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Hypercalcemia, hypercalciuria, and kidney stones in long-term studies of vitamin D supplementation: a systematic review and meta-analysis.
Malihi, Z, Wu, Z, Stewart, AW, Lawes, CM, Scragg, R
The American journal of clinical nutrition. 2016;(4):1039-1051
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Abstract
BACKGROUND Vitamin D supplementation is increasingly being used in higher doses in randomized controlled trials (RCTs). However, adverse events from very large annual doses of vitamin D have been shown in 2 RCTs, whereas in a third RCT, low-dose vitamin D, with calcium supplements, was shown to increase kidney stone risk. OBJECTIVE We analyzed the side effects related to calcium metabolism in RCTs, specifically hypercalcemia, hypercalciuria, and kidney stones, in participants who were given vitamin D supplements for ≥24 wk compared with in subjects in the placebo arm. DESIGN The following 3 main online databases were searched: Ovid Medline (PubMed), EMBASE, and the Cochrane Library. Software was used for the meta-analysis. RESULTS A total of 48 studies with 19,833 participants were identified, which reported ≥1 of the following side effects: hypercalcemia, hypercalciuria, or kidney stones. Of these studies, kidney stones were reported in only 9 trials with a tendency for fewer subjects reporting stones in the vitamin D arm than in the placebo arm (RR: 0.66, 95% CI: 0.41, 1.09; P = 0.10). In 37 studies, hypercalcemia was shown with increased risk shown for the vitamin D group (RR: 1.54; 95% CI: 1.09, 2.18; P = 0.01). Similar increased risk of hypercalciuria was shown in 14 studies for the vitamin D group (RR: 1.64; 95% CI: 1.06, 2.53; P = 0.03). In subgroup analyses, it was shown that the effect of vitamin D supplementation on risk of hypercalcemia, hypercalciuria, or kidney stones was not modified by baseline 25-hydroxyvitamin D, vitamin D dose and duration, or calcium co-supplementation. CONCLUSIONS Long-term vitamin D supplementation resulted in increased risks of hypercalcemia and hypercalciuria, which were not dose related. However, vitamin D supplementation did not increase risk of kidney stones. Additional large RCTs of long-term vitamin D supplementation are required to confirm these findings.
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Comparative effectiveness and safety of various treatment procedures for lower pole renal calculi: a systematic review and network meta-analysis.
Lee, SW, Chaiyakunapruk, N, Chong, HY, Liong, ML
BJU international. 2015;(2):252-64
Abstract
OBJECTIVE To compare the effectiveness of various treatments used for lower pole renal calculi. METHODS We searched PubMed, EMBASE, CINAHL, the Cochrane Collaboration's Database of Systematic Reviews, the Cochrane Collaboration Central Register of Controlled Clinical Trials as well as ClinicalTrials.gov for reports up to 1 April 2014. The search was supplemented with abstract reports from various urology conferences. All randomised, 'blinded' clinical studies including patients treated for lower pole renal calculi of <20 mm were included for review. Two authors independently reviewed 5 194 articles, and identified and selected 13 trials for analysis. Network meta-analysis was performed to generate comparative statistics, while quality was assessed with the Jadad composite scale and risk of bias. RESULTS All treatment methods examined: percutaneous nephrolithotomy (PNL), ureterorenoscopy (URS) and extracorporeal shockwave lithotripsy (SWL) with an adjuvant therapy (such as inversion, hydration and forced diuresis) were more effective than SWL therapy alone, with risk ratios (95% confidence intervals) of being stone free of: PNL 2.19 (1.62-2.96); URS 1.23 (1.03-1.48); and SWL with an adjuvant therapy 1.30 (1.03-1.63). However, patients treated with the other treatment methods also had a higher risk of adverse events (AEs) compared with SWL, but there was no evidence of a convincing difference between the various techniques and AEs. CONCLUSION In stones of <10 mm, SWL with an adjuvant therapy appears to have better stone clearance, lower risk of AEs, and need for further treatment. PNL was most effective treating larger stones, after considering both effectiveness and safety of treatment. These should be considered by both physicians and patients alike when considering the choice of treatment and in the revision of clinical practice guidelines.
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Medical expulsive therapy for pediatric urolithiasis: Systematic review and meta-analysis.
