Outcome 10 years after Shiga toxin-producing E. coli (STEC)-associated hemolytic uremic syndrome: importance of long-term follow-up.

BACKGROUND: Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury in children. HUS is known as an acute disease followed by complete recovery, but patients may present with kidney abnormalities after long periods of time. This study evaluates the long-term outcome of Shiga toxin-producing Escherichia coli-associated HUS (STEC-HUS) in pediatric patients, 10 years after the acute phase of disease to identify risk factors for long-term sequelae. METHODS: Over a 6-year period, 619 patients under 18 years of age with HUS (490 STEC-positive, 79%) were registered in Austria and Germany. Long-term follow-up data of 138 STEC-HUS-patients were available after 10 years for analysis. RESULTS: A total of 66% (n = 91, 95% CI 0.57-0.73) of patients fully recovered showing no sequelae after 10 years. An additional 34% (n = 47, 95% CI 0.27-0.43) presented either with decreased glomerular filtration rate (24%), proteinuria (23%), hypertension (17%), or neurological symptoms (3%). Thirty had sequelae 1 year after STEC-HUS, and the rest presented abnormalities unprecedented at the 2-year (n = 2), 3-year (n = 3), 5-year (n = 3), or 10-year (n = 9) follow-up. A total of 17 patients (36.2%) without kidney abnormalities at the 1-year follow-up presented with either proteinuria, hypertension, or decreased eGFR in subsequent follow-up visits. Patients needing extracorporeal treatments during the acute phase were at higher risk of presenting symptoms after 10 years (p < 0.05). CONCLUSIONS: Patients with STEC-HUS should undergo regular follow-up, for a minimum of 10 years following their index presentation, due to the risk of long-term sequelae of their disease. An initial critical illness, marked by need of kidney replacement therapy or plasma treatment may help predict poor long-term outcome.

Laser written mirror profiles for open-access fiber Fabry-Perot microcavities.

We demonstrate laser-written concave hemispherical structures produced on the endfacets of optical fibers that serve as mirror substrates for tunable open-access microcavities. We achieve finesse values of up to 200, and a mostly constant performance across the entire stability range. This enables cavity operation also close to the stability limit, where a peak quality factor of 1.5 × 104 is reached. Together with a small mode waist of 2.3 µm, the cavity achieves a Purcell factor of C ∼ 2.5, which is useful for experiments that require good lateral optical access or otherwise large separation of the mirrors. Laser-written mirror profiles can be produced with a tremendous flexibility in shape and on various surfaces, opening new possibilities for microcavities.

Induction of remission with tacrolimus in a patient with severe acute, cortisone refractory ulcerative colitis and severe Covid-19 pneumonia: a case report.

BACKGROUND: Therapy regimens used in patients with inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections or viral reactivation. Moreover, it is uncertain whether IBD patients have increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or infected patients may have an increased risk for severe coronavirus disease 2019 (Covid-19). Managing severe acute flare in ulcerative colitis during the Covid-19 pandemic is a challenge for clinicians and their patients. The results of the published studies mainly report on the role of the prior medication, but not how to treat severe acute flare of IBD patients with severe Covid-19 pneumonia. CASE PRESENTATION: We report the case of a 68-year-old patient with a long history of ulcerative colitis. He was initially admitted to an external hospital because of severe acute flare. The initiation of a high-dose oral cortisone therapy did not improve the clinical symptoms. During the inpatient treatment, he was tested positive for SARS-CoV-2. At admission to our hospital the patient showed severe flare of his ulcerative colitis and increased Covid-19 symptoms. A cortisone-refractory course was noticed. After detailed multidisciplinary risk-benefit assessment, we initiated an intravenous tacrolimus therapy and dose of prednisolone was tapered gradually. After clinical response, the therapy was adjusted to infliximab. Additionally, the Covid-19 pneumonia was kept under control despite immunosuppression and the patient could be discharged in clinical remission. CONCLUSIONS: This case suggest the use of tacrolimus as a bridging therapeutic option for severe acute, cortisone refractory ulcerative colitis in Covid-19 patients. Nevertheless, the best treatment strategy for IBD patients presenting a flare during the outbreak has yet to be defined. Further data for IBD patients under calcineurin inhibitor therapy are urgently needed.

