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Series GSE1743

Query DataSets for GSE1743

Status

Public on Sep 23, 2004

Title

De novo kidney transplantation without use of calcineurin inhibitors preserves renal structure and function

Organism

Homo sapiens

Experiment type

Expression profiling by array

Summary

Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression.

Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays.

Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling.

Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival.
Keywords = Cyclosporine
Keywords = Sirolimus
Keywords = Transplantation
Keywords = DNA microarrays
Keywords = calcineurin inhibitors
Keywords: parallel sample

Contributor(s)

Flechner SM, Kurian SM, Solez K, Cook DJ, Rollin H, Burke JT, Hammond JA, Whisenant TC, Lanigan CM, Head SR, Salomon DR

Citation(s)

15476476

Submission date

Sep 09, 2004

Last update date

Aug 10, 2018

Contact name

Sunil Kurian

E-mail(s)

smkurian@scripps.edu