Nephrolithiasis is a highly prevalent disease worldwide with rates ranging from 7 to 13% in North America, 5-9% in Europe, and 1-5% in Asia. Due to high rates of new and recurrent stones, management of stones is expensive and the disease has a high level of acute and chronic morbidity. The goal of this study is to review the epidemiology of stone disease in order to improve patient care. A review of the literature was conducted through a search on Pubmed®, Medline®, and Google Scholar®. This review was presented and peer-reviewed at the 3rd International Consultation on Stone Disease during the 2014 Societe Internationale d'Urologie Congress in Glasgow. It represents an update of the 2008 consensus document based on expert opinion of the most relevant studies. There has been a rising incidence in stone disease throughout the world with a narrowing of the gender gap. Increased stone prevalence has been attributed to population growth and increases in obesity and diabetes. General dietary recommendations of increased fluid, decreased salt, and moderate intake of protein have not changed. However, specific recommended values have either changed or are more frequently reported. Geography and environment influenced the likelihood of stone disease and more information is needed regarding stone disease in a large portion of the world including Asia and Africa. Randomized controlled studies are lacking but are necessary to improve recommendations regarding diet and fluid intake. Understanding the impact of associated conditions that are rapidly increasing will improve the prevention of stone disease.

Epidemiology of stone disease across the world

Oxidative stress has a critical role in the pathophysiology of several kidney diseases, and many complications of these diseases are mediated by oxidative stress, oxidative stress-related mediators, and inflammation. Several systemic diseases such as hypertension, diabetes mellitus, and hypercholesterolemia; infection; antibiotics, chemotherapeutics, and radiocontrast agents; and environmental toxins, occupational chemicals, radiation, smoking, as well as alcohol consumption induce oxidative stress in kidney. We searched the literature using PubMed, MEDLINE, and Google scholar with “oxidative stress, reactive oxygen species, oxygen free radicals, kidney, renal injury, nephropathy, nephrotoxicity, and induction”. The literature search included only articles written in English language. Letters or case reports were excluded. Scientific relevance, for clinical studies target populations, and study design, for basic science studies full coverage of main topics, are eligibility criteria for articles used in this paper.

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Induction of oxidative stress in kidney.

Nanomaterials application in electrochemical detection of heavy metals

Chemical and biological extraction of metals present in E waste: A hybrid technology.

The food and water we consume are often contaminated with a range of chemicals and heavy metals, such as lead, cadmium, arsenic, chromium, and mercury, that are associated with numerous diseases. Although heavy-metal exposure and contamination are not a recent phenomenon, the concentration of metals and the exposure to populations remain major issues despite efforts at remediation. The ability to prevent and manage this problem is still a subject of much debate, with many technologies ineffective and others too expensive for practical large-scale use, especially for developing nations where major pollution occurs. This has led researchers to seek alternative solutions for decontaminating environmental sites and humans themselves. A number of environmental microorganisms have long been known for their ability to bind metals, but less well appreciated are human gastrointestinal bacteria. Species such as Lactobacillus, present in the human mouth, gut, and vagina and in fermented foods, have the ability to bind and detoxify some of these substances. This review examines the current understanding of detoxication mechanisms of lactobacilli and how, in the future, humans and animals might benefit from these organisms in remediating environmental contamination of food.

Bioremediation and Tolerance of Humans to Heavy Metals through Microbial Processes: a Potential Role for Probiotics?

The heavy metal cadmium (Cd) is known to be a widespread environmental contaminant and a potential toxin that may adversely affect human health. Exposure is largely via the respiratory or gastrointestinal tracts; important non-industrial sources of exposure are cigarette smoke and food (from contaminated soil and water). The kidney is the main organ affected by chronic Cd exposure and toxicity. Cd accumulates in the kidney as a result of its preferential uptake by receptor-mediated endocytosis of freely filtered and metallothionein bound Cd (Cd-MT) in the renal proximal tubule. Internalised Cd-MT is degraded in endosomes and lysosomes, releasing free Cd(2+) into the cytosol, where it can generate reactive oxygen species (ROS) and activate cell death pathways. An early and sensitive manifestation of chronic Cd renal toxicity, which can be useful in individual and population screening, is impaired reabsorption of low molecular weight proteins (LMWP) (also a receptor-mediated process in the proximal tubule) such as retinol binding protein (RBP). This so-called 'tubular proteinuria' is a good index of proximal tubular damage, but it is not usually detected by routine clinical dipstick testing for proteinuria. Continued and heavy Cd exposure can progress to the clinical renal Fanconi syndrome, and ultimately to renal failure. Environmental Cd exposure may be a significant contributory factor to the development of chronic kidney disease, especially in the presence of other co-morbidities such as diabetes or hypertension; therefore, the sources and environmental impact of Cd, and efforts to limit Cd exposure, justify more attention.

Heavy metal poisoning: the effects of cadmium on the kidney

Renal stone disease covers kidney and lower urinary tract stones caused by a variety of conditions, including metabolic and inherited disorders, and anatomical defects with or without chronic urinary infection. Most cases are idiopathic, in which there is undoubtedly a genetic predisposition, but where environmental and lifestyle factors play an important role. Indeed, it is becoming apparent that renal stone disease is often part of a larger 'metabolic picture' commonly associated with type 2 diabetes, obesity, dyslipidaemia, and hypertension. Renal stone disease is a growing problem in the UK (and other developed and developing populations) with a cross-sectional prevalence of ~1.2%.This means that there are currently ~720,000 individuals with a history of kidney stones in the UK. Almost 40% of first-time stone formers will form a second stone within 3 years of the first episode if no prophylactic measures are instituted to prevent stone recurrence, since removal or disintegration of the first stone does not treat the underlying cause of stones in the majority of patients. The age of onset is getting younger and the sex ratio (until recently more men than women) is becoming almost even. Metabolic screening remains an important part of investigating renal stone disease, but to the disappointment and frustration of many doctors, medical treatment is still essentially pragmatic, except perhaps in cystinuria, and to a limited extent in primary hyperoxaluria (if pyridoxine-sensitive) ; although newer treatments may be emerging. This review summarizes current thinking and provides a practical basis for the management of renal stone disease.

