To determine the variation in kidney stone composition and its association with risk factors and recurrence among first-time stone formers in the general population.
Medical 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.
There 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).
Calcium 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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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.
Historical matched-cohort study.
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.
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).
ESRD, mortality, cardiovascular mortality, and cancer mortality.
Cox proportional hazards models with adjustment for baseline comorbid conditions.
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.
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.
Background Several registry-based studies, using diagnostic codes, have suggested that preeclampsia is a risk factor for end-stage renal disease (ESRD). However, because the 2 diseases share risk ...factors, the true nature of their association remains uncertain. Our goals were to conduct a population-based study to determine the magnitude of the association between preeclampsia and ESRD and evaluate the role of shared risk factors. Study Design Population-based nested case-control study. Setting & Participants The US Renal Data System was used to identify women with ESRD from a cohort of 34,581 women who gave birth in 1976 to 2010 in Olmsted County, MN. 44 cases of ESRD were identified and each one was matched to 2 controls based on year of birth (±1 year), age at first pregnancy (±2 years), and parity (±1 or ≥4). Predictor Preeclamptic pregnancy, confirmed by medical record review. Outcome ESRD. Measurements Prepregnancy serum creatinine and urine protein measurements were recorded. Comorbid conditions existing prior to pregnancy were abstracted from medical records and included kidney disease, obesity, diabetes, and hypertension. Results There was evidence of kidney disease prior to the first pregnancy in 9 of 44 (21%) cases and 1 of 88 (<1%) controls. Per chart review, 8 of 44 (18%) cases versus 4 of 88 (5%) controls had preeclamptic pregnancies (unadjusted OR, 4.0; 95% CI, 1.21-13.28). Results were similar after independent adjustment for race, education, diabetes, and hypertension prior to pregnancy. However, the association was attenuated and no longer significant after adjustment for obesity (OR, 3.25; 95% CI, 0.93-11.37). Limitations The limited number of ESRD cases and missing data for prepregnancy kidney function. Conclusions Our findings confirm that there is a sizable association between preeclampsia and ESRD; however, obesity is a previously unexplored confounder. Pre-existing kidney disease was common, but not consistently coded or diagnosed.
Since plasma oxalate (POx) concentrations increase at lower glomerular filtration rate (GFR) levels, even among those without enteric (EH) or primary hyperoxaluria (PH), the appropriate thresholds ...for considering a disorder of oxalate metabolism are poorly defined. The current study was completed to establish relationships between POx, GFR, and urine oxalate excretion (UOx) among patients with PH, EH, and routine urinary stone disease (USD).
The most recent POx measurement on all Mayo Clinic patients between 2005 and 2015 were electronically pulled from the Lab Information System together with the closest serum creatinine within 14days and 24h urine study within 60days. After exclusion of patients not in steady state at the time of blood draw, 270 patients were available for study. Records were reviewed for clinical diagnoses to categorize patients as PH, EH, or USD. Waste plasma for Pox was also obtained from controls without USD undergoing clinical GFR testing.
In all 3 groups POx increased as eGFR fell. For any given eGFR, POx was highest in the PH group and lowest in the USD and control groups (p<0.0001). POx was also influenced by UOx excretion (reflecting total body oxalate burden, absorption from diet and endogenous production). Generalized estimating equations of POx vs eGFR revealed higher average POx levels in PH compared to EH,USD or control, and for EH compared to USD or control. GEE prediction models were created that use POx, UOx, age, and serum creatinine to estimate the probability of a PH diagnosis.
New models were developed to help interpret POx when considering PH in clinical practice even when it was not previously suspected and/or eGFR is reduced.
•Relationships between plasma oxalate, GFR and urine oxalate are established among patients with PH, EH and stone disease.•New models help interpret plasma oxalate when considering PH.•The models also help identify PH even when not suspected or when eGFR is reduced.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To predict symptomatic recurrence among community stone formers with one or more previous stone episodes.
A random sample of incident symptomatic kidney stone formers in Olmsted County, Minnesota, ...was followed for all symptomatic stone episodes resulting in clinical care from January 1, 1984, through January 31, 2017. Clinical and radiographic characteristics at each stone episode predictive of subsequent episodes were identified.
