Risk Of Kidney Stone Formation Research Articles

Dietary potassium effects on renal calcium transport at single nucleus resolution

Calcium homeostasis is maintained by the coordination of the intestines, bones, and kidneys. Dietary calcium is absorbed in the intestines, enters the bloodstream, and eventually finds its place in the bone reservoir or undergoes filtration by the glomerulus before being reabsorbed throughout the nephron. The late distal convoluted tubule (DCT2) and connecting tubule (CNT) determine the final rate of urinary calcium excretion, since no calcium reabsorption takes place beyond the connecting tubule (CNT). When excess calcium is excreted in the urine, also known as hypercalciuria, it contributes to the development of osteoporosis and the formation of kidney stones. High dietary potassium intake is strongly associated with a lower risk of kidney stone formation. Yet, the precise mechanism by which potassium intake modulates calcium excretion is not clear. To examine the transcriptional changes linking high dietary potassium intake and calcium transport, we applied single-nucleus RNA-sequencing (snRNA-Seq) in enriched distal nephron cells. To achieve the enrichment, we crossed a Calbindin 1 (Calb1)-driven Cre mouse line with the INTACT (for Isolation of Nuclei TAgged in Specific Cell Types) reporter line, which allows the GFP reporter to be expressed at the nuclear envelope of all calbindin 1-expressing cells. As the Calb1-Cre is constitutively expressed, all cells that have calbindin 1 expression at any time point during development will express the reporter. We examined the GFP expression by immunofluorescence, and found that it is expressed along the entire distal nephron from the distal convoluted tubule (DCT), CNT, to the collecting duct (CD). Male Calb1-Cre-INTACT mice were provided either a normal (NK, 1.05%) or a high (HK, 2%) potassium diet for 4 days and kidneys were snap-frozen for targeted snRNA-Seq using 10X Chromium (n=3 mice per group, targeting 10,000 nuclei per mouse). Our snRNA-seq dataset showed 6 major clusters, including DCT (DCT1 and DCT2), CNT (3 subclusters), CD principal cells (3 subclusters), ɑ-intercalated cells (2 subclusters), β-intercalated cells (2 subclusters), and proliferating cells. We curated a calcium score from the expression of known calciotropic genes ( Slc8a1, Vdr, Trpv5, Calb1, S100g, Ryr2, Trpv6) and used it as an index of calcium handling capacity. The calcium score is the highest in DCT2 and CNT along the distal nephron. In all CNT subclusters of the HK-treated animals, the calcium score is higher compared to the NK-treated animals, suggesting more calcium transport in CNT. Given that HK stimulates aldosterone and causes CNT hypertrophy, we compared the results with mice subjected to low dietary potassium (LK) treatment and metolazone (thiazide) treatment. The aim was to delineate the effects of dietary potassium and aldosterone A comprehensive summary of plasma potassium levels, urinary calcium excretion, aldosterone levels, calcium scores, and CNT morphology has been presented in the table below. Notably, the comparative analysis reveals a significant correlation between aldosterone levels and CNT size, both of which exhibit an inverse relationship with urinary calcium excretion: [Formula: see text] Our results suggest that DCT2 and CNT are the major sites for calcium transport. Yet, CNT exhibit more heightened adaptability in response to physiological or pharmacological perturbations at both transcriptional and morphological levels. Calcium homeostasis coincides with the regulation of aldosterone levels and CNT remodeling. DK51496 and DK133220 to DHE; K01DK121737 and AHA 20CDA35320169 to JWN. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

