Physicochemical metabolic characteristics for calcium oxalate stone formation in patients with gouty diathesis

PURPOSE: We determined why calcium oxalate stones instead of uric acid stones form in some patients with gouty diathesis. MATERIALS AND METHODS: Gouty diathesis was diagnosed from absence of secondary causes of uric acid stones or low urinary pH, and reduced fractional excretion of urate with discriminant score of the relationship between urinary pH and fractional excretion of urate less than 80. From the stone registry 163 patients with gouty diathesis were identified, including 62 with uric acid stones (GD + UA) and 101 patients with calcium oxalate stones (GD + Ca). Metabolic data and 24-hour urinary chemistry study were compared between the 2 groups. RESULTS: Compared with GD + UA, GD + Ca had significantly greater urinary calcium (196 +/- 96 mg per day vs 162 +/- 82 mg per day, p <0.05) and significantly lower urinary citrate (430 +/- 228 vs 519 +/- 288 mg per day, p <0.05), resulting in higher urinary saturation of calcium oxalate. Both groups had low urinary pH (less than 5.5) and high urinary undissociated uric acid (greater than 100 mg/dl). Urinary calcium post-oral calcium load was significantly higher in GD + Ca than in GD + UA (0.227 vs 0.168 mg/dl glomerular filtrate, p <0.001). CONCLUSIONS: Calcium oxalate stones may form in some patients with gouty diathesis due to increased urinary excretion of calcium and reduced excretion of citrate. Relative hypercalciuria in GD + Ca may be due to intestinal hyperabsorption of calcium.     

Urinary inhibitors of crystallization in hypercalciuric children with hematuria and nephrolithiasis

Urinary inhibitors are suggested to play a significant role in reducing crystallization in calcium (Ca) stone former and idiopathic hypercalciuria (IH). Urinary inhibitors such as magnesium (Mg), citrate, and glycosaminoglycans (GAGs) were evaluated, as well as urinary Ca and creatinine (Cr), in IH children with nephrolithiasis (LIT) or with hematuria plus IH (HEM) and were compared with a control group. The mean 24-h urinary excretion of Mg was similar in all groups. However, the urine Ca/Mg ratio was significantly increased (P <0.005) in LIT and HEM groups. A higher mean value for GAGs and citrate was found in the HEM group, but a very low level of GAGs (less than 60% of the normal value) and citrate (less than 30% of the normal value) was found in the LIT group. These data suggest that, despite a high urinary Ca excretion (3.6±0.1 mg/kg per day) in the HEM group, elevated urinary GAGs (32.0±1.0 mg/g Cr) and a normal urinary citrate (428.7±62.3 mg/24 h) excretion may prevent Ca crystallization and thus renal stones. In contrast, in the LIT group low urinary GAG (10.3±0.9 mg/g Cr) and citrate (235.2±52.3 mg/24 h) excretion may precipitate stone formation in the presence of a high urinary Ca excretion. Thus, it is reasonable to suggest that patients with hematuria and IH may not develop overt renal stone due to the presence of normal levels of renal stone inhibitors. Received October 30, 1995; accepted December 15, 1995     

溃疡性结肠炎的外科治疗16例分析

目的探讨溃疡性结肠炎的外科治疗方式。方法对16例行外科手术治疗的溃疡性结肠炎的临床资料进行回顾性分析。结果本组16例行外科手术治疗，占全部收治患者的20．5％（16／78）。手术原因包括保守治疗无效10例，肠梗阻3例，合并息肉可疑癌变3例。行全结直肠切除、回肠造口术8例，全结直肠全切除、回肠肛管吻合术4例，结肠全切除、回直肠吻合术2例，结肠部分切除2例。结论溃疡性结肠炎主要手术指征为内科治疗无效或合并肠梗阻及并发息肉可疑癌变者。全结肠切除、回肠造口术治疗较彻底，全结直肠切除、回肠贮袋肛管吻合术可改善排便控制功能，但吻合口溃疡发生率高。     

Inhibitory effect of fluoride on renal stone formation in rats.

The effect of fluorine (F) on stone formation induced by ethylene glycol (EG) was studied in rats. For different groups, the drinking water was supplemented with EG, sodium fluoride (NaF), EG+NaF, or nothing as control. An isotope-tracing method was used to evaluate experimental stone formation in the kidneys by introducing 45Ca intraperitoneally into rats and then measuring the radioactivity of the kidney. At the end of the 4-week experiment, rats of the EG+NaF group showed a significantly lower incidence of gross urinary stones and lower 45Ca activity in their kidneys compared to the EG group of rats. Both the EG group and EG+NaF group had markedly increased urinary oxalate excretion, with the latter significantly lower than the former (p less than 0.05). Urinary oxalate excretion was relatively lower in the NaF group than in the control group. This study indicates that NaF can inhibit renal stone formation induced by EG by decreasing oxalate synthesis and urinary oxalate excretion, and suggests a possible clinical therapeutic value of NaF in the prevention of oxalate kidney stones.     

