Rapamycin Reduces Proteinuria and Renal Damage in the Rat Remnant Kidney Model

C. Esposito, L. Villa, F. Grosjean, F. Mangione, V. Esposito, F. Castoldi, N. Serpieri, M. Arra, E. Pertile, N. Maggi, R. Valentino, A. Dal Canton

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Abstract

Rapamycin is an immunosuppressive drug used to prevent acute allograft rejection in solid organ transplantation. It shows less nephrotoxicity than calcineurin inhibitors. We evaluated the effect of rapamycin in rats undergoing 5/6 nephrectomy, a model of proteinuric and progressive renal failure. Fourteen days after surgery rats were randomized either to receive rapamycin or to remain untreated (control). Rats were humanely killed on day 91; serum creatinine, creatinine clearance, and proteinuria were assessed. Renal sections were stained with periodic acid-Schiff to evaluate glomerular volume (Gv), glomerulosclerosis (GS) and tubulointerstitial damage (TIS); we evaluated GS and TIS by Sirius red staining (SR). Epithelial-to-mesenchymal transition (EMT) was assessed by immunohistochemistry. Rapamycin affected neither serum creatinine nor creatinine clearance; it reduced Gv (controls, 5.9 ± 3.1 × 106; rapamycin, 1.3 ± 0.7 × 106 μm3) and proteinuria (control, 349 ± 146; rapamycin, 56 ± 27 mg/24 h; P <.05); rapamycin ameliorated GS (control, 78 ± 7; rapamycin, 36 ± 7%; P <.05; SR: control, 13.2 ± 3.5; rapamycin, 3.8 ± 1.0%; P <.05), and TIS (control, 3.25 ± 0.5; rapamycin, 1.0 ± 0.1; P <.05; SR: control, 29 ± 3; rapamycin, 11 ± 3%; P <.05). Rapamycin reduced αSMA (control, 3.25 ± 0.5; rapamycin, 1.0 ± 0.1; P <.05), VIM (control, 3.5 ± 0.6; rapamycin, 1.0 ± 1.4; P <.05), and CD68+ cells infiltration (control, 110 ± 43; rapamycin, 24 ± 1 cells; P <.05). Rapamycin slows the progression of renal damage in the rat remnant kidney and may represent a novel approach to the treatment of chronic kidney disease.

Original languageEnglish
Pages (from-to)1370-1371
Number of pages2
JournalTransplantation Proceedings
Volume41
Issue number4
DOIs
Publication statusPublished - May 2009

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Sirolimus
Proteinuria
Kidney
Creatinine
Staining and Labeling
Periodic Acid
Epithelial-Mesenchymal Transition
Organ Transplantation
Immunosuppressive Agents
Nephrectomy
Serum
Ambulatory Surgical Procedures
Chronic Renal Insufficiency
Renal Insufficiency
Allografts

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Medicine(all)

Cite this

Rapamycin Reduces Proteinuria and Renal Damage in the Rat Remnant Kidney Model. / Esposito, C.; Villa, L.; Grosjean, F.; Mangione, F.; Esposito, V.; Castoldi, F.; Serpieri, N.; Arra, M.; Pertile, E.; Maggi, N.; Valentino, R.; Dal Canton, A.

In: Transplantation Proceedings, Vol. 41, No. 4, 05.2009, p. 1370-1371.

Research output: Contribution to journalArticle

Esposito, C, Villa, L, Grosjean, F, Mangione, F, Esposito, V, Castoldi, F, Serpieri, N, Arra, M, Pertile, E, Maggi, N, Valentino, R & Dal Canton, A 2009, 'Rapamycin Reduces Proteinuria and Renal Damage in the Rat Remnant Kidney Model', Transplantation Proceedings, vol. 41, no. 4, pp. 1370-1371. https://doi.org/10.1016/j.transproceed.2009.04.005
Esposito, C. ; Villa, L. ; Grosjean, F. ; Mangione, F. ; Esposito, V. ; Castoldi, F. ; Serpieri, N. ; Arra, M. ; Pertile, E. ; Maggi, N. ; Valentino, R. ; Dal Canton, A. / Rapamycin Reduces Proteinuria and Renal Damage in the Rat Remnant Kidney Model. In: Transplantation Proceedings. 2009 ; Vol. 41, No. 4. pp. 1370-1371.
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