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1.
Ramon Vilalta Enrique Lara Alvaro Madrid Sara Chocron Marina Muñoz Alex Casquero Jose Nieto 《Pediatric nephrology (Berlin, Germany)》2012,27(12):2323-2326
Background
Atypical hemolytic uremic syndrome (aHUS) is a rare genetic disorder caused by chronic uncontrolled complement activation.Case-diagnosis/treatment
We present a 4-year-old girl with aHUS who had multiple severe clinical manifestations of thrombotic microangiopathy (TMA) including acute kidney injury, dilated cardiomyopathy, and cardiorespiratory arrest. She was managed with intensive plasma exchange and hemodialysis, which could not halt the progression of TMA. The initial single dose of eculizumab only temporarily improved the clinical symptoms of TMA. Sustained improvement of renal, hematological, and cardiac values were only achieved upon institution of chronic treatment with eculizumab. During long-term treatment with eculizumab (>2.5 years), she has had no further clinical manifestations of TMA, and required neither plasma exchange nor hemodialysis.Conclusion
Chronic eculizumab treatment was associated with control of complement-mediated TMA and sustained long-term improvement in renal and cardiac function. 相似文献2.
Prabesh Bajracharya Amrish Jain Rossana Baracco Tej K. Mattoo Gaurav Kapur 《Pediatric nephrology (Berlin, Germany)》2016,31(10):1615-1624
Background
Patients negative for Shiga toxin-producing E. coli (STEC) are categorized as having atypical hemolytic uremic syndrome (HUS) and are associated with an increased risk for complement mutations and poorer prognosis compared with typical HUS. However, STEC identification is limited by the natural history of HUS.Methods
The current study is aimed at identifying HUS patients with poor outcomes based on the presence or absence of diarrhea (D) or Shiga toxin (S). A single-center retrospective review (2003–2012) of 42 HUS patients (follow-up 31.3?±?38.7 months) was carried out. HUS was managed clinically with supportive treatments such as dialysis, plasma therapy, and eculizumab.Results
There was no significant difference in the D+S+ (31 %), D+S? (50 %) and D?S? (19 %) groups in the outcome variables of chronic kidney disease stages I–II (100 % vs 81 % vs 67 %) and proteinuria at follow-up (20 % vs 12.5 % vs 33.3 %), hospitalization duration (16.0?±?8.7 vs 18.1?±?9.5 vs 23.7?±?12.9 days); dialysis requirement (50 % vs 81 % vs 66.7 %), and dialysis duration (10.2?±?1.9 vs 33.3?±?72.8 vs 10.3?±?8.1 days). There was no significant difference in study outcomes in STEC+ (59 %) versus STEC– (41 %) groups. Genetic testing was performed in 12 % of HUS patients based on age, recurrent HUS, familial HUS, persistently low C3, or prolonged dialysis, and 80 % of the patients tested were positive for genetic mutations.Conclusions
Our study does not show poorer outcomes in STEC? HUS. Indications and the cost-effectiveness of genetic testing, eculizumab, and plasmapheresis in STEC? HUS need to be evaluated further.3.
Karolis Ažukaitis Chantal Loirat Michal Malina Irina Adomaitienė Augustina Jankauskienė 《Pediatric nephrology (Berlin, Germany)》2014,29(7):1273-1277
Background
Atypical hemolytic uremic syndrome (aHUS) is a disorder of the complement system which leads to thrombotic microangiopathy. It is caused by either acquired or hereditary defects in the activation or regulation of the alternative complement pathway and is therefore considered to be a disease of local complement dysregulation in microvasculature with predominantly renal involvement. However, extrarenal manifestations are observed in approximately one-fifth of aHUS patients, with the myocardium and central nervous system (CNS) being involved most often. Additionally, there have been a few reports of aHUS with cerebral artery stenoses or periphereal gangrene, suggesting the possibility of ‘macrovascular’ involvement in aHUS.Case-diagnosis/treatment
We present a child with early onset aHUS and a C3 gain-of-function mutation who developed cerebral artery stenoses, leading ultimately to death due to a massive stroke 9 days after successful renal transplantation under prophylactic eculizumab treatment. Similar cases described in the literature are also briefly summarized.Conclusions
The disease course in our patient with aHUS confirms that dysregulated complement activation can induce arterial steno-occlusive lesions in the absence of acute episodes of HUS. Further studies are required to document the frequency of such macrovascular complications and the role of eculizumab treatment in preventing their development and progression. 相似文献4.
