Keyword: Thrombotic Microangiopathy
3 results found.
Congress Abstract
Central Asian Journal of Nephrology, 2(2, Suppl. 1), 2026, cajn_A32, https://doi.org/10.63946/cajn/19538
ABSTRACT:
Background: IgA nephropathy (IgAN) is an immune complex–mediated glomerular disease characterized by marked clinical and histopathological heterogeneity and a variable risk of progression. The coexistence of IgAN with features of TMA poses a particular diagnostic challenge, as a microangiopathic phenotype may emerge in the setting of severe glomerular injury, endothelial dysfunction, complement activation, and additional external triggers. The clinical consequences of such an interaction may be particularly significant in patients with a solitary functioning kidney.
Objective: To characterize the clinicopathological features of severe IgAN presenting with a clinical–hematological TMA phenotype in a young woman with a solitary functioning kidney and to explore the potential contribution of local complement activation and recurrent drug exposures as a putative “second hit” to endothelial injury and rapid deterioration of kidney function.
Case presentation: A 22-year-old woman had a solitary functioning right kidney following neonatal left nephrectomy. Kidney function remained preserved for years; however, persistent microscopic hematuria had been documented since 2022, retrospectively suggesting clinically silent glomerular disease. Between 2022 and 2026, she had substantial cumulative exposure to medications and supplements, including recurrent antiviral, antibacterial, and anti-inflammatory therapies, acne-directed treatments, vitamin/mineral preparations, and dietary supplements. These exposures preceded clinical deterioration and were considered potential external triggers in a susceptible renal background rather than evidence of definite drug-induced TMA. In June–July 2026, she developed recurrent massive edema followed by rapidly progressive kidney dysfunction with azotemia, hyperkalemia, active urinary sediment, and proteinuria, ultimately requiring hemodialysis. During hospitalization, microangiopathic hemolytic anemia, severe thrombocytopenia, schistocytosis, reticulocytosis, and elevated lactate dehydrogenase established a clinical–hematological TMA phenotype (Table 1). Preserved ADAMTS13 activity argued against immune-mediated thrombotic thrombocytopenic purpura (TTP), while autoimmune, anti-GBM, antiphospholipid, and infectious investigations were unrevealing. Given rapidly progressive dysfunction of the solitary kidney and an active nephritic syndrome, methylprednisolone and cyclophosphamide were administered before histopathological confirmation. Two sessions of therapeutic plasma exchange were subsequently performed in the setting of the pronounced TMA phenotype. Hematological parameters improved, whereas kidney function did not recover and dialysis dependence persisted. Kidney biopsy demonstrated advanced IgAN with severe chronic kidney damage (Oxford Classification M0E1S1T2C1) and intense mesangial IgA/C3 codeposition despite normal circulating C3. No definitive histopathological evidence of active TMA was identified.
Conclusion: This case demonstrates previously oligosymptomatic IgAN presenting with rapidly progressive kidney dysfunction, dialysis-dependent kidney failure, and a compelling clinical–hematological TMA phenotype. Preserved ADAMTS13 activity and an unrevealing investigation for major secondary causes supported a microangiopathic process distinct from immune-mediated TTP. Marked mesangial IgA/C3 codeposition despite normal circulating C3 raises the possibility that local complement activation may have amplified glomerular inflammation and endothelial injury. However, these findings are insufficient to establish complement-mediated TMA. The absence of active TMA lesions in a biopsy obtained later in the disease course likewise does not establish renal TMA, but cannot exclude a preceding transient or partially resolved microangiopathic process. A distinctive feature was the substantial cumulative medication and supplement exposure preceding clinical deterioration. In the setting of pre-existing IgAN and a solitary functioning kidney, recurrent drug exposures may have constituted an external “second hit,” potentially promoting immune activation, endothelial stress, and clinical decompensation. The absence of a clear temporal relationship with a single agent, however, precludes attribution to definite drug-induced TMA. Collectively, this case supports a multifactorial, hypothesis-generating model: pre-existing IgAN in a solitary kidney → recurrent external/drug exposures as a potential “second hit” → possible local complement activation and endothelial injury → clinical–hematological TMA phenotype → rapid kidney function deterioration. This proposed sequence should not be interpreted as evidence of direct causality.
Clinical lesson: in patients with IgAN and rapidly deteriorating kidney function, particularly when anemia and thrombocytopenia develop, targeted evaluation for TMA and potential secondary triggers should be considered even when circulating C3 levels are normal.
