Development and preliminary validation of a diagnostic prediction model to optimise outpatient management of patients with urolithiasis using urinary stones and intervention quality of life (USIQoL) measure.

PURPOSE: Patients with urinary calculi undergo resource-intensive follow-up. Application of a PROM, Urinary Stones and Intervention Quality of Life (USIQoL), can potentially optimise current practices if it matches the outcomes of traditional follow-up. Our objective was to develop, and conduct, a preliminary validation of the USIQoL based prediction model to aid triage. METHODS: We performed a two phase prospective cohort study. The 1st phase included development of the USIQoL-based decision model using multicentre data. The 2nd phase involved prospective single-blind external validation for the outpatient application. The aim was to evaluate correlations between the USIQoL scores and key predictors; clinical outcomes and global health ratings (EuroQoL EQ-5D). We used statistical analysis to validate USIQoL cut-off scores to aid triage and the decision to intervene. RESULTS: Of 503 patients invited, 91% (n = 455, Development [305] and Validation [150]; M = 308, F = 147) participated. The relationship between USIQoL domain scores and clinical outcomes was consistently significant (estimated odds: PPH 1.24, p < 0.001, 95% CI 1.13-1.36; PSH 1.22, p < 0.001, 95% CI 1.12-1.33). The ROC values for the model were ≥ 0.75. The optimum domain cut-off scores were derived with rising scores implying increased need to intervene. The model demonstrated satisfactory sensitivity (0.81-0.89) and specificity (0.36-0.47). CONCLUSIONS: The study demonstrates satisfactory correlation between the USIQoL and clinical outcomes making this model a valid aid for triage and optimising outpatient management with the cut-off scores able to identify high risk patients who need active treatment.

Postmenopausal status increases the risk of uric acid stones.

OBJECTIVE: This study investigated the impact of menopause on stone composition in women with urolithiasis. STUDY DESIGN: A cross-sectional study was conducted from March 2013 to March 2018. Women with urolithiasis patients were divided into two groups according to their menopause status. MAIN OUTCOME MEASURES: The clinical demographic characteristics, stone removal, stone composition, and urine chemistry were investigated. Univariate and multivariate survival analyses were performed to identify risk factors for the risk of uric acid stones. RESULTS: Our study enrolled 1221 female patients with stone diseases, 783 (64.1 %) of whom were postmenopausal (66 patients surgically menopause and 717 patients naturally menopause). Postmenopausal women had higher rates of diabetes and hyperuricemia, a higher serum uric acid level, a higher urinary specific gravity, and a lower estimated glomerular filtration rate. Stone analysis revealed calcium oxalate stones in 66.2 % of the patients, apatite stones in 19.4 %, calcium oxalate and calcium phosphate stones in 7.7 %, uric acid stones in 4.4 %, struvite stones in 2.0 %, and brushite stones in 0.2 %. Postmenopausal women had a higher rate of uric acid stones. Multivariate analysis confirmed that postmenopausal status and hyperuricemia were independent risk factors of uric acid stones. Postmenopausal women required more invasive procedures to remove the stones, and they had lower self-voiding rates. CONCLUSIONS: Postmenopausal women had higher rates of stone episodes, specifically related to uric acid stones. Given the prevalence and impact of chronic kidney diseases, factors that impede optimal renal function management in women must be identified to provide tailored treatment recommendations.

Morin hydrate mitigates calcium oxalate urolithiasis by inhibiting oxalate synthesis and modulating crystal formation.