Ana Sánchez-Moreno Francisco De la Cerda Rocío Cabrera Julia Fijo Margarita López-Trascasa Rafael Bedoya Santiago Rodríguez de Córdoba Patricia Ybot-González 《Pediatric nephrology (Berlin, Germany)》2014,29(10):2055-2059
Background
Dense-deposit disease (DDD) is a rare glomerulopathy characterized by electron-dense deposits in the glomerular basement membrane. About 50 % of patients with DDD progress to end-stage kidney disease and require dialysis within 10 years of diagnosis, and the disease often recurs after renal transplantation.Case-Diagnosis/Treatment
We describe a 14-year-old girl with recurrent DDD in her transplanted kidney. Clinical onset was at 8 years of age, when steroid-resistant nephrotic syndrome was diagnosed with microhematuria, severe hypocomplementemia and normal kidney function. Although remission was initially observed after several plasma exchanges, nephrotic proteinuria returned and kidney function further declined 1 year later. The patient received a living-related kidney transplant. Initial allograft function was good, but proteinuria reappeared 3 months after transplantation, accompanied by a slight deterioration in kidney function. After histological confirmation of DDD recurrence and subsequent management with plasmapheresis, the patient was treated for 30 months with eculizumab, a humanized monoclonal antibody that binds to C5 complement protein. This intervention proved effective and resulted in complement inhibition, sustained remission of proteinuria and preservation of renal function. A graft biopsy 6 months later showed no progression of the renal lesions.Conclusions
Early clinical and histological recurrence of DDD in the transplanted kidney in this 14-year-old patient was treated for 30 months with eculizumab. The patient remains asymptomatic, has no proteinuria and her kidney function is intact. 相似文献5.
Nesrin Besbas Bora Gulhan Diana Karpman Rezan Topaloglu Ali Duzova Emine Korkmaz Fatih Ozaltin 《Pediatric nephrology (Berlin, Germany)》2013,28(1):155-158
Background
Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Neonatal cases are extremely uncommon. Plasma therapy is the first choice therapy in patients with aHUS based on the belief of an underlying complement dysregulation. Alternatively, eculizumab, which targets complement 5, is used to block complement activation.Case-diagnosis/treatment
Sudden onset macroscopic hematuria, hypertension, and bruises over the entire body were noted in a 5 day-old newborn. Investigations revealed hemolytic anemia, thrombocytopenia, renal impairment, and a low serum C3, leading to the diagnosis of aHUS. Fresh frozen plasma (FFP) infusions and peritoneal dialysis for acute kidney injury were initiated. This approach yielded full renal and hematological remission. The patient was discharged with FFP infusions, but subsequently developed three life-threatening disease recurrences at 1, 3, and 6 months of age. The last relapse presented with uncontrolled hypertension and impaired renal function while the patient was receiving FFP infusions. After the first dose of eculizumab, his renal and hematological parameters returned to normal and his blood pressure normalized. Genetic screening of the CFH gene revealed a novel homozygous p. Tyr1177Cys mutation.Conclusion
Eculizumab can be considered as an alternative to plasma therapy in the treatment of specific patients with aHUS, even in infants. 相似文献6.
Ha Tran Abanti Chaudhuri Waldo Concepcion Paul C. Grimm 《Pediatric nephrology (Berlin, Germany)》2014,29(3):477-480
Background
Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30–100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver–kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver–kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab.Case Diagnosis/Treatment
An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver–kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence.Conclusion
Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver–kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis. 相似文献7.
Hushi Hu Arvind Nagra Mushfequr R. Haq Rodney D. Gilbert 《Pediatric nephrology (Berlin, Germany)》2014,29(6):1103-1106
Background
Atypical haemolytic uraemic syndrome (aHUS) is a rare disorder usually caused by dysregulation of the alternative complement pathway. Uncontrolled complement activation results in systemic complement-mediated thrombotic microangiopathy (TMA) and subsequent multi-organ damage. The two most common extrarenal complications comprise neurological and cardiovascular involvement. Eculizumab, a humanised anti-C5 monoclonal antibody, has recently been introduced as a therapy for this condition.Case-diagnosis/treatment
A 19-month-old child suffering from aHUS with severe neurological involvement, dilated cardiomyopathy and renal impairment requiring dialysis received eculizumab as first-line treatment, initiated within 12 h of admission, resulting in significant improvements in her neurological state and normalisation of cardiac and renal function. These positive outcomes have been sustained with fortnightly eculizumab therapy (at the time of writing, on-going for 1 year). No further complications of TMA have occurred.Conclusion
Severe cardiac involvement in a child with aHUS is an important indication for prompt, first-line treatment with eculizumab, resulting in rapid normalisation of cardiac function. 相似文献8.