Objective: To characterize the clinicopathological features of severe IgAN presenting with a clinical–hematological TMA phenotype in a young woman with a solitary functioning kidney and to explore the potential contribution of local complement activation and recurrent drug exposures as a putative “second hit” to endothelial injury and rapid deterioration of kidney function.
Case presentation: A 22-year-old woman had a solitary functioning right kidney following neonatal left nephrectomy. Kidney function remained preserved for years; however, persistent microscopic hematuria had been documented since 2022, retrospectively suggesting clinically silent glomerular disease. Between 2022 and 2026, she had substantial cumulative exposure to medications and supplements, including recurrent antiviral, antibacterial, and anti-inflammatory therapies, acne-directed treatments, vitamin/mineral preparations, and dietary supplements. These exposures preceded clinical deterioration and were considered potential external triggers in a susceptible renal background rather than evidence of definite drug-induced TMA. In June–July 2026, she developed recurrent massive edema followed by rapidly progressive kidney dysfunction with azotemia, hyperkalemia, active urinary sediment, and proteinuria, ultimately requiring hemodialysis. During hospitalization, microangiopathic hemolytic anemia, severe thrombocytopenia, schistocytosis, reticulocytosis, and elevated lactate dehydrogenase established a clinical–hematological TMA phenotype (Table 1). Preserved ADAMTS13 activity argued against immune-mediated thrombotic thrombocytopenic purpura (TTP), while autoimmune, anti-GBM, antiphospholipid, and infectious investigations were unrevealing. Given rapidly progressive dysfunction of the solitary kidney and an active nephritic syndrome, methylprednisolone and cyclophosphamide were administered before histopathological confirmation. Two sessions of therapeutic plasma exchange were subsequently performed in the setting of the pronounced TMA phenotype. Hematological parameters improved, whereas kidney function did not recover and dialysis dependence persisted. Kidney biopsy demonstrated advanced IgAN with severe chronic kidney damage (Oxford Classification M0E1S1T2C1) and intense mesangial IgA/C3 codeposition despite normal circulating C3. No definitive histopathological evidence of active TMA was identified.
Conclusion: This case demonstrates previously oligosymptomatic IgAN presenting with rapidly progressive kidney dysfunction, dialysis-dependent kidney failure, and a compelling clinical–hematological TMA phenotype. Preserved ADAMTS13 activity and an unrevealing investigation for major secondary causes supported a microangiopathic process distinct from immune-mediated TTP. Marked mesangial IgA/C3 codeposition despite normal circulating C3 raises the possibility that local complement activation may have amplified glomerular inflammation and endothelial injury. However, these findings are insufficient to establish complement-mediated TMA. The absence of active TMA lesions in a biopsy obtained later in the disease course likewise does not establish renal TMA, but cannot exclude a preceding transient or partially resolved microangiopathic process. A distinctive feature was the substantial cumulative medication and supplement exposure preceding clinical deterioration. In the setting of pre-existing IgAN and a solitary functioning kidney, recurrent drug exposures may have constituted an external “second hit,” potentially promoting immune activation, endothelial stress, and clinical decompensation. The absence of a clear temporal relationship with a single agent, however, precludes attribution to definite drug-induced TMA. Collectively, this case supports a multifactorial, hypothesis-generating model: pre-existing IgAN in a solitary kidney → recurrent external/drug exposures as a potential “second hit” → possible local complement activation and endothelial injury → clinical–hematological TMA phenotype → rapid kidney function deterioration. This proposed sequence should not be interpreted as evidence of direct causality.
Clinical lesson: in patients with IgAN and rapidly deteriorating kidney function, particularly when anemia and thrombocytopenia develop, targeted evaluation for TMA and potential secondary triggers should be considered even when circulating C3 levels are normal.
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.
Congress Abstract
Central Asian Journal of Nephrology, 2(2, Suppl. 1), 2026, cajn_A6, https://doi.org/10.63946/cajn/19525
ABSTRACT:
Introduction: Obstetric thrombotic microangiopathies (TMAs) are rare but potentially life-threatening disorders that include HELLP syndrome, thrombotic thrombocytopenic purpura, and atypical hemolytic uremic syndrome (aHUS). Their overlapping clinical features often complicate timely diagnosis. Differentiating HELLP syndrome from aHUS is particularly challenging when TMA persists and acute kidney injury (AKI) progresses after delivery. Early recognition of aHUS is crucial because targeted complement-inhibitory therapy may significantly improve outcomes.
