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Journal ArticleDOI

Hypercalciuria associated with high dietary protein intake is not due to acid load.

05 Oct 2011-The Journal of Clinical Endocrinology and Metabolism (The Endocrine Society)-Vol. 96, Iss: 12, pp 3733-3740

TL;DR: This study suggests that, at least in the short-term, mechanism other than acid load account for hypercalciuria induced by HPD, and the beneficial effect of KCitrate on nephrolithiasis risk with HPD is through correction of declines in urine pH and citrate.

AbstractContext and Objective: Dietary intake of animal proteins is associated with an increase in urinary calcium and nephrolithiasis risk. We tested the hypothesis that the acid load imposed by dietary proteins causes this hypercalciuria. Design and Setting: In a short-term crossover metabolic study, an alkali salt was provided with a high-protein diet (HPD) to neutralize the acid load imparted by dietary proteins.

Topics: Hypercalciuria (59%), Urinary calcium (52%)

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Citations
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Journal ArticleDOI
TL;DR: Nephrolithiasis is considered a systemic disorder associated with chronic kidney disease, bone loss and fractures, increased risk of coronary artery disease, hypertension, type 2 diabetes mellitus, and the metabolic syndrome, and further understanding of the pathophysiological link between nephrolithsiasis and these systemic disorders is necessary for the development of new therapeutic options.
Abstract: Context: The pathogenetic mechanisms of kidney stone formation are complex and involve both metabolic and environmental risk factors. Over the past decade, major advances have been made in the understanding of the pathogenesis, diagnosis, and treatment of kidney stone disease. Evidence Acquisition and Synthesis: Both original and review articles were found via PubMed search reporting on pathophysiology, diagnosis, and management of kidney stones. These resources were integrated with the authors' knowledge of the field. Conclusion: Nephrolithiasis remains a major economic and health burden worldwide. Nephrolithiasis is considered a systemic disorder associated with chronic kidney disease, bone loss and fractures, increased risk of coronary artery disease, hypertension, type 2 diabetes mellitus, and the metabolic syndrome. Further understanding of the pathophysiological link between nephrolithiasis and these systemic disorders is necessary for the development of new therapeutic options.

165 citations


Journal ArticleDOI
TL;DR: Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this.
Abstract: Potassium was identified as a shortfall nutrient by the Dietary Guidelines for Americans 2010 Advisory Committee. The committee concluded that there was a moderate body of evidence of the association between potassium intake and blood pressure reduction in adults, which in turn influences the risk of stroke and coronary heart disease. Evidence is also accumulating of the protective effect of adequate dietary potassium on age-related bone loss and reduction of kidney stones. These benefits depend on organic anions associated with potassium as occurs in foods such as fruits and vegetables, in contrast to similar blood pressure-lowering benefits of potassium chloride. Benefits to blood pressure and bone health may occur at levels below current recommendations for potassium intake, especially from diet, but dose-response trials are needed to confirm this. Nevertheless, intakes considerably above current levels are needed for optimal health, and studies evaluating small increases in fruit and vegetable intake on bone and heart outcomes for short periods have had disappointing results. In modern societies, Western diets have led to a decrease in potassium intake with reduced consumption of fruits and vegetables with a concomitant increase in sodium consumption through increased consumption of processed foods. Consumption of white vegetables is associated with decreased risk of stroke, possibly related to their high potassium content. Potatoes are the highest source of dietary potassium, but the addition of salt should be limited. Low potassium-to-sodium intake ratios are more strongly related to cardiovascular disease risk than either nutrient alone. This relationship deserves further attention for multiple target tissue endpoints.

156 citations


Cites background from "Hypercalciuria associated with high..."

  • ...Another observation inconsistent with acid loading causing increased urinary calcium is that adding potassium citrate to neutralize the acid load of a high protein diet did not reduce the hypercalciuria induced by the protein in healthy adults (60)....

