Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Mutations in genes encoding regulators of the alternative complement pathway (CFH, MCP, C3, CFI, CFB, THBD, and CFHR1-5) are connected with this disease. Polymorphisms (SNPs) in these genes might also influence the manifestation of aHUS. We have analyzed the genes of CFH, CFI, MCP, and C3 in a cohort of 10 unrelated Czech patients with clinically diagnosed familial aHUS. Surprisingly, 4 patients had mutations only in MCP, without mutations in any of the other genes that cause aHUS. Mutations, as yet unpublished, were widely distributed over the gene (SCR2 domain, signal peptide, and cytoplasmic region). The phenotype of the patients and their close relatives (14 individuals) was also investigated. Functional examination of MCP was also provided and proved lower expression on granulocytes in all mutations. Severity of disease varied, but onset was never earlier than 5 years of age. Penetrance of disease was 50% among carriers. We found that the severity and recurrence of the disease within families varied and might also be dependent on SNPs. Mutations in the MCP gene seems to be a common etiology of aHUS in Czech patients.

• MeSH
• antigeny CD46 genetika   metabolismus   MeSH
• atypický hemolyticko-uremický syndrom MeSH
• dítě MeSH
• dospělí MeSH
• fenotyp MeSH
• genetická predispozice k nemoci MeSH
• granulocyty imunologie   MeSH
• hemolyticko-uremický syndrom genetika   imunologie   terapie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• penetrance MeSH
• prognóza MeSH
• recidiva MeSH
• rodokmen MeSH
• stupeň závažnosti nemoci MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• antigeny CD46 MeSH
• CD46 protein, human MeSH Prohlížeč

A typical hemolytic uremic syndrome (aHUS) presents similarly to thrombotic thrombocytopenic purpura (TTP) and other causes or conditions with thrombotic microangiopathy (TMA), such as disseminated intravascular coagulation or sepsis. Similarity in clinical presentation may hinder diagnosis and optimal treatment selection in the urgent setting in the ICU. However, there is currently no consensus on the diagnosis or treatment of aHUS for ICU specialists. This review aims to summarize available data on the diagnosis and treatment strategies of aHUS in the ICU to enhance the understanding of aHUS diagnosis and outcomes in patients managed in the ICU. To this end, a review of the recent literature (January 2009-March 2016) was performed to select the most relevant articles for ICU physicians. Based on the paucity of adult aHUS cases overall and within the ICU, no specific recommendations could be formally graded for the critical care setting. However, we recognize a core set of skills required by intensivists for diagnosing and managing patients with aHUS: recognizing thrombotic microangiopathies, differentiating aHUS from related conditions, recognizing involvement of other organ systems, understanding the pathophysiology of aHUS, knowing the diagnostic workup and relevant outcomes in critically ill patients with aHUS, and knowing the standard of care for patients with aHUS based on available data and guidelines. In conclusion, managing critically ill patients with aHUS requires basic skills that, in the absence of sufficient data from patients treated within the ICU, can be gleaned from an increasingly relevant literature outside the ICU. More data on critically ill patients with aHUS are needed to validate these conclusions within the ICU setting.

• Klíčová slova
• atypical hemolytic uremic syndrome, eculizumab, intensive care, organ failure, plasma exchange, thrombocytopenia, thrombotic microangiopathy,
• MeSH
• atypický hemolyticko-uremický syndrom diagnóza   etiologie   terapie   MeSH
• diferenciální diagnóza MeSH
• dospělí MeSH
• genetické testování metody   MeSH
• komplement metabolismus   MeSH
• kvalita zdravotní péče normy   MeSH
• lidé MeSH
• péče o pacienty v kritickém stavu normy   MeSH
• protein ADAMTS13 metabolismus   MeSH
• standardní péče MeSH
• výměna plazmy metody   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ADAMTS13 protein, human MeSH Prohlížeč
• komplement MeSH
• protein ADAMTS13 MeSH

