Long-term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after.

BACKGROUND: Despite long-term side effects, calcineurin inhibitors (CNI) remain a cornerstone of immunosuppression in renal transplantation. Few trials assessed the long-term outcome after early CNI withdrawal. METHODS: This intention-to-treat study assessed the 10-year outcome of 108 patients randomly converted from a cyclosporine (CsA)-mycophenolate mofetil (MMF)-prednisone regimen to a dual therapy (CsA-prednisone or MMF-prednisone) at 3 months postgraft. RESULTS: At 10 years, 3.7% in the CsA group and 35.2% in the MMF group remained on the protocol regimen (P<.001). eGFR was higher in the MMF group (64.4±21 vs 49.7±14.7 mL/min/1.73 m², P<.001), although acute rejection (12 vs 4 in the CsA group, P=.03) and Class II DSA incidences were increased. CNI-related toxicity (P=.019) and moderate-to-severe IF/TA (P=.004) were higher in the CsA group. Ten-year graft and patient survivals were not different. In multivariate analysis, acute rejection remained the strongest predictor of graft loss (HR=11.64, 95% CI [5.05-26.79], P<.0001). CONCLUSIONS: MMF withdrawal largely failed due to CNI toxicity, while CsA withdrawal led to increased graft failure due to uncontrolled acute rejection without increasing graft survival. From this study, it remains unclear which patients could benefit from limiting CNI exposure.

Characterization of the novel HLA-B*40:539 allele by sequencing-based typing.

HLA-B*40:539 differs from HLA-B*40:01:01 by one nucleotide substitution in codon 46 in exon 2.

Characterization of the novel HLA-C*06:176:02 allele by sequencing-based typing.

HLA-C*06:176:02 differs from HLA-C*06:176:01 by two nucleotide substitutions in codons 236 and 237 in exon 4.

Characterization of the novel HLA-DRB1*04:04:20 allele by sequencing-based typing.

HLA-DRB1*04:04:20 differs from HLA-DRB1*04:04:01:04 by one nucleotide substitution in codon 135 in exon 3.

Characterization of the novel HLA-B*14:121 allele by sequencing-based typing.

HLA-B*14:121 differs from HLA-B*14:01:01:01 by one nucleotide substitution in codon 319 in exon 6.

Characterization of the novel HLA-C*05:286 allele by sequencing-based typing.

HLA-C*05:286 differs from HLA-C*05:01:01:02 by one nucleotide substitution in codon 283 in exon 5.

Characterization of the novel HLA-B*51:394Q allele by sequencing-based typing.

HLA-B*51:394Q differs from HLA-B*51:01:01:05 by one nucleotide substitution in codon 339 in exon 7.

Characterization of the novel HLA-C*01:263 allele by sequencing-based typing.

HLA-C*01:263 differs from HLA-C*01:02:01:01 by one nucleotide substitution in codon 98 in exon 3.

Characterization of the novel HLA-B*08:302 allele by sequencing-based typing.

HLA-B*08:302 differs from HLA-B*08:01:01:01 by one nucleotide substitution in codon 116 in exon 3.

Characterization of the novel HLA-B*51:370 allele by sequencing-based typing.

HLA-B*51:370 differs from HLA-B*51:01:01:04 by one nucleotide substitution in codon 276 in exon 5.

Characterization of the novel HLA-A*24:585 allele by sequencing-based typing.

HLA-A*24:585 differs from HLA-A*24:02:01:01 by one nucleotide substitution in codon -15 in exon 1.

Characterization of the novel HLA-DRB1*01:140 allele by sequencing-based typing.

HLA-DRB1*01:140 differs from HLA-DRB1*01:02:01:01 by one nucleotide substitution in codon 147 in exon 3.

Characterization of the novel HLA-DPB1*11:01:06 allele by sequencing-based typing.

HLA-DPB1*11:01:06 differs from HLA-DPB1*11:01:01:01 by one nucleotide substitution in codon 21 in exon 2.

Characterization of the novel HLA-DPB1*1348:01 allele by sequencing-based typing.

HLA-DPB1*1348:01 differs from HLA-DPB1*14:01:01:01 by one nucleotide substitution in codon 147 in exon 3.

Characterization of the novel HLA-C*05:282Q allele by next generation sequencing.

HLA-C*05:282Q differs from HLA-C*05:01:01 by one nucleotide substitution in codon -24 in exon 1.

Characterization of the novel HLA-B*44:324:02 allele by sequencing-based typing.

HLA-B*44:324:02 differs from HLA-B*44:324:01 by one nucleotide substitution in codon 99 in exon 3.

Characterization of the novel HLA-DPB1*1463:01N allele by sequencing-based typing.

HLA-DPB1*1463:01N differs from HLA-DPB1*02:01:02:04 by one nucleotide substitution in codon 128 in exon 3.

Characterization of the novel HLA-C*05:01:01:81Q allele by sequencing-based typing.

HLA-C*05:01:01:81Q differs from HLA-C*05:01:01:02 by one nucleotide substitution in position 202 in intron 1 (c.74-2A>G, hg19).

Characterization of the novel HLA-C*12:384 allele by sequencing-based typing.

HLA-C*12:384 differs from HLA-C*12:03:01:02 by one nucleotide substitution in codon 42 in exon 2.

Characterization of the novel HLA-C*03:552 allele by sequencing-based typing.

HLA-C*03:552 differs from HLA-C*03:04:01:01 by one nucleotide substitution in codon 72 in exon 2.