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  • ...(60) concluded that the benefit of potassium citrate is not through the acid-base mechanism, but through correction of decreases in urine pH and citrate....

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Journal ArticleDOI
TL;DR: Diet has no definitive role for struvite stones except for avoiding urinary alkalinization, which may worsen their development, and weight loss and urinary alkalineization provided by a more vegetarian diet.
Abstract: We summarize the data regarding the associations of individual dietary components with kidney stones and the effects on 24-hour urinary profiles. The therapeutic recommendations for stone prevention that result from these studies are applied where possible to stones of specific composition. Idiopathic calcium oxalate stone-formers are advised to reduce ingestion of animal protein, oxalate, and sodium while maintaining intake of 800 to 1200 mg of calcium and increasing consumption of citrate and potassium. There are few data regarding dietary therapy of calcium phosphate stones. Whether the inhibitory effect of citrate sufficiently counteracts increasing urine pH to justify more intake of potassium and citrate is not clear. Reduction of sodium intake to decrease urinary calcium excretion would also be expected to decrease calcium phosphate stone recurrence. Conversely, the most important urine variable in the causation of uric acid stones is low urine pH, linked to insulin resistance as a component of obesity and the metabolic syndrome. The mainstay of therapy is weight loss and urinary alkalinization provided by a more vegetarian diet. Reduction in animal protein intake will reduce purine ingestion and uric acid excretion. For cystine stones, restriction of animal protein is associated with reduction in intake of the cystine precursor methionine as well as cystine. Reduction of urine sodium results in less urine cystine. Ingestion of vegetables high in organic anion content, such as citrate and malate, should be associated with higher urine pH and fewer stones because the amino acid cystine is soluble in more alkaline urine. Because of their infectious origin, diet has no definitive role for struvite stones except for avoiding urinary alkalinization, which may worsen their development.

90 citations


Cites background from "Hypercalciuria associated with high..."

  • ...However, a very recent study concluded that hypercalciuria associated with high dietary protein intake was not due to the acid load.(48) Epidemiological data reveal a positive association between animal protein consumption and new kidney stone formation in men but not women....

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Journal ArticleDOI
14 Mar 2016-BMJ
TL;DR: No new drugs have been developed for stone prevention since the 1980s when potassium citrate was introduced, perhaps because the long observation period needed to demonstrate efficacy discourages investigators from embarking on clinical trials.
Abstract: The prevalence of kidney stones is increasing in industrialized nations, resulting in a corresponding rise in economic burden. Nephrolithiasis is now recognized as both a chronic and systemic condition, which further underscores the impact of the disease. Diet and environment play an important role in stone disease, presumably by modulating urine composition. Dietary modification as a preventive treatment to decrease lithogenic risk factors and prevent stone recurrence has gained interest because of its potential to be safer and more economical than drug treatment. However, not all abnormalities are likely to be amenable to dietary therapy, and in some cases drugs are necessary to reduce the risk of stone formation. Unfortunately, no new drugs have been developed for stone prevention since the 1980s when potassium citrate was introduced, perhaps because the long observation period needed to demonstrate efficacy discourages investigators from embarking on clinical trials. Nonetheless, effective established treatment regimens are currently available for stone prevention.