Damien Noone Aoife Waters Fred G. Pluthero Denis F. Geary Michael Kirschfink Peter F. Zipfel Christoph Licht 《Pediatric nephrology (Berlin, Germany)》2014,29(5):841-851
Background
Deficiency of complement factor H-related (CFHR) proteins and CFH autoantibody-positive hemolytic uremic syndrome (DEAP-HUS) represents a unique subgroup of complement-mediated atypical HUS (aHUS). Autoantibodies to the C-terminus of CFH block CFH surface recognition and mimic mutations found in the genetic form of (CFH-mediated) aHUS. CFH autoantibodies are found in 10–15 % of aHUS patients and occur—so far unexplained—almost exclusively in the background of CFHR1 or CFHR3/CFHR1 deletions.Methods
As a well-defined role for eculizumab in the treatment of complement-mediated aHUS is becoming established, its role in DEAP-HUS is less conspicuous, where a B-cell-depleting and immunosuppressive treatment strategy is being proposed in the literature.Results
We here show eculizumab to be safe and effective in maintaining a disease-free state, without recurrence, in a previously plasma-therapy-dependent DEAP-HUS patient, and in another patient in whom, although showing a good clinical response to plasma therapy, the therapy was hampered by allergic reactions to fresh frozen plasma and contend there is a rationale for the use of eculizumab in concert with an immunosuppressive strategy in the treatment of DEAP-HUS. Considering the high rate of early relapse, the possible coexistence and contribution of both known and unknown complement-gene mutations, the probable pathogenic role of CFHR1 as a complement alternative pathway (CAP) regulator, the experimental nature of measuring and using anti-CFH autoantibodies to guide management, and until the positive reports of immunosuppression in addition to plasma therapy are confirmed in prospective studies, we feel that a complement-directed therapy should not be neglected in DEAP-HUS. Serial CFH autoantibody titer testing may become a valuable tool to monitor treatment response, and weaning patients off eculizumab may become an option once CFH autoantibody levels are depleted.Conclusions
A prospective study of eculizumab treatment in a larger cohort of DEAP-HUS patients is required to validate the applicability of our positive experience. 相似文献9.
Sally Johnson Jelena Stojanovic Gema Ariceta Martin Bitzan Nesrin Besbas Michelle Frieling Diana Karpman Daniel Landau Craig Langman Christoph Licht Carmine Pecoraro Magdalena Riedl Ekaterini Siomou Nicole van de Kar Johan Vande Walle Chantal Loirat C. Mark Taylor 《Pediatric nephrology (Berlin, Germany)》2014,29(10):1967-1978
Background
In 2009, the European Paediatric Study Group for Haemolytic Uraemic Syndrome (HUS) published a clinical practice guideline for the investigation and initial therapy of diarrhea-negative HUS (now more widely referred to as atypical HUS, aHUS). The therapeutic component of the guideline (comprising early, high-volume plasmapheresis) was derived from anecdotal evidence and expert consensus, and the authors committed to auditing outcome.Methods
Questionnaires were distributed to pediatric nephrologists across Europe, North America, and the Middle East, who were asked to complete one questionnaire per patient episode of aHUS between July 1, 2009 and December 31, 2010. Comprehensive, anonymous demographic and clinical data were collected.Results
Seventy-one children were reported with an episode of aHUS during the audit period. Six cases occurred on a background of influenza A H1N1 infection. Of 71 patients, 59 (83 %) received plasma therapy within the first 33 days, of whom ten received plasma infusion only. Complications of central venous catheters occurred in 16 out of 51 patients with a catheter in-situ (31 %). Median time to enter hematological remission was 11.5 days, and eight of 71 (11 %) patients did not enter hematological remission by day 33. Twelve patients (17 %) remained dialysis dependent at day 33.Conclusions
This audit provides a snapshot of the early outcome of a group of children with aHUS in the months prior to more widespread use of eculizumab. 相似文献10.
