Risk of Metabolic Syndrome in Kidney Stone Formers: A Comparative Cohort Study with a Median Follow-Up of 19 Years.
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ABSTRACT: Background
Kidney stone formers (SF) are more likely to develop diabetes mellitus (DM), but there is no study examining risk of metabolic syndrome (MetS) in this population. We aimed to describe the risk of MetS in SF compared to non-SF.Methods and materials
SF referred to a tertiary referral metabolic centre in Southern England from 1990 to 2007, comparator patients were age, sex, and period (first stone) matched with 3:1 ratio from the same primary care database. SF with no documentation or previous MetS were excluded. Ethical approval was obtained and MetS was defined using the modified Association of American Clinical Endocrinologists (AACE) criteria. Analysis with cox proportional hazard regression.Results
In total, 828 SF were included after 1000 records were screened for inclusion, with 2484 age and sex matched non-SF comparators. Median follow-up was 19 years (interquartile range-IQR: 15-22) for both stone formers and stone-free comparators. SF were at significantly increased risk of developing MetS (hazard ratio-HR: 1.77; 95% confidence interval-CI: 1.55-2.03, p < 0.001). This effect was robust to adjustment for pre-existing components (HR: 1.91; 95% CI: 1.66-2.19, p < 0.001).Conclusions
Kidney stone formers are at increased risk of developing metabolic syndrome. Given the pathophysiological mechanism, the stone is likely a 'symptom' of an underlying metabolic abnormality, whether covert or overt. This has implications the risk of further stone events and cardiovascular disease.
SUBMITTER: Geraghty RM
PROVIDER: S-EPMC7957897 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population.Patients and methodsMedical records were manually reviewed and validated for symptomatic kidney stone episodes among Olmsted County, Minnesota, residents from January 1, 1984, through December 31, 2012. Clinical and laboratory characteristics and the risk of symptomatic recurrence were compared between stone compositions.ResultsThere were 2961 validated first-time symptomatic kidney stone formers. Stone composition analysis was obtained in 1508 (51%) at the first episode. Stone formers were divided into the following mutually exclusive groups: any brushite (0.9%), any struvite (0.9%), any uric acid (4.8%), and majority calcium oxalate (76%) or majority hydroxyapatite (18%). Stone composition varied with clinical characteristics. A multivariable model had a 69% probability of correctly estimating stone composition but assuming calcium oxalate monohydrate stone was correct 65% of the time. Symptomatic recurrence at 10 years was approximately 50% for brushite, struvite, and uric acid but approximately 30% for calcium oxalate and hydroxyapatite stones (P<.001). Recurrence was similar across different proportions of calcium oxalate and hydroxyapatite (P for trend=.10). However, among calcium oxalate stones, 10-year recurrence rate ranged from 38% for 100% calcium oxalate dihydrate to 26% for 100% calcium oxalate monohydrate (P for trend=.007).ConclusionCalcium stones are more common (93.5% of stone formers) than has been previously reported. Although clinical and laboratory factors associate with the stone composition, they are of limited utility for estimating stone composition. Rarer stone compositions are more likely to recur.
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Project description:Background and objectivesPrior work has suggested a higher risk of hypertension in kidney stone formers but lacked disease validation and adjustment for potential confounders. Certain types of stone formers may also be at higher risk of hypertension.Design, setting, participants, & measurementsIn our study, incident symptomatic stone formers in Olmsted County from 2000 to 2011 were manually validated by chart review and age and sex matched to Olmsted County controls. We followed up patients through November 20, 2015. Hypertension was also validated by manual chart review, and the risk of hypertension in stone formers compared with controls was assessed both univariately and after adjusting for comorbidities. The risk of hypertension among different subtypes of stone formers was also evaluated.ResultsAmong 3023 coded stone formers from 2000 to 2011, a total of 1515 were validated and matched to 1515 controls (mean age was 45 years old, and 56% were men). After excluding those with baseline hypertension (20% of stone formers and 18% of controls), 154 stone formers and 110 controls developed hypertension. Median follow-up time was 7.8 years in stone formers and 9.6 years in controls. Stone formers were found to have a higher risk of hypertension compared with controls (hazard ratio, 1.50; 95% confidence interval, 1.18 to 1.92), even after adjusting for age, sex, body mass index, serum creatinine, CKD, diabetes, gout, coronary artery disease, dyslipidemia, tobacco use, and alcohol abuse (hazard ratio, 1.58; 95% confidence interval, 1.12 to 2.21). Results were similar after excluding patients who were ever on a thiazide diuretic (hazard ratio, 1.65; 95% confidence interval, 1.16 to 2.38). Stone composition, radiographic stone burden, number of subsequent stone events, and stone removal surgeries were not associated with hypertension (P>0.05 for all).ConclusionsThe risk of hypertension was higher after the first symptomatic kidney stone event. However, kidney stone severity, type, and treatment did not associate with hypertension.
