Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy

Emrullah Akay; Alime Dilayda Uzun Gül

doi:10.32322/jhsm.1979472

Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy

Abstract

Aims: To investigate the association between ADAMTS13 activity and maternal acute kidney injury (AKI) in a clinically selected cohort of patients with hypertensive disorders of pregnancy and to evaluate its potential utility as a biomarker. Methods: This retrospective, single-center cohort study included 75 clinically selected patients with hypertensive disorders of pregnancy who underwent ADAMTS13 testing during clinical evaluation. Clinical and laboratory data were retrospectively analyzed. AKI was defined according to kidney disease; improving global outcomes (KDIGO) criteria. The discriminatory performance of ADAMTS13 activity in relation to AKI was assessed using receiver operating characteristic (ROC) curve analysis with bootstrap internal validation, and Firth penalized logistic regression was performed to evaluate the association between ADAMTS13 activity and maternal AKI. Results: AKI developed in 14.7% of patients. ADAMTS13 activity was significantly lower in patients with AKI than in those without AKI (41.8±15.2% vs. 71.6±11.8%; p<0.001). ROC analysis demonstrated high discriminatory ability (AUC, 0.939; 95% CI, 0.857-1.000; p<0.001). At a cut-off value of 70%, sensitivity was 90.9% and specificity was 59.4%. Internal validation using 2,000 bootstrap repetitions yielded an optimism-corrected AUC of 0.939. In firth penalized logistic regression, each 10-unit decrease in ADAMTS13 activity was associated with higher odds of maternal AKI after adjustment for maternal age and gestational age at delivery (adjusted OR, 3.98; 95% CI, 1.92-8.26; p<0.001). Conclusion: Lower ADAMTS13 activity was independently associated with maternal AKI in this clinically selected cohort of patients with hypertensive disorders of pregnancy and demonstrated high discriminatory ability. These findings suggest potential utility for risk stratification; however, given the retrospective design, clinically selected population, and limited number of AKI events, external validation in larger prospective cohorts is required.

Keywords

Supporting Institution

None.

Project Number

None

Ethical Statement

The study protocol was reviewed and approved by the Başakşehir Çam and Sakura City Hospital Scientific Research Ethics Committee No. 1 (decision dated 25.09.2024, approval number KAEK/25.09.2024.225). The study was conducted in accordance with the principles of the Declaration of Helsinki. The requirement for informed consent was waived by the ethics committee due to the retrospective design of the study.

Thanks

None.

References

Fakhouri F, Scully M, Provôt F, et al. Management of thrombotic microangiopathy in pregnancy and postpartum: report from an international working group. Blood. 2020;136(19):2103-2111. doi:10. 1182/blood.2020005221
Gardikioti A, Venou TM, Gavriilaki E, et al. Molecular advances in preeclampsia and HELLP syndrome. Int J Mol Sci. 2022;23(7):3851. doi: 10.3390/ijms23073851
Frimat M, Gnemmi V, Stichelbout M, Provôt F, Fakhouri F. Pregnancy as a susceptible state for thrombotic microangiopathies. Front Med (Lausanne). 2024;11:1343060. doi:10.3389/fmed.2024.1343060
Scully M, Neave L. Etiology and outcomes: thrombotic microangiopathies in pregnancy. Res Pract Thromb Haemost. 2023;7(2): 100084. doi:10.1016/j.rpth.2023.100084
von Auer C, von Krogh AS, Kremer Hovinga JA, Lämmle B. Current insights into thrombotic microangiopathies: thrombotic thrombocytopenic purpura and pregnancy. Thromb Res. 2015;135(Suppl 1):S30-S33. doi:10.1016/S0049-3848(15)50437-4
Livson S, Heikkinen-Eloranta J, Messing M, Lokki AI, Meri S. Pregnancy-related thrombotic microangiopathy has a spectrum of underlying causes. Pregnancy Hypertens. 2025;40:101212. doi:10.1016/j.preghy.2025.101212
Miodownik S, Pikovsky O, Erez O, Kezerle Y, Lavon O, Rabinovich A. Unfolding the pathophysiology of congenital thrombotic thrombocytopenic purpura in pregnancy: lessons from a cluster of familial cases. Am J Obstet Gynecol. 2021;225(2):177.e1-177.e15. doi:10. 1016/j.ajog.2021.02.018
Naidoo P, Naicker T. A disintegrin and metalloprotease with thrombospondin motif, member 13, and von Willebrand factor in relation to the duality of preeclampsia and HIV infection. Int J Mol Sci. 2025;26(9):4103. doi:10.3390/ijms26094103

