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[Functional renal effects of cyclosporin. Physiopathological mechanisms]
G Deray1, F Martinez, P Cacoub
1Service de Néphrologie, Groupe Hospitalier Pitié-Salpêtrière, Paris.
Abstract:
Animals and humans undergoing a treatment with cyclosporin (CsA) show a reversible increase in renal vascular resistance and decrease in glomerular filtration rate. The causes of these abnormalities have not yet been established. In animals potential mechanisms for CsA induced renal functional impairment are an increase in urinary thromboxane A2 excretion, plasma renin activity and renal sympathetic nervous system activity and an enhancement of vasopressin stimulated Ca++ mobilisation and cell contraction in vascular smooth muscle cells. In human, the problem is far less clear. CsA induces an inhibition in PRA and urinary prostaglandins excretion. Furthermore CsA does not modify urinary and plasma levels of catecholamines. Whatever the mechanism underlying the vasoconstriction induced by CsA, the inhibition of PGI2 synthesis and angiotensin II formation may participate in the decrease in renal blood flow and glomerular filtration rate which is observed in patients receiving CsA.
Insights
Cyclosporin (CsA) treatment causes reversible kidney dysfunction in animals and humans. Potential mechanisms involve altered vascular resistance and filtration, with varying effects on specific biochemical pathways between species.
Area of Science:
- Nephrology
- Pharmacology
Context:
- Cyclosporin (CsA) is an immunosuppressant drug.
- CsA treatment leads to renal functional abnormalities, including increased renal vascular resistance and decreased glomerular filtration rate.
- The exact mechanisms underlying CsA-induced nephrotoxicity are not fully understood.
Purpose:
- To investigate the mechanisms of cyclosporin-induced renal functional impairment in animals and humans.
- To compare the effects of CsA on renal hemodynamics and biochemical markers between species.
Summary:
- In animals, CsA may impair renal function through increased thromboxane A2, plasma renin activity (PRA), and sympathetic nervous system activity, alongside enhanced vasopressin effects.
- In humans, CsA inhibits PRA and urinary prostaglandins but does not alter catecholamines.
- Inhibition of prostacyclin (PGI2) synthesis and angiotensin II formation are potential contributors to CsA-induced renal vasoconstriction and reduced filtration.
Impact:
- Understanding these mechanisms can inform strategies to mitigate CsA-induced kidney damage.
- This research highlights species-specific differences in CsA nephrotoxicity.
- Findings may aid in the development of safer immunosuppressive therapies.