Role of Genetic Testing in Kidney Stone Disease: A Narrative Review.

PURPOSE OF REVIEW: Kidney stone disease (KSD) is a common and potentially life-threatening condition, and half of patients experience a repeat kidney stone episode within 5-10 years. Despite the ~50% estimate heritability of KSD, international guidelines have not kept up with the pace of discovery of genetic causes of KSD. The European Association of Urology guidelines lists 7 genetic causes of KSD as 'high risk'. RECENT FINDINGS: There are currently 46 known monogenic (single gene) causes of kidney stone disease, with evidence of association in a further 23 genes. There is also evidence for polygenic risk of developing KSD. Evidence is lacking for recurrent disease, and only one genome wide association study has investigated this phenomenon, identifying two associated genes (SLC34A1 and TRPV5). However, in the absence of other evidence, patients with genetic predisposition to KSD should be treated as 'high risk'. Further studies are needed to characterize both monogenic and polygenic associations with recurrent disease, to allow for appropriate risk stratification. Durability of test result must be balanced against cost. This would enable retrospective analysis if no genetic cause was found initially. We recommend genetic testing using a gene panel for all children, adults < 25 years, and older patients who have factors associated with high risk disease within the context of a wider metabolic evaluation. Those with a genetic predisposition should be managed via a multi-disciplinary team approach including urologists, radiologists, nephrologists, clinical geneticists and chemical pathologists. This will enable appropriate follow-up, counselling and potentially prophylaxis.

Dietary Sodium and Potassium Intakes and Kidney Stone Prevalence: The National Health and Nutrition Examination Survey 2011-2018.

The associations between dietary sodium intake (DSI), dietary potassium intake (DPI), and kidney stone disease (KSD) are not clear. We examined The National Health and Nutrition Examination Survey 2011-2018 to determine the independent associations between daily DSI, DPI, DSI/DPI, and KSD prevalence. In total, 19,405 participants were included for analysis, of which 1,895 had KSD. Higher DSI was not associated with increased odds of KSD in regression analysis when DSI was modeled as a continuous variable (OR = 0.99, 95% CI: 0.99-1.00, p = 0.2), or when comparing highest quartile of DSI to lowest quartile (OR = 0.84, 95% CI: 0.68-1.04, p = 0.1). Unlike DSI, higher DPI was strongly associated with reduced odds of KSD in regression analysis when DPI was modeled as a continuous variable (OR = 0.99, 95% CI: 0.99-0.99, p = 0.02), or when comparing highest quartile of DPI to lowest quartile (OR = 0.75, 95% CI: 0.60-0.94, p = 0.01). Lastly, higher DSI/DPI was also strongly associated with increased odds of KSD in regression analysis when DSI/DPI was modeled as a continuous variable (OR = 1.1, 95% CI: 1.01-1.20, p = 0.03), or when comparing highest quartile of DPI to lowest quartile (OR = 1.30, 95% CI: 1.10-1.70, p = 0.008). All the observed relationships were independent of total calorie intake. In conclusion, both lower DPI and higher DSI/DPI are associated with an increased risk of KSD. Future prospective studies are needed to clarify these causal relationships.

Association of health-related quality of life with urinary tract infection among kidney stone formers.

Kidney stones and infections significantly affect patients' health-related quality of life (HRQOL); however, the relationship between urinary tract infections (UTIs) and HRQOL in patients with kidney stones remains unclear. This study aimed to investigate the relationship using the validated Chinese version of the Wisconsin Stone Quality of Life questionnaire (C-WISQOL). We prospectively recruited 307 patients with kidney stones to complete the C-WISQOL before and after stone removal. The participants were diagnosed with UTI based on the presence of pyuria or bacteriuria with or without clinical symptoms. The psychometric properties of the C-WISQOL were statistically analyzed. Multivariate linear regression was used to predict the risk factors for impaired HRQOL in patients with stones and UTIs. The questionnaire is a reliable and robust tool for evaluating HRQOL in Chinese-speaking patients with urolithiasis. The UTI and kidney stone co-occurrence was significantly associated with female sex, diabetes mellitus, more previous stone events, higher antibiotic usage, positive stone- or UTI-related symptoms, and postoperative residual stones. The preoperative C-WISQOL scores and improvement in the HRQOL after stone removal in patients clinically diagnosed with UTI were significantly inferior to those in patients without UTI. The regression analyses showed that worse HRQOL was predicted by more previous stone events and positive stone- or UTI-related symptoms. In contrast, the presence of diabetes mellitus and postoperative residual stone fragments predicted a lower improvement in the HRQOL. These findings underscore UTI's harmful impact on perioperative HRQOL in patients with kidney stones and could help strategies benefit those patients.

