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Molecular and clinical response to angiotensin II receptor antagonist in kidney transplant patients with chronic allograft nephropathy

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Transplant International

Abstract

Chronic allograft nephropathy (CAN) represents an important cause of graft loss after kidney transplantation. TGF-β1 is a key factor in fibrogenesis, and the angiotensin II receptor antagonist losartan may decrease the intra-graft synthesis of TGF-β1. The aim of this study was to determine the clinical and molecular effect of losartan in kidney transplant patients (KTPs) with CAN. We studied nine KTPs, after the first year of transplantation, with proteinuria (more than 500 mg/24 h), stable renal function, and histological signs of CAN. Immunosuppression was cyclosporine, azathioprine, and corticoids. Kidney biopsy was performed in all patients at the beginning of the study and 12 weeks after treatment with 50 mg/day of losartan. Quantitation of intra-graft expression of TGF-β1 was performed in all biopsies, by real-time PCR. After losartan treatment there were no differences in patients’ BP and blood creatinine level. The proteinuria significantly dropped to 414.2±377 mg/24 h, P=0.001. Intra-graft expression of TGF-β1 was decreased after treatment. In conclusion, losartan significantly decreases the intra-graft expression of TGF-β1 and proteinuria in KTPs with CAN.

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References

  1. Paul LC. Chronic allograft nephropathy: an update. Kidney Int 1999; 56:783

    Article  CAS  PubMed  Google Scholar 

  2. Colvin R, Chase C, Winn H, Russell P. Chronic allograft arteriopathy: insights from experimental models. In: Orosz C, Sedmak D, Ferguson R (eds) Transplant vascular sclerosis. Landes, Austin, 1995; pp 7–33

  3. Pankewycz O. Transforming growth factor β and renal graft fibrosis. Curr Opin Organ Transplant 2000; 5:336

    Article  Google Scholar 

  4. Kagami S, Border W, Miller D, Noble NA. Angiotensin II stimulates extracellular matrix protein synthesis through induction of transforming growth factor-β1 expression in rat glomerular mesangial cells. J Clin Invest 1994; 93:2431

    CAS  PubMed  Google Scholar 

  5. Mas V, Diller A, Albano S, et al. Intragraft expression of transforming growth factor (TGFβ1) in kidney transplant recipients. Transplantation 2000; 70:612

    CAS  PubMed  Google Scholar 

  6. Mas V, Alvarellos T, Giraudo C, Massari P, De Boccardo G. Intragraft messenger RNA expression of angiotensinogen: relationship with transforming growth factor beta-1 and chronic allograft nephropathy in kidney transplant patients. Transplantation 2002; 74:718

    Article  CAS  PubMed  Google Scholar 

  7. Racusen L, C, Solez K, Colvin R, B et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999; 55:713

    Article  CAS  PubMed  Google Scholar 

  8. Regiment P, Schlepped A, Remiss G. Progression, remission, regression of chronic renal diseases. Lancet 2001; 357:1601

    Article  PubMed  Google Scholar 

  9. Roodnat JI, Mulder PG, Rischen-Vos J, et al. Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation 2001; 72:438

    CAS  PubMed  Google Scholar 

  10. Khanna A, Plummer M, Bromberek C, Bresnahan B, Hariharan S. Expression of TGF-beta and fibrogenic genes in transplant recipients with tacrolimus and cyclosporine nephrotoxicity. Kidney Int 2002; 62:2257

    Article  CAS  PubMed  Google Scholar 

  11. Campistol JM, Inigo P, Jimenez W, et al. Losartan decreases plasma levels of TGF-beta1 in transplant patients with chronic allograft nephropathy. Kidney Int1999; 56:714

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Correspondence to Valeria R. Mas.

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Mas, V.R., Alvarellos, T., Maluf, D.G. et al. Molecular and clinical response to angiotensin II receptor antagonist in kidney transplant patients with chronic allograft nephropathy. Transpl Int 17, 540–544 (2004). https://doi.org/10.1007/s00147-004-0740-5

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  • DOI: https://doi.org/10.1007/s00147-004-0740-5

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