Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study
Introduction: In 2014, a complement assay, which evaluates C5b-9 deposition on endothelial cells, was proposed as a biomarker for atypical hemolytic uremic syndrome (aHUS). Early diagnosis and/or prediction of aHUS (relapse) is pivotal in aHUS kidney transplant recipients who do not receive eculizum...
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Elsevier
2024-01-01
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| Series: | Kidney International Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468024923015322 |
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| author | Caroline Duineveld Romy N. Bouwmeester Lambertus P.W.J. van den Heuvel Nicole C.A.J. van de Kar Jack F.M. Wetzels |
| author_facet | Caroline Duineveld Romy N. Bouwmeester Lambertus P.W.J. van den Heuvel Nicole C.A.J. van de Kar Jack F.M. Wetzels |
| author_sort | Caroline Duineveld |
| collection | DOAJ |
| description | Introduction: In 2014, a complement assay, which evaluates C5b-9 deposition on endothelial cells, was proposed as a biomarker for atypical hemolytic uremic syndrome (aHUS). Early diagnosis and/or prediction of aHUS (relapse) is pivotal in aHUS kidney transplant recipients who do not receive eculizumab prophylaxis. Methods: In this pilot study, serum samples of transplanted patients with aHUS in remission without eculizumab and patients with other primary kidney diseases (controls) were blinded and evaluated in the complement assay. Results: We included 13 patients with aHUS (4 males, 9 females) of median age of 54 years (range: 35–69) and median of 5.9 years (range: 0.25–14.1) after transplantation; and 13 controls (7 males, 6 females) of median age of 42 years (range: 27–60) and median of 5.8 years (range: 1.6–11.7) after transplantation. There were no significant differences in C5b-9 deposits between patients with aHUS and controls on resting cells (median of 136% [range: 93%–382%] and 121% [range: 75%–200%], respectively) and activated cells (median of 196% [range: 99%–388%] and 170% [range: 113%–260%], respectively). Three patients with aHUS and 4 controls showed elevated C5b-9 deposits on resting cells, which should correspond to active aHUS. None of these patients had laboratory signs of thrombotic microangiopathy (TMA). During follow-up (15.8 months, range: 6–21), estimated glomerular filtration rate remained stable in all. In 5 patients with aHUS with a genetic variant, no increase in C5b-9 deposits was found on activated endothelial cells, which contrasts with the literature suggesting that the test should identify carriers of a genetic variant. Conclusion: Our data question the routine use of the ex vivo complement assay in kidney transplant patients. Future studies should evaluate the test characteristics of assay in kidney transplant patients. |
| format | Article |
| id | doaj-art-60f5c8fea2c54c6ca4e276cb83bb0d84 |
| institution | OA Journals |
| issn | 2468-0249 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
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| series | Kidney International Reports |
| spelling | doaj-art-60f5c8fea2c54c6ca4e276cb83bb0d842025-08-20T02:31:47ZengElsevierKidney International Reports2468-02492024-01-019114515110.1016/j.ekir.2023.10.003Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot StudyCaroline Duineveld0Romy N. Bouwmeester1Lambertus P.W.J. van den Heuvel2Nicole C.A.J. van de Kar3Jack F.M. Wetzels4Department of Nephrology, Radboud University Medical Center, Radboud Research Institute, Nijmegen, The Netherlands; Correspondence: Caroline Duineveld, Department of Nephrology 464, Radboud University Nijmegen Medical Center, PO BOX 9101, 6500 HB Nijmegen, The Netherlands.Department of Pediatric Nephrology, Amalia Children’s Hospital, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The NetherlandsDepartment of Pediatric Nephrology, Amalia Children’s Hospital, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The NetherlandsDepartment of Pediatric Nephrology, Amalia Children’s Hospital, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Nijmegen, The NetherlandsDepartment of Nephrology, Radboud University Medical Center, Radboud Research Institute, Nijmegen, The NetherlandsIntroduction: In 2014, a complement assay, which evaluates C5b-9 deposition on endothelial cells, was proposed as a biomarker for atypical hemolytic uremic syndrome (aHUS). Early diagnosis and/or prediction of aHUS (relapse) is pivotal in aHUS kidney transplant recipients who do not receive eculizumab prophylaxis. Methods: In this pilot study, serum samples of transplanted patients with aHUS in remission without eculizumab and patients with other primary kidney diseases (controls) were blinded and evaluated in the complement assay. Results: We included 13 patients with aHUS (4 males, 9 females) of median age of 54 years (range: 35–69) and median of 5.9 years (range: 0.25–14.1) after transplantation; and 13 controls (7 males, 6 females) of median age of 42 years (range: 27–60) and median of 5.8 years (range: 1.6–11.7) after transplantation. There were no significant differences in C5b-9 deposits between patients with aHUS and controls on resting cells (median of 136% [range: 93%–382%] and 121% [range: 75%–200%], respectively) and activated cells (median of 196% [range: 99%–388%] and 170% [range: 113%–260%], respectively). Three patients with aHUS and 4 controls showed elevated C5b-9 deposits on resting cells, which should correspond to active aHUS. None of these patients had laboratory signs of thrombotic microangiopathy (TMA). During follow-up (15.8 months, range: 6–21), estimated glomerular filtration rate remained stable in all. In 5 patients with aHUS with a genetic variant, no increase in C5b-9 deposits was found on activated endothelial cells, which contrasts with the literature suggesting that the test should identify carriers of a genetic variant. Conclusion: Our data question the routine use of the ex vivo complement assay in kidney transplant patients. Future studies should evaluate the test characteristics of assay in kidney transplant patients.http://www.sciencedirect.com/science/article/pii/S2468024923015322atypical hemolytic uremic syndromebiomarkerC5b-9 depositionex vivo complement assaykidney transplantationthrombotic microangiopathy |
| spellingShingle | Caroline Duineveld Romy N. Bouwmeester Lambertus P.W.J. van den Heuvel Nicole C.A.J. van de Kar Jack F.M. Wetzels Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study Kidney International Reports atypical hemolytic uremic syndrome biomarker C5b-9 deposition ex vivo complement assay kidney transplantation thrombotic microangiopathy |
| title | Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study |
| title_full | Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study |
| title_fullStr | Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study |
| title_full_unstemmed | Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study |
| title_short | Ex Vivo Test of Complement Dysregulation in Atypical Hemolytic Uremic Syndrome Kidney Transplant patients: A Pilot Study |
| title_sort | ex vivo test of complement dysregulation in atypical hemolytic uremic syndrome kidney transplant patients a pilot study |
| topic | atypical hemolytic uremic syndrome biomarker C5b-9 deposition ex vivo complement assay kidney transplantation thrombotic microangiopathy |
| url | http://www.sciencedirect.com/science/article/pii/S2468024923015322 |
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