Mirror Syndrome Combined with Postpartum Hemolytic Uremic Syndrome.

BACKGROUND: Mirror syndrome is a rare disease characterized by "triple edema", while Hemolytic Uremic Syndrome (PHUS) is a serious disease that occurs within a short period of time after the end of pregnancy, with a low prevalence and poor prognosis, and it is even rarer for both to occur in the same patient. METHODS: We report a case of mirror syndrome combined with PHUS and analyze the clinical data to improve the understanding of the disease. RESULTS: The patient presented clinically with "triple edema" and was diagnosed with mirror image syndrome. After cesarean section, the patient developed cardiac insufficiency, renal insufficiency, hemolysis, and other symptoms and was diagnosed as PHUS. After active treatment, the maternal prognosis was good. CONCLUSIONS: Mirror syndrome and PHUS are both clinically rare diseases with poor long-term prognosis if not diagnosed and treated in a timely manner; therefore, awareness of the diseases, early and accurate diagnosis and timely and correct treatment should be improved.

Evaluation of the results of the patients who underwent plasmapheresis in the pediatric intensive care unit.

Background/aim: Therapeutic plasma exchange (TPE) is an extracorporeal treatment method that removes large molecular weight substances from plasma. In our study, we aimed to retrospectively examine the indications and procedural methods of the patients who had undergone TPE, and the complications that occurred during the procedure. Materials and methods: Forty-one patients who were monitored in thePICU of Gazi Yasargil Training and Research Hospital and had indications for TPE between 2017 and 2021 were included in the study. Laboratory parameters were checked before and after the TPE procedure. In addition to these, patients' diagnosis, weight, type of procedure and type of device, where the procedure was performed, duration of the procedure, amount of blood and plasma processed, complications, number of procedures, and death during the procedure or independent of the procedure were evaluated. Results: The median age was 93.0 (14.0-167.0) months. Hemolytic uremic syndrome (HUS) was the most common TPE indication with nine patients. The most common complication related to TPE was fever (11 patients), while no complication was observed in 18 patients.When laboratory results were evaluated according to American Society for Apheresis (ASFA) categories, a significant improvement was observed in the values of platelet, AST, ALT, LDH, urea, and creatinine in ASFA1 after TPE. No significant improvement was observed in ASFA2 (p > 0.05). In ASFA3, a significant improvement was observed in INR, AST, ALT, LDH, total bilirubin, creatinine, pH, and lactate values after TPE (p < 0.05). Five patients died from ASFA1, one from ASFA2, and three patients from ASFA3. Conclusion: Since significant adjustments are observed in clinical and laboratory values in sepsis-MOF, which is in the ASFA3 category, we believe that it should be evaluated in the ASFA2 or ASFA1 category in the early treatment of these diseases. In addition, we think that MIS-C cases, which have not been in any category according to ASFA, should be included in the ASFA2 or ASFA3 category, considering our TPE results.

A pediatric case with hemolytic uremic syndrome associated with COVID-19, which progressed to end-stage kidney disease.

BACKGROUND: Hemolytic uremic syndrome (HUS) is a serious cause of acute kidney injury in children. There is a suggestion that coronavirus disease 2019 (COVID-19) may be a trigger for HUS. In this study, we present a pediatric case diagnosed with HUS associated with COVID-19, which progressed to end-stage kidney disease. CASE: A previously healthy 13-year-old girl with fever and vomiting was referred to our hospital. Laboratory investigations revealed direct Coombs-negative hemolytic anemia, thrombocytopenia and renal impairment accompanied by COVID-19 infection. Although anemia and thrombocytopenia showed improvement on the seventh day after admission, the renal impairment persisted. The histopathological findings of a renal biopsy were compatible with both HUS and COVID-19. One month later, the patient had a recurrence of HUS, again testing positive for COVID-19. Kidney function improved with plasma exchange therapy. Eculizumab treatment was recommenced after COVID-19 PCR became negative. Anemia and thrombocytopenia did not recur with eculizumab, while renal impairment persisted. Eculizumab was discontinued after three months when genetic analysis for HUS was negative. Subsequently, the patient was diagnosed with end-stage kidney disease. CONCLUSIONS: COVID-19 can be associated with HUS relapses, leading to chronic kidney disease. Further studies should investigate the mechanism of HUS associated with COVID-19.

