Background: Optimum management to prevent recurrent kidney stones is uncertain.Purpose: To evaluate the benefits and harms of interventions to prevent recurrent kidney stones.Data Sources: MEDLINE, Cochrane, and other databases through September 2012 and reference lists of systematic reviews and randomized, controlled trials (RCTs).Study Selection: 28 English-language RCTs that studied treatments to prevent recurrent kidney stones and reported stone outcomes. Data Extraction:One reviewer extracted data, a second checked accuracy, and 2 independently rated quality and graded strength of evidence. Data Synthesis:In patients with 1 past calcium stone, low-strength evidence showed that increased fluid intake halved recurrent composite stone risk compared with no treatment (relative risk [RR], 0.45 [95% CI, 0.24 to 0.84]). Low-strength evidence showed that reducing soft-drink consumption decreased recurrent symptomatic stone risk (RR, 0.83 [CI, 0.71 to 0.98]). In patients with multiple past calcium stones, most of whom were receiving increased fluid intake, moderate-strength evidence showed that thiazides (RR, 0.52 [CI, 0.39 to 0.69]), citrates (RR, 0.25 [CI, 0.14 to 0.44]), and allopurinol (RR, 0.59 [CI, 0.42 to 0.84]) each further reduced composite stone recurrence risk compared with placebo or control, although the benefit from allopurinol seemed limited to patients with baseline hyperuricemia or hyperuricosuria. Other baseline biochemistry measures did not allow prediction of treatment efficacy. Low-strength evidence showed that neither citrate nor allopurinol combined with thiazide was superior to thiazide alone. There were few withdrawals among patients with increased fluid intake, many among those with other dietary interventions and more among those who received thiazide and citrate than among control patients. Reporting of adverse events was poor.Limitations: Most trial participants had idiopathic calcium stones. Nearly all studies reported a composite (including asymptomatic) stone recurrence outcome. Conclusion:In patients with 1 past calcium stone, increased fluid intake reduced recurrence risk. In patients with multiple past calcium stones, addition of thiazide, citrate, or allopurinol further reduced risk. Primary Lifetime incidence of kidney stones is approximately 13% for men and 7% for women (1, 2). Although often asymptomatic-incidental stones are identified in approximately 5% of individuals who have abdominal ultrasonography or computed tomography imaging (3, 4)-stones may cause renal colic, urinary tract obstruction, and procedure-related illness. In patients with asymptomatic stones who are followed with serial radiography, 11% to 32% develop symptoms or undergo a procedure within 3 to 4 years (5-7). After a symptomatic stone event, the 5-year recurrence rate is 35% to 50% without specific treatment (8). Annual direct costs in the United States may exceed $4.5 billion (1, 9).About 80% of kidney stones are composed of calcium oxalate, calcium phosphate, or both; uric acid and struvite stones are...

Biology has taught us that a protein as abundantly made and conserved among species as Tamm-Horsfall protein (THP or uromodulin) cannot just be a waste product serving no particular purpose. However, for many researchers, THP is merely a nuisance during urine proteome profiling or exosome purification and for clinicians an enigmatic entity without clear disease implications. Thanks to recent human genetic and correlative studies and animal modeling, we now have a renewed appreciation of this highly prevalent protein in not only guarding urinary homeostasis, but also serving as a critical mediator in systemic interorgan signaling. Beyond a mere barrier that lines the tubules, or a surrogate for nephron mass, mounting evidence suggests that THP is a multifunctional protein critical for modulating renal ion channel activity, salt/water balance, renal and systemic inflammatory response, intertubular communication, mineral crystallization and bacterial adhesion. Indeed, mutations in THP cause a group of inherited kidney diseases, and altered THP expression is associated with increased risks of urinary tract infection, kidney stone, hypertension, hyperuricemia and acute and chronic kidney diseases. Despite the recent surge of information surrounding THP's physiological functions and disease involvement, our knowledge remains incomplete regarding how THP is normally regulated by external and intrinsic factors, how precisely THP deficiency leads to urinary and systemic pathophysiology and in what clinical settings THP can be used as a theranostic biomarker and a target for modulation to improve patient outcomes.