Groundwater Hardness and Alkalinity As Risk Factors for Kidney Stone Disease in Alwar, India: An Ecological Study.

INTRODUCTION: Rajasthan is a semi-arid state in India where people still use groundwater for drinking purposes. However, the quality of groundwater as compared to standards have not been studied in any details. This ecological study was done to study the groundwater quality parameters in the stone-belt states, compare the quality of groundwater in Alwar with the rest of Rajasthan, and study the morbidity profile of surgical in-patients in the same district, with special emphasis on kidney stone disease (KSDs). METHODS: The morbidity profile of patients coming to the surgery department of a tertiary teaching hospital between January 2002 and June 2023 was obtained from the medical records department, and water quality data was obtained from the publicly available Water Resources Information System (WRIS) groundwater dataset for the year 2023. The dataset provided detailed information on the chemical parameters of water samples throughout the country that were evaluated to estimate the quality of groundwater. RESULTS: It was found that the groundwater in Alwar is non-potable due to the presence of iron, alkalinity, magnesium, and total dissolved solids (TDS). Iron was estimated to be much higher than the acceptable limit of the Bureau of Indian Standards (BIS) drinking-water quality guidelines (0.3 mg/L). Similarly, most of the chemical parameters in the groundwaters of Rajasthan significantly exceeded the national average. The median electrical conductivity, fluoride, magnesium, sodium, hardness, alkalinity, and turbidity were found to be 1680 µS/cm, 1.05 parts per million (PPM), 41 PPM, 233 PPM, 330 PPM, 310 PPM, 988 PPM, respectively, which are above the WHO recommendations for drinking water guidelines. CONCLUSIONS: The levels of iron and total alkalinity were significantly higher in the study district as compared to the rest of the state. Also, magnesium hardness and TDS levels were very high in the groundwater of the entire state of Rajasthan, making the population vulnerable to KSDs in the long run.

Causal Effects of Inflammatory Bowel Diseases on the Risk of Kidney Stone Disease.

BACKGROUND: Inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis, have been increasingly associated with kidney stone disease, posing significant health challenges globally. OBJECTIVE: This research sought to determine the causal relationship between kidney stone disease risk and inflammatory bowel disorders. METHODOLOGY: This retrospective cohort study included patients with IBDs, such as ulcerative colitis or Crohn's disease, who were diagnosed at least 18 years of age. Information was gathered with an emphasis on patients having comprehensive medical histories and confirmed cases of kidney stone disease from January to December 2022. Medical records were retrospectively evaluated by trained staff to extract treatment information and clinical, radiological, and demographic data. To evaluate relationships, statistical analysis was carried out in SPSS software version 23 using Chi-square tests and descriptive statistics. RESULTS: The study included 320 patients diagnosed with IBDs, among which 198 (61.87%) had Crohn's disease, and 122 (38.13%) were diagnosed with ulcerative colitis. The cohort consisted of 140 females (43.75%) and 180 men (56.25%), with a mean age of 45.5 years. Regarding smoking, 113 people (35.31%) reported being smokers, whereas 207 people (64.69%) did not smoke. Additionally, 18 (5.62%) of the population had an underweight BMI, 136 (42.50%) had a normal BMI, 119 (37.19%) had an overweight BMI, and 47 (14.69%) had an obese BMI. Of the patients, 86 (26.88%) had a prior history of kidney stone disease, while 194 (60.62%) did not. Aminosalicylates were the most often used therapy modality for IBD in 189 (58.97%) of cases, followed by corticosteroids in 117 (36.56%) and immunomodulators in 93 (28.94%). Radiological examinations showed that renal calculi were present in 60 (18.75%) of patients, and kidney stones occurred in 40 (12.50%) of patients throughout the research period. The smoking status (p=0.006) and prior history of kidney stones (p<0.001) were the corresponding p-values for the significant results. CONCLUSION: The study highlights an increased risk of kidney stone disease in IBD patients, particularly among smokers and those with a recurrent history of kidney stones. Of the 320 patients, 198 (61.87%) had Crohn's disease and 122 (38.13%) had ulcerative colitis, with a significant relationship found between kidney stones and both smoking (113 patients, 35.31%, p=0.006) and a prior history of kidney stones (86 patients, 26.88%, p<0.001). The findings emphasize the need for targeted preventive measures and close monitoring of these high-risk groups.