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Project description:RATIONALE & OBJECTIVES:Kidney stones have been associated with increased risk for end-stage renal disease (ESRD). However, it is unclear whether there is also an increased risk for mortality and if these risks are uniform across clinically distinct categories of stone formers. STUDY DESIGN:Historical matched-cohort study. SETTING & PARTICIPANTS:Stone formers in Olmsted County, MN, between 1984 and 2012 identified using International Classification of Diseases, Ninth Revision codes. Age- and sex-matched individuals who had no codes for stones were the comparison group. PREDICTOR:Stone formers were placed into 5 mutually exclusive categories after review of medical charts: incident symptomatic kidney, recurrent symptomatic kidney, asymptomatic kidney, bladder only, and miscoded (no stone). OUTCOMES:ESRD, mortality, cardiovascular mortality, and cancer mortality. ANALYTICAL APPROACH:Cox proportional hazards models with adjustment for baseline comorbid conditions. RESULTS:Overall, 65 of 6,984 (0.93%) stone formers and 102 of 28,044 (0.36%) non-stone formers developed ESRD over a mean follow-up of 12.0 years. After adjusting for baseline hypertension, diabetes mellitus, dyslipidemia, gout, obesity, and chronic kidney disease, risk for ESRD was higher in recurrent symptomatic kidney (HR, 2.34; 95% CI, 1.08-5.07), asymptomatic kidney (HR, 3.94; 95% CI, 1.65-9.43), and miscoded (HR, 6.18; 95% CI, 2.25-16.93) stone formers, but not in incident symptomatic kidney or bladder stone formers. The adjusted risk for all-cause mortality was higher in asymptomatic kidney (HR, 1.40; 95% CI, 1.18-1.67) and bladder (HR, 1.37; 95% CI, 1.12-1.69) stone formers. Chart review of asymptomatic and miscoded stone formers suggested increased risk for adverse outcomes related to diagnoses including urinary tract infection, cancer, and musculoskeletal or gastrointestinal pain. CONCLUSIONS:The higher risk for ESRD in recurrent symptomatic compared with incident symptomatic kidney stone formers suggests that stone events are associated with kidney injury. The clinical indication for imaging in asymptomatic stone formers, the correct diagnosis in miscoded stone formers, and the cause of a bladder outlet obstruction in bladder stone formers may explain the higher risk for ESRD or death in these groups.
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Project description:The spectrum of diseases with overactive renin-angiotensin-aldosterone system (RAS) or elevated circulating FGF23 overlaps, but the relationship between aldosterone and FGF23 remains unclarified. Here, we report that systemic RAS activation sensitively assessed by urinary tetrahydroaldosterone excretion is associated with circulating C-terminal FGF23. We performed a retrospective analysis in the Bern Kidney Stone Registry, a single-center observational cohort of kidney stone formers. Urinary excretion of the main aldosterone metabolite tetrahydroaldosterone was measured by gas chromatography-mass spectrometry. Plasma FGF23 concentrations were measured using a C-terminal assay. Regression models were calculated to assess the association of plasma FGF23 with 24 h urinary tetrahydroaldosterone excretion. We included 625 participants in the analysis. Mean age was 47 ± 14 years and 71% were male. Mean estimated GFR was 94 ml/min per 1.73 m2. In unadjusted analyses, we found a positive association between plasma FGF23 and 24 h urinary tetrahydroaldosterone excretion (β: 0.0027; p = 4.2 × 10-7). In multivariable regression models adjusting for age, sex, body mass index and GFR, this association remained robust (β: 0.0022; p = 2.1 × 10-5). Mineralotropic hormones, 24 h urinary sodium and potassium excretion as surrogates for sodium and potassium intake or antihypertensive drugs did not affect this association. Our data reveal a robust association of RAS activity with circulating FGF23 levels in kidney stone formers. These findings are in line with previous studies in rodents and suggest a physiological link between RAS system activation and FGF23 secretion.