73 citations


Journal ArticleDOI
Abstract: Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) derives dietary reference values (DRVs) for potassium. The Panel decides to set DRVs on the basis of the relationships between potassium intake and blood pressure and stroke. The Panel considers that randomised controlled trials and an observational cohort study carried out in a European adult population provide evidence that a potassium intake of 3,500 mg (90 mmol)/day has beneficial effects on blood pressure in adults. Furthermore, there is consistent evidence from observational cohort studies that potassium intakes below 3,500 mg/day are associated with a higher risk of stroke. Available data cannot be used to determine the average requirement of potassium but can be used as a basis for deriving an adequate intake (AI). A potassium intake of 3,500 mg/day is considered adequate for the adult population and an AI of 3,500 mg/day for adult men and women is proposed. For infants and children, the AIs are extrapolated from the AI for adults by isometric scaling and including a growth factor. An AI of 750 mg (19 mmol)/day is set for infants aged 7–11 months. For children, AIs from 800 mg (20 mmol)/day (1–3 years old) to 3,500 mg/day (15–17 years old) are set. Considering that the daily accretion rate of potassium in fetal and maternal tissues can be met by the adaptive changes which maintain potassium homeostasis during pregnancy, the AI set for adults applies to pregnant women. For lactating women, the amount of potassium needed to compensate for the losses of potassium through breast milk is estimated and an AI of 4,000 mg (102 mmol)/day is proposed. © 2016 European Food Safety Authority. EFSA Journal published by John Wiley and Sons Ltd on behalf of European Food Safety Authority.

43 citations


References
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Journal ArticleDOI
TL;DR: A high dietary calcium intake decreases the risk of symptomatic kidney stones in a cohort of 45,619 men, 40 to 75 years of age, who had no history of kidney stones.
Abstract: Background A high dietary calcium intake is strongly suspected of increasing the risk of kidney stones. However, a high intake of calcium can reduce the urinary excretion of oxalate, which is thought to lower the risk. The concept that a higher dietary calcium intake increases the risk of kidney stones therefore requires examination. Methods We conducted a prospective study of the relation between dietary calcium intake and the risk of symptomatic kidney stones in a cohort of 45,619 men, 40 to 75 years of age, who had no history of kidney stones. Dietary calcium was measured by means of a semiquantitative food-frequency questionnaire in 1986. During four years of follow-up, 505 cases of kidney stones were documented. Results After adjustment for age, dietary calcium intake was inversely associated with the risk of kidney stones; the relative risk of kidney stones for men in the highest as compared with the lowest quintile group for calcium intake was 0.56 (95 percent confidence interval, 0.43 to 0.73; P f...

992 citations


"Hypercalciuria associated with high..." refers background in this paper

  • ...Intake of protein was directly associated with the risk of nephrolithiasis in a prospective study of over 45,000 men followed for more than 4 yr (3)....

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  • ...This hypercalciuria accounts in part for the increased risk of kidney stone formation associated with excess protein consumption (3, 4)....

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Journal ArticleDOI
TL;DR: In men with recurrent calcium oxalate stones and hypercalciuria, restricted intake of animal protein and salt, combined with a normal calcium intake, provides greater protection than the traditional low-calcium diet.
Abstract: Background A low-calcium diet is recommended to prevent recurrent stones in patients with idiopathic hypercalciuria, yet long-term data on the efficacy of a low-calcium diet are lacking. Recently, the efficacy of a low-calcium diet has been questioned, and greater emphasis has been placed on reducing the intake of animal protein and salt, but again, long-term data are unavailable. Methods We conducted a five-year randomized trial comparing the effect of two diets in 120 men with recurrent calcium oxalate stones and hypercalciuria. Sixty men were assigned to a diet containing a normal amount of calcium (30 mmol per day) but reduced amounts of animal protein (52 g per day) and salt (50 mmol of sodium chloride per day); the other 60 men were assigned to the traditional low-calcium diet, which contained 10 mmol of calcium per day. Results At five years, 12 of the 60 men on the normal-calcium, low-animal-protein, low-salt diet and 23 of the 60 men on the low-calcium diet had had relapses. The unadjusted relati...

