Demography and biochemistry of 2800 patients from a renal stones clinic
Department of Clinical Biochemistry, Southampton University Hospitals NHS Trust, C Level MP 6, South Block, Tremona Road, Southampton SO16 6YD, UK. Annals of Clinical Biochemistry
(Impact Factor: 2.34).
02/2013; 50(2). DOI: 10.1258/acb.2012.012122
Because the causes of stones are uncertain, interventions to prevent recurrence have an insecure foundation. Progress depends on careful evaluation of stone formers.
A descriptive retrospective database study of 1983 men and 816 women from the Southampton stones clinic from 1990 to March 2007. Anonymized data from the first attendance were analysed using non-parametric statistical tests.
Sex ratio (2.43:1), age (median 49 y, 2.5th-97.5th percentiles, 23-77 y men, 20-79 y women), recurrent stone formers (30%) and type of stone were similar to other centres. Women more often had a positive family history (24% versus 19% men), previous urinary infection (31% versus 5%) and structural urinary tract abnormality (14% versus 7%); more men had gout (5% versus 1%) and bladder outlet obstruction (3% versus <1%). Calcium, oxalate and uric acid excretion were increased in 43%, 17% and 22% respectively of men and 31%, 7% and 10% of women. Urinary calcium, oxalate and uric acid correlated significantly, r ranging from 0.149 to 0.311 for 24 h excretion and 0.510 to 0.695 for concentrations per litre. Twenty-two percent of men and 8% of women with normal parathyroid hormone had phosphaturia (excretion of phosphate corrected for glomerular filtration rate (TmPO4/GFR) < 0.70 mmol/L); 6% men and 1.6% women also had low plasma phosphate. Many variables correlated significantly but often weakly with age. Creatinine clearance, pH and (men) TmPO4/GFR decreased from 50 y, urine creatinine, calcium and citrate from 60 y.
Risk factors for stones differ between men and women, change with ageing and in some may have a genetic basis. The role of phosphaturia merits further exploration.
Available from: Graeme L Conn
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ABSTRACT: Adenoviruses use the short noncoding RNA transcript virus-associated (VA) RNAI to counteract two critical elements of the host cell defense system, innate cellular immunity and RNA interference, mediated
by the double-stranded RNA-activated protein kinase (PKR) and Dicer/RNA-induced silencing complex, respectively. We progressively
shortened the VA RNAI terminal stem to examine its necessity for inhibition of PKR. Each deletion, up to 15 bp into the terminal stem, resulted
in a cumulative decrease in PKR inhibitory activity. Remarkably, however, despite significant apparent destabilization of
the RNA structure, the final RNA mutant that lacked the entire terminal stem (TSΔ21 RNA) efficiently bound PKR and exhibited
wild-type inhibitory activity. TSΔ21 RNA stability was strongly influenced by solution pH, indicating the involvement of a
protonated base within the VA RNAI central domain tertiary structure. Gel filtration chromatography and isothermal titration calorimetry analysis indicated
that wild-type VA RNAI and TSΔ21 RNA form similar 1:1 complexes with PKR but that the latter lacks secondary binding site(s) that might be provided
by the terminal stem. Although TSΔ21 RNA bound PKR with wild-type Kd, and overall change in free energy (ΔG), the thermodynamics of binding (ΔH and ΔS) were significantly altered. These results demonstrate that the VA RNAI terminal stem is entirely dispensable for inhibition of PKR. Potentially, VA RNAI is therefore a truly bi-functional RNA; Dicer processing of the VA RNAI terminal stem saturates the RNA interference system while generating a “mini-VA RNAI” molecule that remains fully active against PKR.
Journal of Biological Chemistry 07/2008; 283(25):17485-93. DOI:10.1074/jbc.M802300200 · 4.57 Impact Factor
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ABSTRACT: Objectives Nephrolithiasis (kidney stones) is a common disease with the prevalence that is increasing globally. We previously found that trimethyltin (TMT), a by-product of plastic stabilisers, can inhibit the H+/K+ ATPase activity in renal intercalated cells and alter urinary pH, which is a known risk factor for nephrolithiasis. In this study, we conducted a cross-sectional analysis to evaluate the impact of chronic low level occupational TMT exposure on nephrolithiasis.
Methods This study included 216 healthy workers with TMT exposure and 119 workers as controls with no TMT exposure. All study participants were administered a questionnaire and underwent a routine clinical examination including an ultrasonographic screening for kidney stones. Exposures were assessed by measuring TMT concentrations in personal air samples, blood and urine. Logistic regression analysis was used to estimate the ORs and 95% CIs for the risk of kidney stones.
Results TMT exposed workers had a higher prevalence of kidney stones (18.06%) in comparison with control workers (5.88%). High TMT concentrations in personal air samples, blood and urines were positively associated with increased prevalence of kidney stones in workers exposed to TMT compared with controls workers (p-trend values=0.005, 0.008 and 0.002, respectively). The length of employment in plants with elevated TMT levels (duration of the exposure) was significantly associated with the increased prevalence of kidney stones (p trend=0.001). The ORs were 2.66 for <3 years, 3.73 for 3–<10 years and 7.89 for 10+ years of employment compared with control workers.
Conclusions To our knowledge, this is the first report to demonstrate that occupational exposure to TMT is a potential risk factor for nephrolithiasis.
Occupational and environmental medicine 05/2013; 70(8). DOI:10.1136/oemed-2012-101261 · 3.27 Impact Factor
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ABSTRACT: Hypercalciuria is a common poorly understood abnormality among stone formers. We aimed to identify hypercalciuric male stone formers with a primary defect in renal calcium reabsorption and to look for associated risk factors.
A retrospective cross-sectional database study of 623 male idiopathic calcium stone formers with normal plasma ultrafilterable calcium levels attending the Southampton stone clinic. Filtered calcium was estimated from plasma ultrafilterable calcium (60% of total plasma calcium) and 24 h creatinine clearance. Reabsorbed calcium was the difference between filtered and excreted calcium.
276 men had hypercalciuria (urine calcium >7.50 mmol/24 h); 347 had normocalciuria. Hypercalciuric men filtered more calcium than normocalciuric men: median values 247 and 227 mmol/24 h, but the ranges overlapped (175-371 and 153-316 mmol/24 h). However, across the entire filtration range, hypercalciuric men reabsorbed less of the filtered calcium. Among the hypercalciuric men, we noticed differences between those with high and low filtration. We therefore compared data for hypercalciuric men in the highest and lowest filtration quintiles (n=55). Men with high filtration were younger at their first stone episode and had significantly higher plasma ultrafilterable calcium and calcium reabsorption, urinary calcium, oxalate, urate and creatinine excretion and creatinine clearance. 35% with high filtration and 40% with low filtration had recurrent stones; 27% and 20%, respectively, had an affected first-degree relative.
Hypercalciuric men reabsorbed proportionately less filtered calcium than normocalciuric men. Among hypercalciuric men, the risks for stones were higher in those with a high than a low filtered calcium load and presentation was earlier.
Journal of clinical pathology 11/2013; 67(4). DOI:10.1136/jclinpath-2013-201879 · 2.92 Impact Factor
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