Fluconazole as a New Therapeutic Tool to Manage Patients With NPTIIc (SLC34A3) Mutation: A Case Report.

Mutations in the SLC34A3 gene, encoding the sodium/phosphate cotransporter 2C (NPTIIc), induce decreased renal phosphate reabsorption, hypophosphatemia, decreased fibroblast growth factor 23 and parathyroid hormone, and increased 1,25-dihydroxyvitamin D (1,25[OH]2D) levels. The complete phenotype is characterized by hypophosphatemia, hypercalciuria, and nephrolithiasis/nephrocalcinosis, leading to chronic kidney disease and osteoporosis in adults. We report a 15-year-old boy referred for nephrocalcinosis. The patient demonstrated hypercalcemia, hypercalciuria, normal serum phosphate level, normal tubular phosphate reabsorption, and increased serum 1,25(OH)2D level with suppressed serum parathyroid hormone. Compound heterozygous mutations in SLC34A3 were found. Hydrochlorothiazide failed to decrease calciuria. Fluconazole, an inhibitor of 1α-hydroxylase, was effective in normalizing calciuria without decreasing glomerular filtration rate. We conclude that children with SLC334A3 mutations can present with a less-typical phenotype, having normal serum phosphate levels and normal renal phosphate reabsorption. Genetic abnormalities of NPTIIc should be considered in cases of increased 1,25(OH)2D levels without mutations in CYP24A1. The utility of fluconazole to decrease 1,25(OH)2D levels requires confirmation in larger studies.

Accuracy of Automated Flow Cytometry-Based Leukocyte Counts To Rule Out Urinary Tract Infection in Febrile Children: a Prospective Cross-Sectional Study.

Automated flow cytometry of urine remains an incompletely validated method to rule out urinary tract infection (UTI) in children. This cross-sectional analytical study was performed to compare the predictive values of flow cytometry and a dipstick test as initial diagnostic tests for UTI in febrile children and prospectively included 1,106 children (1,247 episodes). Urine culture was used as the gold standard test for diagnosing UTI. The performance of screening tests to diagnose UTI were established using receiver operating characteristic (ROC) analysis. Among these 1,247 febrile episodes, 221 UTIs were diagnosed (17.7% [95% confidence interval {CI}, 15.6 to 19.8%]). The area under the ROC curve for flow cytometry white blood cell (WBC) counts (0.99 [95% CI, 0.98 to 0.99]) was significantly superior to that for red blood cell (0.74 [95% CI, 0.70 to 0.78]) and bacterial counts (0.89 [95% CI, 0.87 to 0.92]) (P < 0.001). Urinary WBC counts also had a significantly higher area under the ROC curve than that of the leukocyte esterase (LE) dipstick (0.92 [95% CI, 0.90 to 0.94]), nitrite dipstick (0.83 [95% CI, 0.80 to 0.87]), or the combination of positive LE and/or nitrite dipstick (0.91 [95% CI, 0.89 to 0.93]) test (P < 0.001). The presence of ≥35 WBC/µl of urine was the best cutoff point, yielding both a high sensitivity (99.5% [95% CI, 99 to 100%]) and an acceptable specificity (80.6% [95% CI, 78 to 83%]). Using this cutoff point would have reduced the number of samples sent to the laboratory for culture by 67%. In conclusion, the determination of urinary WBC counts by flow cytometry provides optimal performance as an initial diagnostic test for UTI in febrile children.

BK Polyomavirus in Pediatric Renal Transplantation-What We Know and What We Do Not.

BK polyomavirus (BKPyV) is still a real threat in the management of kidney transplantation. Immunosuppressive treatment disrupts the equilibrium between virus replication and immune response, and uncontrolled BKPyV replication leads to nephropathy (BKPyV nephropathy). The first evidence of BKPyV reactivation in transplant recipients is the detection of viral shedding in urine, which appears in 20% to 60% of patients, followed by BKPyV viremia in 10-20% of kidney transplant recipients. BKPyV nephropathy eventually occurs in 1-10% of this population, mainly within the first 2 years post-transplantation, causing graft loss in about half of those patients. Few data exist regarding the pediatric population and we focus on them. In this paper, we review the existing diagnostic methods and summarize the evidence on the role of BKPyV humoral and cellular immunity in modulating the clinical course of BKPyV infection and as potential predictors of the outcome. We look at the known risk factors for BKPyV nephropathy in the immunosuppressed patient. Finally, we propose a sensible clinical attitude in order to screen and manage BKPyV infection in kidney transplant children.

Case Report: Sustained Efficacy of Lumasiran at 18 Months in Primary Hyperoxaluria Type 1.

Background: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate, ultimately responsible for kidney stones, kidney failure and systemic oxalosis. Lumasiran, is a liver-directed RNA interference therapeutic agent. It has been shown to reduce hepatic oxalate production by targeting glycolate oxidase, and to dramatically reduce oxalate excretion. Care Report: We present the case of a teenager patient affected by PH1, who entered in the lumasiran compassionate use program. The patient had a rapid and sustained decrease in urinary oxalate/creatinine ratio, with a mean reduction after lumasiran administration of about 70%. During the 18 months long follow-up, urinary oxalate remained low, reaching nearly normal values. Plasma oxalate also decreased dramatically. Normal levels were reached immediately after the first dose and remained consistently low thereafter. During the same follow-up period, eGFR remained stable at about 60 ml/min/1.73 m2, but no new kidney stones were observed. Existing kidney stones did not increase in size. The patient did not suffer renal colic events and did not require further urological interventions. Conclusion: In our severely affected PH1 patient, lumasiran proved to be very effective in rapidly and consistently reducing plasma oxalate and urinary excretion to normal and near-normal levels, respectively. In the 18 months long follow-up post-lumasiran, the eGFR remained stable and the patient showed clinical improvements. As far as we know, this report covers the longest observation period after initiation of this novel RNAi therapy.

Disseminated bartonellosis in a child with steroid-dependent nephrotic syndrome receiving mycophenolate mofetil monotherapy.

Cat scratch disease, usually a benign infectious disease, may develop as multisystem disease with multiorgan involvement, particularly in immunocompromised patients. We report on a patient who developed disseminated bartonellosis while receiving mycophenolate mofetil monotherapy treating steroid-dependent nephrotic syndrome, highlighting that severe infection can be observed in those patients. Therefore, this category of patients should be cautious when having contact with kittens and receives proper prevention advice.

Rhabdomyolysis and Acute Kidney Injury as Leading COVID-19 Presentation in an Adolescent.

Severe acute respiratory syndrome coronavirus 2, the virus responsible of the current COVID-19 pandemic, has limited impact in the pediatric population. Children are often asymptomatic or present mild flu-like symptoms. We report the case of a COVID-19-infected adolescent presenting severe rhabdomyolysis and acute kidney injury without any fever or respiratory symptoms.