Calcium oxalate (CaOx) urolithiasis is a prevalent urinary disorder with significant clinical impact. This study investigates the therapeutic potential of Morin Hydrate (MH), a natural bioflavonoid, in preventing CaOx stone formation. Molecular docking studies revealed that MH binds strongly to glycolate oxidase (GO), suggesting its inhibitory effect on oxalate synthesis. In vitro assays demonstrated that MH effectively inhibits CaOx crystal nucleation, aggregation, and growth, altering crystal morphology to less stable forms. Diuretic activity studies in Wistar rats showed that MH substantially increased urine volume and ion excretion, indicating its moderate diuretic effect. In vivo experiments further supported these findings, with MH treatment improving urinary and serum markers, reducing oxidative stress, and protecting renal tissue, as evidenced by histopathological analysis. Notably, MH administration significantly decreased GO and lactate dehydrogenase activities in urolithiatic rats, indicating a reduction in oxalate production. These results suggest that MH is a promising candidate for the prevention and treatment of CaOx urolithiasis, with the potential for clinical application in reducing the risk and recurrence of kidney stones.

Bridging the knowledge gap: past, present and future of antibiotic use for ureteral stents.

OBJECTIVE: To evaluate the available literature on ureteric stent-related infections, the use of antibiotics and bacterial colonisation to identify the current incidence of stent-related infections, unveil knowledge gaps and generate potential hypotheses for future research. METHODS: A literature review was conducted using PubMed, Cochrane and urological association websites identifying relevant English literature published between 1983 and January 2024. RESULTS: There is a worldwide lack of guidelines for antibiotic prophylaxis for stent placement, exchange or extraction. In patients with a negative preoperative urine culture undergoing ureteroscopy and stent placement, it may be considered to only provide prophylaxis in presence of risk factors. However, in pre-stented patients a preoperative urine culture is important to guide prophylaxis during endourological surgery. During stent indwell time, antibiotic prophylaxis does not show any advantage in preventing urinary tract infections (UTIs). There is no strong evidence to support the use of antibiotics at time of stent removal. In the absence of any clear evidence, management strategies for treating UTIs in patients with ureteric stents vary widely. Stent exchange could be considered to remove the biofilm as a potential source of bacteria. Stent culture can help to guide treatment during infection as urine culture and stent culture can differ. CONCLUSION: In terms of good antibiotic stewardship, urologists should be aware that unnecessary use of antibiotics provokes bacterial resistance. There is a great need for further research in the field of antibiotic prophylaxis and stent-related infections to develop evidence that can help shape clear guidelines for this very common urological practice.

Are very thin patients at a higher risk of complications when submitted to percutane-ous nephrolithotomy?

PURPOSE: To assess the impact of thinness on the outcome of the percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A matched case-control study was performed using a prospectively collected database of all patients who underwent PCNL between June 2011 and October 2021. The patients were stratified into two groups according to their phenotypic characteristics, arbitrarily defined according to their body mass index (BMI): <0kg/m2 (Group 1, very thin patients, G<20) and ≥25 kg/m2 (Group 2, non-thin patients, G≥25). Patients were randomly matched based on Guy's Stone Score (GSS) according to case complexity at a ratio of 1:3. RESULTS: A total of 204 patients were enrolled in this study: 51 patients (G<20) and 153 controls (G≥25). Complications occurred in 15.2% of the patients, with 5.4% of these complications classified as major complications (Clavien grade ≥ 3). According to complications there were no significant differences between the groups. The overall complication rates were 17.6% in the G<20 and 14.4% in the G≥25 (p = 0.653). The major complication rates were 3.9% in the G<20 and 5.8% in the G≥25 (p=0.429). No differences in transfusion or urinary fistula rates were found. CONCLUSIONS: In this study, very thin patients were not at a higher risk of complications when submitted to PCNL than in those with a BMI of ≥25 kg/m2. Apparently, this technique can be used in these patients, just as it is used in any other type of patient, independently of their BMI.

International Alliance of Urolithiasis (IAU) guidelines on the management of pediatric urolithiasis.

