Background <p>Renal hypodysplasia (RHD) is a common and severe form of congenital anomalies of the kidney and urinary tract (CAKUT), often leading to chronic kidney disease (CKD) in children. This study, leveraging a 10-year single-center cohort, aims to elucidate clinical and prognostic characteristics as well as genetic causes in pediatric RHD.</p> Methods <p>We enrolled 322 patients diagnosed with primary RHD by ultrasound at Wuhan Children's Hospital in the past decade. Baseline and follow-up data were collected. Kidney outcomes were investigated using Kaplan–Meier curves and Cox regression model to assess risk factors for early CKD event (eGFR &lt; 75&#xa0;mL/min/1.73 m²). Whole Exome Sequencing and copy number variation analysis were performed to identify genetic causes.</p> Results <p>Among 322 RHD patients, 281 (87.3%) had unilateral kidney involvement, and 41 (12.7%) had bilateral involvement. Patients with bilateral RHD exhibited worse kidney function and CKD stage (<i>P</i> &lt; 0.001), while unilateral RHD was more frequently associated with additional CAKUT. After median follow-up of 4.5&#xa0;years, 72 (22.4%) patients reached the early CKD endpoint. Bilateral kidney involvement (HR = 4.40, 95% CI 2.31–8.39,<i> P</i> &lt; 0.001), urine ACR levels (3–30&#xa0;mg/mmol: HR = 2.24, 95% CI 1.02–4.92,<i> P</i> = 0.044; &gt; 30&#xa0;mg/mmol: HR = 2.55, 95% CI 1.32–4.93, <i>P</i> = 0.005), and extra-urogenital malformations (HR = 2.28, 95% CI 1.26–4.10, <i>P</i> = 0.006) were independent risk factors. Genetic testing revealed <i>PAX2</i>, <i>WT1</i> variants, and 17q12 deletion as the most prevalent pathogenic variations.</p> Conclusions <p>This study reveals distinct clinical and prognostic characteristics between unilateral and bilateral RHD. Bilateral kidney lesions, albuminuria, and extra-urogenital malformations are independent risk factors for kidney function decline. <i>PAX2</i>, <i>WT1</i> variants, and 17q12 deletion are the most common genetic causes.</p> Graphical abstract <p></p>