Introduction Nephrogenic diabetes insipidus (NDI) is a rare condition caused by renal resistance to the action of antidiuretic hormone (ADH) at the level of the distal tubule, resulting in impaired urinary concentration and consequent polyuria. NDI may be hereditary, most commonly X-linked due to AVPR2 gene mutations, or acquired. Objective To characterize the clinical features, management strategies, and outcomes of patients with NDI followed at a tertiary pediatric nephrology center. Methods A retrospective observational study was conducted, including pediatric patients diagnosed with NDI between 1991 and 2024. Data regarding clinical presentation, diagnostic approach, management strategies, and long-term outcomes were collected and analyzed. Results Eight patients (including one set of twins) were identified; seven (87.5%) were male subjects. The median age at diagnosis was 7.5 months (interquartile range (IQR): 6.0-9.0). All patients presented with polydipsia, polyuria (median diuresis: 10.0 (IQR: 9.0-10.2) mL/kg/h), and failure to thrive. Constipation and recurrent fever were observed in two patients (25.0%). At diagnosis, the median serum sodium level was 160.5 mmol/L (IQR: 139-168), and the urine/plasma osmolality ratio was 0.41 (IQR: 0.26-0.49). No patients exhibited metabolic acidosis. All desmopressin tests were negative. Genetic testing was performed in four patients, all of whom had pathogenic X-linked AVPR2 variants. All patients were treated with hydrochlorothiazide and amiloride; indomethacin was added in 5 (62.5%). Serum sodium normalized in all cases. Over a median follow-up period of 16.9 years (IQR: 8.4-17.4), growth improved, but all patients continued to exhibit polyuria and polydipsia. Neurodevelopmental disorders were identified in six patients, including intellectual disability, autism spectrum disorder, language delay, and learning difficulties. Renal function, serum sodium, and imaging findings remained stable throughout follow-up. At the final assessment, all patients remained on hydrochlorothiazide and amiloride. Five transitioned to adult nephrology at a median age of 17.0 years (IQR: 16.0-17.0). Conclusion Although rare, NDI can significantly impact growth and neurodevelopment. The diagnosis should be considered in infants with failure to thrive, especially when accompanied by polyuria and polydipsia. Early recognition and intervention, even if non-specific, may improve long-term outcomes.
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