BACKGROUND: Streptococcus pneumoniae-associated hemolytic uremic syndrome (P-HUS) is a rare and severe disease. Only a few reports have been published about eculizumab use in P-HUS. METHODS: We analyzed demographic, clinical, and laboratory data of patients with P-HUS from our center. RESULTS: The cohort consisted of 4 females and 3 males. All patients had pneumonia. Four were given eculizumab (days 1-3). The eculizumab group required a shorter duration of dialysis and mechanical ventilation (medians 20 vs. 28.5 and 30 vs 38.5 days, respectively) compared with the non-eculizumab group, but this was still much longer than normally reported; the thrombocytopenia resolution was similar in both groups (medians 10 vs. 8 days). Chronic kidney disease (CKD) was correlated with the duration of dialysis and mechanical ventilation duration at 1 year (r = 0.797, P = 0.032 and r = 0.765, P = 0.045) and last follow-up (r = 0.807, P = 0.028 and r = 0.814, P = 0.026, respectively); our scoring system showed even stronger correlations (r = 0.872, P = 0.011 and r = 0.901, P = 0.0057, respectively). The eculizumab group showed slightly better 1-year and last follow-up CKD stage (2.75 vs. 3, P = 0.879 and 2.5 vs. 3.67, P = 0.517). CONCLUSIONS: Despite the fact that the eculizumab group showed better outcomes, eculizumab does not seem to improve the course of P-HUS compared with previous reports. Kidney outcomes are strongly correlated with the duration of dialysis and mechanical ventilation duration. A higher resolution version of the Graphical abstract is available as Supplementary information.

• Klíčová slova
• Chronic kidney disease, Dialysis, Eculizumab, Hemolytic uremic syndrome, Streptococcus pneumoniae,
• MeSH
• atypický hemolyticko-uremický syndrom * komplikace   farmakoterapie   MeSH
• chronická renální insuficience * komplikace   MeSH
• dialýza ledvin MeSH
• hemolyticko-uremický syndrom * komplikace   farmakoterapie   MeSH
• ledviny MeSH
• lidé MeSH
• Streptococcus pneumoniae MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• eculizumab MeSH Prohlížeč

Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries. In about 60% of cases, the genetic origin of the disease can be identified-commonly mutations affecting complementary factor H and MCP protein. Eculizumab, a monoclonal antibody to the C5 component of the complement, represents the current effective treatment.We describe a case of a young woman with a previous history of polyvalent allergies, who developed atypical hemolytic uremic syndrome after vaccination with mRNA vaccine against SARS-CoV-2. The disease manifested by scleral bleeding, acute renal insufficiency, anemia, and thrombocytopenia. The patient was treated with plasma exchanges without sufficient effect; remission occurred only after starting treatment with eculizumab. Genetic examination showed that the patient is a carrier of multiple inherited risk factors (a rare pathogenic variant in CFH, MCPggaac haplotype of the CD46 gene, and the risk haplotype CFH H3). The patient is currently in hematological remission with persistent mild renal insufficiency, continuing treatment with eculizumab/ravulizumab. By this case report, we meant to point out the need for careful monitoring of people after vaccination, as it may trigger immune-mediated diseases, especially in those with predisposing factors.

• Klíčová slova
• acute kidney injury, atypical hemolytic uremic syndrome, complement, eculizumab, genetic risk, mRNA vaccine against SARS-CoV-2, ravulizumab, thrombotic microangiopathies,
• MeSH
• akutní poškození ledvin * komplikace   MeSH
• atypický hemolyticko-uremický syndrom * genetika   diagnóza   MeSH
• COVID-19 * MeSH
• komplement - faktor H genetika   MeSH
• komplement genetika   MeSH
• lidé MeSH
• messenger RNA MeSH
• monoklonální protilátky MeSH
• mRNA vakcíny MeSH
• SARS-CoV-2 MeSH
• vakcinace škodlivé účinky   MeSH
• vakcíny proti COVID-19 škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• komplement - faktor H MeSH
• komplement MeSH
• messenger RNA MeSH
• monoklonální protilátky MeSH
• vakcíny proti COVID-19 MeSH

Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare disease, and up to 70% of the patients have a genetic mutation in the encoding components of complement activation or anti-complement factor H autoantibodies. The risk of recurrence after kidney transplantation is 10% to 80%. Eculizumab, a monoclonal antibody that binds complement protein C5, has shown to be highly effective in patients with aHUS; however, there are only few reports on the efficacy and safety of long-term eculizumab treatment in children with recurrent aHUS. Only 3 case reports regard treatment in patients with complement factor H (CFH/CFHR1/CFHR3) hybrid gene. This report presents the efficacy and safety of long-term eculizumab treatment in a child with recurrent aHUS who has been successfully treated with eculizumab for more than 7 years. The patient presented as a 9-year-old with aHUS due to CFH/CFHR1/CFHR3 hybrid gene and received deceased donor kidney transplantation. After the transplantation, he experienced recurrence of aHUS 2 months later. Daily plasma exchanges were ineffective in the transplanted kidney; the patient became anuric and hemodialysis was needed. Eculizumab was started as therapy and led to complete remission of aHUS including restoration of diuresis. Eculizumab has been given as therapy for 7 years. The young patient is in a sustained remission without any adverse events. This patient is only the sixth patient reported with recurrent aHUS due to CFH/CFHR1/CFHR3 hybrid gene and is the patient with the longest remission of recurrent aHUS ever published.

• MeSH
• aktivace komplementu genetika   MeSH
• atypický hemolyticko-uremický syndrom farmakoterapie   genetika   chirurgie   MeSH
• časové faktory MeSH
• dítě MeSH
• humanizované monoklonální protilátky aplikace a dávkování   MeSH
• komplement - faktor H genetika   MeSH
• lidé MeSH
• monoklonální protilátky aplikace a dávkování   MeSH
• mutace MeSH
• pooperační komplikace farmakoterapie   genetika   MeSH
• recidiva MeSH
• transplantace ledvin škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• CFH protein, human MeSH Prohlížeč
• eculizumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH
• komplement - faktor H MeSH
• monoklonální protilátky MeSH

• Klíčová slova
• atypical haemolytic uremic syndrome, complement system, eculizumab, living-donor kidney transplantation,
• MeSH
• atypický hemolyticko-uremický syndrom chirurgie   MeSH
• dospělí MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• lidé MeSH
• předoperační péče metody   MeSH
• rejekce štěpu prevence a kontrola   MeSH
• transplantace ledvin metody   MeSH
• žijící dárci * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• kazuistiky MeSH
• Názvy látek
• eculizumab MeSH Prohlížeč
• humanizované monoklonální protilátky MeSH

Atypical haemolytic uraemic syndrome is an ultra-rare, life-threatening disease. Causative variants in genes that encode complement factors can be identified in 40-70% of cases. We performed genetic analysis of 21 Czech children with atypical haemolytic uraemic syndrome. Genetic or acquired predisposition to the disease was identified in the majority of our patients: CFHR1 and CFHR3 deletions in 14/21 (67%; 13 of them were positive for anti-complement factor H antibodies), variants in complement genes or DGKE in 13/21 (62%). Multiple genetic findings were identified in eight patients (38%). The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population was estimated to be 0.092 (CI 0.053-0.131) cases per million inhabitants and 0.92 (CI 0.53-1.32) cases per 100,000 births for the entire reporting period. Ten patients were initially treated with plasma exchange and eight with eculizumab or with a combination of eculizumab and plasma exchange. At the last follow-up, 20 patients were alive and one patient had end-stage renal disease.Conclusion: The incidence of atypical haemolytic uraemic syndrome in the Czech paediatric population corresponds to the reported incidence in Europe. We detected the unusually high rate of CFHR1/CFHR3 deletions associated with anti-complement factor H antibodies in Czech paediatric patients. Treatment by eculizumab led to superior outcomes and prevention of the disease relapses compared with plasma exchange therapy. Our results may help to understand the polygenic nature of atypical haemolytic uraemic syndrome as a disease that results from a combination of various risk factors. What is Known: • Atypical haemolytic uraemic syndrome (aHUS) is considered a polygenic and multifactorial disease. Genetic predisposition to aHUS is identified in 40-70% of children. • Anti-complement factor H antibodies are usually found in 6-25% of affected children. What is New: • Potentially causative genetic or acquired factors were confirmed in the majority of patients. The prevailing finding was the unusually high rate of CFHR1/CFHR3 deletions associated with anti-complement factor H antibodies (62% of patients). • The incidence of aHUS in Czech children is 0.092 (CI 0.053-0.131) cases per million inhabitants and 0.92 (CI 0.53-1.32) cases per 100,000 births for the entire reporting period.