Anti-CFH-associated hemolytic uremic syndrome: do we still need plasma exchange?

BACKGROUND: Between 5 and 50% of atypical hemolytic uremic syndrome (aHUS) cases in children are caused by autoantibodies against complement factor H (CFH). Given the acquired autoimmune nature of the disease, plasma exchange (PE) and various immunosuppressive treatments have been used. More recently, eculizumab has been proposed. METHODS: In this multicenter, retrospective study, we report outcomes of 12 children with anti-FH antibody-associated HUS treated with eculizumab associated with various immunosuppressive regimens. RESULTS: Patients were treated with eculizumab for 15.5 [9.5;23.0] months and 3 received PE or IgG adsorption. Three patients received mycophenolate mofetil (MMF) alone, 1 patient received MMF and steroids, 1 patient received MMF and rituximab, 3 patients received MMF/steroids and rituximab, and 4 patients did not receive any immunosuppression. Anti-FH antibody levels significantly decreased but no difference was observed based on the immunosuppressive regimen. Eculizumab was discontinued in 7/10 patients after 11 [7.5;15.5] months and MMF in 6/8 patients after 36 [35;40] months. Anti-FH titers at MMF discontinuation ranged from 257 to 3425 UI/L. None of these patients relapsed and eGFR at last follow-up was above 70 mL/min/1.73 m2 in all patients. CONCLUSIONS: Eculizumab is effective and safe in inducing and maintaining remission in aHUS secondary to anti-FH antibodies and renders reduction of anti-FH titers less urgent. Anti-FH antibody titers decreased in most patients irrespective of the immunosuppressive treatment chosen, so that a strategy consisting of combining eculizumab with MMF monotherapy seems sufficient at least in non-Indian or less severe forms of anti-FH antibody-associated HUS.

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.

Red blood cell-derived arginase release in hemolytic uremic syndrome.

BACKGROUND: Hemolysis is a cardinal feature of hemolytic uremic syndrome (HUS) and during hemolysis excess arginase 1 is released from red blood cells. Increased arginase activity leads to reduced L-arginine, as it is converted to urea and L-ornithine, and thereby reduced nitric oxide bioavailability, with secondary vascular injury. The objective of this study was to investigate arginase release in HUS patients and laboratory models and correlate arginase levels to hemolysis and kidney injury. METHODS: Two separate cohorts of patients (n = 47 in total) with HUS associated with Shiga toxin-producing enterohemorrhagic E. coli (EHEC) and pediatric controls (n = 35) were investigated. Two mouse models were used, in which mice were either challenged intragastrically with E. coli O157:H7 or injected intraperitoneally with Shiga toxin 2. An in vitro model of thrombotic microangiopathy was developed in which Shiga toxin 2- and E. coli O157 lipopolysaccharide-stimulated human blood cells combined with ADAMTS13-deficient plasma were perfused over glomerular endothelial cells. Two group statistical comparisons were performed using the Mann-Whitney test, multiple groups were compared using the Kruskal-Wallis test followed by Dunn's procedure, the Wilcoxon signed rank test was used for paired data, or linear regression for continuous variables. RESULTS: HUS patients had excessively high plasma arginase 1 levels and activity (conversion of L-arginine to urea and L-ornithine) during the acute phase, compared to remission and controls. Arginase 1 levels correlated with lactate dehydrogenase activity, indicating hemolysis, as well as the need for dialysis treatment. Patients also exhibited high levels of plasma alpha-1-microglobulin, a heme scavenger. Both mouse models exhibited significantly elevated plasma arginase 1 levels and activity. Plasma arginase 1 levels correlated with lactate dehydrogenase activity, alpha-1-microglobulin and urea levels, the latter indicative of kidney dysfunction. In the in vitro model of thrombotic microangiopathy, bioactive arginase 1 was released and levels correlated to the degree of hemolysis. CONCLUSIONS: Elevated red blood cell-derived arginase was demonstrated in HUS patients and in relevant in vivo and in vitro models. The excessively high arginase levels correlated to the degree of hemolysis and kidney dysfunction. Thus, arginase inhibition should be investigated in HUS.

