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Conversion from Calcineurin Inhibitors to Everolimus Resulted in Decrease of Serum TGF-beta and Urinary NGAL in Renal Transplant Recipients

N. Alpay, A. Ozkok, Y. Caliskan, T. Akagun, S. Cinar, G. Deniz, M. Sariyar, A. Yildiz

Internal Medicine Nephrology Department, Istanbul University Istanbul Medical Faculty, Istanbul, Turkey
Internal Medicine Nephrology Department, Medeniyet University, Istanbul, Turkey
Internal Medicine Nephrology Department, Giresun University, Giresun, Turkey
Institute of Experimental Medical Research, Istanbul University, Istanbul, Turkey
General Surgery Renal Transplantation, Medicana International Hospital, Istanbul, Turkey

Meeting: 2013 American Transplant Congress

Abstract number: D1744

Background and Aim: Calcineurin inhibitor (CNI) treatment has been implicated for chronic allograft dysfunction in renal transplant recipients. We aimed to investigate the effects of switch from CNI to Everolimus treatment on serum/urinary markers of fibrosis (TGF-beta), inflammation, glomerular and tubular injury.

Patients and Methods: In this prospective-randomized study, 30 renal transplant recipients on CNI treatment were enrolled. Fifteen patients were converted to everolimus and remaining 15 patients were continued on CNI treatment as control group. Age, gender, dialysis vintage, baseline serum creatinine and eGFR-MDRD levels were similar between the groups Biomarkers of fibrosis (serum and urine TGF-beta), inflammation (hs-CRP, urinary MCP-1) glomerular injury (albuminuria) and tubular injury (urinary NGAL) were measured in baseline and 3rd month after conversion.

Results: Baseline urinary MCP-1 levels was associated with urinary NGAL (r=0.75, p<0.001) and urinary TGF-beta (r=0.52, p=0.003). Serum TGF-beta was correlated with serum hs-CRP (r=0.452, p=0.01). After conversion from CNI to Everolimus, serum creatinine (1.70 ± 0.22 vs 1.60 ± 0.29 mg/dL, p=0.002), uric acid (6.21 ± 1.21 vs 5.55 ± 1.39 mg/dL, p=0.01), serum TGF-beta (8727 ± 11222 vs 1942 ± 1415 pg/mL, p=0.03) and urinary NGAL (0.26 ± 0.40 vs 0.12 ± 0.07 ng/ml, p=0.05) were found to be significantly decreased. In contrast, serum total cholesterol and LDL-cholesterol levels increased (213 ± 46 vs 235±64, p=0.02 and 125±32 vs 143 ±46 mg/dL, p=0.03, respectively). Serum NGAL, hs-CRP, urinary MCP-1, albumin excretion rate did not change after conversion.

Conclusion: Conversion from CNI to everolimus resulted in significant decrease of serum TGF-beta and urinary NGAL levels in renal transplant recipients. These results might explain possible beneficial effects of Everolimus on graft survival.

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To cite this abstract in AMA style:

Alpay N, Ozkok A, Caliskan Y, Akagun T, Cinar S, Deniz G, Sariyar M, Yildiz A. Conversion from Calcineurin Inhibitors to Everolimus Resulted in Decrease of Serum TGF-beta and Urinary NGAL in Renal Transplant Recipients [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/conversion-from-calcineurin-inhibitors-to-everolimus-resulted-in-decrease-of-serum-tgf-beta-and-urinary-ngal-in-renal-transplant-recipients/. Accessed May 17, 2025.

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