The immune factors have complex causal regulation effects on kidney stone disease: a mendelian randomization study.

PURPOSE: Previous studies have reported the potential impact of immune cells on kidney stone disease (KSD), but definitive causal relationships have yet to be established. The purpose of this paper is to elucidate the potential causal association between immune cells and KSD by Mendelian randomization (MR) analysis. METHODS: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between immune cell traits and kidney stone disease. We included a total of four immune traits (median fluorescence intensity (MFI), relative cellular (RC), absolute cellular (AC), and morphological parameters (MP)), which are publicly available data. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. RESULTS: After FDR correction, the CD8 on HLA DR + CD8br (OR = 0.95, 95% CI = 0.93-0.98, p-value = 7.20 × 10- 4, q-value = 0.088) was determined to be distinctly associated with KSD, and we also found other 25 suggestive associations between immune cells and KSD, of which 13 associations were suggested as protective factors and 12 associations were suggested as risk factors. There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our Cochrane Q-test, MR Egger's intercept test, and MR-PRESSO, which were all > 0.05. CONCLUSIONS: Our study has explored the potential causal connection between immune cells and KSD by Mendelian randomization analysis, thus providing some insights for future clinical studies.

Identification of novel genetic susceptibility loci for calcium-containing kidney stone disease by genome-wide association study and polygenic risk score in a Taiwanese population.

Approximately 80% of kidney stone diseases contain calcium. Inherited genetic factors are among the variables that influence the development of calcium-containing kidney stone diseases (CKSD). Previous genome-wide association studies (GWAS) on stone diseases have been reported worldwide; however, these are not focused on calcium-containing stones. We conducted a GWAS to identify germline genetic polymorphisms associated with CKSD in a Medical Center in Taiwan; hence, this study was based primarily on a hospital-based database. CKSD was diagnosed using the chart records. Patients infected with urea-splitting-microorganisms and those with at least two urinary pH value below 5.5 were excluded. None of the patients had cystic stones based on stone analysis. Those over 40 years of age with no history of CKSD and no microscopic hematuria on urinalysis were considered as controls. The DNA isolated from the blood of 14,934 patients (63.7% male and 36.3% female) with CKSD and 29,868 controls (10,830 men and 19,038 women) at a medical center was genotyped for approximately 714,457 single nucleotide polymorphisms (SNPs) with minor allele frequency of ≥ 0.05. We used PLINK 1.9 to calculate the polygenic risk score (PRS) to investigate the association between CKSD and controls. The accuracy of the PRS was verified by dividing it into the training and testing groups. The statistical analyses were calculated with the area under the curve (AUC) using IBM SPSS version 22. We identified 432 susceptibility loci that reached a genome-wide threshold of P < 1.0 × 10- 5. A total of 132 SNPs reached a threshold of P < 5 × 10- 8 using a stricter definition of significance on chromosomes 4, 13, 16, 17, and 18. At the top locus of our study, SNPs in DGKH, PDILT, BCAS3, and ABCG2 have been previously reported. RN7SKP27, HDAC4, PCDH15, AP003068.2, and NFATC1 were novel findings in this study. PRS was adjusted for sex and age, resulting in an AUC of 0.65. The number of patients in the top quartile of PRS was 1.39 folds in the risk of CKSD than patients in the bottom quartile. Our data identified the significance of GWAS for patients with CKSD in a hospital-based study. The PRS also had a high AUC for discriminating patients with CKSD from controls. A total of 132 SNP loci of SNPs significantly associated with the development of CKSD. This first survey, which focused on patients with CKSD, will provide novel insights specific to CKSD and its potential clinical biomarkers.

