miR-148b-5p regulates hypercalciuria and calcium-containing nephrolithiasis.

Calcium-containing stones represent the most common form of kidney calculi, frequently linked to idiopathic hypercalciuria, though their precise pathogenesis remains elusive. This research aimed to elucidate the molecular mechanisms involved by employing urinary exosomal microRNAs as proxies for renal tissue analysis. Elevated miR-148b-5p levels were observed in exosomes derived from patients with kidney stones. Systemic administration of miR-148b-5p in rat models resulted in heightened urinary calcium excretion, whereas its inhibition reduced stone formation. RNA immunoprecipitation combined with deep sequencing identified miR-148b-5p as a suppressor of calcitonin receptor (Calcr) expression, thereby promoting urinary calcium excretion and stone formation. Mice deficient in Calcr in distal epithelial cells demonstrated elevated urinary calcium excretion and renal calcification. Mechanistically, miR-148b-5p regulated Calcr through the circRNA-83536/miR-24-3p signaling pathway. Human kidney tissue samples corroborated these results. In summary, miR-148b-5p regulates the formation of calcium-containing kidney stones via the circRNA-83536/miR-24-3p/Calcr axis, presenting a potential target for novel therapeutic interventions to prevent calcium nephrolithiasis.

Association between alcohol consumption and kidney stones in American adults: 2007-2016 NHANES.

Purpose: To investigate the association between alcohol consumption and kidney stones in American adults. Materials and methods: National Health and Nutrition Examination Survey (NHANES) datasets from 2007 to 2016 were utilized. Participants with a history of kidney stones and alcohol consumption aged 20 or older were included. Weighted proportions and regression analysis were used to assess the association between alcohol consumption and kidney stones by adjusting age, gender, race, marital status, education, recreational activities, smoking, and several comorbidities. Results: Eleven population samples (Q1-Q11) were included from the NHANES dataset based on 11 questions compiled from the Alcohol Use Questionnaire (ALQ). In the fully adjusted regression model, none of these 11 samples demonstrated a significant association with urolithiasis, that is, alcohol consumption was not significantly associated with the incidence of kidney stones, even among heavy drinkers. Conclusion: Alcohol consumption is not significantly associated with the prevalence of kidney stones. This finding requires a more adequate sample size and a more detailed review of the history of kidney stones to be further verified.

Comparison of 24-hour urine composition prior to and after stone removal in nephrolithiasis: a prospective observational study.

BACKGROUND: To evaluate 24-hour urine composition prior to and after complete stone removal in nephrolithiasis patients to determine potential relationship between kidney stones and patient metabolic status. METHODS: A prospective observational study was performed with patient enrollment from March 2019 to August 2020. 24-hour urine samples were collected prior to stone removal and 4 weeks after double-J stent removal, and examined the following urinary parameters: volume, creatinine, sodium, calcium, uric acid, citrate, oxalate, potassium, phosphorous, magnesium, and pH value. For each parameter, pairwise t test was performed to compare samples prior to and after stone removal. The number of cases that changed from normal to abnormal or vice versa was also evaluated for each parameter. The study was registered at http://clinicaltrials.gov/ (NCT03846011). RESULTS: A total of 109 patients completed 24-hour urine collections prior to and after stone removal. The urinary calcium and phosphate levels increased significantly after stone removal, showing a mean difference of 0.55 mmol (P=0.015) and 2.35 mmol (P=0.001) respectively. None of the other urinary parameters demonstrated a statistically significant difference when means were compared. The percentage differences for all urinary parameters ranged from 5.4% to 14.1%. The percentages of patients that presented clinically significant changes in urinary parameter values from normal to abnormal or vice versa ranged from 4.6% to 20.1%. CONCLUSIONS: Ideally, evaluation of 24-hour urine compositions should be undertaken after total stone removal, especially for patients with calcium stones. For patients who cannot achieve total stone removal, 24-hour urine samples should be thoroughly interpreted as urinary calcium and phosphate levels might be depleted in the presence of urinary stones.

Predictive value of single-nucleotide polymorphism signature for nephrolithiasis recurrence: a 5-year prospective study.

Background: Genetic variations are linked to kidney stone formation. However, the association of single nucleotide polymorphism (SNPs) and stone recurrence has not been well studied. This study aims to identify genetic variants associated with kidney stone recurrences and to construct a predictive nomogram model using SNPs and clinical features to predict the recurrence risk of kidney stones. Methods: We genotyped 49 SNPs in 1001 patients who received surgical stone removal between Jan 1 and Dec 31 of 2012. All patients were confirmed stone-free by CT scan and then received follow-up at least 5 years. SNP associations with stone recurrence were analyzed by Cox proportion hazard model. A predictive nomogram model using SNPs and clinical features to predict the recurrence risk of kidney stones was developed by use of LASSO Cox regression. Results: The recurrence rate at 3, 5, 7 years were 46.8%, 71.2%, and 78.4%, respectively. 5 SNPs were identified that had association with kidney stone recurrence risk. We used computer-generated random numbers to assign 500 of these patients to the training cohort and 501 patients to the validation cohort. A nomogram that combined the 14-SNPs-based classifier with the clinical risk factors was constructed. The areas under the curve (AUCs) at 3, 5 and 7 years of this nomogram was 0.645, 0.723, and 0.75 in training cohort, and was 0.631, 0.708, and 0.727 in validation cohort, respectively. Results show that the nomogram presented a higher predictive accuracy than those of the SNP classifier or clinical factors alone. Conclusion: SNPs are significantly associated with kidney stone recurrence and should add prognostic value to the traditional clinical risk factors used to assess the kidney stone recurrence. A nomogram using clinical and genetic variables to predict kidney stone recurrence has revealed its potential in the future as an assessment tool during the follow-up of kidney stone patients.

Acetate attenuates hyperoxaluria-induced kidney injury by inhibiting macrophage infiltration via the miR-493-3p/MIF axis.

Hyperoxaluria is well known to cause renal injury and end-stage kidney disease. Previous studies suggested that acetate treatment may improve the renal function in hyperoxaluria rat model. However, its underlying mechanisms remain largely unknown. Using an ethylene glycol (EG)-induced hyperoxaluria rat model, we find the oral administration of 5% acetate reduced the elevated serum creatinine, urea, and protected against hyperoxaluria-induced renal injury and fibrosis with less infiltrated macrophages in the kidney. Treatment of acetate in renal tubular epithelial cells in vitro decrease the macrophages recruitment which might have reduced the oxalate-induced renal tubular cells injury. Mechanism dissection suggests that acetate enhanced acetylation of Histone H3 in renal tubular cells and promoted expression of miR-493-3p by increasing H3K9 and H3K27 acetylation at its promoter region. The miR-493-3p can suppress the expression of macrophage migration inhibitory factor (MIF), thus inhibiting the macrophages recruitment and reduced oxalate-induced renal tubular cells injury. Importantly, results from the in vivo rat model also demonstrate that the effects of acetate against renal injury were weakened after blocking the miR-493-3p by antagomir treatment. Together, these results suggest that acetate treatment ameliorates the hyperoxaluria-induced renal injury via inhibiting macrophages infiltration with change of the miR-493-3p/MIF signals. Acetate could be a new therapeutic approach for the treatment of oxalate nephropathy.