Acute kidney injury in children hospitalised for febrile urinary tract infection.

AIM: To determine (i) prevalence and the risk factors for acute kidney injury (AKI) in children hospitalised for febrile urinary tract infection (fUTI) and (ii) role of AKI as indicator of an underlying VUR. AKI, in fact, is favoured by a reduced nephron mass, often associated to VUR. METHODS: This retrospective Italian multicentre study enrolled children aged 18 years or younger (median age = 0.5 years) discharged with a primary diagnosis of fUTI. AKI was defined using Kidney Disease/Improving Global Outcomes serum creatinine criteria. RESULTS: Of 849 children hospitalised for fUTI (44.2% females, median age 0.5 years; IQR = 1.8), 124 (14.6%) developed AKI. AKI prevalence rose to 30% in the presence of underlying congenital anomalies of the kidney and urinary tract (CAKUT). The strongest AKI predictors were presence of CAKUT (OR = 7.5; 95%CI: 3.8-15.2; p = 9.4e-09) and neutrophils levels (OR = 1.13; 95%CI: 1.08-1.2; p = 6.8e-07). At multiple logistic regression analysis, AKI during fUTI episode was a significant indicator of VUR (OR = 3.4; 95%CI: 1.7-6.9; p = 0.001) despite correction for the diagnostic covariates usually used to assess the risk of VUR after the first fUTI episode. Moreover, AKI showed the best positive likelihood ratio, positive predictive value, negative predictive value and specificity for VUR. CONCLUSION: AKI occurs in 14.6% of children hospitalised for fUTI and is a significant indicator of VUR.

Oral steroids for reducing kidney scarring in young children with febrile urinary tract infections: the contribution of Bayesian analysis to a randomized trial not reaching its intended sample size.

BACKGROUND: This study aimed to evaluate the effect of oral dexamethasone in reducing kidney scars in infants with a first febrile urinary tract infection (UTI). METHODS: Children aged between 2 and 24 months with their first presumed UTI, at high risk for kidney scarring based on procalcitonin levels (≥1 ng/mL), were randomly assigned to receive dexamethasone in addition to routine care or routine care only. Kidney scars were identified by kidney scan at 6 months after initial UTI. Projections of enrollment and follow-up completion showed that the intended sample size could not be reached before funding and time to complete the study ran out. An amendment to the protocol was approved to conduct a Bayesian analysis. RESULTS: We randomized 48 children, of whom 42 had a UTI and 18 had outcome kidney scans (instead of 128 planned). Kidney scars were found in 0/7 and 2/11 patients in the treatment and control groups respectively. The probability that dexamethasone could prevent kidney scarring was 99% in the setting of an informative prior probability distribution (which fully incorporated in the final inference the information on treatment effect provided by previous studies) and 98% in the low-informative scenario (which discounted the prior literature information by 50%). The probabilities that dexamethasone could reduce kidney scar formation by up to 20% were 61% and 53% in the informative and low-informative scenario, respectively. CONCLUSIONS: Dexamethasone is highly likely to reduce kidney scarring, with a more than 50% probability to reduce kidney scars by up to 20%. TRIAL REGISTRATION NUMBER: EudraCT number: 2013-000388-10; registered in 2013 (prospectively registered) A higher resolution version of the Graphical abstract is available as Supplementary information.

Updated Italian recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children.

AIM: Our aim was to update the recommendations for the diagnosis, treatment and follow-up of the first febrile urinary tract infection in young children, which were endorsed in 2012 by the Italian Society of Pediatric Nephrology. METHODS: The Italian recommendations were revised on the basis of a review of the literature published from 2012 to October 2018. We also carried out an ad hoc evaluation of the risk factors to identify children with high-grade vesicoureteral reflux or renal scarring, which were published in the previous recommendations. When evidence was not available, the working group held extensive discussions, during various meetings and through email exchanges. RESULTS: Four major modifications have been introduced. The method for collecting urine for culture and its interpretation has been re-evaluated. We have reformulated the algorithm that guides clinical decisions to proceed with voiding cystourethrography. The suggested antibiotics have been revised, and we have recommended further restrictions of the use of antibiotic prophylaxis. CONCLUSION: These updated recommendations have now been endorsed by the Italian Society of Pediatric Nephrology and the Italian Society for Pediatric Infectivology. They can also be used to compare other recommendations that are available, as a worldwide consensus in this area is still lacking.

Short-term effects of rituximab in children with steroid- and calcineurin-dependent nephrotic syndrome: a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Prednisone and calcineurin inhibitors are the mainstay therapy of idiopathic nephrotic syndrome (INS) in children. However, drug dependence and toxicity associated with protracted use are common. Case series suggest that the anti-CD20 monoclonal antibody rituximab (RTX) may maintain disease remission. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This open-label randomized controlled trial was powered to show that a strategy based on RTX and lower doses of prednisone and calcineurin inhibitors was noninferior to standard doses of these agents in maintaining 3-month proteinuria as low as baseline or up to 1 g/d greater (noninferiority margin). Participants were stratified by the presence of toxicity to prednisone/calcineurin inhibitors and centrally assigned to add RTX (Mabthera, 375 mg/m(2) intravenously) to lower doses of standard agents or to continue with current therapy alone. The risk of relapse was a secondary outcome. RESULTS: Fifty-four children (mean age 11 ± 4 years) with INS dependent on prednisone and calcineurin inhibitors for >12 months were randomized. Three-month proteinuria was 70% lower in the RTX arm (95% confidence interval 35% to 86%) as compared with standard therapy arm (intention-to-treat); relapse rates were 18.5% (intervention) and 48.1% (standard arm) (P = 0.029). Probabilities of being drug-free at 3 months were 62.9% and 3.7%, respectively (P < 0.001); 50% of RTX cases were in stable remission without drugs after 9 months. CONCLUSIONS: Rituximab and lower doses of prednisone and calcineurin inhibitors are noninferior to standard therapy in maintaining short-term remission in children with INS dependent on both drugs and allow their temporary withdrawal.

Use of rituximab in focal glomerulosclerosis relapses after renal transplantation.

BACKGROUND: Focal and segmental glomerulosclerosis (FSGS) accounts for more than 10% of all cases of renal diseases leading to renal failure in children. After renal transplantation, 20% to 40% of FSGS relapse, frequently leading to renal loss.Plasmapheresis is considered the first option to treat relapses by several authors but is often ineffective. The anti-CD20 monoclonal antibody rituximab has been proposed as a possible treatment. METHODS: We reviewed the effect of rituximab in seven children or young adults with pretransplant FSGS and relapse of proteinuria after transplantation who did not respond to intensive plasmapheresis. RESULTS: After treatment, urine protein disappeared in three patients, was reduced by 70% in one patient and by 50% in one patient. No response was observed in one patient who had a quick deterioration of renal function and reached end-stage renal failure after 3 months. One additional patient developed a severe reaction a few minutes after the start of the first rituximab infusion. CONCLUSION: Rituximab is a possible option to treat some resistant cases of FSGS with relapsing proteinuria after transplantation. It is important that therapy is started early after evidence of failure of plasmapheresis, before sclerosis develops in the glomeruli. The response to treatment can occur after several months. During the follow-up period, CD19 cells should be monitored carefully, and additional rituximab infusions considered to maintain B-cell depletion.