Acetazolamide Is an Effective Adjunct for Urinary Alkalization in Patients With Uric Acid and Cystine Stone Formation Recalcitrant to Potassium Citrate

Uric acid (UA) stones are typically red-orange and often appear as sand/ gravel though they may be large. They are totally radiolucent. They account for about 10% of all kidney stones in most countries, and up to 20% in some populations. It is twice as frequent in males, prevalence increases with age, and it is two to three times higher in patients with type 2 diabetes or with features of the metabolic syndrome. Factors that induce the formation of UA stones are a low urine volume, hyperuricosuria, and, more importantly, a permanently low urine pH (< 5). Indeed, below its pKa of 5.35 at 37°C, UA is in non-dissociated form, whose solubility is at best 100 mg/L, whereas urinary UA excretion normally exceeds 600 mg/day and may exceed 1g/day.Because UA solubility increases up to approximately 500 mg/L at urine pH > 6, urine alkalinization, with a target pH of 6.5–7, is the cornerstone of medical treatment. This most often allows dissolution of existing stones and prevention of recurrent stone formation so that urological intervention is infrequently needed. The preferred agent for alkalinization is potassium citrate (30–60 mEq/day in divided doses), because potassium urate is twice more soluble than sodium urate. However, in patients with poor gastric tolerance to potassium citrate or contraindication to potassium supplements, sodium bicarbonate is an acceptable alternative. Limitation of animal proteins, purine-rich foods (including beer), alcoholic drinks and acidified beverages (sodas) are useful measures, together with large fluid intake (> 2–2.5 L/day). Allopurinol may be indicated in cases of symptomatic hyperuricaemia. Regular observance of alkalinisation, with periodic controls of urine pH by the patient, is needed to prevent the rapid formation of UA stones. Patients affected by UANL, especially if overweight, should be evaluated for type 2 diabetes or glucose intolerance and managed accordingly.

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The Impact of Diet on Urinary Risk Factors for Cystine Stone Formation

Nutrients ◽

10.3390/nu13020528 ◽

2021 ◽

Vol 13 (2) ◽

pp. 528

Author(s):

Roswitha Siener ◽

Norman Bitterlich ◽

Hubert Birwé ◽

Albrecht Hesse

Keyword(s):

Risk Factors ◽

Dietary Habits ◽

Sodium Intake ◽

Stone Formation ◽

Dietary Treatment ◽

Vegetarian Diet ◽

Dietary Sodium ◽

Urine Ph ◽

Cystine Stone ◽

The Impact

Despite the importance of dietary management of cystinuria, data on the contribution of diet to urinary risk factors for cystine stone formation are limited. Studies on the physiological effects of diet on urinary cystine and cysteine excretion are lacking. Accordingly, 10 healthy men received three standardized diets for a period of five days each and collected daily 24 h urine. The Western-type diet (WD; 95 g/day protein) corresponded to usual dietary habits, whereas the mixed diet (MD; 65 g/day protein) and lacto-ovo-vegetarian diet (VD; 65 g/day protein) were calculated according to dietary reference intakes. With intake of the VD, urinary cystine and cysteine excretion decreased by 22 and 15%, respectively, compared to the WD, although the differences were not statistically significant. Urine pH was significantly highest on the VD. Regression analysis showed that urinary phosphate was significantly associated with cystine excretion, while urinary sulfate was a predictor of cysteine excretion. Neither urinary cystine nor cysteine excretion was affected by dietary sodium intake. A lacto-ovo-vegetarian diet is particularly suitable for the dietary treatment of cystinuria, since the additional alkali load may reduce the amount of required alkalizing agents.

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Nephrolithiasis

10.2310/tywc.12042 ◽

2018 ◽

Author(s):

José Luiz Nishiura ◽

Ita Pfeferman Heilberg

Keyword(s):

Uric Acid ◽

Calcium Oxalate ◽

Dietary Habits ◽

Stone Formation ◽

Urine Volume ◽

First Episode ◽

Dietary Advice ◽

Dietary Recommendations ◽

Genetic Traits ◽

Oxalate Precipitation

Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment. This review contains 5 highly rendered figure, 3 tables, and 105 references.