An Update and Practical Guide to Renal Stone Management. Commentary

Renal stone disease covers kidney and lower urinary tract stones caused by a variety of conditions, including metabolic and inherited disorders, and anatomical defects with or without chronic urinary

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An Update and Practical Guide to Renal Stone Management

BACKGROUND The prevalence and incidence of kidney stone disease have increased markedly during the past several decades, and studies have demonstrated that inappropriate dietary habits are leading to more obesity and overweight (OW) in children and adults, which may be important in stone formation. Obese and OW patients share most of the same risk factors for cardiovascular morbidity, while the impact of being OW, rather than obese, on urinary metabolic parameters of kidney stone formers (KSF) is less well known. The aims of this study were to investigate urinary metabolic parameters, stone composition and probability of stone formation (Psf) in OW KSF when compared with normal weight (NW) and obese KSF. METHODS The kidney stone database for KSF attending a large metabolic stone clinic was investigated. Patients with a recorded BMI, confirmed diagnosis of kidney stone disease and full metabolic evaluation were divided into three categories: BMI ≤25.0 kg/m(2) (NW group), BMI 25-30 kg/m(2) (OW group) and BMI >30.0 kg/m(2) (obese group). Twenty-four hour urinary volume (U.Vol), pH (U.pH), calcium (U.Ca), oxalate (U.Ox), citrate (U.Cit), uric acid (U.UA), magnesium (U.Mg), sodium (U.Na) and potassium (U.K) excretions, along with stone composition and Psf, were then compared among the groups. RESULTS A total of 2132 patients were studied, of whom 833 (39%) were NW, 863 (40.5%) were OW and 436 (20.5%) were obese. OW and obese KSF were older (mean age 43 ± 15 in NW, 48 ± 13 in OW and 50 ± 12 years in obese; P for trend <0.001), demonstrated increased female predominance and higher prevalence of diabetes, hypertension and gout. There were no statistically significant differences in U.Vol and U.Mg among the groups. However, significantly higher levels of U.Ca, U.Ox, U.Cit, by crude analysis, and U.UA (3.3 ± 1.1 versus 3.8 ± 1.2 versus 4.0 ± 1.2 mmol/L; P < 0.001 for trend), U.Na (151 ± 57 versus 165 ± 60 versus 184 ± 63 mmol/L; P < 0.001 for trend), and lower U.pH (6.3 ± 0.5 versus 6.1 ± 0.5 versus 6.0 ± 0.6; P < 0.001 for trend) by both crude and multivariate adjusted analysis models were demonstrated in OW and obese KSF. Stone composition data (N = 640) showed a significantly higher incidence of uric acid stones in OW and obese groups (P for trend < 0.001). In addition, higher Psf for CaOx, UA and CaOx/UA stone types were detected in OW and obese compared with NW KSF. CONCLUSIONS Similar to obese KSF, OW KSF show clear alterations in metabolic urinary profiles that are associated with increased overall risk of stone formation. This greater risk is primarily due to raised U.UA and U.Na, lower U.pH and higher prevalence of hypercalciuria, along with unchanged levels of the commonly measured urinary lithogenesis inhibitors. Moreover, our study established a higher incidence of uric acid, but not calcium, stones in OW KSF. Thus, appropriate evaluation and follow-up may be warranted even in OW patients who are at risk of increased stone formation. Whether modest weight loss in OW KSF will have a favourable impact on their metabolic urinary profiles and thereby diminish the risk of further stone formation needs exploring.

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Effect of being overweight on urinary metabolic risk factors for kidney stone formation

Background. Mutations in the 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene have been recently identified in patients with atypical primary hyperoxaluria (PH). However, it was not clearly established whether these mutations caused disease via loss of function or activation of the gene product. Methods. Whole-gene sequencing of HOGA1 was conducted in 28 unrelated patients with a high clinical suspicion of PH and in whom Types 1 and 2 had been excluded. Results. Fifteen patients were homozygous or compound heterozygous for mutations in HOGA1. In total, seven different mutations were identified including three novel changes: a missense mutation, c.107C > T (p.Ala36Val), and two nonsense mutations c.117C > A (p.Tyr39X) and c.208C > T (p.Arg70X) as well as the previously documented c.860G > T (p.Gly297Val), c.907C > T (p.Arg303Cys) and in-frame c.944_946delAGG (p.Glu315del) mutations. The recurrent c.700 + 5G > T splice site mutation in intron 5 was most common with a frequency of 67%. Expression studies on hepatic messenger RNA demonstrated the pathogenicity of this mutation. Conclusions. The detection of a patient with two novel nonsense mutations within exon 1 of the gene, c.117C > A (p.Tyr39X) and c.208C > T (p.Arg70X), provides definitive proof that PH Type 3 is due to deficiency of the 4-hydroxy-2-oxoglutarate aldolase enzyme.

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Nikhil Johri

Papers

Heavy metal poisoning: the effects of cadmium on the kidney

An Update and Practical Guide to Renal Stone Management. Commentary

An Update and Practical Guide to Renal Stone Management

Effect of being overweight on urinary metabolic risk factors for kidney stone formation

The enzyme 4-hydroxy-2-oxoglutarate aldolase is deficient in primary hyperoxaluria type 3