SGLT-2 Inhibitors and Their Correlation With Kidney Stones. A Systematic Review

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors have emerged as a valuable class of medications for managing Type 2 Diabetes Mellitus (T2DM) due to their efficacy in glycemic control and cardiovascular and renal benefits. However, concerns have been raised regarding their potential association with an increased risk of kidney stone formation. Objective: This systematic review aimed to comprehensively evaluate the existing literature to determine the association between SGLT-2 inhibitors and kidney stone formation, elucidate potential underlying mechanisms, and discuss implications for clinical practice. Methods: A systematic search of databases including PubMed, Google Scholar, Web of Sciences, Medline, and Scopus was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant research articles investigating the utilization of SGLT-2 inhibitors in humans and their potential correlation with kidney stones were included. Data extraction and quality assessment were performed, and a mixed-methods synthesis approach was used for data analysis. Results: The systematic review identified several studies examining the association between SGLT-2 inhibitors and kidney stones. Overall, SGLT-2 inhibitors were found to be associated with a potential protective effect against kidney stone formation. Mechanistically, SGLT-2 inhibitors promote glycosuria and natriuresis, leading to increased urine flow rate and enhanced urinary volume, which may help dilute and flush out stone-forming substances. However, certain limitations and considerations, including potential adverse events and variations in study designs, were also highlighted. Conclusion: This systematic review provides valuable insights into the potential correlation between SGLT-2 inhibitors and kidney stones. While the observed protective effect against kidney stone formation is promising, further research with longer follow-up durations and larger sample sizes is warranted to establish a more conclusive understanding of this relationship. Nonetheless, clinicians should remain vigilant in monitoring patients using SGLT-2 inhibitors and carefully assess individual risk factors when prescribing these medications.

Relationship Between Body Mass Index and Blood Lipids with Kidney Stone Disease: The Fasa Adults Cohort Study

Background: Urinary stones rank as the third most common disease of the genitourinary system, following urinary tract infections and prostate diseases. Their incidence is influenced by various demographic, environmental, and genetic factors. Objectives: This study aimed to explore the association between Body Mass Index (BMI), blood lipids, and kidney stones. Methods: This cross-sectional study utilized the baseline data of 10 133 participants aged 35 - 70 years from the Fasa cohort study. The dataset included demographic information, biochemical laboratory results, anthropometric measurements, behavioral data, and the presence or absence of kidney stones. Data analysis employed t-tests, chi-square tests, and logistic regression models. Results: Among the 10 133 participants, 54.9% were women, with a mean age of 48.63 ± 9.57 years. The prevalence of kidney stones was 17.3%. The findings indicated a correlation between BMI and triglyceride levels (TG) with kidney stones. Elevated BMI and triglyceride levels were associated with increased odds of developing kidney stones, with odds ratios of 1.048 (95% CI: 1.025 - 1.048) and 1.006 (95% CI: 1.001 - 1.006), respectively. Conclusions: The study revealed a significant relationship between BMI, triglyceride levels, and kidney stones. Individuals with kidney stones exhibited higher mean BMI and TG levels compared to those without. These findings from the Fasa PERSIAN (Prospective Epidemiological Research Studies in Iran) cohort suggest that kidney stone disease is linked to elevated triglyceride levels and BMI. Given that a high-fat diet contributes to increased BMI and elevated serum triglyceride levels, measures to reduce weight, combat obesity, and manage triglyceride levels are warranted to mitigate the risk of kidney stone formation.

Carboxymethylated Desmodium styracifolium polysaccharide reduces the risk of calcium oxalate kidney stone formation by inhibiting crystal adhesion and promoting crystal endocytosis.

The inhibition of cell surface crystal adhesion and an appropriate increase in crystal endocytosis contribute to the inhibition of kidney stone formation. In this study, we investigated the effects of different degrees of carboxymethylation on these processes. An injury model was established by treating human renal proximal tubular epithelial (HK-2) cells with 98.3 ± 8.1 nm calcium oxalate dihydrate (nanoCOD) crystals. The HK-2 cells were protected with carboxy (-COOH) Desmodium styracifolium polysaccharides at 1.17% (DSP0), 7.45% (CDSP1), 12.2% (CDSP2), and 17.7% (CDSP3). Changes in biochemical indexes and effects on nanoCOD adhesion and endocytosis were detected. The protection of HK-2 cells from nanoCOD-induced oxidative damage by carboxymethylated Desmodium styracifolium polysaccharides (CDSPs) is closely related to the protection of subcellular organelles, such as mitochondria. CDSPs can reduce crystal adhesion on the cell surface and maintain appropriate crystal endocytosis, thereby reducing the risk of kidney stone formation. CDSP2 with moderate -COOH content showed the strongest protective activity among the CDSPs.

Corn Silk Polysaccharide Reduces the Risk of Kidney Stone Formation by Reducing Oxidative Stress and Inhibiting COM Crystal Adhesion and Aggregation.