Case Presentation: A 41-year-old woman (gravida 5, para 3) with a high-risk pregnancy, including a history of preeclampsia complicated by placental abruption and recurrent pregnancy loss, was admitted at 28 weeks' gestation with severe preeclampsia complicated by obstetric TMA. On admission, she presented with hypertension (150/90 mmHg) and proteinuria (1.0 g/day), while hemoglobin, platelet count, and kidney function were within the normal range.
On the fourth day of hospitalization, an emergency cesarean section was performed because of progressive placental abruption. The postoperative course was complicated by HELLP syndrome, sepsis, massive hemorrhage, disseminated intravascular coagulation, microangiopathic hemolytic anemia, thrombocytopenia, and severe anuric AKI. Peak laboratory values included hemoglobin 48 g/L, platelet count 48 × 10⁹/L, serum creatinine 563 μmol/L, aspartate aminotransferase 560 U/L, lactate dehydrogenase 5,844 U/L, schistocytes detected on two peripheral blood smears, and a negative direct Coombs test.
Despite elimination of the obstetric trigger by delivery, followed by relaparotomy and hysterectomy, TMA manifestations and dialysis-dependent AKI persisted, prompting differential diagnosis between severe HELLP syndrome and aHUS. The patient underwent hemodiafiltration followed by 24 hemodialysis sessions and remained on maintenance hemodialysis for 2.5 months after discharge. Subsequently, kidney function partially recovered, allowing discontinuation of dialysis, although significant renal impairment persisted (serum creatinine 250–300 μmol/L).
Conclusion: This case highlights the diagnostic challenge of distinguishing HELLP syndrome from aHUS in obstetric TMA. Persistence of TMA for more than 48–72 hours after removal of the obstetric trigger, together with ongoing microangiopathic hemolysis, thrombocytopenia, and severe AKI, should prompt evaluation for aHUS, including assessment of ADAMTS13 activity, complement abnormalities, and genetic risk factors to guide timely initiation of complement-inhibitory therapy. The case emphasizes the importance of early multidisciplinary management and long-term nephrology follow-up, even in patients who achieve partial recovery of kidney function.
Case Presentation: A 41-year-old woman (gravida 5, para 3) with a high-risk pregnancy, including a history of preeclampsia complicated by placental abruption and recurrent pregnancy loss, was admitted at 28 weeks' gestation with severe preeclampsia complicated by obstetric TMA. On admission, she presented with hypertension (150/90 mmHg) and proteinuria (1.0 g/day), while hemoglobin, platelet count, and kidney function were within the normal range.
On the fourth day of hospitalization, an emergency cesarean section was performed because of progressive placental abruption. The postoperative course was complicated by HELLP syndrome, sepsis, massive hemorrhage, disseminated intravascular coagulation, microangiopathic hemolytic anemia, thrombocytopenia, and severe anuric AKI. Peak laboratory values included hemoglobin 48 g/L, platelet count 48 × 10⁹/L, serum creatinine 563 μmol/L, aspartate aminotransferase 560 U/L, lactate dehydrogenase 5,844 U/L, schistocytes detected on two peripheral blood smears, and a negative direct Coombs test.
Despite elimination of the obstetric trigger by delivery, followed by relaparotomy and hysterectomy, TMA manifestations and dialysis-dependent AKI persisted, prompting differential diagnosis between severe HELLP syndrome and aHUS. The patient underwent hemodiafiltration followed by 24 hemodialysis sessions and remained on maintenance hemodialysis for 2.5 months after discharge. Subsequently, kidney function partially recovered, allowing discontinuation of dialysis, although significant renal impairment persisted (serum creatinine 250–300 μmol/L).
Conclusion: This case highlights the diagnostic challenge of distinguishing HELLP syndrome from aHUS in obstetric TMA. Persistence of TMA for more than 48–72 hours after removal of the obstetric trigger, together with ongoing microangiopathic hemolysis, thrombocytopenia, and severe AKI, should prompt evaluation for aHUS, including assessment of ADAMTS13 activity, complement abnormalities, and genetic risk factors to guide timely initiation of complement-inhibitory therapy. The case emphasizes the importance of early multidisciplinary management and long-term nephrology follow-up, even in patients who achieve partial recovery of kidney function.