Nadia Leban Sabra Aloui Dalel Touati Ramzy Lakhdhar Habib Skhiri Gerard Lefranc Abdellatif Achour Mezri Elmay Margarita Lopez-Trascasa Pilar Sanchez-Corral Jemni Chibani Amel Haj Khelil 《International urology and nephrology》2011,43(2):559-564
Background
Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure.Aim
Our objectives were to determine epidemiology, clinical and laboratory characteristics of patients with atypical hemolytic uremic syndrome (aHUS) to determine the relationship between the complement protein deficit and aHUS in the Tunisian population.Methods
We studied retrospectively four cases of atypical HUS in adults admitted in the Nephrology Department of Fattouma Bourguiba Universitary Hospital in Monastir between 2000 and 2008.Results
Three patients had renal failure that required dialysis. One of them received kidney transplantation with no further recurrence of aHUS. Three patients had normal C3, C4, CFH, and FB levels, and in all patients anti-FH autoantibodies were absent. The kidney biopsy of one patient showed in addition to lupus glomerulonephritis histological findings consistent with TMA. A decrease in C3, C4 and CFH levels in this patient was found both before and after the cure.Conclusion
Nephrologists should be aware of autoimmune conditions and genetic abnormalities of the complement regulatory genes as possible pathogenic mechanisms in atypical HUS patients. 相似文献11.
Astrid Godron Sabine Pereyre Catherine Monet Brigitte Llanas Jérôme Harambat 《Pediatric nephrology (Berlin, Germany)》2013,28(10):2057-2060
Background
Mycoplasma pneumoniae can cause various extrapulmonary manifestations but, to our knowledge, no case of Mycoplasma pneumoniae associated with hemolytic uremic syndrome (HUS) has been reported.Case-Diagnosis/Treatment
We describe a 1-year-old boy with M. pneumoniae respiratory tract infection and associated microangiopathic hemolytic anemia, slightly decreased platelet count and mild renal impairment, suggesting a diagnosis of HUS. Assuming M. pneumoniae infection was the cause of HUS in this case, the different possible mechanisms, including an atypical HUS due to preexisting complement dysregulation, an alternative complement pathway activation induced by M. pneumoniae infection at the acute phase, an autoimmune disorder, and a direct role of the bacteria in inducing endothelial injury, are discussed. The signs of HUS resolved with treatment of the M. pneumoniae infection.Conclusions
Hemolytic uremic syndrome may be an unusual complication of M. pneumoniae infection. 相似文献12.
Caroline Rousset-Rouvière Mathilde Cailliez Florentine Garaix Daniele Bruno Daniel Laurent Michel Tsimaratos 《Pediatric nephrology (Berlin, Germany)》2014,29(6):1107-1111
Background
Dense deposit disease (DDD), a C3 glomerulopathy (C3G), is a rare disease with unfavorable progression towards end-stage kidney disease. The pathogenesis of DDD is due to cytotoxic effects related to acquired or genetic dysregulation of the complement alternative pathway, which is at times accompanied by the production of C3 nephritic factor (C3NeF), an auto-antibody directed against the alternative C3 convertase. Available treatments include plasma exchange, CD20-targeted antibodies, and a terminal complement blockade via the anti-C5 monoclonal antibody eculizumab.Case-diagnosis/Treatment
We report here the case of an 8-year-old child with C3NeF and refractory DDD who presented with a nephritic syndrome. She tested positive for C3NeF activity; C3 was undetectable. Genetic analyses of the alternative complement pathway were normal. Methylprednisolone pulses and mycophenolate mofetil treatment resulted in complete recovery of renal function and a reduction in proteinuria. Corticosteroids were tapered and then withdrawn. Four months after corticosteroid discontinuation, hematuria and proteinuria recurred, and a renal biopsy confirmed an active DDD with a majority of extracapillary crescents. Despite an increase in immunosuppressive drugs, including methylprednisolone pulses and rituximab therapy, the patient suffered acute renal failure within 3 weeks, requiring dialysis. Eculizumab treatment resulted in a quick and impressive response. Hematuria very quickly resolved, kidney function improved, and no further dialysis was required. The patient received bimonthly eculizumab injections of 600 mg, allowing for normalization of renal function and reduction of proteinuria to <0.5 g per day. Since then, she continues to receive eculizumab.Conclusion
Complement regulation pathway-targeted therapy may be a specific and useful treatment for rapidly progressing DDD prior to the development of glomerulosclerosis. Our data provide evidence supporting the pivotal role of complement alternative pathway abnormalities in C3G with DDD. 相似文献13.
