Clinical outcomes among children with primary nephrogenic diabetes insipidus

Background Primary nephrogenic diabetes insipidus (NDI) is a rare inherited disorder with limited data on long-term outcomes. This study assessed longitudinal outcomes with primary NDI. Methods This multicenter retrospective study included 63 patients with primary NDI. Growth rates and estimated glomerular filtration (eGFR) analyzed via piecewise linear mixed-effects model during the pediatric period. Results AVPR2 and AQP2 mutations were identified in 74.6% and 9.5% of patients, respectively. The median ages at diagnosis and last follow-up were 0.41 and 12.37 years, respectively. Height Z-scores declined from birth to 1.5 years and improved thereafter, with slopes of 2.616, 0.563, 0.102, and 0.031 per year across breakpoints at 0.5, 1.5, and 7 years. Although none of the patients met the criteria for short stature by age 18, the mean final height Z-score remained below average and was significantly lower than that at birth. Weight and weight-for-height Z-scores initially declined and then improved, with slope changes at 0.5 and 0.7 years. By age 18, 38.9% were overweight or obese. eGFR increased rapidly before 1.4 years (slope 25.61 mL/min/m2/year), and slowly thereafter (slope 0.58), reaching eGFR ≥90 mL/min/m2 at a median age of 5.1 years. The proportion of patients with eGFR < 90 decreased to 34.6% at 14 years, then rose to 43.8% by age 18. Treatment-associated complications included hypokalemia (64.5%), alkalosis (61.1%), and hyperuricemia (60.7%). Conclusions Patients with primary NDI exhibit a dynamic growth trajectory, delayed achievement of normal GFR with subsequent risk of chronic kidney disease, and frequent treatment-associated complications. These findings underscore the need for timely and individualized long-term management.