• Klíčová slova
• Alternative complement pathway, Anti-complement factor H antibodies, Atypical haemolytic uraemic syndrome, Children, DGKE, Next-generation sequencing,
• MeSH
• atypický hemolyticko-uremický syndrom * epidemiologie   genetika   terapie   MeSH
• dítě MeSH
• lidé MeSH
• rizikové faktory MeSH
• výměna plazmy MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika epidemiologie   MeSH
• Evropa MeSH

Hemolytic-uremic syndrome (HUS) is the most common cause of acute renal failure in children below 3 years of age. It is defined by a triad of symptoms which associates hemolytic anemia with fragmented erythrocytes, thrombocytopenia and acute renal failure. Three types of HUS can be distinguished: typical HUS, also called diarrhoea-associated (D+HUS), very rare atypical HUS (D-HUS) and secondary HUS (drug induced, C+HUS, in patients receiving marrow transplantation, etc.). The common event among these entities appears to be vascular endothelial cell injury, which induces mechanical destruction of erythrocytes, activation of platelet aggregation and local intravascular coagulation, especially in the renal microvasculature. D+HUS represents 90% of HUS in children. Evidence of exposure to verotoxin (VT), shiga toxin (ST) producing Escherichia coli (VTEC or STEC) has been demonstrated in many countries in about 85% of cases. Serotype O157:H7 is the most frequent. Early and accurate supportive treatment and early start of dialysis is the major importance and allows a current mortality rate below 5%-10%. Vital prognosis is compromized in cases with multivisceral involvement. After 15 years or more of apparent recovery, 20 to 60% of patients have residual renal symptoms, with up to 20% having chronic renal insufficiency (CRI) or end-stage renal disease (ESRD). Atypical HUS represents less than 10% of HUS in children. Some of these cases (familial) are associated with low C3 levels, hereditary deficiency of factor H or with mutations in factor H gene. The deficiency of von Willebrand factor cleaving protease, as reported in adults with thrombotic thrombocytopenic purpura (TTP), is not present in D+HUS.

• MeSH
• hemolyticko-uremický syndrom * komplikace   diagnóza   terapie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

Thrombotic microangiopathy (TMA) refers to phenotypically similar disorders, including hemolytic uremic syndromes (HUS) and thrombotic thrombocytopenic purpura (TTP). This review explores the role of the influenza virus as trigger of HUS or TTP. We conducted a literature survey in PubMed and Google Scholar using HUS, TTP, TMA, and influenza as keywords, and extracted and analyzed reported epidemiological and clinical data. We identified 25 cases of influenza-associated TMA. Five additional cases were linked to influenza vaccination and analyzed separately. Influenza A was found in 83%, 10 out of 25 during the 2009 A(H1N1) pandemic. Two patients had bona fide TTP with ADAMTS13 activity <10%. Median age was 15 years (range 0.5-68 years), two thirds were male. Oligoanuria was documented in 81% and neurological involvement in 40% of patients. Serum C3 was reduced in 5 out of 14 patients (36%); Coombs test was negative in 7 out of 7 and elevated fibrin/fibrinogen degradation products were documented in 6 out of 8 patients. Pathogenic complement gene mutations were found in 7 out of 8 patients tested (C3, MCP, or MCP combined with CFB or clusterin). Twenty out of 24 patients recovered completely, but 3 died (12%). Ten of the surviving patients underwent plasma exchange (PLEX) therapy, 5 plasma infusions. Influenza-mediated HUS or TTP is rare. A sizable proportion of tested patients demonstrated mutations associated with alternative pathway of complement dysregulation that was uncovered by this infection. Further research is warranted targeting the roles of viral neuraminidase, enhanced virus-induced complement activation and/or ADAMTS13 antibodies, and rational treatment approaches.