Venou TM, Vetsiou E, Varelas C, et al. Increased complement activation and decreased ADAMTS13 activity are associated with genetic susceptibility in patients with preeclampsia/HELLP syndrome compared to healthy pregnancies: an observational case-controlled study. J Pers Med. 2024;14(4):387. doi:10.3390/jpm14040387
El-Gamal RA, Mekawy MA, Abd Elkader AM, Abdelbary HM, Fayek MZ. Combined immature platelet fraction and schistocyte count to differentiate pregnancy-associated thrombotic thrombocytopenic purpura from severe preeclampsia/HELLP. Indian J Hematol Blood Transfus. 2020;36(2):316-323. doi:10.1007/s12288-019-01200-y
Wade AN, Panchmatia R, Calderon P. Hemolysis, elevated liver enzymes, and low platelet count syndrome with severe thrombocytopenia and severe ADAMTS13 activity deficiency. Obstet Gynecol. 2021;137(5):873-876. doi:10.1097/AOG.0000000000004345
Ramadan MK, Badr DA, Hubeish M, Itani S, Hijazi H, Mogharbil A. HELLP syndrome, thrombotic thrombocytopenic purpura or both: appraising the complex association and proposing a stepwise practical plan for differential diagnosis. J Hematol. 2018;7(1):32-37. doi:10.14740/jh347w
Hulstein JJ, van Runnard Heimel PJ, Franx A, et al. Acute activation of the endothelium results in increased levels of active von Willebrand factor in HELLP syndrome. J Thromb Haemost. 2006;4(12):2569-2575. doi:10.1111/j.1538-7836.2006.02205.x
Scully M. Microangiopathic hemolytic anemia in pregnancy. Transfus Med Rev. 2018;32(4):230-236. doi:10.1016/j.tmrv.2018.08.002
Yadla M, Bachalakuri S, Burri S, Kumar V, Sreenivas P. Pregnancy-related acute kidney injury: an observational study of 500 cases. J Nephrol. 2025;38(8):2333-2341. doi:10.1007/s40620-025-02404-4
Ankawi G, Bahkali DM, Alghamdi A, Alghamdi R, Alsaaedi R, Bahkali N. Incidence and outcomes of pregnancy-related acute kidney injury in preeclampsia-complicated pregnancies. J Nephrol. 2025;38(3):1093-1100. doi:10.1007/s40620-025-02258-w
Sukumar S, Lämmle B, Cataland SR. Thrombotic thrombocytopenic purpura: pathophysiology, diagnosis, and management. J Clin Med. 2021;10(3):536. doi:10.3390/jcm10030536
Favaloro EJ, Pasalic L, Henry B, Lippi G. Laboratory testing for ADAMTS13: utility for TTP diagnosis/exclusion and beyond. Am J Hematol. 2021;96(8):1049-1055. doi:10.1002/ajh.26241
Fox LC, Cohney SJ, Kausman JY, et al. Consensus opinion on diagnosis and management of thrombotic microangiopathy in Australia and New Zealand. Nephrology (Carlton). 2018;23(6):507-517. doi:10.1111/nep. 13234
Bommer M, Bloehdorn J. Microangiopathic anemia. Transfus Med Hemother. 2025;52(4):259-270. doi:10.1159/000544724
Burwick RM, Feinberg BB. Complement activation and regulation in preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome. Am J Obstet Gynecol. 2022;226(2 Suppl):S1059-S1070. doi:10.1016/j.ajog.2020.09.038
Rafaqat S, Khalid A, Riaz S, Rafaqat S. Irregularities of coagulation in hypertension. Curr Hypertens Rep. 2023;25(10):271-286. doi:10.1007/s11906-023-01258-0
Bitsadze V, Bouvier S, Khizroeva J, et al. Early ADAMTS13 testing associates with pre-eclampsia occurrence in antiphospholipid syndrome. Thromb Res. 2021;203:101-109. doi:10.1016/j.thromres.2021.04.021
Mawalla WF, Chamba C, Nasser A, et al. Novel ADAMTS13 mutation in a patient with congenital thrombotic thrombocytopenic purpura diagnosed in pregnancy. Am J Hematol. 2025;100(11):2093-2098. doi:10.1002/ajh.70007
Nonaka T, Yamaguchi M, Nishijima K, Moriyama M, Takakuwa K, Enomoto T. Acute presentation of congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) with decreased ADAMTS13 during late pregnancy. J Obstet Gynaecol Res. 2021;47(5):1892-1897. doi: 10.1111/jog.14737
González-Resina R, Herrero-Gutiérrez M, Gómez-Seguí I, et al. Rare onset of congenital thrombotic thrombocytopenic purpura during pregnancy: a novel ADAMTS13 gene variant. Transfusion. 2025;65(10):1982-1988. doi:10.1111/trf.18379
Asmis LM, Serra A, Krafft A, et al. Recombinant ADAMTS13 for hereditary thrombotic thrombocytopenic purpura. N Engl J Med. 2022; 387(25):2356-2361. doi:10.1056/NEJMoa2211113
Mitranovici MI, Pușcașiu L, Oală IE, et al. Importance of ADAMTS13 testing in diagnosis and management of thrombotic thrombocytopenic purpura during pregnancy. Diagnostics (Basel). 2022;12(7):1559. doi:10.3390/diagnostics12071559
Hamroun A, Prouteau C, Lenain R, et al. Follow-up of pregnancy in women with known thrombotic thrombocytopenic purpura: a single-center experience. J Nephrol. 2023;36(9):2519-2529. doi:10.1007/s40620-023-01790-x
Bogdan RG, Anderco P, Ichim C, et al. Atypical hemolytic uremic syndrome: a review of complement dysregulation, genetic susceptibility and multiorgan involvement. J Clin Med. 2025;14(7):2527. doi:10.3390/jcm14072527
Davidesko S, Pikovsky O, Al-Athamen K, et al. von Willebrand factor antigen as a biomarker for severe pregnancy complications in hereditary thrombotic thrombocytopenic purpura. J Thromb Haemost. 2023;21(6): 1623-1629. doi:10.1016/j.jtha.2023.02.022
Taşdemir D, Haksever M. Neurosonographic insights into maternal vitamin D deficiency: early markers of fetal cortical development. Gynecol Obstet Invest. 2026. doi:10.1159/000551073

