Search

Haemolytic uraemic syndrome (HUS) is a thrombotic microangiopathy (TMA) that presents with renal insufficiency, thrombocytopaenia and microangiopathic haemolytic anaemia. Typical HUS is associated with Shiga toxin while atypical HUS (aHUS) is due to overactivation of the alternative complement pathway. aHUS has numerous causes, including drugs, with rare reports of carfilzomib, a proteasome inhibitor used in multiple myeloma, as causative agent. Cases vary in presentation, presenting a diagnostic challenge. Historically, TMAs were treated with plasma exchange. aHUS, however, is considered refractory to plasma exchange and best treated with eculizumab, a monoclonal antibody targeting C5, a terminal complement protein. We report a patient with history of multiple myeloma who presented with headaches, elevated blood pressure, petechiae, ecchymosis and haemolytic anaemia. His condition was determined to be carfilzomib-induced aHUS and he was successfully treated with eculizumab. Early detection and treatment of drug-induced aHUS is vital in reducing morbidity and mortality related to the condition., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Atypical haemolytic uraemic syndrome (aHUS) is a disease of complement dysregulation and can be fatal if not treated in a timely manner. Although normally associated with triggers such as infection or pregnancy, this case demonstrates acute pancreatitis as the triggering event. The patient's initial presentation of thrombocytopaenia and acute renal failure was first attributed to a systemic inflammatory response syndrome due to pancreatitis, but with detailed history and further laboratory investigation, we were able to show that patient was having symptoms associated with aHUS. On early recognition of aHUS, this patient was able to receive the proper standard of care with eculizumab and had a full recovery while preventing renal failure. When patients present with thrombocytopaenia and renal failure in acute pancreatitis, we want to ensure physicians keep aHUS on the differential., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Pregnancy-induced atypical haemolytic uremic syndrome (P-aHUS) is a rare condition characterised by microangiopathic haemolytic anaemia, thrombocytopenia and renal failure. It accounts for approximately 7% of total HUS cases. Here, we present a case of recurrent P-aHUS in a 25-year-old Hispanic woman. Pregnancy was the clear trigger in both instances, and the disease manifested in first week of the postpartum period. Because of her significant obstetric history, a multidisciplinary approach was adopted to monitor her second pregnancy antepartum and post partum. As the patient developed recurrence of P-aHUS 4 days after her delivery, she was immediately administered eculizumab within few hours of disease manifestation. The patient normalised her haematological parameters within 1 week but sustained dialysis-requiring renal failure for a total of 6 weeks. This case highlights the advances as well as the ongoing uncertainties, especially with respect to the use of eculizumab, in this rare but morbid disease., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

A 17-year-old girl presented with fever, myalgia, vomiting for 1 month and oliguria and dyspnoea for 4 days. She was tachycardic,hypertensive, with pedal oedema and decreased breath sounds. She had high serum creatinine (3 mg/dL), anaemia, thrombocytopenia, leucocytosis and eosinophilia with schistocytes. Lactate dehydrogenase, transaminases were high , with low haptoglobin and high ferritin (5269 ng/mL). Complement C3/C4 and fibrinogen were normal. Urinalysis showed large blood and protein and stool studies were negative. Her ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) was normal. Kidney biopsy showed acute interstitial nephritis (AIN) in addition to thrombotic angiopathy. The differentials - haemolytic uraemic syndrome (HUS), thrombotic thrombocytopenia (TTP) and haemophagocytic lymphohistiocytosis (HLH) were ruled out. Her genetic testing was abnormal for large CFHR1-CFHR3 homozygous deletion and heterozygous missense variant in exon 2 of DGKE making the diagnosis of atypical HUS. She received eculizumab and was discharged on oral steroids for AIN and biweekly eculizumab infusions with excellent recovery., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