Inflammatory cytokines and their potential role in kidney stone disease: a Mendelian randomization study.

PURPOSE: Previous studies have reported a complex relationship between inflammatory cytokines and kidney stone disease (KSD). The purpose of this paper is to investigate the potential causal impact of inflammatory cytokines on KSD by Mendelian randomization (MR) analysis. METHODS: In our study, a thorough two-sample Mendelian randomization (MR) analysis was performed by us to determine the potential causal relationship between inflammatory cytokines and kidney stone disease. Utilizing GWAS summary data of inflammatory cytokines and KSD, we performed the first two-sample MR analysis. Genetic variants in GWASs related to inflammatory cytokines were employed as instrumental variables (IVs). The data on cytokines were derived from 14,824 participants and analyzed by utilizing the Olink Target-96 Inflammation Panel. GWAS summary data related to KSD (9713 cases and 366,693 controls) were obtained from the FinnGen consortium. The primary MR analysis method was Inverse variance weighted. Reverse MR analysis, Cochran's Q test, MR Egger, and MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to assess the stability of the results. RESULTS: 91 cytokines were enrolled in the MR analysis after strict quality control of IV. The IVW analysis revealed 2 cytokines as risk factors for KSD: Cystatin D (OR 1.06, 95% CI 1.01-1.11), Fibroblast growth factor 5 (OR 1.06, 95% CI 1.00-1.12), suggesting they are positively associated with the occurrence of kidney stones. We also found 3 protective associations between cytokines and KSD: Artemin (OR 0.86, 95% CI 0.78-0.96), T-cell surface glycoprotein CD6 isoform (OR 0.92, 95% CI 0.88-0.98), STAM-binding protein (OR 0.83, 95% CI 0.69-0.99). There was no horizontal pleiotropy or significant heterogeneity in our MR analysis, as determined by the p-value results of our MR Egger's intercept test, Cochrane Q-test, and MR-PRESSO, which were all > 0.05. CONCLUSIONS: Our study explored a variety of inflammatory cytokines related to KSD through MR analysis, which validated several previous findings and provided some new potential biomarkers for KSD. However, the findings require further investigation to validate their exact functions in the pathogenesis and evolution of KSD.

Intensity-Specific Physical Activity Measured by Accelerometer, Genetic Susceptibility, and the Risk of Kidney Stone Disease: Results From the UK Biobank.

