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

2018 ◽  
Vol 48 (3) ◽  
pp. 225-233 ◽  
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.

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

2018 ◽  
Vol 90 (6) ◽  
pp. 28-34 ◽  
Author(s):  
N L Kozlovskaya ◽  
Yu V Korotchaeva ◽  
E M Shifman ◽  
L A Bobrova
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Multiple Organ ◽  
Aim Analysis ◽  
Uremic Syndrome

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.

scholarly journals Acute Kidney Injury in Children: Etiologies and Results

2020 ◽  
Vol 1 (2) ◽  
pp. 01-05
Author(s):  
Seba Atmane
Keyword(s):  
Acute Kidney Injury ◽  
Peritoneal Dialysis ◽  
Hemolytic Uremic Syndrome ◽  
Kidney Function ◽  
Emergency Treatment ◽  
Kidney Injury ◽  
Obstructive Nephropathy ◽  
Normal Kidney ◽  
Uremic Syndrome

The aim of the study is to show the etiologies and the follow-up of our AKI cases. This was conducted in our hospital, between 2015 and 2018. During this period we included 26 children with AKI (64% femals) with a median age of 7 years (range 40 days to 15 years). In the majority of the cases revealed by digestive signs and that related to the etiology of AKI (Hemolytic Uremic Syndrome post diarrhea). In our study, 44% of the patients have thrombocytopenia associated with AKI. The etiology of AKI is : Nephropathy glomerular in 37% hemolytic and uremic syndrom in 54% and obstructive nephropathy in 9%. Patients survived in 92 % of the cases and 58% of them have recovered normal kidney function, 7% of death. Peritoneal dialysis is the most commonly used emergency treatment for AKI in children at a frequency of 37%., hemodialysis was used less.

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

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.

Novel presentation of Plasmodium vivax malaria with acute kidney injury and hemolytic uremic syndrome

2015 ◽  
Vol 4 (3-4) ◽  
pp. 34-37
Author(s):  
Mohan P. Patel ◽  
Prakash P. Ugale ◽  
Abhijeet B. Jagtap ◽  
Sandip T. Chaudhari ◽  
Pitambar N. Dighore
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Uremic Syndrome ◽  
Plasmodium Vivax ◽  
Vivax Malaria ◽  
Kidney Injury ◽  
Plasmodium Vivax Malaria ◽  
Uremic Syndrome

scholarly journals Collapsing glomerulopathy and hemolytic uremic syndrome associated with falciparum malaria: completely reversible acute kidney injury

2012 ◽  
Vol 37 (2) ◽  
pp. 286-290 ◽  
Author(s):  
Vivek Balkrishna Kute ◽  
Hargovind L. Trivedi ◽  
Aruna V. Vanikar ◽  
Pankaj R. Shah ◽  
Manoj R. Gumber ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Uremic Syndrome ◽  
Falciparum Malaria ◽  
Kidney Injury ◽  
Collapsing Glomerulopathy ◽  
Uremic Syndrome

scholarly journals Acute Kidney Injury with Hemolytic Uremic Syndrome

2021 ◽  
Vol 4 (1) ◽  
pp. 193-198
Author(s):  
Rubina Naqvi ◽  
Khawar Abbas ◽  
Syed Fazal Akhtar
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Uremic Syndrome ◽  
Case Series ◽  
Kidney Injury ◽  
Febrile Illness ◽  
Renal Recovery ◽  
P Value ◽  
Co Morbidity ◽  
Uremic Syndrome

We report here, case series of patients with acute kidney injury (AKI) developing in associationwith hemolytic uremic syndrome (HUS). Different causes of HUS and outcome of patients in this group of patients is aimed to be reported. Patients and Methods: subjects for the study reported here comprised of a cohort of 105 patients admitted with the diagnosis of AKI due to HUS. AKI was defined according to RIFLE criteria and HUS on basis of hematological, biochemical and/or histological features. All patients had normal size kidneys on ultrasonography and no previous co- morbidity. Results: One hundred and five patients with AKI due to HUS were brought to this institute from January 2000 - July 2019; among these 76 were females, mean age of these patients was 27.83±10.50 years. Causes of HUS were febrile illness, with or without diarrhea, diarrhea alone, pregnancy related complications and one each from snake bite, HCV infection / IFN therapy and use of combination of drugs. In pregnancy related HUS one patient had HUS during pregnancy while rest were during postpartum. Renal replacement was required in 95.23 % patients. Complete renal recovery was observed in 22 patients, while 15 died during acute phase of illness. CKD-V developed in 24 patients, 41 patients lost long term follow up, but were dialysis free till last follow up. Treatment with plasmapheresis revealed significantly better renal recovery (p value 0.026) in this group of patients. Conclusion: HUS can be severe life threatening disease; AKI with background of HUS may remain irreversible in many of these patients. Plasmapheresis should be offered to patients with established diagnosis of HUS.