Heated oyster shell with algal ingredient (AAACa) decreases urinary oxalate excretion

In nine normal subjects, four men and five women between 23 and 49 years of age, 800 mg calcium was orally administered as active absorbable algal calcium (AAA Ca) (A) and calcium carbonate (CaCO₃) (B), to compare with non-calcium-containing placebo (C) in a crossover design. Calcium, oxalate, osmolality, creatinine, and pH were measured in the first three morning urine samples and Ca/osmolality, Ca/osmolality/body weight, Ca/creatinine, and oxalate/osmolality were calculated to correct for urine dilution. Ca × oxalate product was also calculated, and Ca oxalate crystal in the sediment was microscopically examined, semiquantitatively estimated as −, +, ++, or +++, and numerically expressed as 0, 1, 2, or 3, respectively. Urinary Ca excretion was similar in groups A and B, but significantly larger than in group C, regardless of the method of correction for dilution. Urinary oxalate excretion with correction for osmolality, however, was significantly lower in A than in B and C, which gave similar values. Urine pH was similar among all three groups. Ca × oxalate product was significantly higher in C than in A, but A and B were not significantly different. AAA Ca appeared to decrease urinary oxalate excretion and Ca × oxalate product more efficiently than CaCO₃, suggesting the possibility of inhibiting the formation of Ca × oxalate kidney stones. Received: January 26, 2000 / Accepted: March 9, 2000     

Perioperative change of ionized magnesium concentration--effect of blood transfusion

In order to evaluate the effect of intra-operative blood transfusion on post-operative decrease of ionized Mg (Mg2+), we performed following studies. 1) We measured ionized Mg (Mg2+), total Mg, ionized Ca (Ca2+), total Ca and citrate before and after operation in 70 patients. 2) We evaluated the effect of citrate on Mg2+ and Ca2+ in vitro. 3) We also measured these values during blood transfusion in 8 patients. There was no significant difference between post-operative Mg2+ of 45 patients without blood transfusion (0.49 +/- 0.07 mmol.l-1, % decrease from pre-operative value was 13.4 +/- 9.2%; mean +/- SD), and that of 25 patients with blood transfusion (0.48 +/- 0.09 mmol.l-1, 17.9 +/- 10.2%). Mean value of post-operative citrate concentration of patients with blood transfusion was 0.15 +/- 0.11 mmol.l-1, and this value decreased Mg2+ about 2% in in vitro study. During blood transfusion, Mg2+ (0.41 +/- 0.05 mmol.l-1) and ionized % (54.5 +/- 8.3%) decreased significantly just like Ca2+ with elevated citrate concentration (0.95 +/- 0.59 mmol.l-1). In conclusion, intra-operative blood transfusion had minor effect on the post-operative decrease of Mg2+, and the major cause was thought to be the dilution of extracellular fluid by Mg-free fluid administered during operation.     

Acute caffeine effects on urine composition and calcium kidney stone risk in calcium stone formers

PURPOSE: Caffeine increases urinary calcium (ca) excretion in nonstone formers. We designed a study to determine the effect of caffeine consumption on urinary composition in stone formers. MATERIALS AND METHODS: A total of 39 normocalcemic patients with calcium stones consumed caffeine (6 mg/kg lean body mass) after 14 hours of fasting. Urinary composition was compared 2 hours before and 2 hours after caffeine consumption. Control subjects included 9 nonstone formers studied contemporaneously with patients plus data from 39 nonstone formers from previous studies matched to each patient by level of fasting calcium/creatinine (Cr), gender and age. RESULTS: Caffeine increased urinary Ca/Cr, magnesium/Cr, citrate/Cr and sodium/Cr but not oxalate/Cr in stone formers and controls. The Tiselius stone risk index for calcium oxalate precipitation increased from 2.4 to 3.1 in stone formers and from 1.7 to 2.5 in nonstone formers. Of the 39 stone formers 32 had an increased Tiselius risk index after caffeine. Post-caffeine increases in Ca/Cr and Na/Cr were highly correlated. CONCLUSIONS: Caffeine consumption may modestly increase risk of calcium oxalate stone formation.     