There were 3364 incident kidney stone formers with 4951 episodes. The stone recurrence rates per 100 person-years were 3.4 (95% CI, 3.2-3.7) after the first episode, 7.1 (95% CI, 6.4-7.9) after the second episode, 12.1 (95% CI, 10.3-13.9) after the third episode, and 17.6 (95% CI, 15.1-20.0) after the fourth or higher episode (P<.001 for trend). A parsimonious model identified the following independent risk factors for recurrence: younger age; male sex; higher body mass index; family history of stones; pregnancy; incident asymptomatic stone on imaging before the first episode; suspected stone episode before the first episode; history of a brushite, struvite, or uric acid stone; no history of calcium oxalate monohydrate stone; kidney pelvic or lower pole stone on imaging; no ureterovesical junction stone on imaging; number of kidney stones on imaging; and diameter of the largest kidney stone on imaging. The model had a C-index corrected for optimism of 0.681 and was used to develop a prediction tool. The risk of recurrence in 5 years ranged from 0.9% to 94%, depending on risk factors, number of past episodes, and years since the last episode.
The revised Recurrence Of Kidney Stone tool predicts the risk of symptomatic recurrence by using readily available clinical characteristics of stone formers.
Antibiotics modify human microbiomes and may contribute to kidney stone risk. In a population-based case-control study using 1247 chart-validated first-time symptomatic kidney stone formers and 4024 ...age- and sex-matched controls, the risk of kidney stones was transiently higher during the first year after antibiotic use. However, this risk was no longer evident after adjustment for comorbidities and excluding participants with prior urinary symptoms. Findings were consistent across antibiotic classes and the number of antibiotic courses received. This suggests that antibiotics are not important risk factors of kidney stones. Rather, kidney stones when they initially cause urinary symptoms are under-recognized, resulting in antibiotic use before a formal diagnosis of kidney stones ( i.e. , reverse causality).
Antibiotics modify gastrointestinal and urinary microbiomes, which may contribute to kidney stone formation. This study examined whether an increased risk of a first-time symptomatic kidney stone episode follows antibiotic use.
A population-based case-control study surveyed 1247 chart-validated first-time symptomatic kidney stone formers with a documented obstructing or passed stone (cases) in Olmsted County, Minnesota, from 2008 to 2013 and 4024 age- and sex-matched controls. All prescriptions for outpatient oral antibiotic use within 5 years before the onset of symptomatic stone for the cases and their matched controls were identified. Conditional logistic regression estimated the odds ratio (OR) of a first-time symptomatic kidney stone across time after antibiotic use. Analyses were also performed after excluding cases and controls with prior urinary tract infection or hematuria because urinary symptoms resulting in antibiotic prescription could have been warranted because of undiagnosed kidney stones.
The risk of a symptomatic kidney stone was only increased during the 1-year period after antibiotic use (unadjusted OR, 1.31; P = 0.001), and this risk was attenuated after adjustment for comorbidities (OR, 1.16; P = 0.08). After excluding cases and controls with prior urinary symptoms, there was no increased risk of a symptomatic kidney stone during the 1-year period after antibiotic use (unadjusted OR, 1.04; P = 0.70). Findings were consistent across antibiotic classes and the number of antibiotic courses received.
The increased risk of a first-time symptomatic kidney stone with antibiotic use seems largely due to both comorbidities and prescription of antibiotics for urinary symptoms. Under-recognition of kidney stones that initially cause urinary symptoms resulting in antibiotic use may explain much of the perceived stone risk with antibiotics ( i.e. , reverse causality).
The urine metabolites and chemistries that contribute to kidney stone formation are not fully understood. This study examined differences between the urine metabolic and chemistries profiles of ...first-time stone formers and controls.
High-resolution
H-nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was performed in 24-hour urine samples from a prospective cohort of 418 first-time symptomatic kidney stone formers and 440 controls. In total, 48 NMR-quantified metabolites in addition to 12 standard urine chemistries were assayed. Analysis of covariance was used to determine the association of stone former status with urine metabolites or chemistries after adjusting for age and sex and correcting for the false discovery rate. Gradient-boosted machine methods with nested cross-validation were applied to predict stone former status.
Among the standard urine chemistries, stone formers had lower urine oxalate and potassium and higher urine calcium, phosphate, and creatinine. Among NMR urine metabolites, stone formers had lower hippuric acid, trigonelline, 2-furoylglycine, imidazole, and citrate and higher creatine and alanine. A cross-validated model using urine chemistries, age, and sex yielded a mean AUC of 0.76 (95% CI, 0.73 to 0.79). A cross-validated model using urine chemistries, NMR-quantified metabolites, age, and sex did not meaningfully improve the discrimination (mean AUC, 0.78; 95% CI, 0.75 to 0.81). In this combined model, among the top ten discriminating features, four were urine chemistries and six NMR-quantified metabolites.
