Keyword: ADAMTS13
2 results found.
Congress Abstract
Central Asian Journal of Nephrology, 2(2, Suppl. 1), 2026, cajn_A23, https://doi.org/10.63946/cajn/19533
ABSTRACT:
Introduction and Aim: Atypical hemolytic uremic syndrome (aHUS) is an ultra-rare orphan disease that requires differential diagnosis from other thrombotic microangiopathies (TMAs). The aim of this study was to determine the diagnostic value of ADAMTS13 activity levels, anti‑complement factor H (anti‑CFH) antibody titers, and genetic screening in verifying aHUS subtypes among the pediatric population in Kazakhstan.
Materials and Methods: A retrospective analysis was conducted on 15 children with aHUS (8 girls and 7 boys) from 8 regions of Kazakhstan between 2019 and 2025. The mean age was 7.2 ± 3.8 years. ADAMTS13 activity was measured in 7 patients (46.6%), and anti‑CFH titers were assessed in 10 patients (66.7%). In the remaining patients, these tests were not performed because they had received fresh frozen plasma transfusions prior to testing. Genetic testing was completed for 10 out of 15 children (66.7%); the remaining 5 patients (33.3%) died before testing could be carried out.
Results: In all patients tested (n = 7, 100%), ADAMTS13 activity was >10%, effectively ruling out thrombotic thrombocytopenic purpura (TTP). Autoimmune aHUS associated with anti‑CFH antibodies was diagnosed in 4 out of 10 children (40%), of whom 3 were of Asian descent and 1 was Caucasian. Genetic testing in 10 children revealed pathogenic variants in complement system genes in 2 patients (20%): one child had a CFHR3/CFHR1 deletion, and another had a CFHR1/CFHR4 microdeletion; both exhibited high anti‑CFH titers (up to 11,490 U/mL). Additionally, one child was found to have a clinically insignificant heterozygous autosomal recessive mutation in the ADAMTS13 gene.
The comprehensive laboratory workup allowed for the stratification of aHUS subtypes and personalized therapy. Patients with idiopathic forms received complement‑blocking therapy with eculizumab alone, while children with anti‑CFH antibodies received combined treatment with eculizumab and immunosuppressive agents.
Conclusions: This is the first comprehensive diagnostic data report on pediatric aHUS in Kazakhstan. Genetically determined aHUS was identified in 20% of the cohort. Anti‑CFH–associated aHUS appears to occur more frequently in the Asian population (reported as 50–60% in Indian cohorts by Khandelwal et al.) compared to Caucasians (5–25%). Our findings represent an intermediate frequency between European and Asian populations, which is consistent with the mixed ethnic composition of the Kazakhstani cohort.
Materials and Methods: A retrospective analysis was conducted on 15 children with aHUS (8 girls and 7 boys) from 8 regions of Kazakhstan between 2019 and 2025. The mean age was 7.2 ± 3.8 years. ADAMTS13 activity was measured in 7 patients (46.6%), and anti‑CFH titers were assessed in 10 patients (66.7%). In the remaining patients, these tests were not performed because they had received fresh frozen plasma transfusions prior to testing. Genetic testing was completed for 10 out of 15 children (66.7%); the remaining 5 patients (33.3%) died before testing could be carried out.
Results: In all patients tested (n = 7, 100%), ADAMTS13 activity was >10%, effectively ruling out thrombotic thrombocytopenic purpura (TTP). Autoimmune aHUS associated with anti‑CFH antibodies was diagnosed in 4 out of 10 children (40%), of whom 3 were of Asian descent and 1 was Caucasian. Genetic testing in 10 children revealed pathogenic variants in complement system genes in 2 patients (20%): one child had a CFHR3/CFHR1 deletion, and another had a CFHR1/CFHR4 microdeletion; both exhibited high anti‑CFH titers (up to 11,490 U/mL). Additionally, one child was found to have a clinically insignificant heterozygous autosomal recessive mutation in the ADAMTS13 gene.
The comprehensive laboratory workup allowed for the stratification of aHUS subtypes and personalized therapy. Patients with idiopathic forms received complement‑blocking therapy with eculizumab alone, while children with anti‑CFH antibodies received combined treatment with eculizumab and immunosuppressive agents.
Conclusions: This is the first comprehensive diagnostic data report on pediatric aHUS in Kazakhstan. Genetically determined aHUS was identified in 20% of the cohort. Anti‑CFH–associated aHUS appears to occur more frequently in the Asian population (reported as 50–60% in Indian cohorts by Khandelwal et al.) compared to Caucasians (5–25%). Our findings represent an intermediate frequency between European and Asian populations, which is consistent with the mixed ethnic composition of the Kazakhstani cohort.