The aim of this study was to construct the sixth in a series of guidelines on the treatment of urolithiasis by the International Alliance of Urolithiasis (IAU) that by providing a clinical framework for the management of pediatric patients with urolithiasis based on the best available published literature. All recommendations were summarized following a systematic review and assessment of literature in the PubMed database from January 1952 to December 2023. Each generated recommendation was graded using a modified GRADE methodology. Recommendations are agreed upon by Panel Members following review and discussion of the evidence. Guideline recommendations were developed that addressed the following topics: etiology, risk factors, clinical presentation and symptoms, diagnosis, conservative management, surgical interventions, prevention, and follow-up. Similarities in the treatment of primary stone episodes between children and adults, incorporating conservative management and advancements in technology for less invasive stone removal, are evident. Additionally, preventive strategies aiming to reduce recurrence rates, such as ensuring sufficient fluid intake, establishing well-planned dietary adjustments, and selective use pharmacologic therapies will also result in highly successful outcomes in pediatric stone patients. Depending on the severity of metabolic disorders and also anatomical abnormalities, a careful and close follow-up program should inevitably be planned in each pediatric patient to limit the risk of future recurrence rates.

Causal associations between 45 dietary intake habits and urolithiasis: insights from genetic studies.

Background: Different dietary habits can have varying effects on human health and metabolism, and these can be intervened and regulated. Kidney stones, as a disease caused by multiple factors, are largely attributed to diet and metabolism, but the potential causal relationship with dietary intake habits remains unclear. Therefore, this study aims to link the predicted dietary intake based on 45 genetic factors with urolithiasis and explore the potential causal relationship. Methods: We extracted complete genome-wide association studies (GWASs) data on 45 dietary intake traits from the UK Biobank study. Data on kidney stones were obtained from the FinnGen database. In both univariable and multivariable Mendelian randomization analyses, we used inverse variance weighted (IVW) as the primary method to calculate P values, odds ratios (ORs), and 95% confidence intervals (CIs). We examined result heterogeneity using Cochran's Q test. We also carefully investigated potential sources of horizontal pleiotropy using the Mendelian randomization (MR)-PRESSO and MR-Egger methods, and conducted linkage disequilibrium score regression (LDSC) analysis on the corrected P values. Results: Through univariable analysis, we identified 11 dietary habits that potentially causally associate with kidney stones among the 45 examined traits, including 9 protective factors and 2 risk factors. Based on the corrected results with false discovery rate (FDR) and sensitivity analysis, we found one relatively robust evidence. We controlled for common stone risk factors, such as body mass index and smoking, as confounders in multivariable analysis, and no significant results were observed after controlling for these confounders. Based on the LDSC analysis, most of the evidence supports significant genetic correlations with urolithiasis among the 11 traits with potential causal associations. Conclusions: This study confirms the impact of certain dietary factors on the development of kidney stones. Our findings contribute to providing evidence for dietary adjustments in daily life or dietary guidance specifically targeting kidney stone patients.

Comparative efficacy of different surgical techniques for pediatric urolithiasis-a systematic review and meta-analysis.

Background: Prior research has assessed a range of surgical treatments for pediatric urolithiasis, emphasizing the necessity of tailor-made therapeutic approaches. These studies also show the adaptability of percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and shock wave lithotripsy (SWL) in managing diverse stone dimensions. The goal of this research was to examine the effectiveness of these varying surgical methods in treating pediatric urolithiasis. Methods: Seven digital databases were explored to gather pertinent studies, following the guidelines established by the PRISMA protocol. The retrieved studies were subsequently scrutinized to draw comparisons between the stone-free rate (SFR) and the rate of complications associated with PCNL, RIRS, and SWL. Results: The SFR evaluation revealed no notable disparity between PCNL and RIRS [odds ratio (OR) 1.43, 95% confidence interval (CI): 0.67-3.05, P=0.36]. However, it was observed that both PCNL and RIRS outperformed SWL in terms of effectiveness (OR 2.51, 95% CI: 1.19-5.29, P=0.02 and OR 2.42, 95% CI: 1.41-4.14, P=0.001 respectively). Regarding the complication rates, no significant differences were observed among the three surgical methods (OR 0.67, 95% CI: 0.49-1.59, P=0.05), albeit with various forms of complications being reported. Certain studies associated PCNL with an elevated rate of complications, specifically urinary tract infections (UTIs) and severe hematuria. Conclusions: Though PCNL and RIRS demonstrated higher effectiveness than SWL in achieving SFR, there was no significant disparity in the rates of complications across all three procedures. The study underscores the significance of personalized treatment plans, taking into account aspects such as the dimension and location of the stone, along with patient-specific characteristics.