HK-2 cells were damaged by 100 nm COM crystals to build an injury model. The cells were protected by CSPs with -COOH contents of 3.92% (CSP0) and 16.38% (CCSP3), respectively. The changes in the biochemical indexes of HK-2 cells and the difference in adhesion amount and aggregation degree of nano-COM on the cell surface before and after CSP protection were detected. CSP0 and CCSP3 protection can obviously inhibit HK-2 cell damage caused by nano-COM crystals, restore cytoskeleton morphology, reduce intracellular ROS level, inhibit phosphoserine eversion, restore the polarity of the mitochondrial membrane potential, normalize the cell cycle process, and reduce the expression of adhesion molecules, OPN, Annexin A1, HSP90, HAS3, and CD44 on the cell surface. Finally, the adhesion and aggregation of nano-COM crystals on the cell surface were effectively inhibited. The carboxymethylated CSP3 exhibited a higher protective effect on cells than the original CSP0, and cell viability was further improved with the increase in polysaccharide concentration. CSPs can protect HK-2 cells from calcium oxalate crystal damage and effectively reduce the adhesion and aggregation of nano-COM crystals on the cell surface, which is conducive to inhibiting the formation of calcium oxalate kidney stones.

24-Hour Urinary Chemistries and Kidney Stone Risk

Rationale & ObjectiveMost previous studies of the relationship between urinary factors and kidney stone risk have either assumed a linear effect of urinary parameters on kidney stone risk or implemented arbitrary thresholds suggesting biologically implausible “all-or-nothing” effects. In addition, little is known about the hierarchy of effects of urinary factors on kidney stone risk. This study evaluated the independent associations between urine chemistries and kidney stone formation and examined their magnitude and shape. Study DesignProspective cohort study. Setting & ParticipantsWe analyzed 9,045 24-hour urine collections from 6,217 participants of the Health Professionals Follow-Up Study and Nurses’ Health Studies I and II. ExposuresUrine volume and pH, and concentrations of calcium, citrate, oxalate, potassium, magnesium, uric acid, phosphorus, and sodium. OutcomeIncident symptomatic kidney stones. Analytical ApproachMultivariable logistic regression analysis incorporating restricted cubic splines to explore potentially non-linear relationships between urinary factors and the risk of forming a kidney stone. Optimal inflection point analysis was implemented for each factor and dominance analysis was performed to establish the relative importance of each urinary factor. ResultsEach urinary factor was significantly associated with stone formation except for urine pH. Higher urinary levels of calcium, oxalate, phosphorus, and sodium were associated with a higher risk of stone formation, whereas higher urine volume, uric acid, citrate, potassium, and magnesium were associated with a lower risk. The relationships were substantially linear for urine calcium, uric acid, and sodium. In contrast, the magnitudes of the relationships were modestly attenuated at levels above the inflection points for urine oxalate, citrate, volume, phosphorus, potassium, and magnesium. Dominance analysis identified three categories of factors' relative importance: higher (calcium, volume and citrate), intermediate (oxalate, potassium and magnesium) and lower (uric acid, phosphorus and sodium). LimitationsPredominantly white participants, lack of information on stone composition. ConclusionsUrine chemistries have complex relationships and differential relative associations with the risk of kidney stone formation.

Association of Chronic Hyperglycemia With the Risk of Urolithiasis.

Background The incidence of urolithiasis is increasing along with elevated rates of chronic hyperglycemia. Therefore, this study aimed to assess the association between high hemoglobin Alc (HbAlc) levels, in the form of type 2 diabetes mellitus (T2DM), and the risk of kidney stone formation among those living in the Eastern Province of Saudi Arabia. Methodology We conducted a cross-sectional study on a total of 501 patients with known cases of urolithiasis who visited King Fahad University Hospital (Khabar, Saudi Arabia). We calculated odds ratios (ORs) of having stones with respect to three parameters, namely, fasting blood glucose level, random blood glucose level, and glycosylated HbA1c testing. Results Of the 501 cases with urinary stones included in this study, the majority (223, 44.5%) were 41-59 years of age, and 350 (69.9%) were males. Our results showed that T2DM was significantly associated with high stone burden, with increased fasting plasma glucose, increased random blood glucose, and increased HbA1c being strong predictors. The significant associations between glycemic control measures and the risk of urolithiasis remained even after adjusting for factors related to insulin resistance. Conclusions According to our results, glycemiccontrol can be an independent risk factor for urolithiasis. This critical finding demonstrates the need for further studies to investigate this particular group of patients.