RATIONALE & OBJECTIVE: Kidney stone disease (KSD), a significant health care problem within both developed and developing countries, has been associated with genetic risk factors. An association between physical activity and KSD risk also has been hypothesized, but studies have yielded inconsistent findings. This study investigated the association between the intensity of physical activity and the incidence of KSD accounting for genetic risk. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: A total of 80,473 participants from the UK Biobank Study. EXPOSURE: Physical activity levels, including total physical activity (TPA), moderate-to-vigorous intensity physical activity (MVPA), and light-intensity physical activity (LPA), were measured using accelerometers and quantified using a machine learning model. A polygenic risk score (PRS) for KSD was also constructed. OUTCOME: Individuals with KSD were identified using the International Classification of Diseases, Tenth Revision (ICD-10), and procedure codes for KSD surgery. ANALYTICAL APPROACH: A Fine and Gray survival model was used to estimate the associations of incident KSD with TPA, MVPA, LPA, and PRS (as categorical variables). Restricted cubic splines were used to examine potential nonlinear associations within the fully adjusted models. RESULTS: During an average follow-up of 6.19 years, 421 participants developed KSD. Participants in the highest quartiles of TPA, MVPA, and LPA had lower adjusted rates of KSD compared with those in the lowest quartiles: HR, 0.50 (95% CI, 0.44-0.56), 0.57 (95% CI, 0.51-0.64), and 0.66 (95% CI, 0.59-0.74), respectively. TPA, MVPA, and LPA were associated with a lower risk of KSD in participants with low and high genetic predisposition for KSD. LIMITATIONS: Selection bias as participants who provided accelerometry data may have been more adherent to health care. CONCLUSIONS: Physical activity was negatively associated with the risk of KSD, regardless of the genetic risk. Future large studies are warranted to confirm and explain the mechanisms underlying these associations. PLAIN-LANGUAGE SUMMARY: The association between the intensity of physical activity (PA) and the incidence of kidney stone disease (KSD) after accounting for genetic risk is unclear. We conducted a comprehensive prospective cohort study utilizing participants from the UK Biobank to assess the intensity of PA using accelerometers. Our study findings indicated that greater total PA, moderate-to-vigorous-intensity PA, and light-intensity PA were each associated with a lower risk of KSD irrespective of an individual's genetic risk. Our study informs the understanding of risk factors for KSD.

Predictive ability of novel and traditional anthropometric measurement indices for kidney stone disease: a cross-sectional study.

BACKGROUND: The aim of our research was to examine the association of novel anthropometric indices (a body shape index (ABSI), waist-to-height ratio (WtHR), conicity index (CI) and body roundness index (BRI)) and traditional anthropometric indices (body mass index (BMI), and waist (WC)) with prevalence of kidney stone disease (KSD) in the general population of United States (U.S.). METHODS: In this study, we conducted a cross-sectional analysis among the participants in the National Health and Nutrition Examination Survey between the years 2007 and 2020. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS), receiver operating characteristic (ROC) curves, and subgroup analysis were performed to analyze the association of ABSI, BRI, WtHR, CI, BMI and WC with prevalence of KSD. RESULTS: In total, 11,891 individuals were included in our study. The RCS plot shown that the linear positive association was found between ABSI, BRI, WtHR, CI, BMI and WC and KSD risk. Additionally, the ROC curve demonstrated that the area under the curve of ABSI, BRI, WtHR, and CI was significantly higher than traditional anthropometric indices, including BMI and WC. CONCLUSIONS: Our study found that the discriminant ability of ABSI, BRI, WtHR, and CI for KSD was higher than BMI and WC. Consequently, ABSI, BRI, WtHR, and CI have the potential to become new indicators for the detection of KSD risk in clinical practice.

Safety and Efficacy of Percutaneous Nephrolithotomy in Solitary Functioning Kidneys: A Retrospective Cohort Study in an Asian Population.

Objective The aim of the study was to assess the safety of preserved renal function after standard percutaneous nephrolithotomy (PCNL) in patients with a single functional kidney. The main parameters to focus on were serum creatinine levels and any associated complications. Materials and methods This retrospective cohort study was conducted in an Eastern population in a single center from 2016 through 2023 at The Kidney Centre Postgraduate Training Institute, Karachi, Pakistan. Results Out of the total 1,550 PCNL procedures performed on adult patients, 47 patients had a solitary functioning kidney with stones, which were evaluated. The stone clearance rate was 95.74% (45 patients), with a mean operative time of 85.96 minutes. Most patients, i.e., 33 (70.21%), had an infracostal approach, and single tract management was sufficient for 45 (95.74%) patients. The most common complication was transfusion, which was required in five (10.64%) patients. Mean preoperative hemoglobin dropped by 1.43mg/dL postoperatively, and mean serum creatinine decreased from 2.45mg/dL to 1.97mg/dL. Among the 24 (51.06%) analyzed stones, all were calcium oxalate. Conclusion In challenging situations such as a solitary kidney with a large stone, PCNL is the procedure of choice. However, the refined technique is of paramount importance. Overall, the use of PCNL in these unique conditions is safe and rewarding.