Association between dietary fiber intake and kidney stones: results from the National Health and Nutrition Examination Survey (2011-2018).

BACKGROUND/OBJECTIVES: Studies on the impact of dietary fiber intake on kidney stones are few, and their results were controversial. This study aimed to explore the association between dietary fiber intake and kidney stones in the nationally representative population of the USA. SUBJECTS/METHODS: This cross-sectional research included 8,588 participants from the National Health and Nutrition Examination Survey, 2011 to 2018. Information regarding dietary fiber intake was obtained from a 24-h recall survey. Participants were categorized into different dietary fiber intake tertiles according to the average of 2 days of dietary recall data. The outcome was self-reported kidney stones. After adjusting for the traditional risk factors, a multivariate logistic regression model was used to examine the association between dietary fiber intake and kidney stones. RESULTS: Eight hundred seventy-two participants had kidney stones. The weighted prevalence (SE) of kidney stones in the lowest tertile, medium tertile, and highest tertile of dietary fiber intake was 11.8% (0.8%), 10.3% (0.8%), and 9.1% (0.8%), respectively. After adjusting for age, sex, race and ethnicity, education level, smoking status, alcohol consumption, physical activity, body mass index, hypertension, diabetes, dyslipidemia, daily water intake, chronic kidney disease stage 3-5, and total energy intake, participants with the highest tertile of fiber intake had a significantly lower risk of kidney stones (odds ratio [OR], 0.68; 95% confidence interval [CI], 0.48-0.95) compared to those in the lowest tertile. Every 5 g/day increment in dietary fiber intake was associated with a significant decrease in risk of kidney stones (OR, 0.90; 95% CI, 0.83-0.98). CONCLUSION: An increase in dietary fiber intake was associated with a lower risk of kidney stones, suggesting adults should be encouraged to maintain an adequate dietary fiber intake to prevent the development of kidney stones. Our results provide evidence to formulate nutrition management strategies for the prevention of kidney stones.

In Vitro and In Vivo Antiurolithic Effect of Betulinic Acid Obtained from Citharexylum mirianthum.

The study aimed to investigate the potential antiurolithic effects of extracts, fractions, and betulinic acid (BA) from Citharexylum mirianthum. In vitro analysis involved precipitating calcium oxalate (CaOx) crystals in urine. For in vivo studies, rats were divided into four groups: naive; vehicle; potassium citrate (KC); and BA. Urolithiasis was induced using ethylene glycol and ammonium chloride. After seven days, urine, blood, and kidney tissues were evaluated. The results showed that methanolic extract, hexane, dichloromethane, and ethyl acetate fractions, as well as BA, reduced CaOx crystal formation. In vivo, the vehicle-treated group exhibited reduced urinary volume and Na+ excretion, while the BA-treated group showed restored urinary volume and Na+ excretion similar to the naive group. BA also significantly reduced urinary monohydrate and dihydrate crystal formation, comparable to the KC group. Other urinary parameters remained unchanged, but plasma analysis revealed decreased Na+, K+, and Ca2+ in the KC group. Renal tissue analysis indicated reduced lipid hydroperoxides and increased reduced glutathione in all urolithiasis groups, with unchanged nitrite levels. BA treatment also improved renal corpuscle morphology. Overall, our findings demonstrate that treatment with BA effectively prevented kidney damage induced by EG+AC ingestion, thereby improving renal function in the urolithiasis model.