Early relapse rate determines further relapse risk: results of a 5-year follow-up study on pediatric CFH-Ab HUS.

BACKGROUND: The complement factor H antibody (CFH-Ab)-associated hemolytic uremic syndrome (HUS) forms a distinct subgroup within the complement-mediated HUS disease spectrum. The autoimmune nature of this HUS subgroup implies the potential benefit of a targeted immunosuppressive therapy. Data on long-term outcome are scarce. METHODS: This observational study evaluates the clinical outcome of 19 pediatric CFH-Ab HUS patients from disease onset until their 5-year follow-up. RESULTS: All but one relapse occurred during the first 2 years, and patients who had no relapse within the first 6 months were relapse-free until the end of the observation period. Kidney function at disease onset determines long-term kidney function: all individuals with normal kidney function at disease onset had normal kidney function after 5 years, and all patients with reduced kidney function at onset had impaired kidney function at the last follow-up. Level of CFH-Ab titer at disease onset was not correlated with a higher risk of recurrences or worse long-term outcome after 5 years. Resolution of CFH-Ab titers after 5 years was common. CONCLUSIONS: CFH-Ab HUS patients have a varied overall long-term course. Early relapses are common, making close surveillance during the first years essential, regardless of the initial CFH-Ab titer.

Liver Stiffness Measured by 2-Dimensional Shear Wave Elastography: Prospective Evaluation of Healthy Volunteers and Patients With Liver Cirrhosis.

OBJECTIVES: We aimed to establish normal values for liver stiffness measurement, performed by 2-dimensional shear wave elastography (LOGIQ E9; GE Healthcare, Wauwatosa, WI), in healthy volunteers, patients with nonhepatic morbidities, and patients with histologically confirmed liver cirrhosis. METHODS: A total of 175 participants were included between July 2016 and February 2018. Three cohorts were analyzed: healthy volunteers (n = 68), patients with healthy livers but nonhepatic morbidities (n = 57), and patients with liver cirrhosis (n = 50). Liver stiffness measurement was performed by 2 observers with different levels of experience to determine interobserver agreement. RESULTS: Of the 175 participants included, 91 were male, and the mean age ± SD was 44.4 ± 19.4 years. The success rate for 175 liver stiffness measurements was 95.4%. The number of unsuccessful measurements was significantly higher in the liver cirrhosis cohort (P = .04). The interobserver agreement was excellent (intraclass correlation coefficient, 0.87). Liver stiffness in the healthy-liver patient cohort (4.93 ± 0.83 kPa) was not significantly different from that in the healthy-volunteer cohort (5.19 ± 1.03 kPa; P = .13). Apart from male sex in the healthy-volunteer cohort, age, body mass index, mild steatosis, and nonhepatic morbidities had no significant impact on liver stiffness. Liver stiffness values in participants without liver disease (healthy volunteers and healthy-liver patients; n = 125) ranged from 3.62 to 7.02 kPa (2.5th-97.5th percentiles). Notably, there was no overlap of liver stiffness measurements between the patients without liver disease and the cirrhosis cohort (13.29 ± 3.27 kPa [7.76-19.49 kPa]). CONCLUSIONS: Liver stiffness values in healthy individuals vary widely and are not dependent on age, body mass index, or specific nonhepatic comorbidities. Liver stiffness values within the normal range can noninvasively rule out cirrhosis, as liver stiffness is significantly higher in cirrhotic patients (P < .001). Two-dimensional shear wave elastography has excellent interobserver agreement.

Kidney Injury by Variants in the COL4A5 Gene Aggravated by Polymorphisms in Slit Diaphragm Genes Causes Focal Segmental Glomerulosclerosis.