Association of serum soluble α­klotho with risk of kidney stone disease: a population-based cross-sectional study.

BACKGROUND: The aim of the study was to explore the association of serum soluble klotho with kidney stone disease (KSD) in the general population over the age of 40 years in the United States. METHODS: We integrated the data in National Health and Nutrition Examination Survey from 2007 to 2016 years. The relationship between serum soluble α­klotho and prevalence of KSD was analyzed by constructing weighted multivariable logistic regression model, restricted cubic spline (RCS) curve, and subgroup analyses. RESULTS: In the study, a total of 13,722 individuals were included in our study. A U-shaped association between serum soluble klotho and the risk of KSD was shown by the RCS curve (P value for nonlinear < 0.05). In the full adjusted model, compared with the lowest quartile of serum soluble α­klotho, the adjusted odd ratios (95% confidence intervals) for KSD across the quartiles were (0.999 (0.859, 1.164), 1.005 (0.858, 1.176), and 1.061 (0.911, 1.235)). Subgroup analyses also showed that the U-shaped association of serum soluble α­klotho with KSD was found among subjects who were age < 60 years, female or male, with or without hypertension, and BMI ≥ 30 kg/m2. CONCLUSIONS: Our findings suggested that serum klotho levels had a U-shaped correlation with risk of KSD. When the Klotho level is at 818.66 pg/mL, prevalence of KSD is lowest. Therefore, maintaining a certain level of serum soluble α­klotho could prevent the occurrence of KSD.

Higher oxidative balance score is associated with lower kidney stone disease in US adults: a population-based cross-sectional study.

PURPOSE: Oxidative balance stress (OBS) was an important indicator for assessing exposure to oxidative stress related to diet and lifestyle. The purpose of this study was to explore the relationship between OBS and kidney stone disease (KSD). METHODS: Secondary dataset analysis was performed by the study from six survey cycles (2007-2018) in the National Health and Nutrition Examination Survey (NHANES). OBS was the exposure factor and ever had kidney stone (yes or no) was the outcome. Weighted univariate or multivariate logistic regression models were used to estimate the associations. RESULTS: The prevalence of KSD among participants was 8.6%. OBS showed a significant negative correlation with KSD (OR: 0.98, 95% CI 0.96-0.999), 35% reduction in KSD in the highest OBS quartile compared to the lowest OBS quartile. Dietary OBS was significantly negatively correlated with KSD (OR: 0.98, 95% CI 0.96-0.9998), but not with lifestyle OBS. In addition, OBS had a negative correlation with KSD in females (OR: 0.97, 95% CI 0.94-0.996), non-diabetic participants (OR: 0.98, 95% CI 0.96-0.99), and hypertensive participants (OR: 0.96, 95% CI 0.93-0.99), but OBS was not observed to be associated with KSD in gout participants. Interestingly, this relationship existed in participants aged 30-60 years and a ratio of family income to poverty (PIR) of 1.3-3.5 (all P value < 0.05). CONCLUSION: Our study revealed that OBS was negative associated with KSD, and high OBS might be a protective factor in KSD. Targeting one of the components of OBS might be beneficial.

Medical management of urolithiasis: Great efforts and limited progress.