Urinary citrate excretion in patients with renal calculi

Urinary citrate excretion was measured with a specific enzymatic technique in normal subjects and in an unselected group of patients with recurrent calcium oxalate stones. Hypocitraturia (citrate levels less than those present in 95 per cent of the normal population) was detected in 7 of 46 patients with stones (15 per cent). Hypocitraturia was the only metabolic abnormality in 6 patients.     

外科治疗15例溃疡性结肠炎的临床体会

目的:探讨溃疡性结肠炎的外科治疗体会,提高对本病救治水平。方法:对15例外科治疗的溃疡性结肠炎的临床资料进行回顾性分析。结果:本组15例患者中,行全结直肠切除、回肠造口术4例;全结肠切除、回肠直肠吻合术4例;全结肠直肠切除、回肠贮袋肛管吻合术7例。结论:全结肠切除、回肠造口术治疗较彻底,全结肠直肠切除、回肠贮袋肛管吻合术可改善排便控制功能但吻合口溃疡发生率高。对于常见的吻合口瘘并发症,通过持续骶前引流等保守治疗,可使吻合口瘘闭合。"J"型全结肠直肠切除、回肠贮袋肛管吻合术是目前治疗溃疡性结肠炎较好的手术方法。     

The effect of Phyllanthus niruri on urinary inhibitors of calcium oxalate crystallization and other factors associated with renal stone formation

OBJECTIVE: To evaluate the effect of an aqueous extract of Phyllanthus niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium and glycosaminoglycans (GAGs). MATERIALS AND METHODS: The effect of chronic (42 days) administration of Pn (1.25 mg/mL/day, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. RESULTS: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (sd) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx + water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx + Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx + water group, at 16.6 (9.6) g/g calculus. CONCLUSION: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi.     

Stone forming risk of calcium citrate supplementation in healthy postmenopausal women

PURPOSE: We evaluated the effect of calcium citrate supplementation alone or in combination with potassium citrate on the stone forming propensity in healthy postmenopausal women. MATERIALS AND METHODS: A total of 18 postmenopausal women without stones underwent a randomized trial of 4 phases comprised of 2 weeks of treatment with placebo, calcium citrate (400 mg calcium twice daily), potassium citrate (20 mEq twice daily), and calcium citrate and potassium citrate (at same doses). During the last 2 days of each phase urine was collected in 24-hour pools for complete stone risk analysis. RESULTS: Compared to placebo, calcium citrate increased urinary calcium and citrate but decreased urinary oxalate and phosphate. Urinary saturation of calcium oxalate, brushite and undissociated uric acid did not change. Potassium citrate decreased urinary calcium, and increased urinary citrate and pH. It decreased urinary saturation of calcium oxalate and undissociated uric acid, and did not change the saturation of brushite. When calcium citrate was combined with potassium citrate, urinary calcium remained high, urinary citrate increased even further and urinary oxalate remained reduced from the calcium citrate alone, thereby marginally decreasing the urinary saturation of calcium oxalate. Urinary pH increased, decreasing urinary undissociated uric acid. The increase in pH increased the saturation of brushite despite the decrease in urinary phosphorus. CONCLUSIONS: Calcium citrate supplementation does not increase the risk of stone formation in healthy postmenopausal women. The co-administered potassium citrate may provide additional protection against formation of uric acid and calcium oxalate stones.     

Endocrine changes and urinary citrate excretion

Urinary citrate affects the ion-activity products of calcium oxalate and calcium phosphate and inhibits the growth of these crystals. Women are less prone to develop calcium stones and because they also excrete more citrate than men, an effect of sex steroids on citrate excretion might be important. We therefore analysed urinary citrate and creatinine before and during treatment with estrogen alone or together with medroxyprogesterone acetate in 29 postmenopausal women and at different gestational ages in 19 pregnant women. Urinary citrate and creatinine was also determined before and after orchidectomy in ten men with carcinoma of the prostate. The excretion of citrate and the ratios between citrate and creatinine were not significantly altered by pregnancy or orchidectomy. Neither did treatment with estrogen or estrogen/medroxyprogesterone acetate affect these variables. We were unable to explain the difference in citrate excretion between men and women by effects of sex steroids.     