Effects of Microgravity on Astronaut Physiology in Long-Term Space Missions and Proposed Countermeasures

The interest in long-term space travel (>6 months) has gained popularity in the space community. This began in the 1970s with multiple short-term missions exploring the Moon and Mars to understand true habitability and early developments of long-term space settlements. With new missions being proposed by major pioneers in aerospace, such as NASA, SpaceX, and JAXA, scientists are concerned with human health, especially the long-term effects. Long-term settlements have been hypothesized to have major short-term and long-term detriments to multiple physiological systems, most notably musculoskeletal, cardiovascular, and neurophysical. This is due to the effects of microgravity; however, more experimentation must be conducted to understand these effects sufficiently. So far, scientists have linked microgravity to decreased osteoblastic differentiation, rapid bone loss, and increased risk of kidney stone formation in the musculoskeletal system. Additionally, the cardiovascular system is impacted by space anemia, which is hypothesized to be reversible but may induce detrimental effects. Finally, microgravity affects the vestibular system significantly, especially spatial recognition. Countermeasures have been proposed to reduce these effects, like inducing artificial gravity, administrating bisphosphonates and other drugs/therapies, and utilizing tactile aids. The long-term effect of microgravity is still an emerging topic of space research, and much more research must be conducted through various programs like the Artificial Gravity Bed Rest Study with the European Space Agency (AGBRESA) to understand long-term results better.

Carboxymethylated Rhizoma alismatis Polysaccharides Regulate Calcium Oxalate Crystals Growth and Reduce the Regulated Crystals' Cytotoxicity.

This study explored the effects of polysaccharides (RAPD) extracted from the traditional anti-stone Chinese medicine Rhizoma alismatis and their carboxymethylated derivatives (RAPs) on the crystal phase, morphology, and size of calcium oxalate (CaOx). It also determined the damaging ability of the regulated crystals on human renal tubular epithelial cells (HK-2). RAPD carboxymethylation with a carboxyl group (-COOH) content of 3.57% was carried out by the chloroacetic acid solvent method. The effects of -COOH content in RAPs and RAP concentration on the regulation of CaOx crystal growth were studied by controlling the variables. Cell experiments were conducted to explore the differences in the cytotoxicity of RAP-regulated crystals. The -COOH contents of RAPD, RAP1, RAP2, and RAP3 were 3.57%, 7.79%, 10.84%, and 15.33%, respectively. RAPs can inhibit the growth of calcium oxalate monohydrate (COM) and induce the formation of calcium oxalate dihydrate (COD). When the -COOH content in RAPs was high, their ability to induce COD formation was enhanced. In the crystals induced by RAPs, a high COD content can lower the damage to cells. In particular, the cytotoxicity of the crystals induced by RAP3 was the lowest. When the concentration of RAP3 increased, the cytotoxicity gradually increased due to the reduced size of the formed COD crystals. An interaction was observed between RAPs and crystals, and the number of RAPs adsorbed in the crystals was positively correlated with the -COOH content in RAPs. RAPs can reduce the damage of CaOx to HK-2 cells by regulating the crystallization of CaOx crystals and effectively reducing the risk of kidney stone formation. RAPs, especially RAP3 with a high carboxyl group content, has the potential to be developed as a novel green anti-stone drug.

Efficacy for Bone Deterioration in Mice with Osteoporosis and Pharmaceutical Properties of a Novel Compound Calcium Carbonate Granule

Osteoporosis (OP) has been a global health concern, and calcium supplements are still an effective method to relieve the disease. In this study, we investigated the pharmaceutical properties, antiosteoporosis, and adverse effects of a novel calcium supplement named compound calcium carbonate granule (CCCG). The dissolution rate, stability of vitamin D3, and drug permeability of the calcium supplements were explored. And the osteoporosis was constructed in mice with retinoic acid (100 mg/kg/d) for 21 days, and orally treated with CCCG (0.34, 0.68, and 1.36 g/kg/d) for 36 days to evaluate the efficacy against osteoporosis and the occurrence of kidney stones. The results showed that CCCG exhibited higher dissolution rate and better vitamin D3 stability than the standard calcium carbonate granule. CCCG also displayed more absorption in Caco-2 cell model. On the other hand, CCCG alleviated the deterioration in femur microstructure and oxidative stress in the liver and kidney, and increased the expression of bone metabolic markers. CCCG also exhibited lower risk of nephrolithiasis than the commercial calcium carbonate granule. In summary, from the perspectives of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative of commonly used ones. Practical Application. Calcium carbonate is widely used to supplement calcium, primarily because of its high calcium load, low cost, and good efficacy. Now, we provided a new calcium supplement named CCCG, which was prepared by inclusion and complexation techniques. Vitamin D3 in CCCG was made into vitamin D-β-cyclodextrin inclusion complex by inclusion technology, which improved the stability of vitamin D3. And calcium carbonate was converted to a water-soluble calcium citrate complex via complexation techniques to accelerate the release of calcium ions and minimize the risk of kidney stone formation. From the perspective of both pharmaceutics and efficacy, we illustrated the profiles of an intriguing calcium supplement, which could possibly be an alternative for the supplemental and preventive treatment of osteoporosis.