Objective: To provide a comprehensive review on the existing literature on medical management of urolithiasis. Methods: A thorough literature review was performed using Medline, PubMed/PMC, Embase, and the Cochrane Database of Systematic Reviews up to December 2022 to identify publications on the medical management of urolithiasis. Studies that assessed dietary and pharmacologic management of urolithiasis were reviewed; studies on medical expulsive therapy were not included in this review. Results: Medical management of urolithiasis ranges from the prophylactic management of kidney stone disease to dissolution therapies. While most treatment concepts have been long established, large randomized controlled trials are scarce. Dietary modification and increased fluid intake remain cornerstones in the conservative management of urolithiasis. A major limitation for medical management of urolithiasis is poor patient compliance. Conclusion: Medical management of urolithiasis is more important in patients with recurrent urolithiasis and patients with metabolic abnormalities putting them at higher risk of developing stones. Although medical management can be effective in limiting stone recurrence, medical interventions often fail due to poor compliance.

Association of novel anthropometric indices with prevalence of kidney stone disease: a population-based cross-sectional study.

BACKGROUND: The purpose of this study was to investigate the correlation between novel anthropometric indices, specifically the body shape index (ABSI) and body roundness index (BRI), and the prevalence of kidney stone disease (KSD) within the general population of the United States (U.S.). METHODS: This study employed a cross-sectional analysis of participants in the National Health and Nutrition Examination Survey from 2007 to 2020. Various statistical methods, including multivariable logistic regression analysis, restricted cubic spline (RCS) plot curve, receiver operating characteristic (ROC) curves, and subgroup analysis, were utilized to examine the association between ABSI and BRI and the risk of KSD. RESULTS: A total of 39,251 individuals were included in the study. First, the RCS plot presented that a linear positive association was found between ABSI and BRI and KSD risk. Second, the results of the multivariable logistic regression analysis revealed that, compared to the lowest quartile, the adjusted odds ratios (with 95% confidence intervals) for the prevalence of KSD across the quartiles of ASBI and BRI were 0.94 (0.67, 1.30), 1.55 (1.15, 2.10), and 1.74 (1.28, 2.35), respectively, in the fully adjusted model. Third, the ROC curve demonstrated that the area under the curve of ABSI, and BRI was significantly higher than traditional anthropometry or body composition measures, including BMI and waist circumference. CONCLUSIONS: The findings of our study indicate that the discriminant ability of ABSI and BRI for KSD is significantly superior to that of BMI and waist circumference. Consequently, ABSI and BRI have the potential to more accurately identify an individual's risk of developing KSD in a clinical setting.

Development and Application of the CRISPR-dcas13d-eIF4G Translational Regulatory System to Inhibit Ferroptosis in Calcium Oxalate Crystal-Induced Kidney Injury.

The CRISPR-Cas system, initially for DNA-level gene editing and transcription regulation, has expanded to RNA targeting with the Cas13d family, notably the RfxCas13d. This advancement allows for mRNA targeting with high specificity, particularly after catalytic inactivation, broadening the exploration of translation regulation. This study introduces a CRISPR-dCas13d-eIF4G fusion module, combining dCas13d with the eIF4G translation regulatory element, enhancing target mRNA translation levels. This module, using specially designed sgRNAs, selectively boosts protein translation in targeted tissue cells without altering transcription, leading to notable protein expression upregulation. This system is applied to a kidney stone disease model, focusing on ferroptosis-linked GPX4 gene regulation. By targeting GPX4 with sgRNAs, its protein expression is upregulated in human renal cells and mouse kidney tissue, countering ferroptosis and resisting calcium oxalate-induced cell damage, hence mitigating stone formation. This study evidences the CRISPR-dCas13d-eIF4G system's efficacy in eukaryotic cells, presenting a novel protein translation research approach and potential kidney stone disease treatment advancements.

Management of de novo nephrolithiasis after kidney transplantation: a comprehensive review from the European Renal Association CKD-MBD working group.