The role of hyperoxaluria in the formation of calcium oxalate urinary calculi, and its association with other biochemical measurements

The part played by hyperoxaluria in the formation of calcium oxalate urinary calculi was studied in 153 patients who had each been diagnosed as having calcium oxalate urinary calculi on one or more occasions. Seventy-seven of the patients excreted normal amounts of calcium (less than 6.2 mmol/d), and 76 had hypercalciuria (excretion greater than or equal to 6.2 mmol/d); each group was divided into a further two groups depending on whether the oxalate concentration was above or below 0.16 mmol/l. Pure calcium oxalate stones were more common in patients whose calcium excretion was normal, and mixed calcium oxalate and phosphate stones were more common among hypercalciuric patients. Urinary concentrations/day of magnesium, citrate, and phosphorus were significantly lower in the two groups in which the oxalate concentrations were below 0.16 mmol/l than in a normal control group, and magnesium and phosphorus were significantly lower in the two groups in which oxalate concentrations were less than 0.16 mmol/l than in the two in which they were above that value. The concentration of citrate was also lower, but not significantly so. In addition, the pH of the urine in patients with mixed stones was significantly higher in all groups than when the stones were composed of pure calcium oxalate.     

Use of a probiotic to decrease enteric hyperoxaluria

BACKGROUND: Patients with inflammatory bowel disease have a 10- to 100-fold increased risk of nephrolithiasis, with enteric hyperoxaluria being the major risk factor for these and other patients with fat malabsorptive states. Endogenous components of the intestinal microflora can potentially limit dietary oxalate absorption. METHODS: Ten patients were studied with chronic fat malabsorption, calcium oxalate stones, and hyperoxaluria thought to be caused by jejunoileal bypass (1) and Roux-en-Y gastric bypass surgery for obesity (4), dumping syndrome secondary to gastrectomy (2), celiac sprue (1), chronic pancreatitis (1), and ulcerative colitis in remission (1). For 3 months, patients received increasing doses of a lactic acid bacteria mixture (Oxadrop), VSL Pharmaceuticals), followed by a washout month. Twenty-four-hour urine collections were performed at baseline and after each month. RESULTS: Mean urinary oxalate excretion fell by 19% after 1 month (1 dose per day, P < 0.05), and oxalate excretion remained reduced by 24% during the second month (2 doses per day, P < 0.05). During the third month on 3 doses per day oxalate excretion increased slightly, so that the mean was close to the baseline established off treatment. Urinary oxalate again fell 20% from baseline during the washout period. Calcium oxalate supersaturation was reduced while on Oxadrop, largely due to the decrease in oxalate excretion, although mean changes did not reach statistical significance. CONCLUSION: Manipulation of gastrointestinal (GI) flora can influence urinary oxalate excretion to reduce urinary supersaturation levels. These changes could have a salutary effect on stone formation rates. Further studies will be needed to establish the optimal dosing regimen.     

Successful management of uric acid nephrolithiasis with potassium citrate

Eighteen patients with uric acid nephrolithiasis (six with uric acid stones alone and 12 with both uric acid and calcium stones) underwent long-term treatment (1 to 5.33 years, mean of 2.78 years) with potassium citrate (30 to 80 mEq/day, usually 60 mEq/day). Urinary pH increased from low (5.30 +/- 0.31 SD) to normal (6.19 to 6.46) during treatment. Urinary content of undissociated uric acid, which was high to begin with at 204 +/- 82 mg/day, decreased to the normal range (64 to 108 mg/day) following treatment. Urinary citrate rose from 503 +/- 225 mg/day to 852 to 998 mg/day. Urinary saturation of calcium oxalate significantly declined with potassium citrate treatment. New stone formation rate declined from 1.20 +/- 1.68 stones/year to 0.01 +/- 0.04 stones/year (P less than 0.001 by chi square). Remission was experienced in 94.4% of patients, and the group stone formation rate declined by 99.2%. Detailed case reports were obtained in five patients showing different responses between sodium alkali and potassium alkali treatment. All five patients had persistently low urinary pH (typically less than 5.5) and normouricosuria, and four had hyperuricemia. Before treatment, they had stones surgically removed or spontaneously passed, which were pure uric acid in composition. When sodium alkali was give (as bicarbonate or citrate, 60 to 118 mEq/day), new stone formation continued in four patients, and a radiolucent (uric acid) calculus become "calcified" in the remaining patient. The stone analysis disclosed calcium oxalate in five patients and calcium phosphate in three patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention of stone formation and bone loss in absorptive hypercalciuria by combined dietary and pharmacological interventions

