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Aims/hypothesisSodium–glucose cotransporter 2 inhibitors (SGLT2Is) may reduce nephrolithiasis risk by increasing urine flow. We aimed to investigate whether initiation of SGLT2I was associated with reduced nephrolithiasis risk.MethodsWe conducted an active-comparator new-user cohort study using the Danish health registries in the period 11 November 2012 to 31 December 2018. Individuals aged ≥40 years initiating SGLT2Is or glucagon-like peptide-1 receptor agonists (GLP1 RAs) were followed from treatment initiation until an inpatient or outpatient diagnosis of nephrolithiasis, death, emigration or end of study. New users of SGLT2Is were matched 1:1 on propensity scores to new users of GLP1 RAs. In supplementary analyses, risk of recurrent nephrolithiasis was assessed in individuals with a history of nephrolithiasis before treatment initiation.ResultsWe identified 24,290 and 19,576 eligible users of SGLT2Is and GLP1 RAs, respectively. After matching, 12,325 patient pairs remained. The median age was 61 years and median follow-up was 2.0 years. The nephrolithiasis rate was 2.0 per 1000 person-years in SGLT2I initiators compared with 4.0 per 1000 person-years in GLP1 RA initiators, with a rate difference of −1.9 per 1000 person-years (95% CI −2.8, −1.0) and an HR of 0.51 (95% CI 0.37, 0.71). For recurrent nephrolithiasis (n = 731 patient pairs), the rate difference was −17 per 1000 person-years (95% CI −33, −1.5) and the HR was 0.68 (95% CI 0.48, 0.97).Conclusions/interpretationInitiation of treatment with SGLT2Is was associated with a clinically significant reduced risk of incident and recurrent nephrolithiasis.

Background Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. Design A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Results Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. Conclusions This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.

Primary hyperparathyroidism (pHPT) is marked by mineral imbalances, often leading to nephrolithiasis and osteoporosis. While imaging remains the cornerstone for stone detection, there is growing interest in biochemical markers that could enhance diagnostic accuracy. This study investigates the calcium-to-magnesium (Ca/Mg) ratio as a novel biomarker for nephrolithiasis, comparing its utility to traditional 24-h urinary calcium excretion and exploring its broader clinical implications. In this retrospective study of 367 pHPT patients, clinical, biochemical, and bone mineral density (BMD) data were analyzed. Nephrolithiasis was diagnosed via imaging, and the diagnostic performance of the Ca/Mg ratio and urinary calcium excretion was assessed through receiver operating characteristic analysis. Multivariable regression was employed to identify predictors of kidney stones. The Ca/Mg ratio, with an optimal cutoff of 6.35, demonstrated superior specificity (78%) compared to 24-h urinary calcium excretion (44%) while maintaining comparable sensitivity (71% vs. 78%). Elevated Ca/Mg ratios strongly correlated with nephrolithiasis, independent of other demographic factors. Hypomagnesemia was linked to a higher prevalence of kidney stones, reduced BMD, and increased serum calcium and creatinine levels, emphasizing its impact on skeletal and renal health. The Ca/Mg ratio emerges as a promising, non-invasive biomarker for nephrolithiasis in pHPT, outperforming traditional urinary calcium measures. It reflects underlying mineral imbalances and offers a practical tool for risk stratification and clinical decision-making. These findings underscore the need for further research into magnesium-targeted interventions, which may transform the management of pHPT-related complications.

Urinary stone disease is an ailment that has afflicted human kind for many centuries. Nephrolithiasis is a significant clinical problem in everyday practice with a subsequent burden for the health system. Nephrolithiasis remains a chronic disease and our fundamental understanding of the pathogenesis of stones as well as their prevention and cure still remains rudimentary. Regardless of the fact that supersaturation of stone-forming salts in urine is essential, abundance of these salts by itself will not always result in stone formation. The pathogenesis of calcium oxalate stone formation is a multistep process and essentially includes nucleation, crystal growth, crystal aggregation, and crystal retention. Various substances in the body have an effect on one or more of the above stone-forming processes, thereby influencing a person’s ability to promote or prevent stone formation. Promoters facilitate the stone formation while inhibitors prevent it. Besides low urine volume and low urine pH, high calcium, sodium, oxalate and urate are also known to promote calcium oxalate stone formation. Many inorganic (citrate, magnesium) and organic substances (nephrocalcin, urinary prothrombin fragment-1, osteopontin) are known to inhibit stone formation. This review presents a comprehensive account of the mechanism of renal stone formation and the role of inhibitors/promoters in calcium oxalate crystallisation.