Consensus statement addressing controversies and guidelines on pediatric urolithiasis.

PURPOSE: We aimed to investigate controversial pediatric urolithiasis issues systematically, integrating expert consensus and comprehensive guidelines reviews. METHODS: Two semi-structured online focus group meetings were conducted to discuss the study's need and content, review current literature, and prepare the initial survey. Data were collected through surveys and focus group discussions. Existing guidelines were reviewed, and a second survey was conducted using the Delphi method to validate findings and facilitate consensus. The primary outcome measures investigated controversial issues, integrating expert consensus and guideline reviews. RESULTS: Experts from 15 countries participated, including 20 with 16+ years of experience, 2 with 11-15 years, and 4 with 6-10 years. The initial survey identified nine main themes, emphasizing the need for standardized diagnostic and treatment protocols and tailored treatments. Inter-rater reliability was high, with controversies in treatment approaches (score 4.6, 92% agreement), follow-up protocols (score 4.8, 100% agreement), and diagnostic criteria (score 4.6, 92% agreement). The second survey underscored the critical need for consensus on identification, diagnostic criteria (score 4.6, 92% agreement), and standardized follow-up protocols (score 4.8, 100% agreement). CONCLUSION: The importance of personalized treatment in pediatric urolithiasis is clear. Prioritizing low-radiation diagnostic tools, effectively managing residual stone fragments, and standardized follow-up protocols are crucial for improving patient outcomes. Integrating new technologies while ensuring safety and reliability is also essential. Harmonizing guidelines across regions can provide consistent and effective management. Future efforts should focus on collaborative research, specialized training, and the integration of new technologies in treatment protocols.

Landscape of peripheral immunity in patients with upper urinary tract urolithiasis and the underlying correlations with renal function.

INTRODUCTION: Inflammatory and immunological responses are reported involved in the pathogenesis and progression of obstructive nephropathy (ON). This study was designed to investigate the characteristics of peripheral immunity in patients with upper urinary tract urolithiasis and analyze the underlying associations with renal function. METHODS: Patients with unilateral upper urinary tract urolithiasis meeting the operation indications were prospectively enrolled. Preoperative circulating immune cells and inflammatory cytokines were detected in our clinical laboratory, and the indicators of renal function and calculi related parameters were particularly recorded. Patients were sectionalized into subgroups on the basis of the lesion of calculi. Characteristics of peripheral immunity in each subgroup were investigated by statistical approaches, and the underlying correlations with the degree of hydronephrosis (HN) and renal function were discussed in corresponding group. RESULTS: Patients with ureteral calculi presented severer HN compared with renal calculi, especial middle ureteral calculi, acting as the chief culprit of ON, exhibiting the highest serum creatine and blood urea nitrogen, most impaired estimated glomerular filtration rate, and severest HN. In addition, serum interleukin-8 (IL-8) and IL-6 were demonstrated presenting statistical differences between ureteral calculi and renal calculi patients, exhibiting underlying values in comprehending ON. However, circulating immune cells were demonstrated no obvious differences among groups. CONCLUSIONS: Circulating inflammatory cytokines, referred in particular to serum IL-8 and IL-6 were partially associated with kidney injury in patients with upper urinary tract urolithiasis. But the specific influences and mechanisms between them needed to be investigated furthermore.

Comparison of ureteoroscopy and laser stone fragmentation between Holmium: YAG laser with MOSES versus non-MOSES technology: a prospective single-center propensity score-matched analysis using similar laser settings.