Adult-onset Still's disease with concurrent thrombotic microangiopathy: Observations from pooled analysis for an uncommon finding.

BACKGROUND: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder that is characterized by quotidian fevers, arthritis, and an evanescent rash. Occurrence of concurrent thrombotic microangiopathy (TMA) in AOSD is rare. The treatment aspects of TMA in AOSD are actively being debated. METHODS: Medline search using MeSH terms and snowballing yielded a total of 29 articles with co-occurrence of AOSD and thrombotic thrombocytopenic purpura (TTP) including our own. Pooled data were synthesized for descriptive analysis. RESULTS: Median age was 35 years with a majority of females (68.96%). A majority of these studies/patients were either Asian (34.48%) or Caucasian (31.03%). Concurrent TMA at the time of AOSD diagnosis was seen in 65.51% patients. Only 3/29 patients had ADAMTS13 level less than 10%, consistent with TTP and 3/29 were diagnosed with hemolytic uremic syndrome (HUS). The remainder were diagnosed clinically. Complication rate was high, and 15/29 (51.72%) patients died or had permanent neurological/renal/vision/gangrenous complications. Median and mean ferritin peak was observed to be higher (7458 and 12 349, respectively) in patients who either died/had partial remission, compared to those who had complete response (3257 and 10 899, respectively), p = .829. CONCLUSIONS: A majority of patients with AOSD-associated TMA either died or had permanent complications. TMA was diagnosed alongside AOSD in 65% patients, while the rest developed TMA during the course of their disease. Blurred vision may precede TMA and could help risk-stratify high-risk AOSD patients clinically. Glycosylated ferritin remains low several weeks to months after disease remission and may be used to monitor severity of disease process. Further studies are necessary to confirm the existing vascular endothelial growth factor hypothesis in AOSD-associated TMA.

Clostridium septicum infection complicating Hemolytic-Uremic Syndrome: a case report and review of the literature.

Clostridium septicum (C. septicum) is a zoonotic bacillus found in 2.8% of healthy human stools. In humans, it can cause serious infections such as bacteremia, myonecrosis, and encephalitis by spreading through the bloodstream. Reports of Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome complicated by C. septicum superinfection are rare, likely because colonic microangiopathic lesions by Shiga toxin-producing Escherichia Coli facilitate bacterial dissemination. Only 13 cases of Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome with C. septicum superinfection have been reported to date, according to our litterature review, with a 50% mortality rate. The lack of clinico-laboratory clues suggesting this condition makes the diagnosis challenging. For these reasons C. septicum superinfection usually goes undiagnosed in patients with Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome, and results in unfavorable outcomes. In this paper, we describe the case of a 5-year-old girl admitted for Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome who developed C. septicum coinfection leading to a fatal outcome. We carried out a review of the available literature on C. septicum infection complicating Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome and we compared the clinical features of the observed cases with those of an historical cohort of uncomplicated Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome. The mechanisms of superinfection are still unclear and clinical features are indistinguishable from those of uncomplicated Shiga toxin-producing Escherichia Coli-related hemolytic-uremic syndrome. However, rapid deterioration of clinical conditions and evidence of neurological involvement, associated with abnormal radiological findings, require immediate management. Although therapeutic approaches have not been directly compared, neurosurgical treatment of amenable lesions may improve the clinical outcome of patients with C. septicum-hemolytic-uremic syndrome.