Context-Although numerous trials have evaluated efficacy of diet, fluid, or supplement interventions for secondary prevention of nephrolithiasis, few are included in previous systematic reviews or referenced in recent nephrolithiasis management guidelines. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Take-home messageHigh water intake reduces recurrent nephrolithiasis risk, and reduced soft drink intake may prevent recurrent colic in men with high baseline soft drink consumption. Data on other diet interventions are inconclusive, although limited data suggest possible benefit from dietary calcium.Financial disclosures: I certify that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: noneThe views expressed in this article are those of the authors and do not necessarily represent the views of the US Department of Veterans Affairs. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptObjective-To determine efficacy and safety of diet, fluid, or supplement interventions for secondary prevention of nephrolithiasis.Evidence acquisition-Systematic review and meta-analysis of trials published January 1950 to March 2008. Sources included Medline and bibliographies of retrieved articles. Eligible trials included adults with a history of nephrolithiasis; compared diet, fluids, or supplements with control; compared relevant outcomes between randomized groups (eg, stone recurrence); had ≥3 mo follow-up; and were published in the English language. Data were extracted on participant and trial characteristics, including study methodologic quality.Evidence synthesis-Eight trials were eligible (n = 1855 participants). Study quality was mixed. In two trials, water intake >2 l/d or fluids to achieve urine output >2.5 l/d reduced stone recurrence (relative risk: 0.39; 95% confidence interval: 0.19-0.80). In one trial, fewer high soft drink consumers assigned to reduced intake had renal colic than controls (34% vs 41%, p = 0.023).Content and results of multicomponent dietary interventions were heterogeneous; in one trial, fewer participants assigned increased dietary calcium, low animal protein, and low sodium had stone recurrence versus controls (20% vs 38%, p = 0.03), while in another trial, more participants assigned diets that incl...

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Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end stage renal disease (ESRD), and in a random sub-cohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/mL. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each standard deviation higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77, (95% CI 0.62, 0.96)) and a 10% lower risk of mortality (hazard ratio 0.90, (95% CI 0.83, 0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.

Persons with chronic kidney disease (CKD) are at a higher risk of developing peripheral artery disease (PAD) and its adverse health outcomes than individuals in the general population who have normal renal function. Classic atherosclerosis risk factors care (e.g., age, smoking, diabetes, hypertension and hyperlipidemia) are common in CKD patients, but CKD also imposes additional unique risk factors that promote arterial disease (e.g., chronic inflammation, hypoalbuminemia and a pro-calcific state). Current nephrology clinical practice is adversely impacted by PAD diagnostic challenges, the complexities of managing two serious comorbid diseases, delayed vascular specialist referral, and slow PAD treatment initiation in CKD patients. Persons with CKD are less likely to be provided recommended ‘optimal’ PAD care. The knowledge that both limb and mortality outcomes are significantly worse in CKD patients, especially those on dialysis, is not a biologic fact, but can serve as a care delivery call to action. Nephrologists can facilitate positive change. This manuscript proposes that patients with PAD and CKD be strategically co-managed by care teams that encompass the skills to create and use evidence-based care pathways. This proposed collaborative multidisciplinary approach will include vascular medicine specialists, nephrologists, wound specialists and mid-level providers. Just as clinical care quality metrics have served as the base for ESRD and acute MI quality improvement, it is time that such quality outcomes metrics be initiated for the large PAD-CKD population. This new system will identify and resolve key gaps in the current care model so that clinical outcomes improve within a cost-effective care frame for this vulnerable population.

25-hydroxyvitamin D [25(OH)D] may not optimally indicate vitamin D receptor activity. Higher concentrations of its catabolic product 24,25-dihydroxyvitmin D [24,25(OH)D] and a higher ratio of 24,25(OH)D to 25(OH)D (the vitamin D metabolite ratio [VMR]) may provide additional information on receptor activity. We compared the strength of associations of these markers with serum PTH concentrations, hip bone mineral density (BMD), and risk of incident hip fracture in community-living older participants in the Cardiovascular Health Study. Among 890 participants, the mean age was 78years, 60% were women, and the mean 25(OH)D was 28±11ng/ml. In cross-sectional analysis, the strength of association of each vitamin D measure with PTH was similar; a 1% higher 25(OH)D, 24,25(OH)D, and VMR were associated with 0.32%, 0.25%, and 0.26% lower PTH, respectively (p<0.05 for all). Among 358 participants with available BMD data, we found no associations of 25(OH)D or VMR with BMD, whereas higher 24,25(OH)D was modestly associated with greater hip BMD (1% higher 24,25(OH)D associated with 0.04% [95% CI 0.01-0.08%] higher BMD). Risk of incident hip fracture risk was evaluated using a case-cohort design. There were 289 hip fractures during a mean follow up time of 8.4years. Both higher 24,25(OH)D and VMR were associated with lower risk of hip fracture (HR per SD higher, 0.73 [0.61, 0.87] and 0.74 [0.61, 0.88], respectively) whereas 25(OH)D was not associated with hip fracture (HR 0.93 [0.79, 1.10]). We conclude that evaluating vitamin D status by incorporating assessment of 24,25(OH)D and the VMR provides information on bone health above and beyond 25(OH)D alone.