The lifetime incidence of kidney stones is 6%-12% in the general population. Nephrolithiasis is a known cause of acute and chronic kidney injury, mediated via obstructive uropathy or crystal-induced nephropathy, and several modifiable and non-modifiable genetic and lifestyle causes have been described. Evidence for epidemiology and management of nephrolithiasis after kidney transplantation is limited by a low number of publications, small study sizes and short observational periods. Denervation of the kidney and ureter graft greatly reduces symptomatology of kidney stones in transplant recipients, which may contribute to a considerable underdiagnosis. Thus, reported prevalence rates of 1%-2% after kidney transplantation and the lack of adverse effects on allograft function and survival should be interpreted with caution. In this narrative review we summarize current state-of-the-art knowledge regarding epidemiology, clinical presentation, diagnosis, prevention and therapy of nephrolithiasis after kidney transplantation, including management of asymptomatic stone disease in kidney donors. Our aim is to strengthen clinical nephrologists who treat kidney transplant recipients in informed decision-making regarding management of kidney stones. Available evidence, supporting both surgical and medical treatment and prevention of kidney stones, is presented and critically discussed. The specific anatomy of the transplanted kidney and urinary tract requires deviation from established interventional approaches for nephrolithiasis in native kidneys. Also, pharmacological and lifestyle changes may need adaptation to the specific situation of kidney transplant recipients. Finally, we point out current knowledge gaps and the need for additional evidence from future studies.

Deficient butyrate metabolism in the intestinal microbiome is a potential risk factor for recurrent kidney stone disease.

Intestinal microbiome dysbiosis is a known risk factor for recurrent kidney stone disease (KSD) with prior data suggesting a role for dysfunctional metabolic pathways other than those directly utilizing oxalate. To identify alternative mechanisms, the current study analyzed differences in the metabolic potential of intestinal microbiomes of patients (n = 17) and live-in controls (n = 17) and determined their relevance to increased risk for KSD using shotgun metagenomic sequencing. We found no differences in the abundance of genes associated with known oxalate degradation pathways, supporting the notion that dysfunction in other metabolic pathways plays a role in KSD. Further analysis showed decreased abundance of key enzymes involved in butyrate biosynthesis in patient intestinal microbiomes. Furthermore, de novo construction of microbial genomes showed that the majority of genes significantly enriched in non-stone formers are affiliated with Faecalibacterium prausnitzii, a major butyrate producer. Specifically pertaining to butyrate metabolism, the majority of abundant genes mapped back to F. prausnitzii, Alistipes spp., and Akkermansia muciniphila. No differences were observed in ascorbate or glyoxylate metabolic pathways. Collectively, these data suggest that impaired bacterial-associated butyrate metabolism may be an oxalate-independent mechanism that contributes to an increased risk for recurrent KSD. This indicates that the role of the intestinal microbiome in recurrent KSD is multi-factorial, which is representative of the highly intertwined metabolic nature of this complex environment. Future bacteria-based treatments must not be restricted to targeting only oxalate metabolism.

Identification of biomarkers and potential therapeutic targets of kidney stone disease using bioinformatics.

PURPOSE: Kidney stone disease (KSD) is a common urological disease, but its pathogenesis remains unclear. In this study, we screened KSD-related hub genes using bioinformatic methods and predicted the related pathways and potential drug targets. METHODS: The GSE75542 and GSE18160 datasets in the Gene Expression Omnibus (GEO) were selected to identify common differentially expressed genes (DEGs). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify enriched pathways. Finally, we constructed a hub gene-miRNA network and drug-DEG interaction network. RESULTS: In total, 44 upregulated DEGs and 1 downregulated DEG were selected from the GEO datasets. Signaling pathways, such as leukocyte migration, chemokine activity, NF-κB, TNF, and IL-17, were identified in GO and KEGG. We identified 10 hub genes using Cytohubba. In addition, 21 miRNAs were predicted to regulate 4 or more hub genes, and 10 drugs targeted 2 or more DEGs. LCN2 expression was significantly different between the GEO datasets. Quantitative real-time polymerase chain reaction (qRT-PCR) analyses showed that seven hub gene expressions in HK-2 cells with CaOx treatment were significantly higher than those in the control group. CONCLUSION: The 10 hub genes identified, especially LCN2, may be involved in kidney stone occurrence and development, and may provide new research targets for KSD diagnosis. Furthermore, KSD-related miRNAs may be targeted for the development of novel drugs for KSD treatment.