Síndrome hemolítico urémico secundario a Streptococcus pneumoniae. Reporte de un caso clínico / Streptococcus pneumoniae associated hemolytic uremic syndrome. Case report

El síndrome hemolítico urémico secundario a Streptococcus pneumoniae (SHU-Sp) es una complicación poco frecuente de las enfermedades invasoras por S. pneumoniae. Presenta una alta morbimortalidad, con requerimiento de transfusiones de glóbulos rojos y plaquetas, terapia de sustitución de la función renal de inicio precoz y más prolongada, así como mayores complicaciones a largo plazo, comparado con las formas secundarias a infección entérica por Escherichia coli productora de toxina Shiga. Presentamos el caso clínico de una preescolar de dos años, previamente sana, vacunada con tres dosis de PCV13, que desarrolló una insuficiencia renal aguda, anemia hemolítica y plaquetopenia, en el contexto de una neumonía con empiema y bacteriemia por S. pneumoniae.

Streptococcus pneumoniae associated hemolytic uremic syndrome (Sp-HUS) is an uncommon complication of invasive pneumococcal infections. Patients with Sp-HUS have a higher mortality and long term morbidity than those due to HUS from Shiga toxin-producing Escherichia coli infections (STEC-HUS). They often require more red blood cells and platelet transfusions, and early initiation of renal substitution therapy, presenting a higher rate of arterial hypertension and chronic renal disease in the long term, compared to STEC-HUS. We report a healthy 2 year-old infant, vaccinated with three doses PCV13, that developed acute renal failure, hemolytic anemia and thrombocytopenia in the course of a complicated pneumococcal pneumonia with empyema and bacteremia.

[When hemorrhagic enterititis can cause anemia and thrombocytopenia without significant kidney damage.] / Quando l'enterite emorragica può determinare anemia e piastrinopenia senza un rilevante danno renale.

A healthy 9-years-old boy was brought to the Emergency Department for widespread abdominal pain associated with bloody diarrhoea and significant tenesmus, in the absence of fever. Blood tests were compatible with an acute gastroenteritis, even though microbiological tests on stools resulted negative. Given the haemorrhagic dysentery, the boy was hospitalized to start empiric antibiotic therapy and intravenous rehydration. Abdominal ultrasound showed a thickening of colonic walls, mimicking an inflammatory intestinal disease at the onset (subsequently denied by gastro-colonoscopy). Seven days after the onset of symptoms, blood tests revealed microangiopathic anaemia with negative Coombs test, associated with thrombocytopenia. Urine dipstick revealed haematuria and proteinuria in nephritic range. No contraction of diuresis or alteration of renal function were observed (being creatinine values always within the normal range). Laboratory tests were consistent with the diagnosis of Haemolytic Uremic Syndrome (Hus) at the onset. Approximately 1% of paediatric patients with bloody diarrhoea can develop Hus. Positivity for Escherichia coli is not always evident in the stools. Thus, the triad of haemolytic anaemia, thrombocytopenia and renal failure could be present in only 60% of Hus at the onset. The finding of haematuria and/or proteinuria on the urine dipstick may be indicative of early kidney damage, allowing for careful monitoring and a rehydration program that can prevent progression of kidney damage and extrarenal complications.

Hemolytic Uremic Syndrome-Induced Acute Kidney Injury Treated via Immunomodulation with the Selective Cytopheretic Device.

INTRODUCTION: Shiga-toxin associated-hemolytic uremic syndrome (STEC-HUS) is a severe cause of acute kidney injury (AKI) in children. Although most children recover, about 5% die and 30% develop chronic renal morbidity. HUS pathophysiology includes activated neutrophils damaging vascular endothelial cells. Therapeutic immunomodulation of activated neutrophils may alter the progression of disease. We present 3 pediatric patients treated with the selective cytopheretic device (SCD). METHODS: We describe a 12 y.o. (patient 1) and two 2 y.o. twins (patients 2 and 3) with STEC-HUS requiring continuous renal replacement therapy (CRRT) who were enrolled in two separate studies of the SCD. RESULTS: Patient 1 presented with STEC-HUS causing AKI and multisystem organ failure and received 7 days of SCD and CRRT treatment. After SCD initiation, the patient had gradual recovery of multi-organ dysfunction, with normal kidney and hematologic parameters at 60-day follow-up. Patients 2 and 3 presented with STEC-HUS with AKI requiring dialysis. Each received 24 h of SCD therapy. Thereafter, both gradually improved, with normalization (patient 2) and near-normalization (patient 3) of kidney function at 60-day follow-up. CONCLUSION: Immunomodulatory treatment with the SCD was associated with improvements in multisystem stigmata of STEC-HUS-induced AKI and was well-tolerated without any device-related adverse events.