scholarly journals Atypical Hemolytic Uremic Syndrome Presenting as Acute Heart Failure—A Rare Presentation: Diagnosis Supported by Skin Biopsy

2019 ◽  
Vol 7 ◽  
pp. 232470961984290
Author(s):  
Asim Kichloo ◽  
Savneek Singh Chugh ◽  
Sanjeev Gupta ◽  
Jay Pandav ◽  
Praveen Chander
Keyword(s):  
Heart Failure ◽  
Skin Biopsy ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Systolic Heart Failure ◽  
Kidney Injury ◽  
Rare Presentation ◽  
History Of ◽  
Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder of uncontrolled complement activation that manifests classically as anemia, thrombocytopenia, and renal failure, although extrarenal manifestations are observed in 20% of the patient most of which involving central nervous system, with relatively rare involvement of the heart. In this article, we report the case of a 24-year-old male with no history of heart disease presenting with acute systolic heart failure along with microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Given his presentation of thrombotic microangiopathy (TMA), along with laboratory results significant for low haptoglobin, platelets, hemoglobin, C3, C4, CH50, and normal ADAMTS13 levels, with no diarrhea and negative STEC polymerase chain reaction in stool, aHUS diagnosis was established with strong clinical suspicion, and immediate initiation of treatment was advised. Kidney biopsy to confirm diagnosis of aHUS was inadvisable because of thrombocytopenia, so the skin biopsy of a rash on his arm was done, which came to be consistent with thrombotic microangiopathy. Our case highlights a relatively rare association between aHUS and cardiac involvement, and the use of skin biopsy to support diagnosis of aHUS in patients who cannot undergo renal biopsy because of thrombocytopenia.

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

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

scholarly journals Factor H Competitor Generated by Gene Conversion Events Associates with Atypical Hemolytic Uremic Syndrome

2017 ◽  
Vol 29 (1) ◽  
pp. 240-249 ◽  
Author(s):  
Elena Goicoechea de Jorge ◽  
Agustín Tortajada ◽  
Sheila Pinto García ◽  
Sara Gastoldi ◽  
Héctor Martín Merinero ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Gene Conversion ◽  
Plasma Levels ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor ◽  
Complement Regulation ◽  
Pathogenic Variants ◽  
Genetic Abnormalities ◽  
Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy caused by complement pathogenic variants, mainly affects the kidney microvasculature. A retrospective genetic analysis in our aHUS cohort (n=513) using multiple ligation probe amplification uncovered nine unrelated patients carrying a genetic abnormality in the complement factor H related 1 gene (CFHR1) that originates by recurrent gene conversion events between the CFH and CFHR1 genes. The novel CFHR1 mutants encode an FHR-1 protein with two amino acid substitutions, L290S and A296V, converting the FHR-1 C terminus into that of factor H (FH). Next-generation massive-parallel DNA sequencing (NGS) analysis did not detect these genetic abnormalities. In addition to the CFHR1 mutant, six patients carried the previously uncharacterized CFH-411T variant. In functional analyses, the mutant FHR-1 protein strongly competed the binding of FH to cell surfaces, impairing complement regulation, whereas the CFH-411T polymorphism lacked functional consequences. Carriers of the CFHR1 mutation presented with severe aHUS during adulthood; 57% of affected women in this cohort presented during the postpartum period. Analyses in patients and unaffected carriers showed that FH plasma levels determined by the nonmutated chromosome modulate disease penetrance. Crucially, in the activated endothelial (HMEC-1) cell assay, reduced FH plasma levels produced by the nonmutated chromosome correlated inversely with impairment of complement regulation, measured as C5b-9 deposition. Our data advance understanding of the genetic complexities underlying aHUS, illustrate the importance of performing functional analysis, and support the use of complementary assays to disclose genetic abnormalities not revealed by current NGS analysis.

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