Background: In vitro studies have shown that the holmium Modulated Optics Enhancement Systems (MOSES) technology can lead to an increase in the efficacy of lithotripsy and a reduction of retropulsion, but clinical evidence comparing it to non-MOSES technology is still scarce. We did a comparison of ureteoroscopy and laser stone fragmentation (URSL) between Holmium:YAG laser with MOSES versus non-MOSES technologies. Methods: Patient data and outcomes were prospectively collected and analyzed regarding patient demographics, stone parameters, and clinical outcomes. Patients undergoing URSL with standard holmium laser without MOSES technology (Group 1) were compared to holmium laser with MOSES (Group 2) using the same clinical laser settings (0.4-1 J, 20-40 Hz) with dusting and pop-dusting technique. The independent t-test, Mann-Whitney U test, and Chi-squared test were used, with a p-value of < 0.05 as significant. Given the different sizes of the cohorts, we performed a propensity score 1:1 matched analysis. Results: A total of 206 patients (1:1 matched) with a male:female ratio of 94:112 and a median age of 56 (range: 39-68) years were analyzed. Groups 1 and 2 were matched for ureteric stones (27.7% and 22.3%, p = 0.42), pre-stenting (37% and 35%, p = 0.66), the mean number of stones (1.76 ± 1.3) and (1.82 ± 1.4, p = 0.73), and ureteral access sheath use (37% and 35%, p = 0.77) respectively.While there was no significant statistical difference in clinical outcomes, the stone size was slightly larger in Group 2, 14.8 ± 10.8 mm vs 11.7 ± 8.0 mm, for a lower operative time 42.7 ± 30.6 min versus 48.5 ± 25 min, lower perioperative complication rates 3.9% versus 4.9% and a higher stone-free rate 90.3% versus 87.4%. Conclusion: While the use of MOSES technology was slightly beneficial for the treatment of stones in terms of clinical outcomes, this was not statistically significant. As this debate continues, there is a need for high-quality randomized studies to show if there is a true difference in these outcomes.

We compare the outcomes of ureteroscopy and laser stone fragmentation (URSL), using Holmium:YAG laser with MOSES vs Non-MOSES technology: It is a prospective single-centre propensity score-matched analysis using similar laser settings It is a single-centre propensity score-matched analysis using similar laser settings. While the use of MOSES technology was slightly beneficial for treatment of stones in terms of clinical outcomes, this was not statistically significant. As this debate continues, there is a need for high quality randomized studies to show if there is a true difference in these outcomes.

Familial aggregation of urolithiasis: findings from a Nationwide Middle Eastern study.

This study aimed to determine the potential effect of genetic factors and positive family history on the familial aggregation of urolithiasis in Iran. Of the total 44,186 participants in the Iran National Stone Survey (INSS) database, 34,953 individuals who were members of 8629 nuclear families were included in this study. The mean prevalence of urolithiasis was 5.7% [95%CI: 5.5 - 6.0%] in this subpopulation. Familial aggregation of urolithiasis was analyzed in 34,745 participants (99.6% of those originally included) utilizing a multivariable logistic regression with second order generalized estimating equations approach (GEE2) to adjust for sex, age, urbanization status and ethnicity. Recurrence risk ratios (λ) were used to evaluate the degree of familial aggregation. Our multivariable analysis demonstrated a strong familial aggregation of urolithiasis within sibling pairs (λs = 78.35), parent-offspring pairs (λo = 40.12) and spouse pairs (λsp = 21.62). The respective ORs were 5.65 [95%CI: 3.49, 9.14] for siblings, 2.85 [95%CI: 2.20, 3.68] for parents and 1.27 [95%CI: 1.06, 1.54] for spouses. Urinary stone disease tends to aggregate in families with a positive history of urolithiasis in either the parents or siblings. Siblings have a more prominent effect in inducing familial aggregation compared to parents. Despite the prominent role of familial genetic components in urolithiasis aggregation, shared environmental factors appear to partake in this phenomenon to some extent, as suggested by urolithiasis aggregation among spouse pairs.

Comparative study of thulium fiber laser versus holmium:yttrium-aluminum-garnet laser for ureteric stone management with semi-rigid ureteroscopy: A prospective, single-center study.

