Impact of the variability of cyclosporin A trough levels on long-term renal allograft function.

Nephrol Dial Transplant

Department of Internal Medicine-Nephrology, University Hospital Charité, Campus Charité Mitte, Humboldt-University, Berlin, Germany.

Published: July 2002

AI Article Synopsis

Article Abstract

Background: Among renal allograft recipients, there is a considerable variability in cyclosporin A (CsA) trough levels. Some of the CsA metabolites are pharmacologically active. The variability of polyclonal CsA trough levels may contribute to the fact that long-term renal allograft survival is still not satisfactory. In a retrospective, single-centre study, we investigated the influence of the variability of polyclonal CsA trough levels on long-term renal allograft function.

Methods: Patients (n=381) received double immunosuppression consisting of CsA and methylprednisolone (MP). For each patient the CsA coefficient of variation (CCV) and the mean CsA trough level during the observation period (5 years) were calculated. Based on receiver operating characteristic (ROC) analysis, patients were divided into two groups: group I, CCV <28.05%, n=231; group II, CCV >28.05%, n=150. Additionally, patients were divided into three groups according to their mean CsA trough level: group A, <270 ng/ml, n=50; group B, 270-370 ng/ml, n=282; group C: >370 ng/ml, n=49.

Results: Compared to group I, patients in group II experienced a higher incidence of acute rejection episodes (40.7% vs 29.4%, P=0.02), reduced 5-year graft survival (81.1% vs 93.3%, P=0.002), and higher serum creatinine levels (1.7+/-1.2 mg/dl vs 1.4+/-0.5 mg/dl, P=0.03). In patients with low mean CsA trough levels, the incidence of acute rejection episodes was elevated (group A vs B, 50.0% vs 30.9%, P=0.008) and 5-year graft survival was reduced (group A vs B, 79.8% vs 89.5%, P=0.005). Multiple logistic regression analysis confirmed that the risk of graft failure within 5 years after transplantation was markedly elevated in group II (RR: 6.2, P=0.013) and in group A (RR: 8.9, P=0.008). Whereas the effect of CCV on 5-year graft survival was still evident in patients with normal or high mean CsA trough levels (>270 ng/ml, 81.9% vs 94.8%, P=0.0005), graft survival was independent from CCV in patients with low mean CsA trough levels (<270 ng/ml, 77.0% vs 81.7%, P=NS).

Conclusions: Both, the intra-individual variability and the mean of polyclonal CsA trough levels influence long-term renal allograft survival. Targeting at sufficiently high mean CsA levels with a low intra-individual variability may help to further improve long-term renal allograft survival.

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/17.7.1310DOI Listing

Publication Analysis

Top Keywords

csa trough
32
trough levels
28
renal allograft
16
graft survival
16
long-term renal
12
5-year graft
12
csa
11
trough
9
variability cyclosporin
8
levels
8

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!