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 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Regulation of fluid and dietary intake habits is essential in comprehensive preventive management of urolithiasis. However, despite large body of epidemiological database, there is dearth of good quality prospective interventional studies in this regard. Often there is conflict in pathophysiological basis and actual clinical outcome. We describe conflicts, controversies and lacunae in current literature in fluid and dietary modifications in prevention of urolithiasis. Adequate fluid intake is the most important conservative strategy in urolithiasis-prevention; its positive effects are seen even at low volumes. Of the citrus, orange provides the most favorable pH changes in the urine, equivalent to therapeutic alkaline citrates. Despite being richest source of citrate, lemon does not increase pH significant due to its acidic nature. Fructose, animal proteins and fats are implicated in contributing to obesity, which is an established risk factor for urolithiasis. Fructose and proteins also contribute to lithogenecity of urine directly. Sodium restriction is commonly advised since natriuresis is associated with calciuresis. Calcium restriction is not advisable for urolithiasis prevention. Adequate calcium intake is beneficial if taken with food since it reduces absorption of dietary oxalate. Increasing dietary fiber does not protect against urolithiasis. Evidence for pyridoxine and magnesium is not robust. There is no prospective interventional study evaluating effect of many dietary elements, including citrus juices, carbohydrate, fat, dietary fiber, sodium, etc. Due to lack of good-quality prospective interventional trials it is essential to test the findings of pathophysiological understanding and epidemiological evidence. Role of probiotics and phytoceuticals needs special attention for future research.
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PMID:Preventive fluid and dietary therapy for urolithiasis: An appraisal of strength, controversies and lacunae of current literature. 2202 52

Hypertension is the leading risk for premature death in the world. High dietary sodium is an important contributor to increased blood pressure and is strongly associated with other important diseases (e.g., gastric cancer, calcium containing kidney stones, osteoporosis, asthma and obesity). The average dietary sodium intake in Canada is approximately 3400 mg/day. It is estimated that 30% of hypertension, more than 10% of cardiovascular events and 1.4 billion dollars/year in health care expenses are caused by this high level of intake in Canada. Since 2006, Canada has had a focused and evolving effort to reduce dietary sodium based on actions from Non Governmental Organizations (NGO), and Federal and Provincial/Territorial Government actions. NGOs initiated Canadian sodium reduction programs by developing a policy statement outlining the health issue and calling for governmental, NGO and industry action, developing and disseminating an extensive health care professional education program including resources for patient education, developing a public awareness campaign through extensive media releases and publications in the lay press. The Federal Government responded by striking a Intersectoral Sodium Work Group to develop recommendations on how to implement Canada's dietary reference intake values for dietary sodium and by developing timelines and targets for foods to be reduced in sodium, assessing key research gaps with funding for targeted dietary sodium based research, developing plans for public education and for conducting evaluation of the program to reduce dietary sodium. While food regulation is a Federal Government responsibility Provincial and Territorial governments indicated reducing dietary sodium needed to be a priority. Federal and Provincial Ministers of Health have endorsed a target to reduce the average consumption of sodium to 2300 mg/day by 2016 and the Deputy Ministers of Health have tasked a joint committee to review the recommendations of the Sodium Work Group and report back to them.
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PMID:Canadian initiatives to prevent hypertension by reducing dietary sodium. 2225 22

Resistant hypertension is defined as blood pressure (BP) that remains above goal (such as 140/90 mmHg or more) in spite of the concurrent use of three antihypertensive agents of different classes. Ideally, one of the three agents should be a diuretic and all agents should be prescribed at optimal dose amounts. Prevalent among 15% of the treated hypertensives, the risk factors for resistant hypertension include older age, chronic kidney disease (CKD), obesity and diabetes mellitus. Causes of resistant hypertension can be classified into four groups: poor adherence, biological-behavioral factors, CKD and secondary causes, and drugs or exogenous substances. However, before labeling the diagnosis of resistant hypertension, it is important to exclude pseudo-resistant hypertension using home BP monitoring in most patients and ambulatory BP monitoring in a few. Before thinking about the next antihypertensive drug, it is important to restrict dietary sodium. Educating the patient on how to interpret the food label and providing feedback by assessing sodium intake with 24 h urine collection are effective sodium restriction strategies. Sodium restriction can lower BP and among patients with proteinuria can even enhance the anti-proteinuric effects of drugs that block the renin-angiotensin system. Sodium restriction is therefore a valuable but a neglected antihypertensive.
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PMID:Resistant hypertension and the neglected antihypertensive: sodium restriction. 2289 70

