To examine the dynamic changes in the formative factors of nephrolithiasis and the final micromorphological changes in an obesity-initiated metabolic syndrome (MS) rat model.Forty five-week-old mal...

Nephrolithiasis is a major public health concern associated with high morbidity and recurrence. Despite decades of research, the pathogenesis of nephrolithiasis remains incompletely understood, and effective prevention is lacking. An increasing body of evidence suggests that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a role in stone formation and stone-related kidney injury. MiRNAs have been studied quite extensively in nephrolithiasis, and a plethora of specific miRNAs have been implicated in the pathogenesis of nephrolithiasis, involving remarkable changes in calcium metabolism, oxalate metabolism, oxidative stress, cell–crystal adhesion, cellular autophagy, apoptosis, and macrophage (Mp) polarization and metabolism. Emerging evidence suggests a potential for miRNAs as novel diagnostic biomarkers of nephrolithiasis. LncRNAs act as competing endogenous RNAs (ceRNAs) to bind miRNAs, thereby modulating mRNA expression to participate in the regulation of physiological mechanisms in kidney stones. Small interfering RNAs (siRNAs) may provide a novel approach to kidney stone prevention and treatment by treating related metabolic conditions that cause kidney stones. Further investigation into these non-coding RNAs will generate novel insights into the mechanisms of renal stone formation and stone-related renal injury and might lead to new strategies for diagnosing and treating this disease.

Kidney stone disease (KSD) is a globally prevalent urinary system disorder whose pathogenesis involves complex interactions among metabolic, genetic, and environmental factors. Although the role of glucose metabolism in KSD has been widely studied, the impact of lipid metabolism abnormalities remains unclear. This review systematically integrates epidemiological, animal model, and molecular mechanism studies to explore the mechanisms by which lipid metabolism disorders promote KSD through key regulatory factors, such as peroxisome proliferator-activated receptors (PPARs), fatty acid-binding proteins (FABPs), and apolipoproteins, synergizing with organelle damage pathways, including mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and ferroptosis. This study revealed that abnormal lipid metabolism accelerates renal papillary calcification and stone formation by inducing oxidative stress, inflammatory cascade reactions, and crystal adhesion. Additionally, small-molecule modulators targeting the PPAR/FABP pathway and novel delivery systems, such as mitochondrion-targeted liposomes, have demonstrated the potential to intervene in the lipid metabolism/organelle damage axis, although clinical translation faces challenges such as species differences (The paradoxical effects of PPARα agonists in rodents versus humans) and safety concerns. This review highlights the importance of lipid metabolism as a new target for KSD prevention and treatment, and it suggests that future research should focus on the analysis of molecular mechanisms and the clinical translation of interdisciplinary technologies (e.g., mitochondrion-targeted delivery systems).

Retrograde intrarenal surgery (RIRS) and percutaneous nephrolithotomy (PCNL) are both important minimally invasive techniques for the treatment of renal stones. With the progress of technology, the application of procedures has been extended. Current surgery choices are made base on stone size, burden and its locations that might limit the predictability and removal of post-operative residual stones. Despite these surgery techniques are maturely used in clinical practice, the patients’ selection have not been standardized in borderline stone. Some patients might suffer several sessions of surgery if intervene decision are not well-designed. In this single-center study, we aimed to determine whether the Hounsfield Unit (HU) value of no-contrast computer computed tomography (NCCT) might offer better guidance in the selection of RIRS or PCNL in renal stones of 2-3 cm, not only in facilitating the stone disintegration, also in providing the potential optimal and less session of setting with great outcomes. A total of 158 patients with kidney stones (2-3 cm) who underwent PCNL/RIRS from March 2016 to January 2019 were enrolled in this study. Gender, stone sizes, locations, average HU value of stone, surgery time, hospital stay time, stone free rate and complications at the time of hospitalization and 3 month follow-up were measured to identify the surgery efficiency. Upon consideration of HU value, the mean surgery time were significantly decreased in RIRS comparing to cRIRS group (47.73 ± 15.52 versus 72.41 ± 27.71 min, p<0.05). Statistically, the surgery time was strong influenced by the HU values both in RIRS (OR: 93.8, p<0.01) and PCNL (OR, 8.21, p<0.05). HU values proved to have a strong positive relation with surgery time in RIRS while a low positive related in PCNL (p<0.05). Overall, for renal stones of 2-3 cm, RIRS proved to be a safe and efficacious treatment option if HU value and other parameters could be comprehensively accounted. Considering HU value before 2-3cm kidney stone lithotripsy seems to be necessary, which might save the surgery time and reduce the potential risk of renal injury, as even if residual stone were detected post-op, ESWL could also be employed and work efficiently. Some patients might not have to perform several sessions of RIRS. Taken together, individual precision surgery might provide ideal treatment and prognosis for patients requiring long-term continuous clinical procedures.

Dear Editor,We read with interest Dr. Pan and his colleagues’ recent article published in Renal Failure: ‘The feasibility of one-stage flexible ureteroscopy lithotripsy in solitary kidney patients ...

Nephrolithiasis associated with metabolic syndrome represents a growing global public health burden with a 5-year recurrence rate of up to 50%. Current first-line preventive strategies, primarily potassium citrate and thiazide diuretics, only correct urinary chemical abnormalities symptomatically, and patient adherence remains below 50% at 1 year. Importantly, these approaches fail to address the core pathological basis of tubular injury driven by metabolic dysregulation. Mitochondrial dysfunction is the central mechanistic hub linking systemic metabolic stress to intrarenal lithogenic susceptibility. In the setting of metabolic syndrome, impaired mitochondrial biogenesis and excessive mitochondrial reactive oxygen species (mtROS) production in renal tubular epithelial cells activate the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, establishing a self-perpetuating vicious cycle of “metabolic disturbance, mitochondrial damage, inflammatory amplification, calcium oxalate crystal deposition'. This core pathogenic loop has not been targeted by existing therapeutic strategies. Liraglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), exerts pleiotropic renoprotective effects independent of its canonical glucose-lowering actions. It coordinately activates peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) through two complementary pathways: transcriptional upregulation through the PKA/CREB axis, and post-translational deacetylation via the AMPK/SIRT1 pathway. This dual activation restores mitochondrial homeostasis, reprograms tubular lipid metabolism, attenuates oxidative stress, and suppresses inflammatory cascades. This review is the first to systematically integrate the mitochondrial pharmacology of liraglutide with the pathophysiology of nephrolithiasis. It critically appraises the strengths and limitations of preclinical and clinical evidence, identifies key knowledge gaps in the field, and proposes a phased translational research roadmap encompassing mechanistic validation, biomarker development, and clinical trial design. This work provides a solid theoretical foundation for repurposing GLP-1RAs for the prevention of this condition.