Objective: To compare the efficacy and safety of thulium fiber laser (TFL) and holmium:yttrium-aluminum-garnet (Ho:YAG) laser for ureteric stone management with semi-rigid ureteroscopy. Methods: In a prospective study from January 2020 to December 2021, we compared 40 patients in each group who underwent semi-rigid ureteroscopic lithotripsy with TFL and that with Ho:YAG laser. Stone volume, stone density, stone fragmentation rates, total lasing time, total operative time, endoscopic vision, retropulsion and stone free rates were analyzed in both groups and compared. Results: Mean stone volume was comparable in the TFL group and the Ho:YAG laser group (282.45 [standard deviation, SD 139.79] mm3 vs. 279.49 [SD 312.52] mm3; p=0.964). Mean stone density was also comparable in the TFL group and the Ho:YAG laser group (1135.30 [SD 317.04] Hounsfield unit vs. 1131.75 [SD 283.03] Hounsfield unit; p=0.959). The mean stone fragmentation rates calculated as stone volume divided by lasing time were 25.85 (SD 10.61) mm3/min and 21.37 (SD 14.13) mm3/min in the TFL group and the Ho:YAG laser group, respectively (p=0.113). The mean total lasing time (10.15 [SD] 4.69 min vs. 11.43 [SD 4.56] min; p=0.222), mean operative time (25.13 [SD 9.51] min vs. 25.54 [SD 10.32] min; p=0.866), and mean total hospital stay (2.62 [SD 0.77] days vs. 2.61 [SD 0.84] days; p=0.893) were comparable in the TFL group and in the Ho:YAG group. The vision was better and retropulsion was less in the TFL group. The stone-free rate at 1 month postoperatively was slightly better in the TFL group (100% vs. 90%; p=0.095). Conclusion: TFL technology was associated with the comparable total surgical time, total lasing time, and stone fragmentation rate with Ho:YAG laser. However, TFL had better endoscopic vision, lesser stone retropulsion, and slightly better stone-free rates.

Targeting protein receptors and enzymes for precision management of urolithiasis: A comprehensive review.

Urolithiasis, characterized by the formation of solid crystalline structures within the urinary tract, presents a significant global health burden with high recurrence rates and limited treatment efficacy. Recent research has identified various protein receptors and enzymes implicated in the pathogenesis of urolithiasis, offering potential targets for therapeutic intervention. Protein receptors such as the calcium-sensing receptor and vasopressin V2 receptor play crucial roles in regulating urinary calcium excretion and water reabsorption, respectively, influencing stone formation. Additionally, modulation of receptors like the angiotensin II receptor and aldosterone receptor can impact renal function and electrolyte balance, contributing to stone prevention. Furthermore, enzymes such as urease inhibitors and xanthine oxidase inhibitors offer targeted approaches to prevent the formation of specific stone types. This review discusses the potential of targeting these receptors and enzymes for the treatment of urolithiasis, exploring associated drugs and their mechanisms of action. Despite promising avenues for personalized and precision medicine approaches, challenges such as the need for robust clinical evidence and ensuring cost-effectiveness must be addressed for the translation of these interventions into clinical practice. By overcoming these challenges, receptor-targeted therapies and enzyme inhibitors hold promise for revolutionizing the management of urolithiasis and reducing its global burden.

Successful Kidney Transplantation in a Young Male with Type 2 Xanthinuria.

Type-II Xanthanuria is an genetic disorder associated with diminished serum uric acid levels. Patients with xanthanuria has absence of xanthine oxidase or xanthine dehydrogenase activity, the enzyme that converts hypoxanthine to xanthine and xanthine to uric acid. Deficiency of these enzyme leads to elevated levels of xanthine in urine which further leads to precipitation of xanthine in urine which further helps to formation of renal stones and ultimately leads to chronic kidney disease and end stage renal disease. We report a 23 years old male, who reached ESRD due to Type 2 xanthinuria, which was confirmed by genetic studies, who later successfully underwent renal transplant surgery and currently having normal life with functioning graft.

