Atypical hemolytic-uremic syndrome as one of the causes of acute kidney injury in pregnant women

Obstetric atypical hemolytic uremic syndrome (aHUS) is one of the reasons for the development of acute kidney injury (AKI) and can determine the prognosis of both mother and child. Aim. Analysis of clinical manifestations, course and outcomes of obstetric aHUS. Materials and methods. 45 patients with aHUS development during pregnancy or immediately after childbirth were observed between 2011 and 2017, age from 16 to 42 years. Results and discussion. All patients had AKI (serum creatinine 521,5±388,0 µmol/l, oliguria or anuria that required initiation of hemodialysis). 93.3% pts had extrarenal manifestations of TMA with the development of multiple organ failure (MOF). The mean number of damage organs was 3,7±1,2. In all patients, the development of aHUS was preceded by obstetric complications, surgery, infection, etc. In the outcome: 53.4% women showed complete recovery of renal function, 11.1% developed CKD 4-5 stages, 35.5% had dialysis-dependent end-stage renal failure (ESDR). Maternal mortality was 23.9%. Perinatal mortality was 32.6%. The early start of eculizumab treatment (within 1-2 weeks from the onset of aHUS), compared with therapy start after 3 weeks, increased the chances of favorable outcome for mother in 5.33 times, and the chances for normalization of renal function in 48.7 times. Conclusion. Obstetric aHUS is characterized by the development of AKI in 100% of cases. In most patients, the obstetric aHUS occurs with the development of MOF. Timely diagnosis of aHUS and immediate treatment by eculizumab allows not only to save the life of patients, but also completely restore their health.

Download Full-text

Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome with Acute Kidney Injury

American Journal of Nephrology ◽

10.1159/000492865 ◽

2018 ◽

Vol 48 (3) ◽

pp. 225-233 ◽

Cited By ~ 4

Author(s):

Mercedes Cao ◽

Bruna N. Leite ◽

Tamara Ferreiro ◽

María Calvo ◽

Constantino Fernández ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hemolytic Uremic Syndrome ◽

Kidney Function ◽

Case Reports ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Complete Recovery ◽

Genetic Abnormalities ◽

Uremic Syndrome ◽

Meta Analyses

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. Methods: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. Results: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. Conclusion: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.

Download Full-text

Atypical hemolytic uremic syndrome and pre-eclampsia: cause or effect?

Voprosy ginekologii akušerstva i perinatologii ◽

10.20953/1726-1678-2021-4-55-63 ◽

2021 ◽

Vol 20 (4) ◽

pp. 55-63

Author(s):

Yu.V. Korotchaeva ◽

◽

N.L. Kozlovskaya ◽

E.M. Shifman ◽

V.M. Guryeva ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

Comparison Group ◽

Atypical Hemolytic Uremic Syndrome ◽

Complete Recovery ◽

Multiple Organ ◽

Control Group ◽

Early Postpartum ◽

Organ Failures ◽

Uremic Syndrome

Objective. To study the risk factors for transformation of pre-eclampsia (PE) into atypical hemolytic uremic syndrome (aHUS). Patients and methods. The study included 102 patients with PE, who were divided into two groups. The main group consisted of 59 women with PE and aHUS in the early postpartum period. In the comparison group, there were 43 patients who previously had severe PE, which was not complicated by the development of aHUS. Results. The complications associated with severe PE such as hemorrhage (76.3% vs 48.8%, p = 0.004), placental abruption (33.9% vs 6.9%, p = 0.001), and intrauterine fetal demise (32.2% vs 6.9%, p = 0.002) were significantly more frequent in patients with aHUS compared with the control group. Most of these complications occurred in patients in whom PE lasted more than one week. Also, patients with aHUS had significantly more severe microangiopathic hemolytic anemia (hemoglobin 61.0 [52.5; 73.5] g/L vs 88.0 [73.0; 104.0] g/L, p < 0.001, lactate dehydrogenase 2846.0 [1340.5; 5037.5] IU/L vs 801.0 [497.0; 1269.0] IU/L, p < 0.001), thrombocytopenia (49.5 [31.0; 71.5] K/μL vs 67.0 [43.0; 108.0] K/μL, p = 0.002), hypercreatininemia (424.5 [281.0; 605.0] μmol/L vs 99.0 [86.0; 134.0] μmol/L, p < 0.001) and more severe multiple organ dysfunction syndrome (average number of organ failures – 3.58 vs 1.88, p < 0.001). Among patients with aHUS, complete recovery of renal function was achieved in 42 (71.2%) of 59 women, 9 (15.2%) of 59 women remained on hemodialysis, 8 (13.6%) of 59 women died. In the comparison group, all women showed positive dynamics within 72 hours after childbirth with normalization of all clinical and laboratory parameters. Conclusion. PE itself is a risk factor for the development of aHUS, and patients with severe PE should be considered at high risk for thrombotic microangiopathy. Prolongation of pregnancy in patients with PE increases the risk of developing aHUS by 5 times. Key words: pre-eclampsia, pregnancy-associated atypical hemolytic uremic syndrome, pregnancy, thrombotic microangiopathy, eculizumab