Kidney injury due to focal segmental glomerulosclerosis (FSGS) is the most common primary glomerular disorder causing end-stage renal disease. Homozygous mutations in either glomerular basement membrane or slit diaphragm genes cause early renal failure. Heterozygous carriers develop renal symptoms late, if at all. In contrast to mutations in slit diaphragm genes, hetero- or hemizygous mutations in the X-chromosomal COL4A5 Alport gene have not yet been recognized as a major cause of kidney injury by FSGS. We identified cases of FSGS that were unexpectedly diagnosed: In addition to mutations in the X-chromosomal COL4A5 type IV collagen gene, nephrin and podocin polymorphisms aggravated kidney damage, leading to FSGS with ruptures of the basement membrane in a toddler and early renal failure in heterozygous girls. The results of our case series study suggest a synergistic role for genes encoding basement membrane and slit diaphragm proteins as a cause of kidney injury due to FSGS. Our results demonstrate that the molecular genetics of different players in the glomerular filtration barrier can be used to evaluate causes of kidney injury. Given the high frequency of X-chromosomal carriers of Alport genes, the analysis of genes involved in the organization of podocyte architecture, the glomerular basement membrane, and the slit diaphragm will further improve our understanding of the pathogenesis of FSGS and guide prognosis of and therapy for hereditary glomerular kidney diseases.

Ig-like transcript 4 as a cellular receptor for soluble complement fragment C4d.

Complement regulation leads to the generation of complement split products (CSPs) such as complement component (C)4d, a marker for disease activity in autoimmune syndromes or antibody-mediated allograft rejection. However, the physiologic role of C4d has been unknown. By screening murine thymoma BW5147 cells expressing a cDNA library generated from human monocyte-derived dendritic cells with recombinant human C4d, we identified Ig-like transcript (ILT)4 and ILT5v2 as cellular receptors for C4d. Both receptors, expressed on monocytes, macrophages, and dendritic cells, also interacted with the CSPs C3d, C4b, C3b, and iC3b. However, C4d did not bind to classic complement receptors (CRs). Interaction between cell surface-resident ILT4 and soluble monomeric C4d resulted in endocytosis of C4d. Surprisingly, binding of soluble ILT4 to C4d covalently immobilized to a cellular surface following classic complement activation could not be detected. Remarkably, C4d immobilized to a solid phaseviaits intrinsic thioester conferred a dose-dependent inhibition of TNF-α and IL-6 secretion in monocytes activatedviaFc-cross-linking of up to 50% as compared to baseline. Similarly, C4d conferred an attenuation of intracellular Ca(2+)flux in monocytes activatedviaFc-cross-linking. In conclusion, ILT4 represents a scavenger-type endocytotic CR for soluble monomeric C4d, whereas attenuation of monocyte activation by physiologically oriented C4d on a surface appears to be dependent on a yet to be identified C4d receptor.-Hofer, J., Forster, F., Isenman, D. E., Wahrmann, M., Leitner, J., Hölzl, M. A., Kovarik, J. K., Stockinger, H., Böhmig, G. A., Steinberger, P., Zlabinger, G. J. Ig-like transcript 4 as a cellular receptor for soluble complement fragment C4d.

Therapeutic plasma exchange in children: One center's experience.