Velázquez, N, Zapata, D, Wang, HH, Wiener, JS, Lipkin, ME, Routh, JC
Journal of pediatric urology. 2015;(6):321-7
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Abstract
OBJECTIVE Kidney stone disease has become more common among children and young adults. Despite its well-documented success in adults, published success rates of medical expulsive therapy (MET) for pediatric urolithiasis vary widely. Our objective was to determine whether the aggregated evidence supports the use of MET in children. METHODS We searched the Cochrane Controlled Trials Register, clinicaltrials.gov, MEDLINE, and EMBASE databases, and recently presented meeting abstracts for reports in any language. In addition, the bibliographies of included studies were then hand-searched. The protocol was prospectively registered at PROSPERO (CRD42013005960). Inclusion criteria were children (aged ≤ 18 years) with urolithiasis treated with medications with the specific goal of increasing spontaneous stone passage rate, including but not limited to alpha-adrenergic blockers (e.g., tamsulosin or doxazosin), calcium channel blockers (e.g., nifedipine), or other adjuvant medications (e.g., steroids or tolterodine). Manuscripts were then assessed and data abstracted in duplicate, with differences resolved by the senior author. Risk of bias was assessed using standardized instruments. Descriptive statistical analyses were performed as appropriate. RESULTS We identified 11,197 studies, five of which (3 randomized controlled trials, 2 retrospective cohorts) were included in the pooled meta-analysis. Although we found little evidence of significant publication bias, we were unable to assess the likelihood of other forms of bias (allocation, selection) for most included studies due to reporting limitations. The pooled results demonstrate that MET significantly increased the odds of spontaneous stone passage (OR 2.21, 95% CI 1.40-3.49). Between-study heterogeneity was not statistically significant (I(2) = 14%, p = 0.36). Bivariate meta-regression models revealed no significant association between the likelihood of stone passage and study COI (p = 0.9), study country (p = 0.7), patient age (p = 0.4), patient gender (p = 0.4), duration of follow-up (p = 0.3), or stone size (p = 0.7). Side effects of MET were reported to be minimal. Relatively few patients reported any adverse effects at all; the most commonly reported issue was somnolence. Concerns about biases affecting the published outcomes of the included studies exist due to the low quality of the randomized controlled trials reviewed for analysis. However, there was little visual evidence of publication bias noted on the funnel plot, as confirmed by the Begg test (p = 0.5). CONCLUSIONS Consistent with the adult literature, pediatric studies demonstrate that treatment with MET results in increased odds of spontaneous ureteral stone passage and a low rate of adverse events. Although the accumulated literature is limited by inconsistent and/or incomplete reporting, there is nonetheless a clear, cumulative positive effect of MET on stone passage among children. The available evidence thus supports a prominent role for MET in treatment algorithms for pediatric urolithiasis.
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Self-Fluid Management in Prevention of Kidney Stones: A PRISMA-Compliant Systematic Review and Dose-Response Meta-Analysis of Observational Studies.
Xu, C, Zhang, C, Wang, XL, Liu, TZ, Zeng, XT, Li, S, Duan, XW
Medicine. 2015;(27):e1042
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Abstract
Epidemiologic studies have suggested that daily fluid intake that achieves at least 2.5 L of urine output per day is protective against kidney stones. However, the precise quantitative nature of the association between fluid intake and kidney stone risk, as well as the effect of specific types of fluids on such risk, are not entirely clear.We conducted a systematic review and dose-response meta-analysis to quantitatively assess the association between fluid intake and kidney stone risk. Based on a literature search of the PubMed, Embase, and Cochrane Library databases, 15 relevant studies (10 cohort and 5 case-control studies) were selected for inclusion in the meta-analysis with 9601 cases and 351,081 total participants.In the dose-response meta-analysis, we found that each 500 mL increase in water intake was associated with a significantly reduced risk of kidney stone formation (relative risk (RR) = 0.93; 95% CI: 0.87, 0.98; P < 0.01). Protective associations were also found for an increasing intake of tea (RR = 0.96; 95% CI: 0.93, 0.99; P = 0.02) and alcohol (RR = 0.80, 95% CI: 0.75, 0.85; P < 0.01). A borderline reverse association were observed on coffee intake and risk of kidney stone (RR = 0.88; 95% CI: 0.76, 1.00; P = 0.05). The risk of kidney stones was not significantly related to intake of juice (RR = 1.02, 95% CI: 0.95, 1.10; P = 0.64), soda (RR = 1.03; 95% CI: 0.90, 1.17; P = 0.65), or milk (RR = 0.96; 95% CI: 0.88, 1.03; P = 0.21). Subgroup analysis and sensitivity analyses showed inconsistent results on coffee, alcohol, and milk intake.Increased water intake is associated with a reduced risk of kidney stones; increased consumption of tea and alcohol may reduce kidney stone risk. An average daily water intake was recommended for kidney stone prevention.
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The Efficacy of Medical Expulsive Therapy (MET) in Improving Stone-free Rate and Stone Expulsion Time, After Extracorporeal Shock Wave Lithotripsy (SWL) for Upper Urinary Stones: A Systematic Review and Meta-analysis.
Skolarikos, A, Grivas, N, Kallidonis, P, Mourmouris, P, Rountos, T, Fiamegos, A, Stavrou, S, Venetis, C, ,
Urology. 2015;(6):1057-64
Abstract
In this meta-analysis, we included randomized studies on medical expulsive therapy implemented following shock wave lithotripsy for renal and ureteral stones. Pooled results demonstrated the efficacy of α-blockers, nifedipine, Rowatinex, and Uriston in increasing stone clearance. In addition, the time to stone elimination, the intensity of pain, the formation of steinstrasse, and the need for auxiliary procedures were reduced mainly with α-blockers. Expulsion rate was not correlated with the type of α-blocker, the diameter, and the location of stone. Our results show that medical expulsive therapy for residual fragments after shock wave lithotripsy should be implemented in clinical practice.