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Clinical course and cystine stone formation during tiopronin treatment

Urological Research ◽

10.1007/bf00307941 ◽

1995 ◽

Vol 23 (2) ◽

pp. 111-117 ◽

Cited By ~ 33

Author(s):

�. Lindell ◽

T. Denneberg ◽

E. Hellgren ◽

J. -O. Jeppsson ◽

H. -G. Tiselius

Keyword(s):

Clinical Course ◽

Stone Formation ◽

Cystine Stone

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Is idiopathic recurrent calcium urolithiasis in males a cellular disease? Laboratory findings in plasma, urine and erythrocytes, emphasizing the absence and presence of stones, oxidative and mineral metabolism: an observational study

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm.2005.103 ◽

2005 ◽

Vol 43 (6) ◽

Cited By ~ 11

Author(s):

Paul Otto Schwille ◽

Mahimaidos Manoharan ◽

Angelika Schmiedl

Keyword(s):

Ascorbic Acid ◽

Uric Acid ◽

Plasma Levels ◽

Mineral Metabolism ◽

Stone Formation ◽

Healthy Controls ◽

Laboratory Findings ◽

Cross Sectional ◽

Calcium Urolithiasis

AbstractBackground: The site of origin of idiopathic recurrent calcium urolithiasis (IRCU) – a disorder characterized by stones composed of calcium oxalate (CaOx) and/or calcium phosphate (CaPi) – is uncertain, because in urine such risk factors for stones as disturbed Ox, Ca and Pi are not regularly observed. Aims: To evaluate whether imbalance of antioxidants and oxidants might be present in IRCU patients that is then followed by abnormal urine, plasma and intracellular mineral homeostasis, and stones. Methods: Males were investigated in the laboratory under standardized conditions, and three trials were organized. Trial 1 was cross-sectional, comparing IRCU patients with (n=111) and without stones in situ (n=126), focussing on abnormalities of oxypurines and minerals in urine and plasma, and metabolic activity (MA) of the disease. Trial 2 was partly controlled (n=14 healthy subjects; n=53 IRCU patients), comparing the plasma levels of total antioxidant status (TAS) and uric acid, the major antioxidant in humans, using the subsets Low (n=26) and High (n=27) TAS among IRCU patients in terms of plasma levels of uric acid, ascorbic acid, albumin, α-tocopherol and minerals, urinary minerals, CaOx and CaPi (hydroxyapatite) supersaturation. Trial 3, comprising stone-free IRCU patients (n=8) and healthy controls (n=8), compared minerals and mineral ratios in plasma and red blood cells (RBCs). Established analytical methodologies were used throughout. Results: In trial 1, uricemia, hypoxanthinuria and proteinuria were elevated, fractional urinary clearance (FE) of uric acid was decreased in stone-bearing patients, and MA correlated positively with uricemia and urinary total protein excretion. In trial 2, TAS was significantly decreased in IRCU patients vs. healthy controls; low TAS coincided with low plasma uric acid and albumin, unchanged ascorbic acid, α-tocopherol and parathyroid hormone, but increased FE-uric acid and Pi excretion; the latter correlated negatively with TAS. In trial 3, plasma minerals were significantly decreased in IRCU patients vs. controls, and Ca/Pi, (Ca/Pi)/Mg and (Ca/Pi)/Na molar ratios increased; the latter ratio was also increased in RBCs, and correlated highly positively with the same ratio in plasma. Conclusions: In IRCU 1) renal stones in situ in combination with high fasting uricemia, high hypoxanthinuria and protein-uria, and high MA suggest that a systemic metabolic anomaly underlies stone formation; 2) antioxidant deficit is frequent, unrelated to the presence or absence of stones but apparently related to poor renal uric acid recycling, low uricemia and albuminemia, exaggerated urinary Pi excretion, and low MA; 3) the combination of low plasma TAS, disordered Ca/Pi and other mineral ratios in urine, plasma and RBCs, but unchanged urinary Ca salt supersaturation is compatible with the view that CaPi solid and Ca microlith formation start inside oxidatively damaged cells.

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Cross-talk between renal lithogenesis and atherosclerosis: an unveiled link between kidney stone formation and cardiovascular diseases

Clinical Science ◽

10.1042/cs20171574 ◽

2018 ◽

Vol 132 (6) ◽

pp. 615-626 ◽

Cited By ~ 10

Author(s):

Asokan Devarajan

Keyword(s):

Risk Factors ◽

Uric Acid ◽

Cardiovascular Diseases ◽

Kidney Stone ◽

Arterial Wall ◽

Stone Formation ◽

Crystal Nucleation ◽

Cvd Risk Factors ◽

Cvd Risk ◽

Kidney Stone Formation

The prevalence of kidney stones and cardiovascular diseases (CVDs) are increasing throughout the world. Both diseases are chronic and characterized by accumulation of oxidized proteins and lipids in the renal tissue and arterial wall, respectively. Emerging studies have revealed a positive association between nephrolithiasis and CVDs. Based on preclinical and clinical evidences, this review discusses: (i) stone forming risk factors, crystal nucleation, aggregation, injury-induced crystal retention, and stone formation, (ii) CVD risk factors such as dyslipidemia, perturbation of gut microbiome, obesity, free radical-induced lipoprotein oxidation, and retention in the arterial wall, subsequent foam cell formation, and atherosclerosis, (iii) mechanism by which stone forming risk factors such as oxalate, calcium, uric acid, and infection contribute toward CVDs, and (iv) how CVD risk factors, such as cholesterol, phospholipids, and uric acid, contribute to kidney stone formation are described.