The role of the kidney in glucose homeostasis and the potential of the kidney as a therapeutic target in type 2 diabetes is little appreciated. Hyperglycemia is an important pathogenic component in the development of microvascular and macrovascular complications in type 2 diabetes mellitus. Inhibition of renal tubular glucose re-absorption that leads to glycosuria has been proposed as a new mechanism to attain normoglycemia and thus prevent and diminish these complications, thus representing an innovative therapeutic strategy for the treatment of hyperglycemia and/or obesity in patients with type 1 or type 2 diabetes by enhancing glucose and energy loss through the urine. Sodium glucose co-transporter 2 (SGLT2) has a key role in re-absorption of glucose in kidney. Competitive inhibitors of SGLT2 have been discovered and a few of them have also been advanced in clinical trials for the treatment of diabetes.
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PMID:SGLT2 inhibition: a novel prospective strategy in treatment of diabetes mellitus. 2343 84

Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mice lacking the gene encoding SGLT5. Sodium-dependent fructose uptake disappeared in renal brush border membrane vesicles from SGLT5-deficient mice, and the increased urinary fructose in SGLT5-deficient mice indicated that SGLT5 was the major fructose reabsorption transporter in the kidney. From this, we hypothesized that urinary fructose excretion induced by SGLT5 deficiency would ameliorate fructose-induced hepatic steatosis. To test this hypothesis we compared SGLT5-deficient mice with wild-type mice under conditions of long-term fructose consumption. Paradoxically, however, fructose-induced hepatic steatosis was exacerbated in the SGLT5-deficient mice, and the massive urinary fructose excretion was accompanied by reduced levels of plasma triglycerides and epididymal fat but fasting hyperinsulinemia compared with fructose-fed wild-type mice. There was no difference in food consumption, water intake, or plasma fructose between the two types of mice. No compensatory effect by other transporters reportedly involved in fructose uptake in the liver and kidney were indicated at the mRNA level. These surprising findings indicated a previously unrecognized link through SGLT5 between renal fructose reabsorption and hepatic lipid metabolism.
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PMID:SGLT5 reabsorbs fructose in the kidney but its deficiency paradoxically exacerbates hepatic steatosis induced by fructose. 2345 Oct 68

Elevation of blood pressure (BP) and the risk for progression to hypertension (HTN) is of increasing concern in children and adolescents. Indeed, it is increasingly recognized that target organ injury may begin with even low levels of BP elevation. Sodium intake has long been recognized as a modifiable risk factor for HTN. While it seems clear that sodium impacts BP in children, its effects may be enhanced by other factors including obesity and increasing age. Evidence from animal and human studies indicates that sodium may have adverse consequences on the cardiovascular system independent of HTN. Thus, moderation of sodium intake over a lifetime may reduce risk for cardiovascular morbidity in adulthood. An appetite for salt is acquired, and intake beyond our need is almost universal. Considering that eating habits in childhood have been shown to track into adulthood, modest sodium intake should be advocated as part of a healthy lifestyle.
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PMID:Sodium intake and blood pressure in children. 2394 20

Most patients with type 2 diabetes mellitus (T2DM) are overweight or obese. Both T2DM and overweight/obesity are associated with increased patient risk of cardiovascular events and mortality. Despite being the recognized cornerstone of treatment, weight loss and maintenance of weight loss are difficult for patients with T2DM, particularly as treatments for T2DM may cause weight gain. Sodium glucose cotransporter 2 (SGLT2) inhibitors, a new class of drug for the treatment of patients with T2DM, reduce renal glucose reabsorption, resulting in urinary glucose excretion. Due to the caloric loss associated with decreased glucose in urine, treatment with SGLT2 agents offers the benefit of weight loss to patients, as well as reduction in hyperglycemia. Clinical trials of SGLT2 inhibitors in patients with T2DM, ranging in length from 4 to 90 weeks, have shown patient weight reductions from baseline of up to 4.7 kg. Such weight loss may have beneficial effects on adherence to medication, glycemic control, and cardiovascular risk in patients with T2DM.
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PMID:Impact of sodium glucose cotransporter 2 inhibitors on weight in patients with type 2 diabetes mellitus. 2411 67