Although NMR-quantified metabolites did not improve discrimination, several urine metabolic profiles were identified that may improve understanding of kidney stone pathogenesis.
This retrospective analysis investigated plasma oxalate (POx) as a potential predictor of end-stage kidney disease (ESKD) among primary hyperoxaluria (PH) patients. PH patients with type 1, 2, and 3, ...age 2 or older, were identified in the Rare Kidney Stone Consortium (RKSC) PH Registry. Since POx increased with falling estimated glomerular filtration rate (eGFR), patients were stratified by chronic kidney disease (CKD) subgroups (stages 1, 2, 3a, and 3b). POx values were categorized into quartiles for analysis. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for risk of ESKD were estimated using the Cox proportional hazards model with a time-dependent covariate. There were 118 patients in the CKD1 group (nine ESKD events during follow-up), 135 in the CKD 2 (29 events), 72 in CKD3a (34 events), and 45 patients in CKD 3b (31 events). During follow-up, POx Q4 was a significant predictor of ESKD compared to Q1 across CKD2 (HR 14.2, 95% CI 1.8-115), 3a (HR 13.7, 95% CI 3.0-62), and 3b stages (HR 5.2, 95% CI 1.1-25),
< 0.05 for all. Within each POx quartile, the ESKD rate was higher in Q4 compared to Q1-Q3. In conclusion, among patients with PH, higher POx concentration was a risk factor for ESKD, particularly in advanced CKD stages.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background Uterine fibroids are a common problem for reproductive-aged women, yet little comparative effectiveness research is available to guide treatment choice. Uterine artery embolization and ...magnetic resonance imaging–guided focused ultrasound surgery are minimally invasive therapies approved by the US Food and Drug Administration for treating symptomatic uterine fibroids. The Fibroid Interventions: Reducing Symptoms Today and Tomorrow study is the first randomized controlled trial to compare these 2 fibroid treatments. Objective The objective of the study was to summarize treatment parameters and compare recovery trajectory and adverse events in the first 6 weeks after treatment. Study Design Premenopausal women with symptomatic uterine fibroids seen at 3 US academic medical centers were enrolled in the randomized controlled trial (n = 57). Women meeting identical criteria who declined randomization but agreed to study participation were enrolled in a nonrandomized parallel cohort (n = 34). The 2 treatment groups were analyzed by using a comprehensive cohort design. All women undergoing focused ultrasound and uterine artery embolization received the same postprocedure prescriptions, instructions, and symptom diaries for comparison of recovery in the first 6 weeks. Return to work and normal activities, medication use, symptoms, and adverse events were captured with postprocedure diaries. Data were analyzed using the Wilcoxon rank sum test or χ2 test. Multivariable regression was used to adjust for baseline pain levels and fibroid load when comparing opioid medication, adverse events, and recovery time between treatment groups because these factors varied at baseline between groups and could affect outcomes. Adverse events were also collected. Results Of 83 women in the comprehensive cohort design who underwent treatment, 75 completed postprocedure diaries. Focused ultrasound surgery was a longer procedure than embolization (mean SD, 405 146 vs 139 44 min; P <. 001). Of women undergoing focused ultrasound (n = 43), 23 (53%) underwent 2 treatment days. Immediate self-rated postprocedure pain was higher after uterine artery embolization than focused ultrasound (median interquartile range, 5 1–7 vs 1 1–4; P = . 002). Compared with those having focused ultrasound (n = 39), women undergoing embolization (n = 36) were more likely to use outpatient opioid (75% vs 21%; P < . 001) and nonsteroidal antiinflammatory medications (97% vs 67%; P < . 001) and to have a longer median (interquartile range) recovery time (days off work, 8 6–14 vs 4 2–7; P < . 001; days until return to normal, 15 10–29 vs 10 10–15; P = . 02). There were no significant differences in the incidence or severity of adverse events between treatment arms; 86% of adverse events (42 of 49) required only observation or nominal treatment, and no events caused permanent sequelae or death. After adjustment for baseline pain and uterine fibroid load, uterine artery embolization was still significantly associated with higher opioid use and longer time to return to work and normal activities ( P < . 001 for each). Results were similar when restricted to the randomized controlled trial. Conclusion Women undergoing uterine artery embolization have longer recovery times and use more prescription medications, but women undergoing focused ultrasound have longer treatment times. These findings were independent of baseline pain levels and fibroid load.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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