| S-EPMC9110437 | biostudies-literature
Project description:BackgroundsPrevious studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium oxalate stone formers (CSFs) compared to non-stone formers (NSFs).MethodsBiobanked urine samples from CSFs (n = 24) undergoing stone removal surgery and age- and sex- matched NSFs (n = 21) were studied. Urinary EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.ResultsUrine excretion of calcium, oxalate, phosphorus, and calcium oxalate supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion, whereas excretion of EVs expressing FGF23 negatively (P < 0.05) correlated with both urinary calcium and phosphorus excretion. Urinary EVs with markers of HIP1 and ANO4 correlated negatively (P < 0.05) with clinical stone events and basement membrane calcifications on papillary tip biopsies.ConclusionsUrinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation differed between CSFs and NSFs. Further validation of these and other populations of urinary EVs in larger cohort could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.
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Project description:Elevated serum 1,25-dihydroxyvitamin D (1,25(OH)2D) concentrations have been reported among cohorts of recurrent calcium (Ca) kidney stone-formers and implicated in the pathogenesis of hypercalciuria. Variations in Ca and vitamin D metabolism, and excretion of urinary solutes among first-time male and female Ca stone-formers in the community, however, have not been defined.In a 4-year community-based study we measured serum Ca, phosphorus (P), 25-hydroxyvitamin D (25(OH)D), 1,25(OH)2D, 24,25-dihydroxyvitamin D (24,25(OH)2D), parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF-23) concentrations in first-time Ca stone-formers and age- and gender frequency-matched controls.Serum Ca and 1,25(OH)2D were increased in Ca stone-formers compared to controls (P = 0.01 and P = 0.001). Stone-formers had a lower serum 24,25(OH)2D/25(OH)D ratio compared to controls (P = 0.008). Serum PTH and FGF-23 concentrations were similar in the groups. Urine Ca excretion was similar in the two groups (P = 0.82). In controls, positive associations between serum 25(OH)D and 24,25(OH)2D, FGF-23 and fractional phosphate excretion, and negative associations between serum Ca and PTH, and FGF-23 and 1,25(OH)2D were observed. In SF associations between FGF-23 and fractional phosphate excretion, and FGF-23 and 1,25(OH)2D, were not observed. 1,25(OH)2D concentrations associated more weakly with FGF-23 in SF compared with C (P <0.05).Quantitative differences in serum Ca and 1,25(OH)2D and reductions in 24-hydroxylation of vitamin D metabolites are present in first-time SF and might contribute to first-time stone risk.
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Project description:BackgroundKidney stones are a frequent and potentially severe condition, affecting 5-10% of the European population. Causes are multifactorial, diet in particular plays a major role in the formation and management of kidney stones. The aim of this scoping review is to assess the methods used to study the diet of adult kidney stone formers.MethodsWe conducted a systematic search in Medline Ovid SP, Embase, Cinahl, Cochrane (CENTRAL), Web of Sciences databases on June 10th, 2020. Self-report methods (such as food frequency questionnaires or 24-h dietary recalls), objective nutritional biomarkers and controlled diets were considered. We analyzed the selected publications based on the origin of participants, study design and dietary assessment methods used.ResultsWe screened 871 publications and included 162 of them. Most studies included participants from North America and Europe and were observational. Short and cost-effective tools such as food frequency questionnaires and other questionnaires were the most frequently used. Moreover, food diary was a frequently selected method to study the diet of kidney stone formers. New technologies (e.g. online questionnaires, phone applications, connected tools) were rarely used.ConclusionAccurate reporting of the methods used in nutritional studies is of key importance to interpret results and build evidence. Assessing long-term dietary intake is still a challenge for nutritional epidemiology. A combination of self-report methods with objective dietary biomarkers and new technologies probably represents the best way forward.
