Risdiplam, a survival motor neuron 2 (SMN2) splicing modifier for pediatric spinal muscular atrophy (SMA), requires a comprehensive real-world safety evaluation. This study analyzed 1059 pediatric adverse event reports from the FDA Adverse Event Reporting System (2020 Q1-2025 Q4) with risdiplam as the primary suspect drug. Female patients slightly predominated, with 50.9% aged 0-5 years. Disproportionality analyses identified 25 positive signals. Infections and infestations, general disorders, and gastrointestinal disorders were most frequent. Pneumonia, pyrexia, diarrhoea, respiratory tract infection, and nasopharyngitis were most commonly reported. Notably, nephrolithiasis emerged as a novel unlabeled signal in pediatric patients (reporting odds ratio = 11.32). Median time-to-onset was 119 days, with approximately one-third of events occurring within 30 days and another one-third after 1 year. The Weibull model revealed that the top 5 most frequently reported PTs and top 5 SOCs all exhibited an early-onset pattern. Network toxicology identified 75 overlapping targets, with CASP3, HDAC1, and PDGFRA as core targets implicated in calcium signaling, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and apoptosis pathways. Molecular docking confirmed stable binding (- 10.1 to - 8.6 kcal/mol). Risdiplam demonstrates a generally acceptable long-term safety profile in clinical practice, yet vigilant monitoring of respiratory, infectious, gastrointestinal, and renal adverse events remains essential to optimize the benefit-risk balance.

Renal stones remain a prevalent renal disorder characterized by high recurrence rates and limited therapeutic options, encouraging continued research into novel agents capable of treating established stone disease. Camelus dromedarius hump fat has long been used in North African alternative medicine to treat various dermal and inflammatory diseases. This study aims to evaluate the antioxidant activity, specifically radical scavenging, and the therapeutic potential of this fat against Calcium oxalate stones induced by Ethylene glycol in a Wistar rat model. Twenty Wistar rats were divided into four groups (n=5). The first group serves as the control. The three other groups received EG in their drinking water until stones formed. Rats were fed a fresh dromedary hump fat diet at 45% w/w daily. Urinary parameters (volume, pH, electrolytes), serum biochemical assessments, and measured creatinine clearance were analyzed. Renal histopathology was performed to evaluate tissue changes. The EG-treated rats showed significant disturbances in all physiological parameters, including decreases in urinary volume, pH, and urinary electrolyte excretion. DHF demonstrated strong antioxidant activities, with DPPH scavenging (69.158%-85.571%), FRAP values (70.785%-83.971%), and ABTS (59.145%-89.195%), indicating potential to reduce oxidative stress. In addition to that, treatments with the DHF diet significantly increase urinary volume from 6.3 ± 0.2 ml to 10.12 ± 0.1 ml (p < 0.001). These alterations extend to serum creatinine and urea levels. A high increase in serum creatinine and urea levels was shown. The DHF-treated group showed a creatinine clearance of 3.46 ± 0.68 ml/min on day 21. Importantly, the DHF diet protected the liver from EG-induced damage, as evidenced by serum levels of gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine aminotransferase (ALT) that were near control levels. In contrast, the EG-only group exhibited marked elevations in enzyme levels (p < 0.01). These findings suggest that the DHF 45% w/w diet may exert its protective effect by reducing oxidative stress and preserving tubular epithelial integrity, thereby improving urinary electrolyte excretion, decreasing crystal formation, and protecting renal tissue.

APRT deficiency leads to 2,8-DHA nephropathy. It manifests as recurrent radiolucent calculi and progressive renal failure. These stones are misidentified as uric acid stones. We report a 30-year-old male with recurrent left-sided nephrolithiasis, resulting in a poorly functioning left kidney. He subsequently presented with acute obstructive uropathy in his hypertrophied right kidney. FTIR post-ureteroscopy identified the composition as 2,8-DHA. This case underscores the necessity of precise stone analysis in recurrent urolithiasis. Increased awareness and knowledge of the limitations of some methods of laboratory analysis for renal stones should help to identify this type of stone and prevent renal damage.

Large and complex kidney stones remain difficult to treat, particularly when stones extend into several calyces. RLPL provides access to the collecting system without renal parenchymal puncture, whereas multiple-tract Mini-PCNL relies on several percutaneous tracts to reach different stone-bearing areas. We retrospectively analyzed patients with moderate-to-complex kidney stones treated with either procedure between January 2017 and December 2025. Propensity score matching was used to reduce baseline differences between groups. The main endpoint was stone-free status at 3 months; perioperative outcomes and complications were also recorded. Among 153 eligible patients, 108 received multiple-tract Mini-PCNL and 45 underwent RLPL. Matching produced 35 pairs. At 3 months, stone-free status was achieved in 71.4% of patients undergoing RLPL and 68.6% of those undergoing multiple-tract Mini-PCNL, with no significant difference detected between groups (risk difference 2.9%, 95% CI: -22.9% to 22.9%; P = 1.000). RLPL demonstrated significantly less hemoglobin drop but required longer operative time and postoperative hospitalization. Overall complication rates were 20.0% and 17.1%, respectively (P = 1.000). On exploratory multivariable analysis, residual stones were independently associated with higher BMI and larger stone diameter, whereas surgical approach was not an independent predictor. RLPL may serve as a complementary option for selected patients with complex kidney stones rather than a replacement for multiple-tract Mini-PCNL.

Nephrolithiasis incidence has risen with frequent recurrence, and injury to renal tubular epithelial cells is central to its pathology. Ferroptosis, an iron-dependent form of regulated cell death, has been implicated in kidney diseases, but its role in nephrolithiasis remains unclear. In this study, we investigated whether CD74 is associated with ferroptosis-related tubular injury during nephrolithiasis and explored the potential involvement of NF-κB signaling. A glyoxylate-induced mouse model showed prominent calcium oxalate deposition, impaired renal function, altered expression of ACSL4 and GPX4, and increased oxidative stress. Integrating bulk transcriptomics, protein-protein interaction networks, bioinformatics, and a public single-cell RNA-sequencing dataset, we identified CD74 as a candidate ferroptosis-associated gene showing increased expression during nephrolithiasis progression. In vitro, oxalate exposure in human HK-2 cells induced CD74 upregulation together with ferroptosis-associated molecular and biochemical changes. CD74 knockdown improved cell viability and redox homeostasis and attenuated ferroptosis-associated marker changes, whereas CD74 overexpression aggravated oxidative injury and ferroptosis. Mechanistically, CD74 modulation was associated with changes in NF-κB signaling activity, and pharmacological modulation of NF-κB partially reversed the corresponding cellular phenotypes. Together, these findings support a potential role of CD74-associated NF-κB signaling in ferroptosis-related tubular injury during nephrolithiasis. These findings suggest that the CD74/NF-κB axis may represent a potential therapeutic direction and provide mechanistic insight for future studies.