BACKGROUND: Therapeutic plasma exchange (TPE) has evolved to an accepted therapy for selected indications. However, it is technically challenging in children. Moreover, data on safety and efficacy are mainly derived from adult series. The aim of this study was to review the procedure in the context of clinical indications, effectiveness, and safety. STUDY DESIGN AND METHODS: All TPE procedures performed at a tertiary care hospital during a 12-year period (2005-2016) were retrospectively evaluated. RESULTS: Eighteen patients with a median age of 8.5 (0.2-17) years underwent a total of 280 TPE sessions. Eleven (61%) patients were treated for renal diseases. Three (17%) patients were diagnosed with neurological diseases, two had liver failure, and one patient each had sepsis and stem cell transplant-associated thrombotic microangiopathy. Seven patients (39%) were classified as American Society for Apheresis Category I, four (22%) as Category II, two (13%) each as Category III and IV, and two (13%) were not classified. Two patients with atypical hemolytic-uremic syndrome received TPE as long-term therapy over 2 and 5 years. All procedures were performed using the filtration technique and heparin anticoagulation. Twelve (67%) patients showed full or partial recovery after TPE, six had no response or an uncertain response. Minor adverse events occurred in 30/280 (10.6%) procedures, and one major complication (0.4%) was reported. CONCLUSION: TPE is a safe apheresis method in children, even when performed as a long-term therapy. Efficacy is high under selected conditions. A highly skilled and experienced staff is mandatory to ensure patient safety and efficacy.

Resveratrol enhances TNF-α production in human monocytes upon bacterial stimulation.

BACKGROUND: Resveratrol is a key component of red wine that has been reported to have anti-carcinogenic and anti-aging properties. Additional studies conducted in vitro and in animal models suggested anti-inflammatory properties. However, data from primary human immune cells and in vivo studies are limited. METHODS: A pilot study was performed including 10 healthy volunteers. Plasma cytokine levels were measured over 48h after oral application of 5g resveratrol. To verify the in vivo findings, cytokine release and gene expression in human peripheral blood mononuclear cells (PBMC) and/or monocytes was assessed after treatment with resveratrol or its metabolites and stimulation with several toll-like receptor (TLR)-agonists. Additionally, the impact on intracellular signaling pathways was analyzed using a reporter cell line and Western blotting. RESULTS: Resveratrol treated individuals showed a significant increase in tumor necrosis factor-α (TNF-α) levels 24h after treatment compared to baseline. Studies using human PBMC or isolated monocytes confirmed potentiation of TNF-α production with different TLR agonists, while interleukin (IL)-10 was inhibited. Moreover, we observed significantly enhanced nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation using a reporter cell line and found increased phosphorylation of p105, which is indicative of alternative NF-κB pathway activation. GENERAL SIGNIFICANCE: By administering resveratrol to healthy humans and utilizing primary immune cells we were able to detect TNF-α enhancing properties of the agent. In parallel, we found enhanced alternative NF-κB activation. We report on a novel pro-inflammatory property of resveratrol which has to be considered in concepts of its biologic activity.

Successful living-related renal transplantation in a patient with factor H antibody-associated atypical hemolytic uremic syndrome.

CFH-Ab-associated aHUS requires different diagnostic and therapeutic approaches and then the genetically defined aHUS forms. The risk of post-transplant recurrence with graft dysfunction in CFH-Ab aHUS is not well documented. It is suggested that recurrence can be expected if a significant CFH-Ab load persists at the time of transplantation. A pretransplant procedure to reduce CFH-Ab titer seems reasonable, but accurate recommendations are lacking. Whether further prophylactic interventions after transplantation are necessary has to be decided on an individual basis. We report the case of a late diagnosed CFH-Ab HUS with initial ESRD and a successful living-related renal transplantation over a post-transplant period of four and a half years on the basis of a prophylactic pretransplant IVIG admission.

Favorable four-yr outcome after renal transplantation in a patient with complement factor H antibody and CFHR1/CFHR3 gene mutation-associated HUS.

UNLABELLED: aHUS is a clinical challenge for successful renal transplantation. CASE REPORT: A 14-yr-old girl lost her kidneys at the age of 7, due to CFH antibodies and CFH-related protein (CFHR1/CFHR3) homozygous deletion-associated aHUS. CFH, CFI, and MCP gene mutations were excluded. The patient was a candidate for renal transplantation despite persistent presence of CFH antibodies (up to 539 AU/mL). Treatment with MMF, IVIG, and repeated PF (n = 8) was introduced while being placed on urgent waiting list. Three years after aHUS onset, the patient underwent the deceased donor renal transplantation "under cover" of PF, as PF was performed directly prior to surgery and, then, PFs were repeated up to overall 14 sessions. Quadruple immunosuppression (basiliximab + tacrolimus + MMF + prednisolone) was used. Moderate symptoms of aHUS (hemolysis, low platelets, and low C3) were present within first seven days post-transplant and then normalized with PF therapy. The patient remained stable during four yr of further follow-up after transplantation. CONCLUSION: Specific pre- and post-transplant management allowed successful renal transplantation in a CFH antibody-positive patient.