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Nephrolithiasis

10.2310/im.12042 ◽

2017 ◽

Author(s):

José Luiz Nishiura ◽

Ita Pfeferman Heilberg

Keyword(s):

Uric Acid ◽

Calcium Oxalate ◽

Dietary Habits ◽

Stone Formation ◽

Urine Volume ◽

First Episode ◽

Dietary Advice ◽

Dietary Recommendations ◽

Genetic Traits ◽

Oxalate Precipitation

Nephrolithiasis is a highly prevalent condition, but its incidence varies depending on race, gender, and geographic location. Approximately half of patients form at least one recurrent stone within 10 years of the first episode. Renal stones are usually composed of calcium salts (calcium oxalate monohydrate or dihydrate, calcium phosphate), uric acid, or, less frequently, cystine and struvite (magnesium, ammonium, and phosphate). Calcium oxalate stones, the most commonly encountered ones, may result from urinary calcium oxalate precipitation on the Randall plaque, which is a hydroxyapatite deposit in the interstitium of the kidney medulla. Uric acid nephrolithiasis, which is common among patients with metabolic syndrome or diabetes mellitus, is caused by an excessively acidic urinary pH as a renal manifestation of insulin resistance. The medical evaluation of the kidney stone patient must be focused on identifying anatomic abnormalities of the urinary tract, associated systemic diseases, use of lithogenic drugs or supplements, and, mostly, urinary risk factors such as low urine volume, hypercalciuria, hyperuricosuria, hypocitraturia, hyperoxaluria, and abnormalities in urine pH that can be affected by dietary habits, environmental factors, and genetic traits. Metabolic evaluation requires a urinalysis, stone analysis (if available), serum chemistry, and urinary parameters, preferably obtained by two nonconsecutive 24-hour urine collections under a random diet. Targeted medication and dietary advice are effective to reduce the risk of recurrence. Clinical, radiologic, and laboratory follow-ups are needed to prevent stone growth and new stone formation, to assess treatment adherence or effectiveness to dietary recommendations, and to allow adjustment of pharmacologic treatment. This review contains 5 highly rendered figure, 3 tables, and 105 references.

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Prevention of Recurrent Calcium Stone Formation with Potassium Citrate Therapy in Patients with Distal Renal Tubular Acidosis

The Journal of Urology ◽

10.1016/s0022-5347(17)46963-1 ◽

1985 ◽

Vol 134 (1) ◽

pp. 20-23 ◽

Cited By ~ 141

Author(s):

Glenn M. Preminger ◽

Khashayar Sakhaee ◽

Carolyn Skurla ◽

Charles Y.C. Pak

Keyword(s):

Renal Tubular Acidosis ◽

Stone Formation ◽

Potassium Citrate ◽

Distal Renal Tubular Acidosis ◽

Calcium Stone ◽

Renal Tubular

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Renal stone disease: causes, evaluation and medical treatment

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302006000400027 ◽

2006 ◽

Vol 50 (4) ◽

pp. 823-831 ◽

Cited By ~ 42

Author(s):

Ita Pfeferman Heilberg ◽

Nestor Schor

Keyword(s):

Medical Treatment ◽

Renal Stone ◽

Salt Intake ◽

Current Knowledge ◽

Stone Formation ◽

Potassium Citrate ◽

Blood Analysis ◽

Dietary Recommendations ◽

Metabolic Disturbances ◽

Mineral Density

The purpose of the present review is to provide an update about the most common risk factors or medical conditions associated with renal stone formation, the current methods available for metabolic investigation, dietary recommendations and medical treatment. Laboratory investigation of hypercalciuria, hyperuricosuria, hyperoxaluria, cystinuria, hypocitraturia, renal tubular acidosis, urinary tract infection and reduction of urinary volume is based on the results of 24-hr urine collection and a spot urine for urinary sediment, culture and pH. Blood analysis for creatinine, calcium and uric acid must be obtained. Bone mineral density has to be determined mainly among hypercalciurics and primary hyperparathyroidism has to be ruled out. Current knowledge does not support calcium restriction recommendation because it can lead to secondary hyperoxaluria and bone demineralization. Reduction of animal protein and salt intake, higher fluid intake and potassium consumption should be implemented. Medical treatments involve the use of thiazides, allopurinol, potassium citrate or other drugs according to the metabolic disturbances. The correction of those metabolic abnormalities is the basic tool for prevention or reduction of recurrent stone formation.

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