810 citations


Journal ArticleDOI
TL;DR: To test the possibility that the counteraction of retained endogenous acid by base mobilized from the skeleton may contribute to the decrease in bone mass that occurs normally with aging, postmenopausal women who were given a constant diet were administered potassium bicarbonate.
Abstract: Background In normal subjects, a low level of metabolic acidosis and positive acid balance (the production of more acid than is excreted) are typically present and correlate in degree with the amount of endogenous acid produced by the metabolism of foods in ordinary diets abundant in protein. Over a lifetime, the counteraction of retained endogenous acid by base mobilized from the skeleton may contribute to the decrease in bone mass that occurs normally with aging. Methods To test that possibility, we administered potassium bicarbonate to 18 postmenopausal women who were given a constant diet (652 mg [16 mmol] of calcium and 96 g of protein per 60 kg of body weight). The potassium bicarbonate was given orally for 18 days in doses (60 to 120 mmol per day) that nearly completely neutralized the endogenous acid. Results During the administration of potassium bicarbonate, the calcium and phosphorus balance became less negative or more positive -- that is, less was excreted in comparision with the amount inges...

531 citations


"Hypercalciuria associated with high..." refers background in this paper

  • ...menopausal women (17, 23, 24), elderly men (24), and...

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Journal ArticleDOI
TL;DR: The present metabolic balance studies were carried out to study further the relationship between acid retention and calcium balance during chronic ammonium chloride acidosis.
Abstract: Acute acid loads have been shown to titrate extraand intracellular buffers (1, 2). The state of titration of these buffers is reflected by the level of serum bicarbonate. With sustained acid loading, serum bicarbonate ultimately stabilizes at some reduced level despite continuing acid retention, indicating that an additional buffer system is titrated. It has been suggested that such additional quantities of buffer could arise from the slow dissolution of bone mineral during chronic metabolic acidosis (3). The present metabolic balance studies were carried out to study further the relationship between acid retention and calcium balance during chronic ammonium chloride acidosis.

527 citations


"Hypercalciuria associated with high..." refers background in this paper

  • ...source of acid load (21), or of sulfur-containing amino...

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Journal ArticleDOI
TL;DR: Even after controlling for known confounders including weight loss, women and men with relatively lower protein intake had increased bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly persons.
Abstract: Few studies have evaluated protein intake and bone loss in elders. Excess protein may be associated with negative calcium balance, whereas low protein intake has been associated with fracture. We examined the relation between baseline dietary protein and subsequent 4-year change in bone mineral density (BMD) for 391 women and 224 men from the population-based Framingham Osteoporosis Study. BMD (g/cm2) was assessed in 1988-1989 and in 1992-1993 at the femur, spine, and radius. Usual dietary protein intake was determined using a semiquantitative food frequency questionnaire (FFQ) and expressed as percent of energy from protein intake. BMD loss over 4 years was regressed on percent protein intake, simultaneously adjusting for other baseline factors: age, weight, height, weight change, total energy intake, smoking, alcohol intake, caffeine, physical activity, calcium intake, and, for women, current estrogen use. Effects of animal protein on bone loss also were examined. Mean age at baseline (+/-SD) of 615 participants was 75 years (+/-4.4; range, 68-91 years). Mean protein intake was 68 g/day (+/-24.0; range, 14-175 g/day), and mean percent of energy from protein was 16% (+/-3.4; range, 7-30%). Proportional protein intakes were similar for men and women. Lower protein intake was significantly related to bone loss at femoral and spine sites (p < or = 0.04) with effects similar to 10 lb of weight. Persons in the lowest quartile of protein intake showed the greatest bone loss. Similar to the overall protein effect, lower percent animal protein also was significantly related to bone loss at femoral and spine BMD sites (all p < 0.01) but not the radial shaft (p = 0.23). Even after controlling for known confounders including weight loss, women and men with relatively lower protein intake had increased bone loss, suggesting that protein intake is important in maintaining bone or minimizing bone loss in elderly persons. Further, higher intake of animal protein does not appear to affect the skeleton adversely in this elderly population.

504 citations


"Hypercalciuria associated with high..." refers background in this paper

  • ...Although some studies have associated HPD with negative calcium balance (5), lower bone mineral density (6), and increased fractures (36), others have reported improved bone mineral density (37) and lower fracture risk (38, 39)....

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