De novo tacrolimus-induced thrombotic microangiopathy in the early stage after renal transplantation successfully treated with conversion to everolimus.

BACKGROUND: Calcineurin inhibitor (CNI)-induced thrombotic microangiopathy (TMA) is a rare complication after renal transplantation. It may be difficult to distinguish from CNI toxicity and acute antibody-mediated rejection (AMR). Its clinical presentation may vary from isolated localised forms up to catastrophic systemic presentations. CASE: We report a case of tacrolimus-induced TMA soon after renal transplantation in an 11-year-old boy who received his second renal transplantation. His first graft was lost because of AMR. On day 12 after his second renal transplantation, his renal function started worsening and a kidney biopsy was performed, which showed histopathological signs of TMA. The diagnosis of tacrolimus-induced TMA was established after excluding AMR and other causes of de novo TMA. Genetic complement investigation disclosed two complement factor H risk polymorphisms as possible modifiers of TMA emergence. Treatment was based on replacing tacrolimus with everolimus, with a subsequent normalisation of renal function. CONCLUSION: A prompt diagnosis of de novo TMA by early allograft biopsy is essential for the allograft outcome and genetic investigations for possible complement abnormalities are reasonable, not only for patients with a systemic aspect of their post-transplant TMA. Replacing tacrolimus with everolimus effectively controlled the TMA and stabilised renal function in our patient.

Severe visual loss caused by unrecognized malignant hypertension in a 15-year-old girl.

A 15-year-old girl presented with acute bilateral loss of central visual acuity due to hypertensive retinopathy level IV. She was found to have unrecognized malignant arterial hypertension associated with end-stage renal failure. At the time of diagnosis she also had severe left ventricular hypertrophy (LVH). Hypertension was successfully treated with combined anti-hypertensive therapy, but renal function did not recover. The patient underwent successful kidney transplant 4 months later and over a period of 20 months hypertensive retinopathy and LVH gradually resolved. This report emphasizes the importance of routine measurement of blood pressure and describes the possible consequences of unrecognized arterial hypertension in children. Early diagnosis and appropriate treatment are necessary to avoid development and progression of target organ damage and promote better long-term cardiovascular prognosis.

Complement factor H-antibody-associated hemolytic uremic syndrome: pathogenesis, clinical presentation, and treatment.

The presence of circulating autoantibodies, primarily to complement factor H antibodies (CFH-Abs) in plasma characterizes the autoimmune form of atypical hemolytic uremic syndrome (aHUS). This acquired form of aHUS defines a distinct subgroup of aHUS patients, which requires diagnostic and treatment approaches in part different from those of the genetically defined forms. The mechanisms leading to CFH-Ab production and disease onset are not completely understood, but CFH-Ab HUS seems to be secondary to a combination of genetic predisposition and environmental factors. Early diagnosis of this specific aHUS entity is important, as prompt induction of plasma exchange and concomitant immunosuppression leads to a favorable outcome. Nevertheless, information on clinical features and outcome in children is limited. Here, we review the literature on the biological and clinical features of CFH-Ab HUS and discuss therapeutic options.

Diagnosis and treatment of the hemolytic uremic syndrome disease spectrum in developing regions.

