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Differential Impact of Delayed Graft Function in Deceased Donor Renal Transplant Recipients With and Without Donor-specific HLA-antibodies

Haller, Jana BSc1; Wehmeier, Caroline MD1; Hönger, Gideon BSc1,2,3; Hirt-Minkowski, Patricia MD1; Gürke, Lorenz MD4; Wolff, Thomas MD4; Steiger, Jürg MD1; Amico, Patrizia MD1; Dickenmann, Michael MD1; Schaub, Stefan MD1,2,3

doi: 10.1097/TP.0000000000002802
Original Clinical Science—General
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Background. Delayed graft function (DGF) and pretransplant donor-specific HLA-antibodies (DSA) are both regarded as risk factors for rejection and lower graft survival. However, the combined impact of DGF and DSA has not been studied in detail.

Methods. We investigated 375 deceased donor kidney transplantations, which had DSA assignment by single-antigen bead technology and which had surveillance biopsies at 3 of 6 months. Median follow-up time was 6.1 years.

Results. DGF occurred in 137 of 375 patients (37%), and DSA were present in 85 of 375 patients (23%). The incidence of DGF was similar in DSA-positive (DSApos)-patients and DSA-negative (DSAneg)-patients (40% versus 36%; P = 0.45). In DSAneg-patients, 5-year graft survival was not different with/without DGF (81% versus 83%; P = 0.48). By contrast, in DSApos-patients, 5-year graft survival was significantly lower with DGF (64% versus 79%; P = 0.01). Moreover, DSApos-patients with DGF had a higher 1-year incidence of subclinical rejection, which were mostly antibody-mediated or mixed rejection phenotypes. Graft loss due to rejection was significantly more frequent in DSApos-patients with DGF (5/34; 15%) compared to DSApos-patients without DGF (2/51; 4%), and DSAneg-patients with/without DGF (3/103; 3% and 4/187; 2%, respectively) (P = 0.005). In a multivariate Cox model, DSA with DGF was an independent predictor for graft (hazard ratio = 2.84 [95% confidence interval, 1.54-5.06]; P = 0.001) and death-censored graft loss (hazard ratio = 4.65 [95% confidence interval, 1.83-11.51]; P = 0.002).

Conclusions. DGF has a much more detrimental impact in DSApos-patients than in DSAneg-patients, which is likely related to a higher incidence of antibody-mediated rejection. If possible, the combined risks of DGF and DSA should be avoided.

1 Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.

2 Transplantation Immunology, Department of Biomedicine, University of Basel, Basel, Switzerland.

3 HLA-Diagnostic and Immunogenetics, Department of Laboratory Medicine, University Hospital Basel, Basel, Switzerland.

4 Vascular and Transplantation Surgery, University Hospital Basel, Basel, Switzerland.

Received 25 February 2019. Revision received 25 April 2019.

Accepted 13 May 2019.

S.S. was supported by the Swiss National Foundation (grant 32003B_169310). The other authors declare no conflicts of interest.

J.H. and S.S. participated in research design. All authors participated in writing of the article. J.H., C.W., G.H., P.H.M., P.A., and S.S. participated in the performance of the research. J.H. and S.S. participated in data analysis.

Correspondence: Stefan Schaub, MD, MSc, Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. (stefan.schaub@usb.ch).

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