Download Full-text

Postpartum atypical hemolytic uremic syndrome: Evaluating thrombotic microangiopathy in the pregnant woman

Obstetric Medicine ◽

10.1177/1753495x20926043 ◽

2020 ◽

pp. 1753495X2092604

Author(s):

S So ◽

E Fischer ◽

M Gangadharan Komala ◽

B Bose

Keyword(s):

Acute Kidney Injury ◽

Pregnant Woman ◽

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

Post Partum ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Uremic Syndrome ◽

In Pregnancy

Acute kidney injury in women during pregnancy and the puerperium is often ascribed to hypertensive complications of pregnancy, especially pre-eclampsia. However, rarer causes, including atypical hemolytic uremic syndrome (aHUS) can be triggered by pregnancy. We present a case of a woman with post-partum acute kidney injury due to aHUS, which was successfully treated with the C5a inhibitor eculizumab. We also present a summary of the evaluation and management of thrombotic microangiopathy in pregnancy.

Download Full-text

Atypical Hemolytic Uremic Syndrome after ChAdOx1 nCoV-19 Vaccination in a Patient with Homozygous CFHR3/CFHR1 Gene Deletion

Nephron ◽

10.1159/000519461 ◽

2021 ◽

pp. 1-5

Author(s):

Francisco Ferrer ◽

Marisa Roldão ◽

Cátia Figueiredo ◽

Karina Lopes

Keyword(s):

Hemolytic Uremic Syndrome ◽

Alternative Pathway ◽

Atypical Hemolytic Uremic Syndrome ◽

Clinical Manifestations ◽

Kidney Injury ◽

Time Lapse ◽

Normal Activity ◽

Factor H ◽

Complement Alternative Pathway ◽

Uremic Syndrome

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy (TMA) affecting the kidneys. Compared with typical HUS due to an infection from shiga toxin-producing <i>Escherichia coli</i>, atypical HUS involves a genetic or acquired dysregulation of the complement alternative pathway. In the presence of a mutation in a complement gene, a second trigger is often necessary for the development of the disease. We report a case of a 54-year-old female, with a past medical history of pulmonary tuberculosis, who was admitted to the emergency service with general malaise and reduction in urine output, 5 days after vaccination with ChAdOx1 nCoV-19. Laboratory results revealed microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given the clinical picture of TMA, plasma exchange (PEX) was immediately started, along with hemodialysis. Complementary laboratory workup for TMA excluded thrombotic thrombocytopenic purpura and secondary causes. Complement study revealed normal levels of factors H, B, and I, normal activity of the alternate pathway, and absence of anti-factor H antibodies. Genetic study of complement did not show pathogenic variants in the 12 genes analyzed, but revealed a deletion in gene CFHR3/CFHR1 in homozygosity. Our patient completed 10 sessions of PEX, followed by eculizumab, with both clinical and laboratorial improvement. Actually, given the short time lapse between vaccination with ChAdOx1 nCoV-19 and the clinical manifestations, we believe that vaccine was the trigger for the presentation of aHUS in this particular case.

Download Full-text

Neonatal Atypical Hemolytic Uremic Syndrome in the Eculizumab Era

American Journal of Perinatology Reports ◽

10.1055/s-0041-1731057 ◽

2021 ◽

Vol 11 (02) ◽

pp. e95-e98

Author(s):

Sara Madureira Gomes ◽

Rita Pissarra Teixeira ◽

Gustavo Rocha ◽

Paulo Soares ◽

Hercilia Guimaraes ◽

...