Details

Primary Language

English

Subjects

Obstetrics and Gynaecology

Journal Section

Research Article

Authors

Emrullah Akay ^*
0000-0003-3792-7777
Türkiye

Alime Dilayda Uzun Gül
0000-0001-8519-629X
Türkiye

Publication Date

September 19, 2026

Submission Date

June 26, 2026

Acceptance Date

August 5, 2026

Published in Issue

Year 2026 Volume: 9 Number: 5

DOI

https://doi.org/10.32322/jhsm.1979472

IZ

https://izlik.org/JA66HR22TP

Cite

RIS / Bibtex

APA

Akay, E., & Uzun Gül, A. D. (2026). Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy. Journal of Health Sciences and Medicine, 9(5), 1348-1355. https://doi.org/10.32322/jhsm.1979472

AMA

1.Akay E, Uzun Gül AD. Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy. J Health Sci Med / JHSM. 2026;9(5):1348-1355. doi:10.32322/jhsm.1979472

Chicago

Akay, Emrullah, and Alime Dilayda Uzun Gül. 2026. “Association Between ADAMTS13 Activity and Maternal Acute Kidney Injury in a Clinically Selected Cohort With Hypertensive Disorders of Pregnancy”. Journal of Health Sciences and Medicine 9 (5): 1348-55. https://doi.org/10.32322/jhsm.1979472.

EndNote

Akay E, Uzun Gül AD (September 1, 2026) Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy. Journal of Health Sciences and Medicine 9 5 1348–1355.

IEEE

[1]E. Akay and A. D. Uzun Gül, “Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy”, J Health Sci Med / JHSM, vol. 9, no. 5, pp. 1348–1355, Sept. 2026, doi: 10.32322/jhsm.1979472.

ISNAD

Akay, Emrullah - Uzun Gül, Alime Dilayda. “Association Between ADAMTS13 Activity and Maternal Acute Kidney Injury in a Clinically Selected Cohort With Hypertensive Disorders of Pregnancy”. Journal of Health Sciences and Medicine 9/5 (September 1, 2026): 1348-1355. https://doi.org/10.32322/jhsm.1979472.

JAMA

1.Akay E, Uzun Gül AD. Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy. J Health Sci Med / JHSM. 2026;9:1348–1355.

MLA

Akay, Emrullah, and Alime Dilayda Uzun Gül. “Association Between ADAMTS13 Activity and Maternal Acute Kidney Injury in a Clinically Selected Cohort With Hypertensive Disorders of Pregnancy”. Journal of Health Sciences and Medicine, vol. 9, no. 5, Sept. 2026, pp. 1348-55, doi:10.32322/jhsm.1979472.

Vancouver

1.Emrullah Akay, Alime Dilayda Uzun Gül. Association between ADAMTS13 activity and maternal acute kidney injury in a clinically selected cohort with hypertensive disorders of pregnancy. J Health Sci Med / JHSM. 2026 Sep. 1;9(5):1348-55. doi:10.32322/jhsm.1979472