Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment.
Atypical hemolytic uremic syndrome; Complement regulatory protein mutation; Eculizumab; Renal impairment; Thrombotic microangiopathy
Atypical hemolytic uremic syndrome (aHUS), a rare variant of thrombotic microangiopathy, is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. The condition is associated with poor clinical outcomes with high morbidity and mortality. Atypical HUS predominantly affects the kidneys but has the potential to cause multi-organ system dysfunction. This uncommon disorder is caused by a genetic abnormality in the complement alternative pathway resulting in over-activation of the complement system and formation of microvascular thrombi. Abnormalities of the complement pathway may be in the form of mutations in key complement genes or autoantibodies against specific complement factors. We discuss the pathophysiology, clinical manifestations, diagnosis, complications, and management of aHUS. We also review the efficacy and safety of the novel therapeutic agent, eculizumab, in aHUS, pregnancy-associated aHUS, and aHUS in renal transplant patients.
Raina Rupesh; Krishnappa Vinod; Blaha Taryn; Kann Taylor; Hein William; Burke Linda; Bagga Arvind
Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy
2019
2019-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1111/1744-9987.12763" target="_blank" rel="noreferrer noopener">10.1111/1744-9987.12763</a>
Pediatric intradialytic hypotension: recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup
Blood pressure monitoring; Blood volume monitoring; Children; Dialysate cooling; Intradialytic hypotension; Mannitol; Midodrine; Sodium profiling
Intradialytic hypotension (IDH) is a common adverse event resulting in premature interruption of hemodialysis, and consequently, inadequate fluid and solute removal. IDH occurs in response to the reduction in blood volume during ultrafiltration and subsequent poor compensatory mechanisms due to abnormal cardiac function or autonomic or baroreceptor failure. Pediatric patients are inherently at risk for IDH due to the added difficulty of determining and attaining an accurate dry weight. While frequent blood pressure monitoring, dialysate sodium profiling, ultrafiltration-guided blood volume monitoring, dialysate cooling, hemodiafiltration, and intradialytic mannitol and midodrine have been used to prevent IDH, they have not been extensively studied in pediatric population. Lack of large-scale studies on IDH in children makes it difficult to develop evidence-based management guidelines. Here, we aim to review IDH preventative strategies in the pediatric population and outlay recommendations from the Pediatric Continuous Renal Replacement Therapy (PCRRT) Workgroup. Without strong evidence in the literature, our recommendations from the expert panel reflect expert opinion and serve as a valuable guide.
Raina Rupesh; Lam Stephanie; Raheja Hershita; Krishnappa Vinod; Hothi Daljit; Davenport Andrew; Chand Deepa; Kapur Gaurav; Schaefer Franz; Sethi Sidharth Kumar; McCulloch Mignon; Bagga Arvind; Bunchman Timothy; Warady Bradley A
Pediatric Nephrology (Berlin, Germany)
2019
2019-05
<a href="http://doi.org/10.1007/s00467-018-4190-1" target="_blank" rel="noreferrer noopener">10.1007/s00467-018-4190-1</a>
Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy.
Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.
Raina Rupesh; Bedoyan Jirair K; Lichter-Konecki Uta; Jouvet Philippe; Picca Stefano; Mew Nicholas Ah; Machado Marcel C; Chakraborty Ronith; Vemuganti Meghana; Grewal Manpreet K; Bunchman Timothy; Sethi Sidharth Kumar; Krishnappa Vinod; McCulloch Mignon; Alhasan Khalid; Bagga Arvind; Basu Rajit K; Schaefer Franz; Filler Guido; Warady Bradley A
Nature reviews. Nephrology
2020
2020-04-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
journalArticle
<a href="http://doi.org/10.1038/s41581-020-0267-8" target="_blank" rel="noreferrer noopener">10.1038/s41581-020-0267-8</a>