A 42-year-old Hispanic female and long-distance runner was seen for evaluation of fatigue. Her physical examination showed petechiae and ecchymoses in upper extremities, abdominal distension and bilateral ankle oedema. Laboratory workup revealed anaemia, thrombocytopenia, hypoalbuminemia and proteinuria of 1.4 g/24 hours. No schistocytes were found on peripheral blood smear. CT of her abdomen revealed diffuse small lymphadenopathy and hepatomegaly. Bone marrow biopsy demonstrated normal trilineage hematopoiesis with no hemophagocytosis. The patient was started on oral prednisone with no improvement and was subsequently admitted to the hospital for pulsed steroids, intravenous immunoglobulin and rituximab. Her proteinuria became nephrotic range, and a renal biopsy revealed features of thrombotic microangiopathy limited to the glomerular capillaries. ADAMTS13 was low which is >10% of normal, and a diagnosis of atypical haemolytic-uraemic syndrome (aHUS) was made. Eculizumab was started with prompt response. Whole exome sequencing demonstrated mutation in SPTA1, which has been associated with red blood cell membrane diseases but has not been described in patients with aHUS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Historically, patients with kidney diseases caused by genetic or acquired dysregulation of the complement alternative pathway have been grouped into clinical syndromes, C3 glomerulopathy (C3GN/DDD) and thrombotic microangiopathy (TMA), specifically atypical haemolytic uremic syndrome (aHUS). Recent data suggested that these diseases share a common pathophysiology and that patients can transition between glomerulopathies in this spectrum. Histopathologically, the main difference cited is the immunofluorescence (IF) findings, with C3 predominance in C3 glomerulopathy (compared with immunoglobulins and complements in immune complex-mediated membranoproliferative glomerulonephritis (MPGN)) and negative IF in TMA. We report a case in which a patient presented with hypertension, seizures, proteinuria, renal impairment and immune complex-mediated MPGN on kidney biopsy. Months later, she presented with classical TMA. She failed to respond to steroids and plasma exchange therapy but subsequently made a remarkable haematological and renal recovery after eculizumab treatment, thus supporting an underlying complement dysregulation and a diagnosis of aHUS., Competing Interests: Competing interests: WFC has received speaking honoraria from Octaplasma., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We present the case of a 21-month-old girl with two rare and life-threatening conditions, atypical haemolytic uraemic syndrome (aHUS) and haemophagocytic lymphohistiocytosis (HLH), triggered by a cytomegalovirus (CMV) infection. Soon after admission, the girl became anuric and required continuous venovenous haemodiafiltration.Initial treatments included methylprednisolone, fibrinogen and plasma infusion (for HLH), plasmapheresis (for thrombotic microangiopathy), immunoglobulins (for inflammation), ganciclovir (for CMV infection) and the antibiotic cefotaxime. On day 5, eculizumab (600 mg) was given for aHUS, with rapid improvement in haematological and nephrological parameters. Despite a subsequent isolated episode of right heart thrombosis that resolved with heparin treatment, the patient showed a favourable response to eculizumab (300 mg/15 days), with improved renal function, normal haematological values, and no treatment complications. In conclusion, eculizumab effectively treated aHUS in this case despite a comorbid immunological disease., Competing Interests: Competing interests: GMF-R has received lecture honoraria from Alexion Pharma GmbH. The other authors declare no competing financial interests., (© BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

We present the case of a 18-month-old girl with renal and cardiac manifestations of atypical haemolytic uraemic syndrome (aHUS), and a novel complement factor H mutation. Transient haematological remission was achieved with intensive plasmapheresis, but cardiac function deteriorated and renal function was not restored. Initiation of eculizumab after 6 months of dialysis significantly improved organ function. At 43 months after presentation, haematological values had normalised and cardiac function had improved. Dialysis was discontinued after 10 months (the longest reported time in a patient with aHUS) and the estimated glomerular filtration rate had recovered to 70 mL/min/1.73 m(2). In conclusion, treatment of aHUS with eculizumab, even after long-term dialysis, can significantly improve renal function. Discontinuation of dialysis and resolution of cardiac function has implications on the potential recovery and treatment choice of such patients. Earlier initiation of eculizumab, however, might have prevented the irreversible renal sclerosis and cardiac dysfunction., (2016 BMJ Publishing Group Ltd.)

The pathophysiology of atypical haemolytic-uraemic syndrome (aHUS) occurring de novo after renal transplantation may include genetic mutations of regulators of complement activation, but they are still rarely determined. A 41-year-old female renal transplant recipient presented two very different episodes of thrombotic microangiopathy. The first episode was associated with antibody-mediated rejection and the second was an isolated, acute aHUS, successfully treated with eculizumab. The diagnosis included a genetic analysis and we found a synonymous variant in the Complement Factor H (CFH) gene, c2634C>T (p.His878=) and low factor H (FH) activity during both events. In conclusion, the diagnosis of aHUS should be considered when TMA is associated with an AMR episode. In this setting, a silent polymorphism of factor H may be responsible for these rare cases of "de novo" aHUS after transplantation., (2014 BMJ Publishing Group Ltd.)