Hyperhydration to Improve Kidney Outcomes in Children with Shiga Toxin-Producing E. coli Infection: a multinational embedded cluster crossover randomized trial (the HIKO STEC trial).

BACKGROUND: Shiga toxin-producing E. coli (STEC) infections affect children and adults worldwide, and treatment remain solely supportive. Up to 15-20% of children infected by high-risk STEC (i.e., E. coli that produce Shiga toxin 2) develop hemolytic anemia, thrombocytopenia, and kidney failure (i.e., hemolytic uremic syndrome (HUS)), over half of whom require acute dialysis and 3% die. Although no therapy is widely accepted as being able to prevent the development of HUS and its complications, several observational studies suggest that intravascular volume expansion (hyperhydration) may prevent end organ damage. A randomized trial is needed to confirm or refute this hypothesis. METHODS: We will conduct a pragmatic, embedded, cluster-randomized, crossover trial in 26 pediatric institutions to determine if hyperhydration, compared to conservative fluid management, improves outcomes in 1040 children with high-risk STEC infections. The primary outcome is major adverse kidney events within 30 days (MAKE30), a composite measure that includes death, initiation of new renal replacement therapy, or persistent kidney dysfunction. Secondary outcomes include life-threatening, extrarenal complications, and development of HUS. Pathway eligible children will be treated per institutional allocation to each pathway. In the hyperhydration pathway, all eligible children are hospitalized and administered 200% maintenance balanced crystalloid fluids up to targets of 10% weight gain and 20% reduction in hematocrit. Sites in the conservative fluid management pathway manage children as in- or outpatients, based on clinician preference, with the pathway focused on close laboratory monitoring, and maintenance of euvolemia. Based on historical data, we estimate that 10% of children in our conservative fluid management pathway will experience the primary outcome. With 26 clusters enrolling a mean of 40 patients each with an intraclass correlation coefficient of 0.11, we will have 90% power to detect a 5% absolute risk reduction. DISCUSSION: HUS is a devastating illness with no treatment options. This pragmatic study will determine if hyperhydration can reduce morbidity associated with HUS in children with high-risk STEC infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT05219110 . Registered on February 1, 2022.

Complement Inhibitors in the Management of Complement-Mediated Hemolytic Uremic Syndrome and Paroxysmal Nocturnal Hemoglobinuria.

