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Kidney Week

Abstract: SA-PO968

Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant Patients: A Pilot Study

Session Information

Category: Glomerular Diseases

  • 1402 Glomerular Diseases: Clinical, Outcomes, and Trials

Authors

  • Duineveld, Caroline, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Bouwmeester, Romy N., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Van De Kar, Nicole, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Wetzels, Jack F., Radboudumc, Nijmegen, Gelderland, Netherlands
Background

In 2014 the ex-vivo complement assay, which evaluated C5b-9 deposition on cultured endothelial cells, was proposed a possible biomarker for patients with aHUS. In our center eculizumab prophylaxis is not used in aHUS patients after kidney transplantation (Tx). A sensitive biomarker could improve management. The endothelial assay has not been studied in kidney transplant patients.

Methods

Pilot study. Serum samples of transplanted patients with aHUS who were in remission without eculizumab treatment, and transplanted patients with other primary kidney diseases (controls) were blindly evaluated in the complement assay (Noris lab).

Results

We included 13 patients (M 4; F 9) with aHUS, age 54 yrs (range 35-69), time after Tx 5.9 yrs (range 0.25-14.1), and 13 controls (M 7; F 6; age 42 yrs (27-60), time after Tx 5.8 yrs (1.6-11.7). All but 1 patient were treated with a calcineurin inhibitor. There were no significant differences in C5b9 deposits on resting (R) or activated (A) endothelial cells between aHUS patients (R 136%, range 93-382%, A 196%, range 99-388%) and controls (R 121%, range 75-200%; A 170%, range 113-260%, Figure 1). Three aHUS patients and 4 controls showed elevated C5b-9 deposits on resting cells, which should correspond to active aHUS or TMA. None of these patients has laboratory signs of TMA, and during follow-up of 15.8 m (range 6-21), eGFR has remained stable in all. Notably, in 5 aHUS patients with a genetic variant no increase in deposits were found on activated endothelial cells, which contrasts with literature suggesting that a positive test should identify carriers of a genetic variant.

Conclusion

Our data questions the accuracy of the ex-vivo complement assay in kidney transplant patients. We hypothesize that endothelial injury due to transplantation related factors may result in a positive test result. Further study is necessary before the test can be used in routine care for aHUS transplant patients.

Funding

  • Commercial Support – This work was supported by a research grant from the Dutch Board of Health Insurance Companies (Zorgverzekeraars Nederland).