In type 2 diabetes (T2DM), glycaemic control delays the development and slows the progression of complications. Although there are numerous glucose-lowering agents in clinical use, only approximately half of T2DM patients achieve glycaemic control, while undesirable side-effects, such as hypoglycaemia and body weight gain, often impede treatment in those taking these medications. Thus, there is a need for novel agents and treatment options. Sodium-glucose cotransporter-2 inhibitors (SGLT-2-i) have recently been developed for the treatment of T2DM. The available data suggest a good tolerability profile for the three available drugs - canagliflozin, dapagliflozin and empagliflozin - approved by the US Food and Drug Administration (FDA) for the American market as well as in other countries. The most frequently reported adverse events with SGLT-2-i are female genital mycotic infections, urinary tract infections and increased urination. The pharmacodynamic response to SGLT-2-i declines with increasing severity of renal impairment, requiring dosage adjustments or restrictions with moderate-to-severe renal dysfunction. Most patients treated with SGLT-2-i also have a modest reduction in blood pressure and modest effects on serum lipid profiles, some of which are beneficial (increased high-density lipoprotein cholesterol and decreased triglycerides) and others which are not (increased low-density lipoprotein cholesterol, LDL-C). A number of large-scale and longer-term cardiovascular trials are now ongoing. In patients treated with dapagliflozin, a non-significant excess number of breast and bladder cancers has been reported; considered as due to a bias, this is nevertheless being followed in the ongoing trials. No other significant safety issues have been reported so far. Although there is some benefit for several cardiovascular risk factors such as HbA1c, high blood pressure, obesity and increases in LDL-C, adequately powered trials are still required to determine the effects of SGLT-2-i on macrovascular outcomes.
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PMID:Adverse effects and safety of SGLT-2 inhibitors. 2555 69

Sodium-glucose cotransporter 2 (SGLT2) inhibition induces glucosuria and decreases blood glucose levels in diabetic patients and lowers hypoglycemic risk. SGLT1 is expressed in the kidney and intestine; SGLT1 inhibition causes abdominal symptoms such as diarrhea and reduces incretin secretion. Therefore, SGLT2 selectivity is important. Ipragliflozin is highly selective for SGLT2. In type 2 diabetes mellitus (T2DM), urinary glucose excretion increased to 90 g/24 h after 28 d of treatment with ipragliflozin 300 mg/d. Twelve weeks of ipragliflozin 50 mg/d vs placebo reduced glycated hemoglobin and body weight by 0.65% and 0.66 kg, respectively, in Western T2DM patients, and by 1.3% and 1.89 kg, respectively, in Japanese patients. Ipragliflozin (highly selective SGLT2 inhibitor) improves glycemic control and reduces body weight and lowers hypoglycemic risk and abdominal symptoms. Ipragliflozin can be a novel anti-diabetic and anti-obesity agent.
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PMID:Ipragliflozin: A novel sodium-glucose cotransporter 2 inhibitor developed in Japan. 2568 84

Diabetic kidney disease represents a considerable burden; around one-third of patients with type 2 diabetes develop chronic kidney disease. In health, the kidneys play an important role in the regulation of glucose homeostasis via glucose utilization, gluconeogenesis and glucose reabsorption. In patients with diabetes, renal glucose homeostasis is significantly altered with an increase in both gluconeogenesis and renal tubular reabsorption of glucose. Environmental factors, both metabolic (hyperglycaemia, obesity and dyslipidaemia) and haemodynamic, together with a genetic susceptibility, lead to the activation of pro-oxidative, pro-inflammatory and pro-fibrotic pathways resulting in kidney damage. Hyperfiltration and its haemodynamic-driven insult to the kidney glomeruli is an important player in proteinuria and progression of kidney disease towards end-stage renal failure. Control of glycaemia and blood pressure are the mainstays to prevent kidney damage and slow its progression. There is emerging evidence that some hypoglycaemic agents may have renoprotective effects which are independent of their glucose-lowering effects. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors may exert a renoprotective effect by a number of mechanisms including restoring the tubuloglomerular feedback mechanism and lowering glomerular hyperfiltration, reducing inflammatory and fibrotic markers induced by hyperglycaemia thus limiting renal damage. Simultaneous use of an SGLT-2 inhibitor and blockade of the renin-angiotensin-aldosterone system may be a strategy to slow progression of diabetic nephropathy more than either drug alone. The use of dipeptidyl peptidase-4 inhibitors and glucagon-like peptide 1 receptor agonists may exert a renoprotective effect by reducing inflammation, fibrosis and blood pressure. Given the burden of diabetic kidney disease, any additional renoprotective benefit with hypoglycaemic therapy is to be welcomed. Large randomized controlled trials are currently underway investigating if these new anti-diabetic agents can provide renoprotection in diabetes.
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PMID:Beat it early: putative renoprotective haemodynamic effects of oral hypoglycaemic agents. 2585 86


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