Urinary Lithiasis Risk Assessment after Bariatric Surgery.

Malabsorption is a consequence of gastric bypass (GB). GB increases the risk of kidney stone formation. This study aimed to evaluate the accuracy of a screening questionnaire for assessing the risk of lithiasis in this population. We performed a monocentric retrospective study to evaluate a screening questionnaire administered to patients who underwent gastric bypass surgery between 2014 and 2015. Patients were asked to answer a questionnaire that included 22 questions divided into four parts: medical history, episodes of renal colic before and after bypass surgery, and eating habits. A total of 143 patients were included in the study, and the mean age of the patients was 49.1 ± 10.8 years. The time between gastric bypass surgery and the completion of the questionnaire was 50.75 ± 4.95 months. The prevalence of kidney stones in the study population was 19.6%. We found that with a score of ≥6, the sensitivity and specificity were 92.9% and 76.5%, respectively. Positive and negative predictive values were 49.1% and 97.8%, respectively. The ROC curve showed an Area Under the Curve (AUC) of 0.932 ± 0.029 (p < 0.001). We developed a reliable and short questionnaire to identify patients at a high risk of kidney stones after gastric bypass. When the results of the questionnaire were equal to or greater than six, the patient was at a high risk of kidney stone formation. With a good predictive negative value, it could be used in daily practice to screen patients who have undergone gastric bypass and are at a high risk of renal lithiasis.

Effect of preoperative metabolic profiling to reduce the risk of kidneystones after bariatric surgery in patients with a historyofstoneformation.

Roux-en-Y gastric bypass (RYGB) is associated with an increased risk of kidney stone formation. This is not observed after sleeve gastrectomy (SG). Aim of this study was to assess whether preoperative metabolic profiling is helpful in selecting the most optimal bariatric procedure for patients with a kidney stone history. General hospital, the Netherlands. Patients with a kidney stone history and in the run up to bariatric surgery were screened with non-contrast abdominal computed tomography (CT), serum profiling, and 24-hour urine analysis. Those with stones on radiologic imaging and/or high preoperative urinary oxalate were advised to undergo SG instead of RYGB. Pre- and postoperative urine and serum profile differences between both groups were evaluated retrospectively. Postoperatively, RYGB (N = 28, M:F = 8:20) was associated with a 23.5% reduction in urinary volume, a 85% increase in urinary oxalate excretion with a 230% increase in calcium oxalate (CaOx) supersaturation and a 62% decrease in urinary citrate. Although SG (N = 30, M:F = 12:18) was also associated with a reduction in urinary volume, it had no adverse effects on urinary oxalate and citrate excretion, nor on calcium oxalate supersaturation (CaOx-SS). Both RYGB and SG showed favorable effects on postoperative sodium, calcium, uric acid, and phosphate excretion. This study indicates that preoperative metabolic profiling is important to select the optimal bariatric procedure in patients with an a priori increased risk of kidney stone development. These patients should be strongly encouraged to undergo SG instead of RYGB to prevent progressive or recurrent kidney stone disease.

Structure and mechanism of oxalate transporter OxlT in an oxalate-degrading bacterium in the gut microbiota

An oxalate-degrading bacterium in the gut microbiota absorbs food-derived oxalate to use this as a carbon and energy source, thereby reducing the risk of kidney stone formation in host animals. The bacterial oxalate transporter OxlT selectively uptakes oxalate from the gut to bacterial cells with a strict discrimination from other nutrient carboxylates. Here, we present crystal structures of oxalate-bound and ligand-free OxlT in two distinct conformations, occluded and outward-facing states. The ligand-binding pocket contains basic residues that form salt bridges with oxalate while preventing the conformational switch to the occluded state without an acidic substrate. The occluded pocket can accommodate oxalate but not larger dicarboxylates, such as metabolic intermediates. The permeation pathways from the pocket are completely blocked by extensive interdomain interactions, which can be opened solely by a flip of a single side chain neighbouring the substrate. This study shows the structural basis underlying metabolic interactions enabling favourable symbiosis.

