Search

Background: Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS) is a severe condition mainly affecting children. It is one of the leading causes of acute kidney injury in the pediatric population. There is no established therapy for this disease. INM004 is an anti-Shiga toxin composed of equine polyclonal antibodies. This study is aimed at assessing the safety, pharmacokinetics, and efficacy of INM004 in pediatric patients with STEC-HUS., Methods: Phase 2, open-label clinical trial with an historical control arm. Patients in the treatment arm received two doses of INM004. The primary endpoints were the safety profile, pharmacokinetics, and efficacy (dialysis days) of INM004. Secondary endpoints included other kidney and extrarenal outcomes. Propensity score matching was used for efficacy comparisons between arms., Results: Fifty-seven and 125 patients were enrolled in the treatment and control arm, respectively. After propensity score matching, 52 patients remained in each arm. INM004 was well-tolerated. Eight adverse events were considered possibly related, none of which were serious or severe. In the primary efficacy endpoint, patients of the treatment arm presented a non-statistically significant difference of two dialysis days. On secondary endpoints, non-statistically significant trends toward fewer patients needing dialysis and dialysis for more than 10 days, and shorter time to glomerular filtration rate normalization, were observed favoring the treatment arm., Conclusions: INM004 showed an adequate safety profile. Efficacy non-statistically significant trends suggesting a beneficial effect in the amelioration of kidney injury were observed. These results encourage the conduction of a phase 3 study of INM004 in pediatric patients with STEC-HUS., Competing Interests: Declarations Ethics approval This trial was performed following the principles of the Declaration of Helsinki and Good Clinical Practice. The protocol was approved by the local Ethics Committees of each of the participating centers and the Argentine National Food and Drug Regulatory Agency (ANMAT) after approval by the Ethics Committee accredited by the corresponding Health Authority within the jurisdiction (Disposition Number: DI-2022–7068-APN-ANMAT#MS). Conflict of interest AF, IP, AB, LA, PC, MA, OA, MCB, MVB, PB, MLFT, LF, LG, JM, FR, CS, AS, and APS declare reimbursement for conduction of clinical trial as investigator of the study. MR, MP, VZ, LS, CM, MV, SS, MC, IR, and FG report personal fees from Inmunova S.A., (© 2024. The Author(s).)

Background: Shiga toxin-producing Escherichia coli (STEC) infection is the most common cause of hemolytic uremic syndrome (HUS). Only few studies correlated serotypes and stx genotypes with disease severity. This study aimed to update STEC serotypes, stx genotypes, and virulence factors (eae and ehxA) in a cohort of patients with STEC-HUS and investigate whether they influence the severity of disease., Methods: In this multicentric study, children hospitalized between 2005 and 2016 with STEC-HUS confirmed by the National Reference Laboratory were included. Serotypes (O157, O145, O121, and others), stx genotypes (stx 1a , stx 2a , stx 2c, stx 2d , and others), and virulence factors were analyzed, and their association with dialysis requirement (>10 days); severe neurological, cardiovascular, and/or bowel involvement; and death was assessed., Results: The records of 280 patients were reviewed; 160 females, median age 21 months (IQR18m). STEC O157 was isolated in 206 (73.6%) patients, O145 in 47 (16.8%), O121 in 15 (5.4%), and other serotypes in 12 (4.2%). The stx 2a / 2c genotype was carried by 179 (63.9%) strains, stx 2a by 94 (33.6%), stx 1a /stx 2a by five (1.8%), and stx 1a only by two (0.7%). All strains except six harbored eae and ehxA genes. Fifty-nine (21.1%) patients had severe neurological involvement, 29 (10.4%) severe bowel injury, 14 (5%) cardiovascular involvement, 53 (18.9%) required > 10 days of dialysis, and 12 (4.3%) died. Neither serotypes nor stx genotypes detected were significantly linked to severity., Conclusions: Serotype O157 and virulence stx 2a/2c , eae, ehxA genotype are prevalent in Argentina, and no relationship was found between severity and serotypes and genotypes of STEC detected., (© 2021. IPNA.)

The objective of this study was to describe the epidemiology, clinical presentation, treatment and nephrology follow-up of children with Wilms tumor. Data from 46 patients were collected. The clinical presentation occurred at a young age (< 40 months old), with initial symptoms of pain, abdominal mass, and fever. The prevalent histology type was mixed nephroblastoma. All patients received pre-surgery chemotherapy followed by, in most cases, unilateral nephrectomy. Patients with a high histological risk had a 7.2 relative risk of death (75 % confidence interval: 1.5-33.7) compared to the rest, and a 2.5 relative risk of recurrence (75 % confidence interval: 1.0-6.4). Disease-free survival at 5 years was 70 %. Once cancer treatment was completed, 80 % of patients maintained a stage-I kidney function. The most important prognostic factor was histology. These patients required a long-term nephrology follow-up., Competing Interests: The authors report no conflicts of interest in this work., (Sociedad Argentina de Pediatría.)

Objectives: (1) Evaluate mortality rate in patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, (2) determine the leading causes of death, and (3) identify predictors of mortality at hospital admission., Methods: We conducted a multicentric, observational, retrospective, cross-sectional study. It included patients under 18 years old with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome hospitalized between January 2005 and June 2016. Clinical and laboratory data were obtained from the Argentine National Epidemiological Surveillance System of Hemolytic Uremic Syndrome. Clinical and laboratory variables were compared between deceased and non-deceased patients. Univariate and multivariate analyses were performed. ROC curves and area under the curve were obtained., Results: Seventeen (3.65%) out of the 466 patients died, being central nervous system involvement the main cause of death. Predictors of death were central nervous system involvement, the number of days since the beginning of diarrhea to hospitalization, hyponatremia, high hemoglobin, high leukocyte counts, and low bicarbonate concentration on admission. In the multivariate analysis, central nervous system involvement, sodium concentration, and hemoglobin were independent predictors. The best cut off for sodium was ≤ 128 meq/l and for hemoglobin ≥ 10.8 g/dl., Conclusions: Mortality was low in children with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome, being central nervous system involvement the main cause of death. The best mortality predictors found were central nervous system involvement, hemoglobin, and sodium concentration. Hyponatremia may be a new Shiga toxin-producing Escherichia coli hemolytic uremic syndrome mortality predictor.