| S-EPMC8995246 | biostudies-literature
Project description:Sodium thiosulfate (STS) reduced calcium stone formation in both humans and genetic hypercalciuric stone forming (GHS) rats. We sought to measure urine chemistry changes resulting from STS administration in people. DESIGN SETTING PARTICIPANTS MEASUREMENTS: STS was given to healthy and hypercalciuric stone forming adults. Five normal non-stone forming adults (mean age 33 years), and 5 people with idiopathic hypercalciuria and calcium kidney stones (mean age 66 years) participated. Two baseline 24-hour urine collections were performed on days 2 and 3 of 3 days of self-selected diets. Subjects then drank STS 10 mmol twice a day for 7 days and did urine collections while repeating the self-selected diet. Results were compared by non-parametric Wilcoxon signed rank test. The primary outcome was the resulting change in urine chemistry.STS administration did not cause a significant change in urinary calcium excretion in either group. In both groups, 24 hour urinary ammonium (P = 0.005) and sulfate excretion (P = 0.007) increased, and urinary pH fell (P = 0.005); citrate excretion fell (P<0.05) in hypercalciuric participants but not in non-stone formers. Among stone formers with hypercalciuria, 3 of 5 patients had measurement of serum HCO3 concentration after the STS period: it did not change. The net effect was an increase in supersaturation of uric acid, and no change in supersaturation of calcium oxalate or calcium phosphate.The basis for studies demonstrating that STS prevented stones in rats and people was not reflected by the changes in urine chemistry reported here. Although serum HCO3 did not change, urine tests suggested an acid load in both non-stone forming and hypercalciuric stone-forming participants. The long term safety of STS needs to be determined before the drug can be tested in humans for long-term prevention of stone recurrence.
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Project description:ObjectivesTo examine the longitudinal associations between fitness and metabolic syndrome (MetS) in community-dwelling adults over 29 years of follow-up.DesignOngoing, population-based cohort study of adults aged ≥ 33 years at baseline residing in the city of Bad Schönborn, Germany.MethodsThe sample comprised 89 persons (41 females; mean age 40.1 years at baseline) who participated at baseline (in the year 1992) and 29-years follow-up (in the year 2021). Fitness (predictor variable) was assessed using 15 standardized and validated tests that measured strength, gross motor coordination, mobility/ flexibility and cardiorespiratory fitness/ endurance, and a z-transformed fitness score was calculated for analysis. MetS (outcome of interest) was assessed through five criteria related to waist circumference, blood glucose, HDL cholesterol, triglycerides, and blood pressure, and a sum score was created for analysis. We ran partial correlations to examine the association between fitness score at baseline and MetS score at 29-years follow-up, adjusted for age, sex, socio-economic status, smoking status, sleep quality, and physical activity engagement in minutes/ week.ResultsA higher fitness score at baseline was significantly associated with a lower MetS score indicative of better metabolic health at 29-years follow-up (r=-0.29; p = 0.011). These associations were present in participants aged ≤ 40 years (r=-0.33; p = 0.025) as well as those aged > 40 years (r=-0.43; p = 0.045).ConclusionsFitness may be a predictor of longitudinal metabolic health, and potentially also mediates previously reported longitudinal associations between physical activity and metabolic health. More research is needed to confirm these observations, and to also explore underlying mechanisms.
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Project description:Here we define precision medicine approaches and discuss how these may be applied to renal stone-formers to optimise diagnosis and a management. Using the gene discovery of monogenic stone disorders as examples, we discuss the benefits of personalising therapies for renal stone-formers to provide improved prevention and treatment of these disorders.
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