PD34-09 THE ASSOCIATION BETWEEN ORGANOPHOSPHATE INSECTICIDES AND KIDNEY STONE FORMATION AMONG U.S. ADULTS

You have accessJournal of UrologyCME1 Apr 2023PD34-09 THE ASSOCIATION BETWEEN ORGANOPHOSPHATE INSECTICIDES AND KIDNEY STONE FORMATION AMONG U.S. ADULTS Frank Glover, Mohammad Hajiha, Michael Eisenberg, Federico Belladelli, Francesco Del Giudice, Nicolas Seranio, Wade Muncey, and Kenneth Ogan Frank GloverFrank Glover More articles by this author , Mohammad HajihaMohammad Hajiha More articles by this author , Michael EisenbergMichael Eisenberg More articles by this author , Federico BelladelliFederico Belladelli More articles by this author , Francesco Del GiudiceFrancesco Del Giudice More articles by this author , Nicolas SeranioNicolas Seranio More articles by this author , Wade MunceyWade Muncey More articles by this author , and Kenneth OganKenneth Ogan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003327.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Kidney stones pose a significant disease burden within the U.S., where an estimated 10% of adults are affected. While several risk factors have been identified in the etiology of kidney stones (e.g., hydration status, diet, and genetic conditions) the pathogenesis remains to be fully elucidated. Recently, the contribution of environmental exposures in the pathogenesis of adverse urological outcomes has gained attention though data is limited. Organophosphate (OP) insecticides are widespread toxicants, and their use has been associated with endocrine disruption, metabolic dysregulation, and increased risk of chronic diseases. Currently, the association between kidney stone formation and OP exposure is unknown. The purpose of this study was to investigate the relationship between OP exposure and kidney stones. METHODS: Data for nationally representative U.S. cohort of 2373 individuals was leveraged from the National Health and Nutrition Examination (NHANES) Survey, annually conducted, population-based cross-sectional study. Trained individuals collected biological specimens via blood and urine draws, and sociodemographic data via in-person questionnaires. Urinary measurements of dialkyl phosphates (DAPs) were used as surrogates for OP exposure. Kidney stone history was evaluated based on questionnaire data, where individuals with kidney stones responded “yes” to either ever having kidney stones, or passed a kidney stone within the last year. Chi-square, ANOVA and multivariable, weighted logistic regression were used to analyze the relationship between DAP exposure, sociodemographic variables, and history of kidney stones. RESULTS: Stratification of total urinary DAPs by quartiles revealed a significant increased odds of kidneys stones in the fourth quartile compared to the first quartile (Q2 OR=1.65 95%CI [0.72,3.77], Q3 OR=2.72 95%CI [0.92,7.99], Q4 OR=3.08 95%CI [1.05,9.01]. CONCLUSIONS: Our study represents the first evaluation of OP exposure on risk of kidney stone formation, and these preliminary results suggest a potential role for OP exposure in the pathogenesis of kidney stone formation. Future studies are warranted to validate these findings, and to investigate potential mechanisms underlying these associations. Source of Funding: No funding © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e923 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Frank Glover More articles by this author Mohammad Hajiha More articles by this author Michael Eisenberg More articles by this author Federico Belladelli More articles by this author Francesco Del Giudice More articles by this author Nicolas Seranio More articles by this author Wade Muncey More articles by this author Kenneth Ogan More articles by this author Expand All Advertisement PDF downloadLoading ...

Pancreatic exocrine insufficiency is a risk factor for kidney stones in patients with chronic pancreatitis

