Hemolytic uremic syndromes (HUSs) are a heterogeneous group of conditions, only some of which are mediated by complement (complement-mediated HUS). We report the outcome of the 2023 International Society of Nephrology HUS International Forum where a global panel of experts considered the current state of the art, identified areas of uncertainty, and proposed optimal solutions. Areas of uncertainty and areas for future research included the nomenclature of HUS, novel complement testing strategies, identification of biomarkers, genetic predisposition to atypical HUS, optimal dosing and withdrawal strategies for C5 inhibitors, treatment of kidney transplant recipients, disparity of access to treatment, and the next generation of complement inhibitors in complement-mediated HUS. The current rationale for optimal patient management is described.
- MeSH
- atypický hemolyticko-uremický syndrom genetika imunologie terapie farmakoterapie diagnóza MeSH
- biologické markery krev MeSH
- hemolyticko-uremický syndrom * terapie imunologie diagnóza MeSH
- inhibitory komplementu terapeutické užití MeSH
- komplement imunologie MeSH
- lidé MeSH
- nefrologie * normy metody MeSH
- společnosti lékařské normy MeSH
- transplantace ledvin škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- chronická renální insuficience * farmakoterapie imunologie ošetřování MeSH
- dialýza ledvin MeSH
- hemolyticko-uremický syndrom farmakoterapie imunologie MeSH
- kontraindikace MeSH
- lidé MeSH
- nemoci, jimž lze předcházet očkováním klasifikace MeSH
- transplantace ledvin MeSH
- vakcinace normy MeSH
- vakcíny klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- chronická renální insuficience * MeSH
- hemolyticko-uremický syndrom farmakoterapie imunologie MeSH
- kontraindikace MeSH
- lidé MeSH
- nemoci, jimž lze předcházet očkováním klasifikace MeSH
- transplantace ledvin MeSH
- vakcinace * normy MeSH
- vakcíny klasifikace terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course. We retrospectively analyzed data of 33 pediatric patients between 1999 and 2015 in the Czech Republic. We tested the association of a C3 concentration with biochemical parameters and the clinical data reflecting the severity of the disease. We found significant correlation between the initial C3 and the duration of renal replacement therapy (r = - 0.62, p = 0.0001) and the initial glomerular filtration rate (r = 0.36, p = 0.026). Patients with C3 < 0.825 g/L needed renal replacement therapy and also had significantly more renal complications (p = 0.015).Conclusion: Based on our study, decreased C3 concentrations can be used as one of the risk factors that can help predict the need for acute dialysis and a more severe course of disease in children with diarrhea-associated hemolytic uremic syndrome. What is Known: • Shiga toxin modulates the function of complement regulatory proteins and thus contributes to complement activation in patients with diarrhea-associated hemolytic uremic syndrome. • Risk factors that can predict the need for acute renal replacement therapy and poor outcome in patients with diarrhea-associated hemolytic uremic syndrome are mainly the combination of oligoanuria, dehydration, leukocytosis, high hematocrit > 23%, and neurological involvement. What is New: • A lowered concentration of C3 at the time of initial presentation of diarrhea-associated hemolytic uremic syndrome was associated with more severe renal failure and the need for renal replacement therapy along with the development of more extra renal complications. • Decreased C3 at admission can predict complicated course of diarrhea-associated hemolytic uremic syndrome.