Metabolic Profile of Calcium Oxalate Stone Patients with Enteric Hyperoxaluria and Impact of Dietary Intervention.

This study investigated the risk profile and the impact of dietary intervention in calcium oxalate stone formers with enteric hyperoxaluria under controlled, standardized conditions. Thirty-seven patients were included in the study. Dietary and 24-h urinary parameters were obtained on the self-selected diet and a balanced, standardized diet. Tests for [13C2]oxalate absorption, calcium- and ammonium chloride-loading were performed. Mean [13C2]oxalate absorption was 18.8%. A significant positive association was observed between urinary oxalate excretion and intestinal oxalate absorption. In addition, urinary oxalate excretion was significantly correlated with dietary oxalate intake. Mean urinary oxalate excretion decreased from 0.841 mmol/24 h on the usual diet to 0.662 mmol/24 h on the balanced diet, corresponding to a reduction of 21.3%. Besides hyperoxaluria, hypocitraturia and hypomagnesuria were the most common urinary abnormalities at baseline, being present in 83.8% and 81.1% of patients, respectively. Urinary citrate increased by 50.9% and magnesium excretion increased by 25.2% on the balanced diet. As a result, the relative supersaturation of calcium oxalate declined significantly (by 36.2%) on the balanced diet. Since 41% of patients on the balanced diet still had a urine volume of less than 2.0 L/24 h, efforts should be made to increase urine volume by increasing fluid intake and reducing intestinal fluid losses. Dietary intervention proved to be effective in reducing urinary oxalate excretion and should be a cornerstone of the treatment of patients with enteric hyperoxaluria.

Mendelian randomization study of urolithiasis: exploration of risk factors using human blood metabolites.

BACKGROUND: Urolithiasis is a highly prevalent global disease closely associated with metabolic factors; however, the causal relationship between blood metabolites and urolithiasis remains poorly understood. METHOD: In our study, we employed a bi-directional two-sample Mendelian randomization (MR) analysis to investigate the causal associations between urolithiasis and metabolites. The random-effects inverse-variance weighted (IVW) estimation method was utilized as the primary approach, complemented by several other estimators including MR-Egger, weighted median, colocalization and MR-PRESSO. Furthermore, the study included replication and meta-analysis. Finally, we conducted metabolic pathway analysis to elucidate potential metabolic pathways. RESULTS: After conducting multiple tests for correction, glycerol might contribute to the urolithiasis and dehydroisoandrosterone sulfate (DHEA-S) might inhibit this process. Furthermore, several blood metabolites had shown potential associations with a causal relationship. Among the protective metabolites were lipids (dehydroisoandrosterone sulfate and 1-stearoylglycerol (1-monostearin)), amino acids (isobutyrylcarnitine and 2-aminobutyrate), a keto acid (acetoacetate) and a carbohydrate (mannose). The risk metabolites included lipids (1-palmitoylglycerophosphoethanolamine, glycerol and cortisone), a carbohydrate (erythronate), a peptide (pro-hydroxy-pro) and a fatty acid (eicosenoate). In reverse MR analysis, urolithiasis demonstrated a statistically significant causal relationship with butyrylcarnitine, 3-methyl-2-oxobutyrate, scyllo-inositol, leucylleucine and leucylalanine. However, it was worth noting that none of the blood metabolites exhibited statistical significance after multiple corrections. Additionally, we identified one metabolic pathway associated with urolithiasis. CONCLUSION: The results we obtained demonstrate the causal relevance between two metabolites and urolithiasis, as well as identify one metabolic pathway potentially associated with its development. Given the high prevalence of urolithiasis, further investigations are encouraged to elucidate the mechanisms of these metabolites and explore novel therapeutic strategies.