IntroductionMost patients with chronic pancreatitis (CP) develop pancreatic exocrine insufficiency (PEI) over the course of the disease. PEI may lead to hyperoxaluria and development of urinary oxalate stones. It has been postulated that the patients with CP may be at increased risk of kidney stone formation, but the data is scarce. We aimed to estimate incidence and risk factors for nephrolithiasis in a Swedish cohort of patients with CP. Patients and methodsWe performed retrospective analysis of an electronical medical database of patients diagnosed with definite CP during 2003–2020. We excluded patients <18 years of age, those with missing relevant data in medical charts, patients with probable CP (according to the M-ANNHEIM classification system) and those in whom kidney stones were diagnosed before CP diagnosis. ResultsSome 632 patients with definite CP were followed over a median of 5.3 (IQR 2.4–6.9) years. There were 41 (6.5%) patients diagnosed with kidney stones, of whom 33 (80.5%) were symptomatic. Comparing to patients without kidney stones, patients with nephrolithiasis were older, with median age of 65 (IQR 51–72) years, and a male predominance (80% vs 63%). Cumulative incidence of kidney stones was 2.1%, 5.7%, 12.4% and 16.1% at 5, 10, 15, and 20 years after CP diagnosis, respectively. Multivariable cause-specific Cox regression analysis revealed PEI as independent risk factor for nephrolithiasis (adjusted HR 4.95, 95%CI 1.65–14.84; p = 0.004). Another risk factors were increase in BMI (aHR 1.16 95% CI 1.04–1.30; p = 0.001 per unit increment), and a male sex (4.51, 95% CI 1.01–20.3, p = 0.049). ConclusionPEI and increase in BMI are risk factors for kidney stone development in patients with CP. Male CP patents are particularly at increased risk of nephrolithiasis. This should be taken into consideration in general clinical approach to raise awareness among patients and medical workers.

Effect of Two Different Dietary Weight Loss Strategies on Risk Factors for Urinary Stone Formation and Cardiometabolic Risk Profile in Overweight Women

Overweight has been suggested to increase the risk of kidney stone formation. Although weight reduction might affect risk factors for urolithiasis, findings on the impact of different dietary weight loss strategies are limited. This randomized, controlled study evaluated the effect of a conventional energy-restricted modified diet with (MR group) or without meal replacement (C group) on risk factors for stone formation in overweight women without a history of urolithiasis. Of 105 participants, 78 were included into the per-protocol analysis. Anthropometric, clinical, biochemical, and 24 h urinary parameters were collected at baseline and after 12 weeks. Although both dietary interventions resulted in a significant weight reduction, relative weight loss and rate of responders were higher in the MR group. Weight loss improved cardiometabolic risk profile in both groups. Unfortunately, the benefit of decreased GPT activity in the C group was offset by a significant increase in homocysteine and a decline in GFR. While the relative supersaturation of calcium oxalate decreased significantly in both groups, a significant decline in serum uric acid concentration and relative supersaturation of uric acid was observed only in the MR group. Finally, the energy-restricted modified diet with meal replacement showed significant advantages over the energy-restricted modified diet alone.

The relationship between uric acid and dyslipidemia in type 2 diabetic patients with urolithiasis

Background and objective: Diabetes mellitus (DM) is characterized by insulin resistance which canincrease the risk of kidney stone formation. This study aimed to find out the association between serum levels of uric acid and lipid profile in DM patients with urolithiasis in comparison to those without. Methods: This cross-sectional study was conducted at P K Das institute of medical sciences,Vaniamkulam, Palakkad, Kerala, India with the approval of the institutional ethical review committee for human studies. A total of 60 patients were included in the study.Group A patients with DM and urolithiasis, and group B patients with DM but without urolithiasis. Biochemical parameters studied were glucose, urea, creatinine, uric acid, creatinine, serum uric acid to creatinine ratio, lipid profile, HbA1c, and triglyceride glucose index. Statistical analysis was done using SPSS version 21. Results: We found a significant increase in uric acid, urea, serum uric acid to creatinine ratio, and triglyceride glucose index levels in diabetic urolithiasis cases as compared to diabetes mellitus cases without urolithiasis. We also found that total cholesterol, triglycerides, LDL-C, and VLDL-C levels were significantly increased, and HDL-cholesterol was significantly decreased in diabetic urolithiasis cases. Serum uric acid was positively correlated with total cholesterol, triglycerides, LDL-C, and VLDL-C and negatively correlated with HDL-C in diabetic urolithiasis cases. Conclusions: From this study, it is demonstrated that patients with diabetic urolithiasis are having high insulin resistance, altered lipoprotein metabolism, and increased level of serum uric acid. The dyslipidemia components are strongly associated with increased uric acid.