- MeSH
- aktivace komplementu imunologie MeSH
- biologické markery krev MeSH
- dialýza ledvin statistika a číselné údaje MeSH
- dítě MeSH
- hemolyticko-uremický syndrom komplikace imunologie MeSH
- kojenec MeSH
- komplement C3 analýza MeSH
- ledviny patofyziologie MeSH
- lidé MeSH
- předškolní dítě MeSH
- prognóza MeSH
- průjem komplikace imunologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- ROC křivka MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
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
- 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
- MeSH
- finanční podpora výzkumu jako téma MeSH
- hemolyticko-uremický syndrom diagnóza imunologie MeSH
- lidé MeSH
- testování histokompatibility MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kongresy MeSH
- srovnávací studie MeSH
- Klíčová slova
- enterohemolyzin,
- MeSH
- dítě MeSH
- hemolyticko-uremický syndrom diagnóza etiologie imunologie mikrobiologie MeSH
- infekce vyvolané Escherichia coli diagnóza epidemiologie mikrobiologie MeSH
- lidé MeSH
- mikrobiologické techniky * statistika a číselné údaje MeSH
- protilátky MeSH
- průjem diagnóza etiologie mikrobiologie MeSH
- séroskupina MeSH
- shiga toxiny klasifikace MeSH
- shiga-toxigenní Escherichia coli * chemie izolace a purifikace klasifikace patogenita MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- klinická studie MeSH
- MeSH
- bakteriální toxiny biosyntéza MeSH
- cytotoxiny biosyntéza imunologie MeSH
- dítě MeSH
- ELISA MeSH
- Escherichia coli imunologie izolace a purifikace metabolismus MeSH
- feces mikrobiologie MeSH
- hemolyticko-uremický syndrom epidemiologie imunologie mikrobiologie MeSH
- infekce vyvolané Escherichia coli epidemiologie etiologie imunologie MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Česká republika MeSH
The frequency of Vero cytotoxin 1 (VT1)-neutralizing antibody (NAb) in serum specimens from 790 age-stratified (0 to 70 years) control individuals from Toronto was 61 of 790 (7.7%), with a peak of 19% in the 20- to 30-year-old age group and a second peak of 16.7% in the 60- to 70-year-old age group. A total of 568 serum specimens, including 538 from the 790 Toronto control subjects, 21 from patients from three outbreaks of VT-producing Escherichia coli (VTEC) infection, and 9 known VT1-NAb-positive serum specimens from patients with hemolytic-uremic syndrome (HUS), were then tested for the presence of anti-VT1 immunoglobulin G (IgG) by an enzyme-linked immunosorbent assay (ELISA). The mean ELISA values of 522 VT1-NAb-negative serum specimens and 46 VT1-NAb-positive serum specimens were 0.09 +/- 0.06 (range, 0 to 0.56) and 0.78 +/- 0.66 (range, 0.16 to 2.91), respectively (P < 0.001; Student's t test). With a breakpoint of 0.21 (mean ELISA value of the VT1-NAb-negative sera + 2 standard deviations), the sensitivity, specificity, positive predictive value, and negative predictive value of the VT1 IgG ELISA compared with those of the VT1-NAb assay were, respectively, 95.7, 98.7, 86.3, and 99.6%. There were nine discrepant serum specimens, of which seven were anti-VT1 IgG positive and VT1-NAb negative and two were anti-VT1 IgG negative and VT1-NAb positive. The ELISA was also used for testing 238 control serum specimens from The Netherlands, Japan, and India and acute- and convalescent-phase serum specimens from 42 Toronto patients with HUS. The frequencies of anti-VT1 IgG (with VT1-NAb frequencies in parantheses) in control sera from the Netherlands, Japan, and India were 6% (3%), 1.1% (0%), and 12% (10%), respectively, with no age clustering. The frequencies of anti-VT1 IgG seropositivity in HUS patients were 5 of 14 (35.7%) in patients with unknown toxin exposure, 2 of 22 (9.1%) in individuals with known exposure to VT1 plus VT2 or VT1 alone, and 0 of 6 (0%) in patients exposed to only VT2. Development of serum anti-VT1 IgG response appears to be the exception rather than the rule in sporadic HUS patients infected with VTEC expressing VT1. However, in two family outbreaks associated with VTEC strains expressing VT1 alone and VT1 plus VT2, respectively, the presence of anti-VT1 IgG in virtually all exposed individuals who remained symptom free suggests that the presence of antibody was associated with protection.
- MeSH
- bakteriální toxiny * imunologie MeSH
- dítě MeSH
- dospělí MeSH
- ELISA * MeSH
- epidemický výskyt choroby MeSH
- Escherichia coli * imunologie MeSH
- hemolyticko-uremický syndrom imunologie krev mikrobiologie MeSH
- imunoglobulin G imunologie krev MeSH
- incidence MeSH
- infekce vyvolané Escherichia coli epidemiologie imunologie krev MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mléko mikrobiologie MeSH
- nemoci přenášené potravou epidemiologie mikrobiologie MeSH
- neutralizační testy MeSH
- novorozenec MeSH
- prediktivní hodnota testů MeSH
- předškolní dítě MeSH
- protilátky bakteriální * imunologie krev MeSH
- průjem epidemiologie mikrobiologie MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- shiga toxin 1 MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- senioři MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Geografické názvy
- Indie MeSH
- Japonsko MeSH
- Kanada MeSH
- Nizozemsko MeSH