Sevgi Gurkan Billie Fyfe Lynne Weiss Xue Xiao Yuzhou Zhang Richard J. Smith 《Pediatric nephrology (Berlin, Germany)》2013,28(10):1975-1981
Background
Hyperactivity of the alternative complement pathway is the principle defect in C3 glomerulopathies (C3G). Eculizumab, a monoclonal antibody that binds C5 to prevent formation of the membrane attack complex, has been shown to be beneficial in some patients with this disease.Methods
In this open-label, proof-of-concept efficacy-and-safety study, a patient with the initial diagnosis of dense deposit disease (DDD) and allograft recurrence of C3 glomerulonephritis (C3GN) was treated with eculizumab every other week for 1 year. The patient had pathological evidence of C3GN and proteinuria >1 g/day at enrollment. He underwent graft biopsy before enrollment and repeat biopsy at 6 and 12 months.Results
Although no mutations were identified in complement genes, functional studies were positive for C3 nephritic factors and elevated levels of soluble membrane attack complex (sMAC). On therapy, sMAC levels normalized and although proteinuria initially decreased, it increased reaching pre-treatment levels at 12 months. Although serum creatinine remained stable, repeat allograft biopsies showed progression of disease.Conclusions
Clinical and histopathologic data suggest a partial response to eculizumab in this patient. While eculizumab blocked activation of the terminal complement cascade, persistent dysregulation of the alternative pathway remained, indicating eculizumab alone cannot control disease in this patient. Additional research is required to identify effective anticomplement therapy for this group of C3G patients. 相似文献14.
Kaan Gulleroglu Kibriya Fidan Veysel S. Hançer Umut Bayrakci Esra Baskin Oguz Soylemezoglu 《Pediatric nephrology (Berlin, Germany)》2013,28(5):827-830
Background
Atypical hemolytic uremic syndrome (aHUS) is associated with defective regulation of the complement pathway. Neurological involvement is the most common extrarenal complication and represents a major cause of mortality and morbidity.Case-diagnosis/treatment
Two girls aged 11 and 6 years, respectively, developed aHUS and were treated immediately with plasma exchange (PE) and fresh frozen plasma infusion (PI). Although initial improvement in renal function was seen in both cases, the first patient showed progressing thrombotic microangiopathy (TMA) despite daily PE, and neurological manifestations (seizures, vision loss, loss of balance, and confusion) developed after 1 month. The second patient developed cerebral TMA (seizures, vision loss, and nystagmus) 6 days after initial presentation and remained unresponsive to PE/PI. Neurological symptoms were similar in both patients, even though they had different complement protein mutations. Treatment with eculizumab achieved complete control of neurological symptoms within 24 h and gradually normalized hematological and renal parameters in both children.Conclusions
Based on our two cases, we conclude that eculizumab is a rapid-acting, effective, and life-saving treatment for pediatric patients with aHUS and severe neurological involvement, which works by inhibiting complement-mediated TMA in the kidney and other organs, such as the brain. 相似文献15.
Ozan Ozkaya Hulya Nalcacioglu Demet Tekcan Gurkan Genc Bilge Can Meydan B. Handan Ozdemir M. Kemal Baysal Hasan Tahsin Keceligil 《Pediatric nephrology (Berlin, Germany)》2014,29(7):1283-1287
Background
Dense deposit disease (DDD) (also known as membranoproliferative glomerulonephritis type II) in childhood is a rare glomerulonephritis with frequent progression to end-stage renal disease (ESRD) and a high recurrence after kidney transplantation. The pathophysiologic basis of DDD is associated with the uncontrolled systemic activation of the alternative pathway (AP) of the complement cascade.Case-diagnosis/treatment
A 14-year-old girl presented with edema and nephrotic range proteinuria. Blood tests showed hypoalbuminemia, nephrotic range proteinuria, normal renal function, and a low C3 level. Renal biopsy confirmed the diagnosis of crescentic DDD. Complement analysis revealed strong AP activation (low C3), positive C3 nephritic factor (C3NeF), and a decreased complement factor H (CFH) levels with CFH polymorphisms. Therapy with eculizumab was considered after the failure of corticosteroid and plasmapheresis to modulate the ongoing massive proteinuria and persistence of low serum C3 levels. There was a marked clinical and biochemical response following the administration of eculizumab.Conclusions
Our case emphasizes the efficacy of eculizumab in the management of crescentic DDD in a patient with a normal renal function, in a short follow-up period. Considering previously reported cases, it appears that eculizumab represents a promising new approach which may prevent progression to ESRD in a subset of patients with DDD. 相似文献16.