Congress Abstract
Central Asian Journal of Nephrology, 2(2, Suppl. 1), 2026, cajn_A14, https://doi.org/10.63946/cajn/19528
ABSTRACT:
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired clonal hematopoietic disorder characterized by complement-mediated intravascular hemolysis and thrombosis. Renal involvement is clinically relevant: impaired renal function (eGFR <90 mL/min/1.73 m²) was reported in 42.8% of 4,439 patients in the International PNH Registry. Pregnancy is a high-risk setting. A 2025 meta-analysis of 190 pregnancies in 135 women with PNH reported fetal survival of 82% with eculizumab versus 69% without it, while preterm birth occurred in 32% and 44%, respectively. Coexisting hemolysis, thrombocytopenia, and renal dysfunction during pregnancy may mimic thrombotic microangiopathy (TMA).
Case Presentation: A 33-year-old woman in her third pregnancy had longstanding thrombocytopenia previously considered immune/idiopathic. In March 2025, she developed acute kidney injury (AKI), with serum creatinine 143 μmol/L and eGFR 42.8 mL/min/1.73 m². Nephrology admission revealed dark urine, anemia, thrombocytopenia, proteinuria up to 5 g/L, hematuria, and 24-hour proteinuria of 1.98 g/day. Marked intravascular hemolysis was demonstrated by LDH >2136 U/L, indirect bilirubin 20.9 μmol/L, and haptoglobin 0.1 g/L. Renal function subsequently recovered. TMA was initially suspected, including thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome. ADAMTS13 activity was 93%, arguing against severe ADAMTS13 deficiency. Persistent hemolysis prompted flow cytometry, which identified a PNH clone: type II erythrocytes 0.14%, type III erythrocytes 38.24%, FLAER−/CD24− granulocytes 7.8%, and FLAER−/CD14− monocytes 34.4%. Urinary hemosiderin was positive, reticulocytes were 8.9%, and LDH remained >1684 U/L. PNH with chronic intravascular hemolysis was diagnosed. At approximately 19 weeks, a multidisciplinary team considered eculizumab; because renal function was preserved and there was no transfusion dependence, anticoagulant prophylaxis and close monitoring were chosen. At approximately 27 weeks, pregnancy was complicated by severe preeclampsia and subsequently resulted in preterm delivery with antenatal fetal death.
Conclusion: PNH should be considered in pregnant patients with unexplained AKI and/or proteinuria accompanied by thrombocytopenia and intravascular hemolysis. Preserved ADAMTS13 activity and identification of a PNH clone were pivotal in distinguishing PNH from TTP. Early recognition and multidisciplinary nephrology–hematology–obstetric management are essential because renal, thrombotic, and pregnancy-related complications may be severe.
Case Presentation: A 33-year-old woman in her third pregnancy had longstanding thrombocytopenia previously considered immune/idiopathic. In March 2025, she developed acute kidney injury (AKI), with serum creatinine 143 μmol/L and eGFR 42.8 mL/min/1.73 m². Nephrology admission revealed dark urine, anemia, thrombocytopenia, proteinuria up to 5 g/L, hematuria, and 24-hour proteinuria of 1.98 g/day. Marked intravascular hemolysis was demonstrated by LDH >2136 U/L, indirect bilirubin 20.9 μmol/L, and haptoglobin 0.1 g/L. Renal function subsequently recovered. TMA was initially suspected, including thrombotic thrombocytopenic purpura (TTP) and atypical hemolytic uremic syndrome. ADAMTS13 activity was 93%, arguing against severe ADAMTS13 deficiency. Persistent hemolysis prompted flow cytometry, which identified a PNH clone: type II erythrocytes 0.14%, type III erythrocytes 38.24%, FLAER−/CD24− granulocytes 7.8%, and FLAER−/CD14− monocytes 34.4%. Urinary hemosiderin was positive, reticulocytes were 8.9%, and LDH remained >1684 U/L. PNH with chronic intravascular hemolysis was diagnosed. At approximately 19 weeks, a multidisciplinary team considered eculizumab; because renal function was preserved and there was no transfusion dependence, anticoagulant prophylaxis and close monitoring were chosen. At approximately 27 weeks, pregnancy was complicated by severe preeclampsia and subsequently resulted in preterm delivery with antenatal fetal death.
Conclusion: PNH should be considered in pregnant patients with unexplained AKI and/or proteinuria accompanied by thrombocytopenia and intravascular hemolysis. Preserved ADAMTS13 activity and identification of a PNH clone were pivotal in distinguishing PNH from TTP. Early recognition and multidisciplinary nephrology–hematology–obstetric management are essential because renal, thrombotic, and pregnancy-related complications may be severe.