The correlation between promoter hypermethylation of VDR, CLDN, and CasR genes and recurrent stone formation

ObjectivesRecurrent Kidney stone formation is a main medical problem imposing a significant burden on both healthcare and the economy worldwide. Environmental and genetic factors have been linked to a bigger risk of kidney stone formation. We aim to assess the role of methylation on recurrent stone formation in three target genes.MethodsWe aimed to check the association between promoter hypermethylation vitamin D receptor (VDR), calcium-sensing receptor (CaSR), and claudin 14 (CLDN14) genes in recurrent kidney stones. We enrolled 30 consecutive recurrent kidney stone formers (age 18–60 years) (cases) and 30 age and gender-matched controls.3. To identify promoter methylation, two target regions from each candidate gene were bisulfited after blood collection and DNA extraction. Methylation quantification was done through methylation-specific high resolution melting (MS-HRM).ResultsThe mean age of the patients and controls (mean ± SD) was 49.58 ± 14.23 years and BMI 36.12 ± 2.72. The methylation status in all six target regions was meaningfully different between the stone-former group and controls when methylation was considered in three clusters of unmethylated, methylated, and hypermethylated. A higher effect in VDR and CLDN was observed compare to CasR (p-value < 0.001, and < 0.005 versus p-value < 0.256).ConclusionsMethylation as an important epigenetic mechanism should be considered more in recurrent stone formations. Promoter hypermethylation of VRD and CLDN genes may have an essential role in recurrent kidney stones formations.

Association of water intake and hydration status with risk of kidney stone formation based on NHANES 2009-2012 cycles.

Evaluating the association of water intake and hydration status with nephrolithiasis risk at the population level. It is a cross-sectional study in which daily total plain water intake and total fluid intake were estimated together with blood osmolality, urine creatinine, urine osmolality, urine flow rate (UFR), free water clearance (FWC) and urine/blood osmolality ratio (Uosm:Bosm). The associations of fluid intake and hydration markers with nephrolithiasis were evaluated using multivariable logistic regression. General US population. A total of 8195 adults aged 20 years or older from the National Health and Nutritional Examination Survey 2009-2012 cycles. The population medians (interquartile ranges, IQR) for daily total plain water intake and total fluid intake were 807 (336-1481) and 2761 (2107-3577) ml/d, respectively. The adjusted OR (95 % CI) of nephrolithiasis for each IQR increase in total plain water intake and total fluid intake were 0·92 (95 % CI 0·79, 1·06) and 0·84 (95 % CI 0·72, 0·97), respectively. The corresponding OR of nephrolithiasis for UFR, blood osmolality, Uosm:Bosm and urine creatinine were 0·87 (95 % CI 0·76, 0·99), 1·18 (95 % CI 1·06, 1·32), 1·38 (95 % CI 1·17, 1·63) and 1·27 (95 % CI 1·11, 1·45), respectively. A linear protective relationship of fluid intake, UFR and FWC with nephrolithiasis risk was observed. Similarly, positive dose-response associations of nephrolithiasis risk with markers of insufficient hydration were identified. Encouraging a daily water intake of >2500 ml/d and maintaining a urine output of 2 l/d was associated with a lower prevalence of nephrolithiasis. This study verified the beneficial role of general water intake recommendations in nephrolithiasis prevention in the general US population.

The Association of Urine Creatinine With Kidney Stone Prevalence in US Adults: Data From NHANES 2009-2018.

BackgroundThe primary objective of this project is to explore the association of urine creatinine (UCR) with the prevalence rate of kidney stones.MethodThe National Health and Nutrition Examination Survey (NHANES) database was employed to conduct a cross-sectional study. The analysis samples included adults aged ≥20 years from five consecutive cycles of the NHANES 2009–2018. The association between UCR and kidney stones was detected using univariate and multivariate logistic regression analyses. Further, subgroup analyses were performed to evaluate the subgroup effects.ResultsAfter adjustment for all confounders, multiple logistic regression analysis revealed a weak positive relationship between UCR and kidney stone (OR = 1.015, 95% CI: 1.008–1.021). In the subgroup analysis stratified by sex, age, or race, the risk further increased in men (OR = 1.014, 95% CI: 1.005–1.023), women (OR = 1.015, 95% CI: 1.005–1.025), white race (OR = 1.022, 95% CI: 1.013–1.030), aged 40–59 years (OR = 1.017, 95% CI: 1.006–1.028), and aged 60–80 years (OR = 1.017, 95% CI: 1.006–1.028).ConclusionsOur results confirmed a moderately increased risk of kidney stone formation attributed to high levels of UCR, especially in middle-aged and older adults and the white race. However, because of the cross-sectional design of the study, causal inferences cannot be made.