Kidney stones and kidney function loss: A cohort study

7-129 Clinical Science Building, University of Alberta, 8440 112 Street, Edmonton, Alberta T6B 2G3, Canada.
BMJ (online) (Impact Factor: 17.45). 08/2012; 345(aug29 2):e5287. DOI: 10.1136/bmj.e5287
Source: PubMed


To investigate whether the presence of kidney stones increase the risk of end stage renal disease (ESRD) or other adverse renal outcomes.
A registry cohort study using validated algorithms based on claims and facility utilisation data. Median follow-up of 11 years.
Alberta, Canada, between 1997 and 2009.
3,089,194 adult patients without ESRD at baseline or a history of pyelonephritis. Of these, 1,954,836 had outpatient serum creatinine measurements and were included in analyses of chronic kidney disease and doubling of serum creatinine level.
One or more kidney stones during follow-up.
Incident ESRD, development of stage 3b-5 chronic kidney disease (estimated glomerular filtration rate <45 mL/min/1.73 m(2)), and sustained doubling of serum creatinine concentration from baseline.
23,706 (0.8%) patients had at least one kidney stone, 5333 (0.2%) developed ESRD, 68,525 (4%) developed stage 3b-5 chronic kidney disease, and 6581 (0.3%) experienced sustained doubling of serum creatinine. Overall, one or more stone episodes during follow-up was associated with increased risk of ESRD (adjusted hazard ratio 2.16 (95% CI 1.79 to 2.62)), new stage 3b-5 chronic kidney disease (hazard ratio 1.74 (1.61 to 1.88)), and doubling of serum creatinine (hazard ratio 1.94 (1.56 to 2.43)), all compared with those without kidney stones during follow-up. The excess risk of adverse outcomes associated with at least one episode of stones seemed greater in women than in men, and in people aged <50 years than in those aged ≥ 50. However, the risks of all three adverse outcomes in those with at least one episode of stones were significantly higher than in those without stones in both sexes and age strata. The absolute increase in the rate of adverse renal outcomes associated with stones was small: the unadjusted rate of ESRD was 2.48 per million person days in people with one or more episodes of stones versus 0.52 per million person days in people without stones.
Even a single kidney stone episode during follow-up was associated with a significant increase in the likelihood of adverse renal outcomes including ESRD. However, the increases were small in absolute terms.