Abstract Context The pathogenesis of nephrolithiasis in primary hyperparathyroidism (PHPT) remains to be elucidated. The latest guidelines suggest parathyroidectomy in patients with asymptomatic PHPT with hypercalciuria (> 400 mg/d) and increased stone risk profile. Objective The objective of this work is to evaluate the association of urinary stone risk factors and nephrolithiasis in patients with asymptomatic sporadic PHPT and its clinical relevance. Design A total of 157 consecutive patients with sporadic asymptomatic PHPT were evaluated by measurement of serum and 24-hour urinary parameters and kidney ultrasound. Results Urinary parameters were tested in the univariate analysis as continuous and categorical variables. Only hypercalciuria and hypomagnesuria were significantly associated with nephrolithiasis in the univariate and multivariate analysis adjusted for age, sex, body mass index, estimated glomerular filtration rate, parathyroid hormone, 25-hydroxyvitamin D, serum calcium, and urine volume (odds ratio, OR 2.14 [1.10-4.56]; P = .04; OR 3.06 [1.26-7.43]; P = .013, respectively). Hypomagnesuria remained associated with nephrolithiasis in the multivariate analysis (OR 6.09 [1.57-23.5], P = .009) even when the analysis was limited to patients without concomitant hypercalciuria. The urinary calcium/magnesium (Ca/Mg) ratio was also associated with nephrolithiasis (univariate OR 1.62 [1.27-2.08]; P = .001 and multivariate analysis OR 1.74 [1.25-2.42], P = .001). Hypomagnesuria and urinary Ca/Mg ratio had a better, but rather low, positive predictive value compared with hypercalciuria. Conclusions Hypomagnesuria and urinary Ca/Mg ratio are each associated with silent nephrolithiasis and have potential clinical utility as risk factors, besides hypercalciuria, for kidney stones in asymptomatic PHPT patients. The other urinary indices that have been commonly thought to be associated with kidney stones in PHPT are not supported by our results.

BackgroundNephrolithiasis (NL) is a complex multifactorial disease affecting up to 10%–20% of the human population and causing a significant burden on public health systems worldwide. It results from a combination of environmental and genetic factors. Hyperoxaluria is a major risk factor for NL.MethodsWe used a whole exome-based approach in a patient with calcium oxalate NL. The effects of the mutation were characterised using cell culture and in silico analyses.ResultsWe identified a rare heterozygous missense mutation (c.1519C>T/p.R507W) in the SLC26A6 gene that encodes a secretory oxalate transporter. This mutation cosegregated with hyperoxaluria in the family. In vitro characterisation of mutant SLC26A6 demonstrated that Cl−-dependent oxalate transport was dramatically reduced because the mutation affects both SLC26A6 transport activity and membrane surface expression. Cotransfection studies demonstrated strong dominant-negative effects of the mutant on the wild-type protein indicating that the phenotype of patients heterozygous for this mutation may be more severe than predicted by haploinsufficiency alone.ConclusionOur study is in line with previous observations made in the mouse showing that SLC26A6 inactivation can cause inherited enteric hyperoxaluria with calcium oxalate NL. Consistent with an enteric form of hyperoxaluria, we observed a beneficial effect of increasing calcium in the patient’s diet to reduce urinary oxalate excretion.

We aimed to investigate the prevalence, characteristics, and management of nephrolithiasis in primary hyperparathyroidism (PHPT) patients. Medical records of patients who underwent parathyroidectomy at a tertiary care hospital in British Columbia from January 2016 to April 2023 were retrospectively reviewed. Demographic data, laboratory results, imaging reports, and urologic consultations were examined. Descriptive statistics and relevant statistical tests, including logistic regressions, were utilized for data analysis. Of the 413 PHPT patients included in the study population, 41.9% harbored renal stones, and nearly half (48.6%) required urological interventions. Male sex, elevated preoperative serum ionized calcium (iCa) and 24-h urinary calcium (24 ​h urine Ca) levels were independent risk factors for stone formation. Additionally, male sex, younger age, and lower preoperative serum 25-hydroxyvitamin D (25(OH)D) level were associated with higher odds of requiring urological intervention for stones. This study identified significant prevalence of asymptomatic renal calcifications in PHPT patients, with a substantial proportion necessitating urological intervention. These findings emphasize the importance of incorporating screening and treatment of renal stones into the management of PHPT patients. [Display omitted] •Of 413 hyperparathyroid study patients 41.9% had kidney stones.•Preoperative renal US diagnosed a significant number of asymptomatic kidney stones.•Routine renal imaging for all primary hyperparathyroidism patients is indicated.

