Cardiac involvement in pediatric hemolytic uremic syndrome.

BACKGROUND: Cardiac involvement is a known but rare complication of pediatric hemolytic uremic syndrome (HUS). We conducted a nationwide observational, retrospective case-control study describing factors associated with the occurrence of myocarditis among HUS patients. METHODS: Cases were defined as hospitalized children affected by any form of HUS with co-existent myocarditis in 8 French Pediatric Intensive Care Units (PICU) between January 2007 and December 2018. Control subjects were children, consecutively admitted with any form of HUS without coexistent myocarditis, at a single PICU in Lyon, France, during the same time period. RESULTS: A total of 20 cases of myocarditis were reported among 8 PICUs, with a mean age of 34.3 ± 31.9 months; 66 controls were identified. There were no differences between the two groups concerning the season and the typical, Shiga toxin-producing Escherichia coli (STEC-HUS), or atypical HUS (aHUS). Maximal leukocyte count was higher in the myocarditis group (29.1 ± 16.3G/L versus 21.0 ± 9.9G/L, p = 0.04). The median time between admission and first cardiac symptoms was of 3 days (range 0-19 days), and 4 patients displayed myocarditis at admission. The fatality rate in the myocarditis group was higher than in the control group (40.0% versus 1.5%, p < 0.001). Thirteen (65%) children from the myocarditis group received platelet transfusion compared to 19 (29%) in the control group (p = 0.03). CONCLUSION: Our study confirms that myocarditis is potentially lethal and identifies higher leukocyte count and platelet transfusion as possible risk factors of myocarditis. A higher resolution version of the Graphical abstract is available as Supplementary information.

[Nephrocalcinosis in children]. / Néphrocalcinose de l'enfant.

Nephrocalcinosis is defined by calcium phosphate or calcium oxalate deposits in the kidney parenchyma, particularly in tubular epithelial cells and interstitial tissue. It should be differentiated from urolithiasis where calcium salts deposits are located in the kidney and urinary tract. The epidemiology of nephrocalcinosis in children is unknown but the condition is not so rare, with an increased incidence in preterm infants. Often detected as an incidental finding, nephrocalcinosis may be classified according to the radiological type: medullary, cortical or diffuse. Nephrocalcinosis in children can be caused by a variety of etiology. The most common causes concern medullary nephrocalcinosis and include hereditary tubular disorders, in particular distal renal tubular acidosis and Dent disease, metabolic disorders such as idiopathic hypercalciuria and hyperoxaluria, and iatrogenic causes such as vitamin D intoxication. In the newborn, the main cause is hypercalciuria of the premature baby, whose multifactorial origin is largely iatrogenic. Primary hyperoxaluria which can lead to early onset nephrocalcinosis and usually to chronic kidney disease should always be considered and further investigated. In order to provide a specific diagnosis, it is essential to take into account the family history, the clinical context and complete laboratory data. Early initiation of an appropriate etiological treatment is recommended and may prevent or delay the progression to chronic kidney disease in some cases.

Outcome of children with Shiga toxin-associated haemolytic uraemic syndrome treated with eculizumab: a matched cohort study.

BACKGROUND: Treatment with eculizumab in Shiga toxin-associated haemolytic and uraemic syndrome (STEC-HUS) remains controversial despite its increasing utilization. The aim of our study was to evaluate the outcomes of children treated with eculizumab for STEC-HUS in a single-centre matched cohort study. METHODS: Data were retrospectively collected from medical records of children diagnosed with STEC-HUS. The outcomes of patients treated with eculizumab for STEC-HUS were compared with those of a control group of untreated patients matched for age, sex and severity of acute kidney injury with a 1:2 matching scheme. RESULTS: Eighteen children (median age 40.6 months) with STEC-HUS treated with eculizumab were compared with 36 matched control patients (median age 36.4 months) who did not receive eculizumab. All patients survived in the two groups. Within 1 month of HUS onset, the evolution of haematological and renal parameters did not differ between the two groups. At 12 months of follow-up, renal outcome was not significantly different between the two groups. At the last follow-up, the prevalence of decreased glomerular filtration rate in the eculizumab group (27%) was not statistically different from that in controls (38%), as was the prevalence of proteinuria and high blood pressure. Children who received eculizumab more often had extrarenal sequelae during follow-up. Eculizumab treatment appeared to be safe in children with STEC-HUS. CONCLUSION: The benefit of eculizumab on renal and extrarenal outcomes in STEC-HUS could not be established based on our findings. However, efficacy and safety are not best assessed by the observational design and small sample size of our study. Randomized controlled trials are thus required to determine the efficacy of eculizumab in this indication.

Long-term outcome of diarrhea-associated hemolytic uremic syndrome is poorly related to markers of kidney injury at 1-year follow-up in a population-based cohort.

BACKGROUND: Hemolytic uremic syndrome due to Shiga toxin-producing E. coli (STEC-HUS) is the main cause of acute kidney injury in young children. Most fully recover kidney function; however, some develop long-term sequelae. We aimed to determine whether kidney injury 1 year after HUS onset is associated with long-term kidney outcome in pediatric STEC-HUS. METHODS: A retrospective population-based study of children < 15 years with STEC-HUS between 1992 and 2012 was performed. Mixed effects logistic regression was used to investigate associations between kidney injury at 1 year and long-term kidney outcome. RESULTS: Ninety-eight STEC-HUS cases were reported. Of 96 patients who survived acute phase, 84 were evaluated at 1-year follow-up of whom 42 (44% of survivors) showed ≥ 1 signs of kidney injury. Data from 81 patients were collected after median follow-up of 8.7 (IQR 3.5-12.7) years. At last follow-up, 42 (44% of survivors) had ≥ 1 signs of kidney injury including decreased estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 (n = 30), proteinuria (n = 17), or hypertension (n = 5). Among 42 patients with kidney injuries at 1-year follow-up, only 22 (52%) still had kidney disease at last follow-up. Conversely, of 33 patients without kidney injury at 1-year and available long-term outcome data, 11 (33%) had proteinuria or decreased GFR at last follow-up. There was no statistically significant association between kidney injury at 1 year and long-term kidney outcome. CONCLUSIONS: Since kidney sequelae may appear at variable time intervals after acute HUS, all patients need lifelong follow-up to detect early signs of chronic kidney disease and propose measures to slow progression.