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Available from: R. Todd Alexander
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    • "Nephrolithiasis (kidney stones) is a painful condition that recurs in 50% of patients (Johnson et al. 1979) and is associated with kidney function loss, including end stage renal disease (Alexander et al. 2012). The prevalence of nephro lithiasis has increased markedly in Europe, Asia, and the Americas over the last three decades (Romero et al. 2010). "
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    ABSTRACT: High ambient temperatures are a risk factor for nephrolithiasis, but the precise relationship between temperature and kidney stone presentation is unknown. OBJECTIVES Our objective was to estimate associations between mean daily temperature and kidney stone presentation according to lag time and temperatures. METHODS Using a time series design and distributed lag non-linear models, we estimated the relative risk (RR) of kidney stone presentation associated with mean daily temperatures, including cumulative RR for a 20-day period, and RR for individual daily lags through 20 days. Our analysis used MarketScan data for 60,433 patients who presented for evaluation or treatment of kidney stones from 2005-2011 in Atlanta, Chicago, Dallas, Los Angeles, and Philadelphia. RESULTS Associations between mean daily temperature and kidney stone presentation were not monotonic, and there was variation in the exposure-response curve shapes and the strength of associations at different temperatures. However, in most cases RRs increased for temperatures above the reference value of 10°C. The cumulative RR for a daily mean temperature of 30°C versus 10°C was 1.38 in Atlanta (95% CI: 1.07, 1.79), 1.37 in Chicago (95% CI: 1.07, 1.76), 1.36 in Dallas (95% CI: 1.10, 1.69), 1.11 in Los Angeles (95% CI: 0.73, 1.68), and 1.47 in Philadelphia (95% CI: 1.00, 2.17). Kidney stone presentations also were positively associated with temperatures < 2°C in Atlanta, and < 10°C in Chicago and Philadelphia. In 4 cities, the strongest association between kidney stone presentation and a daily mean temperature of 30 versus 10°C was estimated for lags ≤ 3 days. CONCLUSIONS In general, kidney stone presentations increased with higher daily mean temperatures, with the strongest associations estimated for lags of only a few days. These findings further support an adverse effect of high temperatures on nephrolithiasis.
    Full-text · Article · Jul 2014 · Environmental Health Perspectives
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    • "Overall, renal stone disease is a frequent condition in the general population, that has been shown in several cohort studies to be consistently more frequent in male than in female subjects (Alexander et al. 2012;Pearle et al. 2005;Stamatelou et al. 2003;Yasui et al. 2008). In these studies, hypercalciuria represents the most common risk factor for nephrolithiases (Cirillo et al. 2003) and is closely related to dietary habits, in particular to sodium intake; low-salt diet and hyperhydration represent therefore the mainstay approach for the prevention of non-cystinuric kidney stones (Borghi et al. 2002). "
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    ABSTRACT: Cystinuria is an autosomal recessive disease that causes L-cystine precipitation in urine and nephrolithiasis. Disease severity is highly variable; it is known, however, that cystinuria has a more severe course in males. The aim of this study was to compare L-cystine metastability in first-morning urine collected from 24 normal female and 24 normal male subjects. Samples were buffered at pH 5 and loaded with L-cystine (0.4 and 4 mM final concentration) to calculate the amount remaining in solution after overnight incubation at 4 °C; results were expressed as Z scores reflecting the L-cystine solubility in each sample. In addition, metabolomic analyses were performed to identify candidate compounds that influence L-cystine solubility. L-cystine solubility Z score was +0.44 ± 1.1 and -0.44 ± 0.70 in female and male samples, respectively (p < 0.001). Further analyses showed that the L-cystine solubility was independent from urine concentration but was significantly associated with low urinary excretion of inosine (p = 0.010), vanillylmandelic acid (VMA) (p = 0.015), adenosine (p = 0.029), and guanosine (p = 0.032). In vitro L-cystine precipitation assays confirmed that these molecules induce higher rates of L-cystine precipitation in comparison with their corresponding dideoxy molecules, used as controls. In silico computational and modeling analyses confirmed higher binding energy of these compounds. These data indicate that urinary excretion of nucleosides and VMA may represent important factors that modulate L-cystine solubility and may represent new targets for therapy in cystinuria.
    Full-text · Article · Dec 2013 · Amino Acids
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    • "The development of renal stones, even a single episode, is a risk factor for CKD, doubling of serum creatinine level, and ESRD [12,13,16]. Many studies have also demonstrated that ATV/r use is a risk for renal dysfunction and CKD [22-25]. "
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    ABSTRACT: Although ritonavir-boosted atazanavir (ATV/r) is known to be associated with nephrolithiasis, little is known about the incidence of nephrolithiasis in patients treated with ritonavir-boosted Darunavir (DRV/r), the other preferred protease inhibitor. In a single-center cohort, the incidence of nephrolithiasis was compared between HIV-infected patients who commenced DRV/r-containing antiretroviral therapy and those on ATV/r. The effects of ATV/r use over DRV/r were estimated by univariate and multivariate Cox hazards models. Renal stones were diagnosed in only one patient (0.86 per 1000 person-years) of the DRV/r group (n=540) and 37 (20.2 per 1000 person-years) of the ATV/r group (n=517). The median [interquartile (IQR)] observation period in the DRV/r group was 27.1 months (IQR 18.1-38.4 months), and 40.6 months (IQR 17.5-42.7) for the ATV/r group. The total observation period was 1,163.6 person-years and 1,829.6 person-years for the DRV/r group and for the ATV/r group, respectively. In the 37 patients on ATV/r who developed nephrolithiasis, the median time from commencement of ATV/r to diagnosis was 28.1 months (IQR 18.4-42.7), whereas nephrolithiasis in the single patient of the DRV/r group occurred 11.2 month after the introduction of DRV/r. ATV/r use over DRV/r was significantly associated with nephrolithiasis by uni- and multivariate analyses (HR=26.01; 95% CI, 3.541-191.0; p=0.001) (adjusted HR=21.47; 95% CI, 2.879-160.2; p=0.003). The incidence of nephrolithiasis was substantially lower in patients on DRV/r than those on ATV/r. The results suggest that DRV/r should be selected for treatment of HIV-infected patients at risk of chronic kidney disease.
    Full-text · Article · Oct 2013 · PLoS ONE
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