BACKGROUND: Complement-mediated HUS (CM-HUS) and paroxysmal nocturnal hemoglobinuria (PNH) are rare hematologic disorders that cause dysregulation and hyperactivation of the complement system. Historically, treatment of CM-HUS involved plasma exchange (PLEX), often with limited benefit and variable tolerance. Conversely, PNH was treated with supportive care or hemopoietic stem cell transplant. Within the last decade, monoclonal antibody therapies that block terminal complement pathway activation, have emerged as less invasive and more efficacious options for management of both disorders. This manuscript seeks to discuss a relevant clinical case of CM-HUS and the evolving landscape of complement inhibitor therapies for CM-HUS and PNH. AREAS OF UNCERTAINTY: Eculizumab, the first humanized anti-C5 monoclonal antibody, has been the standard of care in treating CM-HUS and PNH for over a decade. Although eculizumab has remained an effective agent, the variability in ease and frequency of administration has remained an obstacle for patients. The development of novel complement inhibitor therapies with longer half-lives, has allowed for changes in frequency and route of administration, thus improving patient QOL. However, there are limited prospective clinical trial data given disease rarity, and limited information on variable infusion frequency and length of treatment. THERAPEUTIC ADVANCES: Recently, there has been a push to formulate complement inhibitors that improve QOL while maintaining efficacy. Ravulizumab, a derivative of eculizumab, was developed to allow for less frequent administration, while remaining efficacious. In addition, the novel oral and subcutaneous therapies, danicopan and crovalimab, respectively, along with pegcetacoplan are currently undergoing active clinical trials, and poised to further reduce treatment burden. CONCLUSION: Complement inhibitor therapies have changed the treatment landscape for CM-HUS and PNH. With a significant emphasis on patient QOL, novel therapies continue to emerge and require an in-depth review of their appropriate use and efficacy in these rare disorders. CLINICAL CASE: A 47-year-old woman with hypertension and hyperlipidemia presented with shortness of breath and was found to have hypertensive emergency in the setting of acute renal failure. Her serum creatinine was 13.9 mg/dL; elevated from 1.43 mg/dL 2 years before. The differential diagnosis for her acute kidney injury (AKI) included infectious, autoimmune, and hematologic processes. Infectious work-up was negative. ADAMTS13 activity level was not low at 72.9%, ruling out thrombotic thrombocytopenic purpura (TTP). Patient underwent a renal biopsy, which revealed acute on chronic thrombotic microangiopathy (TMA). A trial of eculizumab was initiated with concurrent hemodialysis. The diagnosis of CM-HUS was later confirmed by a heterozygous mutation in complement factor I (CFI), resulting in increased membrane attack complex (MAC) cascade activation. The patient was maintained on biweekly eculizumab and was eventually transitioned to ravulizumab infusions as an outpatient. Her renal failure did not recover, and the patient remains on hemodialysis while awaiting kidney transplantation.

Prognostic factors among patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome: A retrospective cohort study using a nationwide inpatient database in Japan.

INTRODUCTION: Shiga toxin-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic uremic syndrome (STEC-HUS). Understanding its prognostic factors is essential for immediate interventions. We examined early-phase unfavorable prognostic factors among patients with STEC-HUS using a nationwide database. MATERIAL AND METHODS: This is a retrospective cohort study to analyze practice patterns and identify prognostic factors among patients with STEC-HUS. We used the Diagnosis Procedure Combination Database, which includes approximately half of the acute-care hospitalized patients in Japan. We enrolled patients who were hospitalized for STEC-HUS from July 2010 to March 2020. The composite unfavorable outcome included in-hospital death, mechanical ventilation, dialysis, and rehabilitation at discharge. Unfavorable prognostic factors were assessed using a multivariable logistic regression model. RESULTS: We included 615 patients with STEC-HUS (median age, 7 years). Of them, 30 (4.9%) patients had acute encephalopathy and 24 (3.9%) died within 3 months of admission. Unfavorable composite outcome was observed in 124 (20.2%) patients. Significant unfavorable prognostic factors were age of 18 years or older, methylprednisolone pulse therapy, antiepileptic drug administration, and respiratory support within 2 days of admission. DISCUSSION: Patients requiring early steroid pulse therapy, antiepileptic drugs, and respiratory support were considered to be in poor general condition; such patients should receive aggressive intervention to avoid worse outcomes.

Síndrome urémico hemolítico del adulto / Adult hemolytic uremic syndrome

El síndrome urémico hemolítico (SUH), descripto en 1955, se caracteriza por la tríada de anemia hemolítica no inmunomediada, trombocitopenia y lesión renal aguda. En su patogenia interviene la toxina Shiga, producida con mayor frecuencia por E. coli O157:H. Puede manifestarse a cualquier edad, aunque es infrecuente en adultos, y se desarrolla en forma esporádica o en brote. Se presenta con un cuadro de dolor abdominal, diarrea, fiebre y vómitos. Puede afectar el sistema nervioso central, pulmones, páncreas y corazón. En adultos, el síndrome evoluciona tras un período de incubación de 1 semana posterior a la diarrea y tiene alta morbimortalidad, a diferencia de los casos pediátricos. Presentamos el caso de una paciente adulta, que cursó internación por síndrome urémico hemolítico. (AU)

