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INTRODUCTION: Nephroprotection in pediatric chronic kidney disease (CKD) has a major positive impact, both on residual renal function and on quality of life, by delaying the need for renal replacement therapy. To this day, nephroprotective drugs used in children are mainly limited to angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers; interestingly, as suggested by trials conducted in adults with CKD, sodium-glucose cotransporter 2 inhibitors (SGLT2i) might also be beneficial to pediatric patients. However, there are no validated data to this date documenting the effect of SGLT2i in pediatric patients with CKD. METHODS: We present a retrospective single-center study reporting the use of dapagliflozin in pediatric patients with CKD, aiming to evaluate dapagliflozin safety profile as well as its potential for renal protection. Our study describes 7 patients with a mean age of 13.3 years (+/- 7.029) presenting with identified glomerulopathy, leading to CKD and already treated by ACE inhibitors. Patients received a daily dose of dapagliflozin of 5 or 10 mg. RESULTS: Over a period of 15 months, all patients reported the medication as easy to use. After an initial dip, estimated glomerular filtration rate decline slope stabilized in all patients. Urinary albumin-over-creatinine ratio had a strong tendency to decrease after 6 months of treatment (p = 0.0684). Systolic blood pressure also had a tendency to decrease after 6 months of treatment (p = 0.1). No significant side effect was reported by the patients. CONCLUSION: The promising results presented in this study support the use of SGLT2i in pediatric patients with CKD, although larger, randomized controlled trials in pediatric patients are necessary to better characterize their effectiveness in this particular population.
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BACKGROUND: The use of genetic testing in pediatric patients with chronic kidney diseases (CKD) has increased exponentially in the past few years, particularly with the emergence of novel sequencing techniques. However, the genetic yield remains unexpectedly low in nephrology, with an impact on diagnosis, prognosis and treatment. Moreover, the increasing diversity of genetic testing possibilities can be seen as an obstacle by clinicians, in the absence of a strong background in genetics. Here, we propose a step-by-step, multidisciplinary strategy for the diagnostic evaluation of pediatric patients with CKD, and appropriate genetic test selection to maximize the yield of genetic testing. METHODS: A total of 126 pediatric patients were enrolled in a retrospective file analysis. Genetic testing techniques used included phenotype-associated next-generation panel sequencing (N = 41), Sanger and SNaPshot sequencing (N = 3) and/or whole exome sequencing (N = 2). RESULTS: Overall genetic yield reached 63% and genetic testing significantly impacted patient management in 70%. The distribution of kidney diseases among patients was balanced and matched previously described pediatric cohorts in terms of glomerulopathies, tubulopathies and ciliopathies. Genetic analyses led to significant treatment modifications, kidney biopsy sparing and personalized nephroprotection, as well as tailored genetic counseling. Of note, the evaluation of Human Phenotype Ontology term accuracy in the cohort showed that causal mutations were precisely identified in 85% of the patients at most. CONCLUSION: Here we suggest a step-by-step, multidisciplinary strategy to maximize the yield of genetic testing in pediatric patients with CKD. This approach optimizes patient care while avoiding unnecessary treatments or procedures.