There has been rapid progress in the understanding of the pathophysiology of the hemolytic uremic syndrome (HUS) disease spectrum; thus, complex diagnostic and therapeutic requirements have emerged in parallel. Current recommendations for diagnosis and therapy were rapidly adapted from the prior skilled scientific groundwork. However, such recommendations can be realized only when highly specialized laboratories and sufficient financial resources are available. Thus, many recommendations are not feasible for patients living and working in developing countries. More than one-third of the world's population has no access to essential drugs and more than half of this group lives in the poorest regions of Africa and Asia. From this perspective, distinct initial diagnostic and therapeutic recommendations, as well as international cooperations are needed to complete proper diagnostic work-ups in a stringent and cost-efficient manner and to enable patients to be adequately treated with available resources. However, while costs for complement-targeted drugs remain tremendously high, state-of-the-art treatment options remain unavailable for the vast majority of patients in developing areas.

Research gaps in the neurodevelopmental assessment of children with complex congenital heart defects: a scoping review.

Background: Children with congenital heart defects (CHD) are at risk for a range of developmental disabilities that challenge cognition, executive functioning, self-regulation, communication, social-emotional functioning, and motor skills. Ongoing developmental surveillance is therefore key to maximizing neurodevelopmental outcome opportunities. It is crucial that the measures used cover the spectrum of neurodevelopmental domains relevant to capturing possible predictors and malleable factors of child development. Objectives: This work aimed to synthesize the literature on neurodevelopmental measures and the corresponding developmental domains assessed in children aged 1-8 years with complex CHD. Methods: PubMed was searched for terms relating to psycho-social, cognitive and linguistic-communicative outcomes in children with CHD. 1,380 papers with a focus on complex CHD that reported neurodevelopmental assessments were identified; ultimately, data from 78 articles that used standardized neurodevelopmental assessment tools were extracted. Results: Thirty-nine (50%) of these excluded children with syndromes, and 9 (12%) excluded children with disorders of intellectual development. 10% of the studies were longitudinal. The neurodevelopmental domains addressed by the methods used were: 53% cognition, 16% psychosocial functioning, 18% language/communication/speech production, and 13% motor development-associated constructs. Conclusions: Data on social communication, expressive and receptive language, speech motor, and motor function are underrepresented. There is a lack of research into everyday use of language and into measures assessing language and communication early in life. Overall, longitudinal studies are required that include communication measures and their interrelations with other developmental domains.

Eicosanoid modulation by the short-chain fatty acid n-butyrate in human monocytes.

n-Butyrate deriving from bacterial fermentation in the mammalian intestine is a key determinant in gastrointestinal homeostasis. We examined the effects of this short-chain fatty acid and Toll-like receptor 2 (TLR) and TLR4 engagement on inflammatory/immunity-associated genes, cyclo-oxygenases (COXs), prostaglandins (PGs) and leukotrienes (LTs) in human monocytes. Before RNA isolation, freshly isolated human monocytes were co-incubated for different time-points with 1 mm n-butyrate alone or in combination with bacterial stimuli. Based on a knowledge-driven approach, a signature of 180 immunity/inflammation-associated genes was picked and real-time PCR analysis was performed. Pathway analysis was carried out using a web-based database analysing program. Based on these gene expression studies the findings were evaluated at the protein/mediator level by Western blot analysis, FACS and ELISA. Following co-incubation with n-butyrate and lipopolysaccharide, key enzymes of the eicosanoid pathway, like PTGS2 (COX-2), TXS, ALOX5, LTA4H and LTC4S, were significantly up-regulated compared with stimulation with lipopolysaccharide alone. Furthermore, release of the lipid mediators PGE(2), 15d-PGJ(2), LTB(4) and thromboxane B(2) was increased by n-butyrate. Regarding signalling, n-butyrate had no additional effect on mitogen-activated protein kinase and interfered differently with early and late phases of nuclear factor-κB signalling. Our results suggest that among many other mediators of eicosanoid signalling n-butyrate massively induces PGE(2) production by increasing the expression of PTGS2 (COX-2) in monocytes following TLR4 and TLR2 activation and induces secretion of LTB(4) and thromboxane B(2). This underscores the role of n-butyrate as a crucial mediator of gut-specific immunity.