Rosanna Coppo Roberto Bonaudo R. Licia Peruzzi Alessandro Amore Andrea Brunati Renato Romagnoli Mauro Salizzoni Miriam Galbusera Eliana Gotti Erica Daina Marina Noris Giuseppe Remuzzi 《Pediatric nephrology (Berlin, Germany)》2016,31(5):759-768
Background
The risk of disease recurrence after a kidney transplant is high in patients with atypical hemolytic uremic syndrome (aHUS) and mutations in the complement factor H (FH) gene (CFH). Since FH is mostly produced by the liver, a kidney transplant does not correct the genetic defect. The anti-C5 antibody eculizumab prevents post-transplant aHUS recurrence, but it does not cure the disease. Combined liver–kidney transplantation has been performed in few patients with CFH mutations based on the rationale that liver replacement provides a source of normal FH.Methods
We report the 9-year follow-up of a child with aHUS and a CFH mutation, including clinical data, extensive genetic characterization, and complement profile in the circulation and at endothelial level. The outcome of kidney and liver transplants performed separately 3 years apart are reported.Results
The patient showed incomplete response to plasma, with relapsing episodes, progression to end-stage renal disease, and endothelial-restricted complement dysregulation. Eculizumab prophylaxis post-kidney transplant did not achieve sustained remission, leaving the child at risk of disease recurrence. A liver graft given 3 years after the kidney transplant completely abrogated endothelial complement activation and allowed eculizumab withdrawal.Conclusions
Liver transplant may definitely cure aHUS and represents an option for patients with suboptimal response to eculizumab.17.
Elena Román-Ortiz Santiago Mendizabal Oteiza Sheila Pinto Margarita López-Trascasa Pilar Sánchez-Corral Santiago Rodríguez de Cordoba 《Pediatric nephrology (Berlin, Germany)》2014,29(1):149-153
Background
Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulation of the complement system. Outcomes of kidney transplantation are poor owing to aHUS recurrence and loss of graft. Patients carrying CFH mutations or CFH/CFHR1 hybrid genes present a very high risk of recurrence despite preventive plasmapheresis. Evaluation of recent data suggests that prophylactic eculizumab pretransplant might be the preferred therapy if available.Case-diagnosis/treatment
We report 3-year follow-up data in a 9-year-old boy with aHUS and successful renal transplant treated with prophylactic eculizumab without recurrence. He presented with aHUS at age 3, irreversible renal failure and uncontrolled severe hypertension with concentric left ventricular hypertrophy, recurrent acute pulmonary edema, and congestive heart failure despite five hypotensive agents and bilateral nephrectomy. Complement analysis demonstrated the presence of a CFH/CFHR1 hybrid gene inherited from his mother and a SNP risk CFH haplotype inherited from his father. Kidney transplant was performed with prophylactic eculizumab and subsequent fortnightly administration. Three years post-transplant, graft function remains stable (serum creatinine 0.9 mg/dl), hypertension is controlled, no left ventricular hypertrophy, no opportunistic infections, and negative clinical chemistry parameters for hemolysis.Conclusion
Eculizumab is a safe and effective therapy for preventing TMA recurrence and provides long-term graft function in aHUS with the CFH/CFHR1 hybrid gene. 相似文献18.
Therese Rosenblad Johan Rebetz Martin Johansson Zivile Békássy Lisa Sartz Diana Karpman 《Pediatric nephrology (Berlin, Germany)》2014,29(11):2225-2228
Background
Immunoglobulin A (IgA) nephropathy is a chronic glomerulonephritis with excessive glomerular deposition of IgA1, C3 and C5b-9, which may lead to renal failure.Case Diagnosis/Treatment
We describe the clinical course of an adolescent with rapidly progressive disease leading to renal failure in spite of immunosuppressive treatment. Due to refractory disease the patient was treated with eculizumab (anti-C5) for 3 months in an attempt to rescue renal function. Treatment led to clinical improvement with stabilization of the glomerular filtration rate and reduced proteinuria. Discontinuation of treatment led to a rapid deterioration of renal function. This was followed by a single dose of eculizumab, which again reduced creatinine levels temporarily.Conclusions
Early initiation of eculizumab therapy in patients with progressive IgA nephropathy may have a beneficial effect by blocking complement-mediated renal inflammation. 相似文献19.
20.
Naoko Ito Hiroshi Hataya Ken Saida Yoshiro Amano Yoshihiko Hidaka Yaeko Motoyoshi Toshiyuki Ohta Yasuhiro Yoshida Chikako Terano Tadashi Iwasa Wataru Kubota Hidetoshi Takada Toshiro Hara Yoshihiro Fujimura Shuichi Ito 《Clinical and experimental nephrology》2016,20(2):265-272