OBJECTIVE: 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\'.
RESULTS: 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.

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.
METHODS: 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.
CONCLUSIONS: 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 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.

BACKGROUND: 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.

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.

OBJECTIVE: 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.

OBJECTIVE: 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.

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.

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.
METHODS: Prospective cohort study.
METHODS: A total of 80,473 participants from the UK Biobank Study.
METHODS: 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.
RESULTS: Individuals with KSD were identified using the International Classification of Diseases, Tenth Revision (ICD-10), and procedure codes for KSD surgery.
METHODS: 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.
CONCLUSIONS: 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.
UNASSIGNED: 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.

UNASSIGNED: To provide a comprehensive review on the existing literature on medical management of urolithiasis.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.