• Klíčová slova
• ADAMTS13, Complement, Hemolytic uremic syndrome, Influenza vaccine, Neuraminidase, Plasma exchange, Thrombotic-thrombocytopenic purpura,
• MeSH
• alternativní dráha komplementu genetika   imunologie   MeSH
• anurie epidemiologie   etiologie   terapie   MeSH
• atypický hemolyticko-uremický syndrom epidemiologie   etiologie   imunologie   terapie   MeSH
• chřipka lidská komplikace   imunologie   prevence a kontrola   MeSH
• ledviny krevní zásobení   imunologie   patologie   MeSH
• lidé MeSH
• mikrocévy imunologie   patologie   MeSH
• mutace MeSH
• neuraminidasa imunologie   MeSH
• oligurie epidemiologie   etiologie   terapie   MeSH
• protein ADAMTS13 imunologie   metabolismus   MeSH
• trombotická trombocytopenická purpura epidemiologie   etiologie   imunologie   terapie   MeSH
• vakcíny proti chřipce škodlivé účinky   MeSH
• virové proteiny imunologie   MeSH
• virus chřipky A imunologie   MeSH
• výměna plazmy MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ADAMTS13 protein, human MeSH Prohlížeč
• NA protein, influenza A virus MeSH Prohlížeč
• neuraminidasa MeSH
• protein ADAMTS13 MeSH
• vakcíny proti chřipce MeSH
• virové proteiny MeSH

OBJECTIVE: The aim of this study is to draw attention to a nosological unit called thrombotic microangiopathy (TMA). This syndrome represents a serious pathological condition characterized by microangiopathic haemolytic anemia (MAHA), thrombocytopenia and various organ dysfunction. Patients are most often presented with symptoms of the HELLP syndrome but if the clinical picture is not restituted within 48-72 hours after delivery, other TMAs should be considered. SETTING: Department of Obstetrics and Gynecology, 1st Medical Faculty and General Teaching Hospital Prague; Clinic of Nephrology, 1st Medical Faculty and General Teaching Hospital Prague; Department of Obstetrics and Gynecology, Regional Hospital Kolín. DESIGN: Review article and case reports. METHODS: Review of the literature and description of two cases of TMA. CONCLUSION: The authors present a basic overview of the issue of TMA, which requires interdisciplinary cooperation of obstetricians, anesthesiologists, nephrologists and hematologists. In the second part of the article, we present two TMA case reports and finally show the differential diagnostic and therapeutic scheme as agreed by the authorities in the field.

• Klíčová slova
• HELLP syndrome, acute fatty liver of pregnancy, atypical hemolytic uremic syndrome, eculizumab, hemolytic uremic syndrome, thrombotic microangiopathy, thrombotic thrombocytopenic purpura,
• MeSH
• kardiovaskulární komplikace v těhotenství diagnóza   terapie   MeSH
• lidé MeSH
• těhotenství MeSH
• trombotická trombocytopenická purpura MeSH
• trombotické mikroangiopatie diagnóza   terapie   MeSH
• týmová péče o pacienty MeSH
• Check Tag
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• přehledy MeSH