99%

Abnormalities of Arachidonate Metabolism in Experimental Ciclosporin Nephrotoxicity

Benigni¹,

Perico²

1989

Am J Nephrol

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Increase in Urinary Thromboxane B2 in Rats Caused by Cyclosporine

Cited by 77 publications

References 0 publications

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

Evolution of Ciclosporin Nephrotoxicity in Patients Treated for Autoimmune Uveitis

The effects of cyclosporin a on eicosanoid excretion in patients with rheumatoid arthritis

Abnormalities of Arachidonate Metabolism in Experimental Ciclosporin Nephrotoxicity

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