Preschool Children with Hearing Loss: Social Communication and Parenting Stress.

Studies on parenting stress (PS) in parents of children with hearing loss (HL) have found relationships between child behavior, language skills and parenting stress. The role of early social communication skills has not been researched before. The aim of this cross-sectional study was to investigate the relationship between child behavior, social communication and PS. The study was performed in a subgroup of a total population sample from the AChild (Austrian Children with Hearing Impairment-Longitudinal Databank) study. Preschool children (n = 81) with all degrees of HL and average cognitive functioning and their families were included, and the Parenting Stress Index (PSI) was used. Through factor component analysis, compound scores for externalizing/internalizing problem behavior and hyperactivity were analyzed. Although mean PS was not elevated, the proportion of those with elevated scores was higher compared with the norm population. There was a strong correlation between child behavior problems and PS (strongest correlation: externalizing problem behavior r = 0.643; p < 0.001). All three problem behaviors accounted for 49.7% of the variance in PS. An indirect effect of social communication on PS was almost completely mediated by problem behavior (especially hyperactivity). The importance of social communication development with respect to problem behavior and PS is highlighted.

Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae.

BACKGROUND: The aim of this study was to evaluate the long-term prognosis of children with hemolytic uremic syndrome (HUS). METHODS: Over a 6-year period, 619 pediatric patients with the clinical diagnosis of HUS were registered in Austria and Germany, and a subset (n = 274) was prospectively followed up for 5 years. RESULTS: Infection with enterohemorrhagic Escherichia coli (EHEC) was confirmed in 79% of cases. Five years after diagnosis, 70% of EHEC-infected patients (95% confidence interval [CI], .63-.76) were fully recovered. The remaining 30% had persistent hypertension (9%), neurological symptoms (4%), decreased glomerular filtration rate (7%), and/or proteinuria (18%). Hypertension and proteinuria developed in a total of 18% of patients who had no sequelae 1 year after the acute phase (95% CI, 12-26). Multivariate logistic regression analysis demonstrated an association between the use of plasma therapy during acute phase and poor long-term outcome (odds ratio, 2.9-13; 95% CI, 2.4-33; P < .05), but this treatment was also used more frequently in severe cases. In contrast, the use of antibiotic therapy in the diarrheal phase and other established risk factors for developing HUS, such as Shiga toxin 2 and EHEC serotypes traditionally considered to be "high risk," were not associated with adverse long-term outcome. In particular, there was no difference between O157 and non-O157 EHEC. CONCLUSIONS: This study identified an association between the use of plasma treatment and poor long-term outcome and confirms already known risk factors for poor prognosis. Follow-up investigations for at least 5 years are recommended to detect late-emerging sequelae.

Immunogenicity of meningococcus C vaccination in a patient with atypical hemolytic uremic syndrome (aHUS) on eculizumab therapy.

We report successful kidney transplantation in a 10-yr-old boy with aHUS and heterozygous factor H mutation using the terminal complement inhibitor eculizumab to avoid recurrence of aHUS in the renal graft. Vaccination against meningococcus C (Men C) is essential in patients with dysfunction of the complement system, as induced by eculizumab. In our patient, we report waning SBA titers but maintenance of protective SBA titers (≥1:8) after kidney transplantation under immunosuppressive therapy with mycophenolate mofetil, tacrolimus, steroids, and eculizumab over a 27-month observational period. Our case illustrates that a humoral immune response to conjugate Men C vaccination may be mounted and maintained despite chronic renal disease, kidney transplantation, immunosuppressive drugs, and immunomodulatory therapy with eculizumab. However, it remains unclear whether serologically defined protective SBA titers mediate true protection from invasive meningococcal disease in an immunocompromised patient, particularly under treatment with a complement inhibitor. Thus, close monitoring of SBA titers seems mandatory in this patient.