Infant urinary tract infection in Sweden - A national study of current diagnostic procedures, imaging and treatment.

BACKGROUND: Urinary tract infection (UTI) in infants is a common, potentially life-threatening bacterial infection, and must be managed carefully through the entire chain of care from diagnosis, choice of treatment, follow-up and risk stratification of future complications. This Swedish nationwide study of infant UTI was conducted to evaluate the current management of infant UTI, yield of investigations and the Swedish UTI guidelines' ability to detect abnormalities of importance in the urinary tract. METHODS: Infants < 1 year with a first episode of UTI were included in a prospective multicenter study. Treatment and follow-up were provided by local pediatricians. Clinical and laboratory findings and imaging results were reported to the coordinating center. The current management and results were compared with a previous Swedish study. RESULTS: One thousand three hundred six infants were included. Urine sampling was performed with clean catch technique in 93% of patients. Initial oral antibiotic treatment was used in 63%, predominantly third generation cephalosporines. Permanent kidney abnormalities were found in 10% and dilating vesicoureteral reflux (VUR) in 8%. Higher rates of male gender, non-E. coli infection and ultrasound dilatation were seen in infants < 1 month. UTI recurrences were reported in 18%. CONCLUSIONS: Infant UTI is still generating a considerable amount of follow-up examinations. There is a significant shift towards clean catch as the main urine sampling method. Voiding cystourethrography is performed less frequently reducing the findings of low grade VUR. The incidence of renal scarring is comparable with earlier studies which suggests that the Swedish guidelines are able to identify individuals with risk for long-term complications.

Genetic determinants of renal scarring in children with febrile UTI.

BACKGROUND: Febrile urinary tract infections (UTIs) are among the most severe bacterial infections in infants, in which a subset of patients develops complications. Identifying infants at risk of recurrent infections or kidney damage based on clinical signs is challenging. Previous observations suggest that genetic factors influence UTI outcomes and could serve as predictors of disease severity. In this study, we conducted a nationwide survey of infant genotypes to develop a strategy for infection management based on individual genetic risk. Our aims were to identify genetic susceptibility variants for renal scarring (RS) and genetic host factors predisposing to dilating vesicoureteral reflux (VUR) and recurrent UTIs. METHODS: To assess genetic susceptibility, we collected and analyzed DNA from blood using exome genotyping. Disease-associated genetic variants were identified through bioinformatics analysis, including allelic frequency tests and odds ratio calculations. Kidney involvement was defined using dimercaptosuccinic acid (DMSA) scintigraphy. RESULTS: In this investigation, a cohort comprising 1087 infants presenting with their first episode of febrile UTI was included. Among this cohort, a subset of 137 infants who underwent DMSA scanning was subjected to gene association analysis. Remarkable genetic distinctions were observed between patients with RS and those exhibiting resolved kidney involvement. Notably, the genetic signature indicative of renal scarring prominently featured mitochondrial genes. CONCLUSIONS: In this nationwide study of genetic susceptibility to RS after febrile UTIs in infancy, we identified a profile dominated by mitochondrial polymorphisms. This profile can serve as a predictor of future complications, including RS and recurrent UTIs.

Is kidney biopsy necessary in children with idiopathic nephrotic syndrome?

AIM: To investigate the need, in the Northern European setting, to perform kidney biopsy in children with steroid-sensitive nephrotic syndrome. METHODS: In this retrospective study 124 individuals aged 1-18 years with idiopathic nephrotic syndrome, followed in the paediatric hospitals in southern Sweden from 1999 to 2018, were included. RESULTS: There was a median follow-up time of 6.5 (0.2-16.8) years. The majority (92%) of children were steroid-sensitive and of them, 60.5% were frequently relapsing or steroid-dependent. Microscopic haematuria was found at onset in 81.1% and hypertension in 8.7%. At least one kidney biopsy was performed in 93 (75%). The most common indication was a steroid-dependent or relapsing course (58.4%). One of 79 steroid-sensitive children had another histological diagnosis than minimal change nephropathy 1.3%, 95% confidence interval (0.002, 0.068). Bleeding occurred after eight biopsies (6.6%). Twenty individuals (30.7%) were transferred to adult units, 18 still on immunosuppression. CONCLUSION: We have in our cohort of unselected children with idiopathic nephrotic syndrome confirmed that a kidney biopsy rarely gives important medical information in steroid-sensitive children without any other complicating factor and that the liberal policy of kidney biopsy in the Nordic countries safely can be changed.

Eculizumab treatment for rescue of renal function in IgA nephropathy.

BACKGROUND: Immunoglobulin A (IgA) nephropathy is a chronic glomerulonephritis with excessive glomerular deposition of IgA1, C3 and C5b-9, which may lead to renal failure. CASE DIAGNOSIS/TREATMENT: We describe the clinical course of an adolescent with rapidly progressive disease leading to renal failure in spite of immunosuppressive treatment. Due to refractory disease the patient was treated with eculizumab (anti-C5) for 3 months in an attempt to rescue renal function. Treatment led to clinical improvement with stabilization of the glomerular filtration rate and reduced proteinuria. Discontinuation of treatment led to a rapid deterioration of renal function. This was followed by a single dose of eculizumab, which again reduced creatinine levels temporarily. CONCLUSIONS: Early initiation of eculizumab therapy in patients with progressive IgA nephropathy may have a beneficial effect by blocking complement-mediated renal inflammation.

Molecular determinants of disease severity in urinary tract infection.

The most common and lethal bacterial pathogens have co-evolved with the host. Pathogens are the aggressors, and the host immune system is responsible for the defence. However, immune responses can also become destructive, and excessive innate immune activation is a major cause of infection-associated morbidity, exemplified by symptomatic urinary tract infections (UTIs), which are caused, in part, by excessive innate immune activation. Severe kidney infections (acute pyelonephritis) are a major cause of morbidity and mortality, and painful infections of the urinary bladder (acute cystitis) can become debilitating in susceptible patients. Disease severity is controlled at specific innate immune checkpoints, and a detailed understanding of their functions is crucial for strategies to counter microbial aggression with novel treatment and prevention measures. One approach is the use of bacterial molecules that reprogramme the innate immune system, accelerating or inhibiting disease processes. A very different outcome is asymptomatic bacteriuria, defined by low host immune responsiveness to bacteria with attenuated virulence. This observation provides the rationale for immunomodulation as a new therapeutic tool to deliberately modify host susceptibility, control the host response and avoid severe disease. The power of innate immunity as an arbitrator of health and disease is also highly relevant for emerging pathogens, including the current COVID-19 pandemic.