Patients with suspected nephrolithiasis were randomly assigned to ultrasonography performed by an emergency physician or a radiologist or to CT for initial study. Ultrasonography was associated with a lower cumulative radiation dose, with no significant difference in complications.

Calcium oxalate nephrolithiasis is increasingly recognized as a disorder influencednot only by diet and host oxalate handling, but also by the gut-kidneymicrobiome axis. Emerging multi-omics studies suggest that disturbances inintestinal and urinary microbiota, together with altered microbial metabolites,may contribute to disrupted oxalate homeostasis, inflammatory signaling, epithelialinjury, and crystal retention. We performed a narrative, semi-structuredreview of PubMed, Embase, and Web of Science (2010-2025), focusing onoxalate metabolism, gut and urinary microbiota, and microbiome-targeted interventionsin nephrolithiasis, with emphasis on calcium oxalate stones. Human andexperimental studies examining microbial composition, microbial metabolites,host transport and genetic determinants, and nutritional or microbial therapieswere qualitatively synthesized. Current evidence indicates that loss of oxalatedegradinggut bacteria and broader dysbiosis are associated with hyperoxaluriaand increased calcium oxalate stone risk, whereas microbiome-supportive dietarypatterns may be protective. Multi-omics analyses reveal coordinated alterationsacross stool, urine, and stone-associated microbiota, implicating pathways involvingshort-chain fatty acids, bile acids, and unconjugated bilirubin in oxalatehandling, inflammation, and lithogenesis. Nutritional modulation may favorablyinfluence this axis, while probiotics, synbiotics, and engineered livebiotherapeutics show encouraging preclinical results. Fecal microbiota transplantationremains highly preliminary in this field, and overall human data remainlimited and heterogeneous. The gut-kidney microbiome-oxalate axis providesan integrative framework linking diet, host pathways, microbial metabolites, andmulti-site microbial communities to calcium oxalate nephrolithiasis, and may helpinform future microbiome-based prevention and adjunctive managementstrategies.

Abstract Background Nephrocalcinosis is common in cats with nephrolithiasis. Understanding the association between these disorders might facilitate understanding of their pathogenesis. Hypothesis/Objectives Nephrocalcinosis is associated with nephrolithiasis. Animals Kidneys were evaluated postmortem in 175 client-owned cats. Methods An observational cross-sectional study. High-resolution microradiography identified nephroliths and classified parenchymal mineralization as striated or punctate. Percentage mineralization was quantified on microradiographs. Associations of nephrocalcinosis and nephrolithiasis at cat level (disease in either the left or right kidney) and individual kidney level were estimated using chi-squared tests and logistic regression with odds ratios (ORs) and 95% confidence intervals (CIs). Results Nephrolithiasis was present in 54% of cats (95/175) and nephrocalcinosis in 84% (147/175). Cats with nephroliths were older than those without (median, 15 vs 13 years; P = .004). At the cat level, nephrocalcinosis was associated with higher odds of nephrolithiasis (OR, 3.5; 95% CI, 1.6-7.4; P = .002), but the association was attenuated after age adjustment (OR, 3.1; 95% CI, 1.0-10.1; P = .05; n = 115). At the kidney level, striated mineralization was associated with nephrolithiasis (OR, 13.9; 95% CI, 2.0-95.9; P = .01), whereas punctate mineralization was not significantly associated with nephrolithiasis. Percentage mineralization was higher in cats with nephroliths than in those without it (P = .004). Conclusions and clinical importance Nephrocalcinosis, particularly striated medullopapillary patterns, was associated with nephrolithiasis in cats. Pattern-specific mineralization may represent a preventive target for the management of nephrolithiasis.