Hemolytic uremic syndrome (HUS), described in 1955, is characterized by the triad of non-immune mediated hemolytic anemia, thrombocytopenia, and acute kidney injury. Shiga toxin, produced most frequently by E coli O157:H, is involved in its pathogenesis. Hus can manifest at any age, although it is rare in adults and develops sporadically or in outbreaks. HUS presents with a picture of abdominal pain, diarrhea, fever and vomiting. It can affect the central nervous system, lungs, pancreas, and heart.In adults, the syndrome evolves after an incubation period of 1 week after diarrhea, with high morbidity and mortality, unlike pediatric cases.We present the case of an adult patient who was hospitalized for hemolytic uremic syndrome. (AU)

[Thrombotic microangiopathy]. / Thrombotische Mikroangiopathien.

In the emergency room, patients with anemia and thrombocytopenia are common. Although these findings can often be explained by the medical situation, thrombotic microangiopathy is an important differential diagnosis. In this case, occlusion of the smallest vessels consequently leads to functional impairment of the affected organs. Patients generally present with symptoms of organ dysfunction, e.g., in the kidney or brain. Characteristically, Coombs-negative fragmentation of erythrocytes with hemolysis occurs in the area of the occluded vessels. Lactate dehydrogenase levels are elevated, and platelets and haptoglobin are reduced. Differential diagnoses beyond thrombotic microangiopathy that should be considered are numerous and diverse in their pathophysiology. Rapid workup is needed, because sometimes a specific treatment must be initiated rapidly. For example, thrombotic thrombocytopenic purpura leads to death in about 90% of patients if left untreated. However, by reconstitution of the underlying deficiency of the so-called ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) by plasma separation, survival can be ensured in most cases. Complement-mediated hemolytic uremic syndrome should also be considered and, if suspected, treated with complement inhibition. In many cases, however, thrombotic microangiopathy reflects a disorder elsewhere and may be a manifestation of severe hypertension or a coagulation disorder, such as disseminated intravascular coagulation or antiphospholipid syndrome. It can also be observed as a consequence of drug therapies or metabolic derangement. Systemic workup is therefore necessary for rapid clarification of differential diagnoses.

Long-term kidney outcomes in non-dialyzed children with Shiga-toxin Escherichia coli associated hemolytic uremic syndrome.

BACKGROUND: Long-term kidney outcomes of non-dialyzed children with Shiga-toxin Escherichia Coli hemolytic uremic syndrome (STEC-HUS) have been scantily studied. Therefore, we aimed to evaluate kidney outcomes and prognostic markers in these patients. METHODS: Non-dialyzed STEC-HUS patients followed for at least 5 years were included. They were grouped and compared according to kidney status at last visit: complete recovery (CR) or chronic kidney disease (CKD). Predictors of CKD evaluated at diagnosis were sex, age, leukocytes, hematocrit, hemoglobin (Hb), and serum creatinine (sCr). Peak sCr and time of follow-up were also analyzed. RESULTS: A total of 122 patients (62 female, median age at diagnosis 1.6 years) with a median follow-up of 11.3 years were included. At last visit, 82 (67%) had CR, 36 (30%) had CKD stage 1, and 4 (3%) had stage 2. No patient developed CKD stage 3-5. Median time to CKD was 5 years (IQR 3.1-8.76 years). Of the 122 patients, 18% evolved to CKD in the first 5 years, increasing to 28% at 10 and 33% at 20 years of follow-up. Serum Cr at diagnosis and peak sCr were significantly higher in patients with CKD than in those with CR. CONCLUSIONS: One third of non-dialyzed STEC-HUS patients evolved to CKD after a median time of 5 years. However, CKD may appear even after 15 years of CR. Serum Cr was significantly higher among patients who evolved to CKD. These data reinforce that all non-dialyzed patients should be followed until adulthood. A higher resolution version of the Graphical abstract is available as Supplementary information.