Keyword(s):

Renal Failure ◽

Renal Function ◽

Hemolytic Uremic Syndrome ◽

Perinatal Asphyxia ◽

Atypical Hemolytic Uremic Syndrome ◽

Congenital Infection ◽

High Morbidity ◽

Severe Renal Failure ◽

Emergency Cesarean ◽

Uremic Syndrome

AbstractThe atypical hemolytic uremic syndrome (aHUS) in the newborn is a rare disease, with high morbidity. Eculizumab, considered a first-line drug in older children, is not approved in neonates and in children weighing less than 5 kg. We present a 5-day-old female newborn, born at 36 weeks' twin gestation, by emergency cesarean section due to cord prolapse, with birth weight of 2,035 g and Apgar score of 7/7/7, who develops microangiopathic hemolytic anemia, thrombocytopenia, and progressive acute renal failure. In day 5, after diagnosis of aHUS, a daily infusion of fresh frozen plasma begins, with improvement of thrombocytopenia and very slight improvement in renal function. The etiologic study (congenital infection, Shiga toxin, ADAMTS13 activity, directed metabolic study) was normal. C3c was slightly decreased. On day 16 for maintenance of anemia and severe renal failure, she started 300 mg/dose eculizumab. Anemia resolves in 10 weeks and creatinine has normal values after 13 weeks of treatment. The genetic study was normal. In this case, eculizumab is effective in controlling microangiopathy and in the recovery of renal function. Diagnosis of neonatal aHUS can be challenging because of phenotypic heterogeneity and potential overlap with other manifestations that may confound it, such as perinatal asphyxia or sepsis/disseminated intravascular coagulation.

Download Full-text

Complement C5 inhibition protects against hemolytic anemia and acute kidney injury in anthrax peptidoglycan-induced sepsis in baboons

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2104347118 ◽

2021 ◽

Vol 118 (37) ◽

pp. e2104347118

Author(s):

Ravi Shankar Keshari ◽

Narcis Ioan Popescu ◽

Robert Silasi ◽

Girija Regmi ◽

Cristina Lupu ◽

...

Keyword(s):

Acute Kidney Injury ◽

Hemolytic Anemia ◽

Complement Activation ◽

Inflammatory Responses ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Injury ◽

Multiple Organ ◽

Immune Recognition ◽

Gram Positive ◽

Terminal Complement

Late-stage anthrax infections are characterized by dysregulated immune responses and hematogenous spread of Bacillus anthracis, leading to extreme bacteremia, sepsis, multiple organ failure, and, ultimately, death. Despite the bacterium being nonhemolytic, some fulminant anthrax patients develop a secondary atypical hemolytic uremic syndrome (aHUS) through unknown mechanisms. We recapitulated the pathology in baboons challenged with cell wall peptidoglycan (PGN), a polymeric, pathogen-associated molecular pattern responsible for the hemostatic dysregulation in anthrax sepsis. Similar to aHUS anthrax patients, PGN induces an initial hematocrit elevation followed by progressive hemolytic anemia and associated renal failure. Etiologically, PGN induces erythrolysis through direct excessive activation of all three complement pathways. Blunting terminal complement activation with a C5 neutralizing peptide prevented the progressive deposition of membrane attack complexes on red blood cells (RBC) and subsequent intravascular hemolysis, heme cytotoxicity, and acute kidney injury. Importantly, C5 neutralization did not prevent immune recognition of PGN and shifted the systemic inflammatory responses, consistent with improved survival in sepsis. Whereas PGN-induced hemostatic dysregulation was unchanged, C5 inhibition augmented fibrinolysis and improved the thromboischemic resolution. Overall, our study identifies PGN-driven complement activation as the pathologic mechanism underlying hemolytic anemia in anthrax and likely other gram-positive infections in which PGN is abundantly represented. Neutralization of terminal complement reactions reduces the hemolytic uremic pathology induced by PGN and could alleviate heme cytotoxicity and its associated kidney failure in gram-positive infections.

Download Full-text