Background and Objectives: The nephrotic syndrome (NS) is the most common acquired childhood kidney disease. Steroids represent the cornerstone of the therapeutic strategy, representing the first-line approach, but optimal therapeutic management is debated. This study aimed to compare different steroid therapeutic management protocols. Patients and Methods: A total of 140 NS pediatric patients were enrolled retrospectively. All the kids were divided among three different groups according to the three different steroid therapeutic schemes: 2240 mg/m² (group 1), 3360 mg/m² (group 2), or 3640 mg/m² (group 3) and divided in frequently relapsing (FR-NS) or steroid-dependent (SD) NS. Results: Within group 1, 50% of the population developed FR-NS; 100% of those kids were between 2 and 6 years old. Within the second group, 54% of the patients developed FR-NS, and 83% of these kids were between 2 and 6 years old, i.e., 45% of the group population. Within group 3, 45% of the patients developed FR-NS, and 70% of these kids were among 2 and 6 years old, i.e., 32% of the group population. This group exhibits the lowest percentage (42%) of patients in the highest relapse category (≥5 relapses) compared to the other protocols, indicating that this protocol might be more effective at reducing the number of frequent relapses. No specific predictor factors of FR- or SD-NS were revealed in the studied cohort. Conclusions: A longer steroid scheme does not correlate with a better outcome, nor does it reduce the number of relapses or prevent steroid failure.

Pediatric cystic kidney diseases lie at the intersection of autosomal dominant polycystic kidney disease (ADPKD) and a broad spectrum of ciliopathies. The pediatric phenotype often reflects a spectrum that includes ARPKD-like presentations, nephronophthisis-related disease, Joubert syndrome-associated kidney involvement, Bardet–Biedl syndrome, and other ciliopathies that can mimic or overlap with PKD. While ADPKD is traditionally attributed to pathogenic variants in PKD1 and PKD2, the widespread deployment of next-generation sequencing has uncovered causal variants in novel loci, including GANAB (~0.3%), DNAJB11 (~0.1%), ALG5, ALG9, and recently, IFT140 and NEK8. This review outlines the expanding genetic and clinical landscape of ADPKD, integrating recent cohort data and molecular insights. We discuss radiologically atypical presentations, overlapping syndromic ciliopathies, and the mechanisms of metabolic reprogramming and primary ciliary dysregulation in cyst pathogenesis. Recent milestones in clinical trials and emerging therapeutic strategies, including perspectives on early risk stratification before the transition to adulthood, are also evaluated. Ultimately, this review emphasizes the necessity of gene-based classifications and precise genotype–phenotype correlations, aligned with the 2025 KDIGO Clinical Practice Guideline for ADPKD, to optimize risk stratification and advance precision medicine in the clinical management of ADPKD.