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Mutations in SLC34A3/NPT2c are associated with kidney stones and nephrocalcinosis.
Dasgupta, D, Wee, MJ, Reyes, M, Li, Y, Simm, PJ, Sharma, A, Schlingmann, KP, Janner, M, Biggin, A, Lazier, J, et al
Journal of the American Society of Nephrology : JASN. 2014;(10):2366-75
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Abstract
Compound heterozygous and homozygous (comp/hom) mutations in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium (Na(+))-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a disorder characterized by renal phosphate wasting resulting in hypophosphatemia, correspondingly elevated 1,25(OH)2 vitamin D levels, hypercalciuria, and rickets/osteomalacia. Similar, albeit less severe, biochemical changes are observed in heterozygous (het) carriers and indistinguishable from those changes encountered in idiopathic hypercalciuria (IH). Here, we report a review of clinical and laboratory records of 133 individuals from 27 kindreds, including 5 previously unreported HHRH kindreds and two cases with IH, in which known and novel SLC34A3 mutations (c.1357delTTC [p.F453del]; c.G1369A [p.G457S]; c.367delC) were identified. Individuals with mutations affecting both SLC34A3 alleles had a significantly increased risk of kidney stone formation or medullary nephrocalcinosis, namely 46% compared with 6% observed in healthy family members carrying only the wild-type SLC34A3 allele (P=0.005) or 5.64% in the general population (P<0.001). Renal calcifications were also more frequent in het carriers (16%; P=0.003 compared with the general population) and were more likely to occur in comp/hom and het individuals with decreased serum phosphate (odds ratio [OR], 0.75, 95% confidence interval [95% CI], 0.59 to 0.96; P=0.02), decreased tubular reabsorption of phosphate (OR, 0.41; 95% CI, 0.23 to 0.72; P=0.002), and increased serum 1,25(OH)2 vitamin D (OR, 1.22; 95% CI, 1.05 to 1.41; P=0.008). Additional studies are needed to determine whether these biochemical parameters are independent of genotype and can guide therapy to prevent nephrocalcinosis, nephrolithiasis, and potentially, CKD.
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Percussion, diuresis, and inversion therapy for the passage of lower pole kidney stones following shock wave lithotripsy.
Liu, LR, Li, QJ, Wei, Q, Liu, ZH, Xu, Y
The Cochrane database of systematic reviews. 2013;(12):CD008569
Abstract
BACKGROUND Lower pole kidney stones typically have poor rates of spontaneous clearance from the body. Some studies have suggested that diuresis, percussion and inversion therapy could be beneficial for people with lower pole kidney stones following shock wave lithotripsy. There is however controversy about the relative benefits, harms, and efficacy of these interventions for the management of lower pole kidney stones. OBJECTIVES To identify the benefits and harms of percussion, diuresis, and inversion therapy to facilitate the passage of lower pole kidney stones following shock wave lithotripsy. SEARCH METHODS We searched the Cochrane Renal Group's specialised register up to 27 November 2013 through contact with the Trials' Search Co-ordinator using search terms relevant to this review. SELECTION CRITERIA All randomised controlled trials (RCTs) and quasi-RCTs looking at the benefits and harms of percussion, diuresis, and inversion therapy for aiding passage of lower pole kidney stones following shock wave lithotripsy were sought for assessment. The first phases of randomised cross-over studies were also eligible for inclusion. DATA COLLECTION AND ANALYSIS Two authors independently assessed study quality and extracted data. Results were expressed as relative risk (RR) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS We identified two small studies (177 participants) for inclusion and analysis. One study (69 participants) compared percussion, diuresis and inversion therapy following shock wave lithotripsy versus observation-only after shock wave lithotripsy. This study reported significantly higher stone-free rates in the intervention group (RR 0.62, 95% CI 0.47 to 0.82) and a significant reduction in stone burden (MD -3.30, 95% CI -3.58 to -3.03) compared to the observation-only group. They reported no significant differences in complication rates (RR 3.00, 95% CI 0.12 to 76.24).The second study (108 participants) compared percussion, diuresis, and inversion therapy plus shock wave lithotripsy with shock wave lithotripsy therapy alone. This study reported significantly higher stone-free rates in the intervention group (RR 0.36, 95% CI 0.17 to 0.80) and a significant reduction in stone burden (MD -0.30, 95% CI -0.04 to -0.56) compared to the control group. They reported no significant differences in complication rates (RR 2.54, 95% CI 0.10 to 63.72).For both studies selection bias was unclear; there was high risk of bias for performance bias; and detection, attrition and reporting bias were low. AUTHORS' CONCLUSIONS Limited evidence from two small studies indicated that percussion, diuresis, and inversion therapy may be safe and effective therapies to assist clearance of lower pole kidney stone fragments following shock wave lithotripsy. Methodological quality in both studies was assessed as moderate. Further well-designed and adequately powered studies are required to inform clinical practice.