Acute renal and immunological effects of low-dose cyclosporin in humans

L. De Nicola, C. Libetta, B. Memoli, V. Bellizzi, G. Colucci, P. Imperatore, W. Taccone, L. Oriente, V. Sepe, G. Conte

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. In recent years a reduction of oral cyclosporin A (CsA) dose has been adopted to minimize its adverse renal effects. To date, however, little is known about the intrinsic renal and immunological effects of low-dose CsA. Methods. Four oral doses of the drug (2, 3, 4 and 5 mg/kg body wt) and placebo (P) were randomly administered in two half-doses to seven healthy subjects. Studies were performed during water diuresis 4 h after administration of the 2nd half-dose, i.e. when the biological activity of the drug is considered maximal. Renal function was evaluated after all doses. In the same subjects, the levels of interleukin-2 (IL-2) and IL-2 receptor (IL-2R), that are the main immunological targets of CsA, were measured in the supernatant of peripheral blood mononuclear cells cultured with phytohaemagglutinin (PHA) after P, 3 and 5 mg/kg of the drug. Results. CsA induced a dose-dependent and proportional decrease of GFR and RPF associated with increasing renal vascular resistances (RVR) in presence of unmodified blood pressure. Similarly, Na+ urinary excretion decreased in a dose-dependent manner due to both GFR reduction and to an higher tubular reabsorption mainly localized at the level of the proximal nephron. All these changes were significant only after 4 and 5 mg/kg. A significant suppression of PHA-stimulated IL-2 and IL-2R cell release was observed following 5 mg/kg only. Conclusions. This study suggests that nephrotoxic and immunosuppressive effects of low-dose CsA are strictly linked.

Original languageEnglish
Pages (from-to)1739-1744
Number of pages6
JournalNephrology Dialysis Transplantation
Volume10
Issue number9
Publication statusPublished - 1995

Fingerprint

Cyclosporine
Kidney
Interleukin-2 Receptors
Interleukin-2
Pharmaceutical Preparations
Diuresis
Nephrons
Phytohemagglutinins
Immunosuppressive Agents
Vascular Resistance
Blood Cells
Healthy Volunteers
Placebos
Blood Pressure
Water

Keywords

  • Cyclosporin A
  • Humans
  • Interleukin-2
  • Interleukin-2 receptor
  • Renal haemodynamics
  • Sodium excretion

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

De Nicola, L., Libetta, C., Memoli, B., Bellizzi, V., Colucci, G., Imperatore, P., ... Conte, G. (1995). Acute renal and immunological effects of low-dose cyclosporin in humans. Nephrology Dialysis Transplantation, 10(9), 1739-1744.

Acute renal and immunological effects of low-dose cyclosporin in humans. / De Nicola, L.; Libetta, C.; Memoli, B.; Bellizzi, V.; Colucci, G.; Imperatore, P.; Taccone, W.; Oriente, L.; Sepe, V.; Conte, G.

In: Nephrology Dialysis Transplantation, Vol. 10, No. 9, 1995, p. 1739-1744.

Research output: Contribution to journalArticle

De Nicola, L, Libetta, C, Memoli, B, Bellizzi, V, Colucci, G, Imperatore, P, Taccone, W, Oriente, L, Sepe, V & Conte, G 1995, 'Acute renal and immunological effects of low-dose cyclosporin in humans', Nephrology Dialysis Transplantation, vol. 10, no. 9, pp. 1739-1744.
De Nicola L, Libetta C, Memoli B, Bellizzi V, Colucci G, Imperatore P et al. Acute renal and immunological effects of low-dose cyclosporin in humans. Nephrology Dialysis Transplantation. 1995;10(9):1739-1744.
De Nicola, L. ; Libetta, C. ; Memoli, B. ; Bellizzi, V. ; Colucci, G. ; Imperatore, P. ; Taccone, W. ; Oriente, L. ; Sepe, V. ; Conte, G. / Acute renal and immunological effects of low-dose cyclosporin in humans. In: Nephrology Dialysis Transplantation. 1995 ; Vol. 10, No. 9. pp. 1739-1744.
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AU - Libetta, C.

AU - Memoli, B.

AU - Bellizzi, V.

AU - Colucci, G.

AU - Imperatore, P.

AU - Taccone, W.

AU - Oriente, L.

AU - Sepe, V.

AU - Conte, G.

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