PURPOSE: We determined whether dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate treatment, would prevent stone formation and avert bone loss in 18 men and 10 women with type I absorptive hypercalciuria. MATERIALS AND METHODS: Patients were treated with thiazide (20) or indapamide (8) and potassium citrate (average dose 35 mEq. daily) for 1 to 11 years (mean 3.7) while maintained on low calcium oxalate diet. Serum and urinary chemistry studies and bone mineral density were measured at baseline and at the end of treatment. New stones formed were quantitated during 3 years before and during treatment. RESULTS: During treatment urinary calcium significantly decreased (346 +/- 85 to 248 +/- 79 mg. daily, p <0.001) but urinary oxalate did not change. Urinary pH and citrate significantly increased, and urinary saturation of calcium oxalate significantly decreased by 46%. Stone formation rate decreased significantly from 2.94 to 0.05 per year (p <0.001). L2-L4 bone mineral density increased significantly by 5.7% compared to normal peak value, and by 7.1% compared with normal age and gender matched value. Femoral neck bone mineral density also increased significantly. CONCLUSIONS: Dietary restriction of calcium and oxalate, combined with thiazide and potassium citrate, satisfactorily controlled hypercalciuria, prevented the secondary increase in urinary oxalate, reduced urinary saturation of calcium oxalate, virtually eliminated recurrent stone formation, and increased bone density of the spine and femoral neck. Thus, this dietary pharmacological program controlled stone formation as well as bone loss that often accompany type 1 absorptive hypercalciuria.     

Studies of dietary influence on urinary oxalate in calcium oxalate stone formers

In order to examine the effect of diet on the urinary excretion of oxalate, a spinach loading and milk loading experiment was performed in normal subjects and patients with single calcium oxalate stones and recurrent calcium oxalate stones after a rat experiment. When spinach (100 g, total oxalate 642.57 mg, insoluble oxalate 282.21 mg, taken oxalate 444.57 mg) was given with a low calcium diet to the patients, the increase of urinary oxalate was more prominent in those with recurrent stones; the mean urinary oxalate increased from 39.84 to 84.18 mg/day (P less than 0.01) in the group with recurrent stones, from 36.95 to 55.12 mg/day (P less than 0.05) in the group with single stones and from 33.99 to 42.78 mg/day in the control group. These increases in oxalate excretion could be ameliorated by the concurrent oral administration of milk (calcium 343 mg). Moreover, diurnal variation in oxalate excretion was observed. It was more evident under spinach load in the group with recurrent stones than in the control group. Urinary oxalate increased promptly, reaching peak levels between 4 and 6 hours after loading in the group with recurrent stones and single stones, and between 2 and 4 hours in the control group. The influence of the spinach load disappeared within 24 hours.     

炎性肠病45例手术治疗及疗效评价

目的 探讨炎性肠病的手术治疗方法 及疗效评估.方法 回顾性分析近6年经外科手术治疗的45例炎性肠病患者的临床资料.结果 急诊手术16例,Crohn病9例,溃疡性结肠炎(UC)7例.择期手术29例,Crohn病4例,UC 25例.其中13例Crohn病患者行小肠部分切除6例,内瘘者行小肠及结肠部分切除、吻合术1例,回肠穿...     

Urinary mineral excretion among normal Taiwanese children

Prompted by a large population of children with renal stones seen in 20 of our country's teaching hospitals over the past 10 years, this study of urinary mineral excretion in normal children was performed. Fasting urine from 1,072 normal Taiwanese school children and 24-h urine collections from 125 children separated into three age groups were analysed for calcium (Ca), phosphate, magnesium (Mg), uric acid, sodium (Na) and creatinine (Cr). Fasting Ca/Cr ratios were not different between the sexes. Ca/Cr ratios were higher in the 17- to 18-year age group as were 24-h urinary Ca excretions. Urinary Mg/Cr ratios were higher in girls than boys and 24-h urinary Mg excretion was highest in the younger age groups. Urinary Mg excretion in Taiwanese children is 54%–86% lower than previously reported in Caucasian children. Both uric acid/Cr ratios and 24-h urinary uric acid excretion were highest in the youngest children. Urinary Na/Cr ratios and 24-h urinary Na excretion were higher in the two younger age groups. There was no correlation between 24-h urinary Ca and Na excretion.     

Effects of pyruvate salts, pyruvic acid, and bicarbonate salts in preventing experimental oxalate urolithiasis in rats

Sodium pyruvate, potassium pyruvate, pyruvic acid, sodium bicarbonate and potassium bicarbonate were added to a calcium-oxalate lithogenic diet (a glycolic-acid diet) in order to determine their effects in preventing lithogenicity. Male Wistar-strain rats who had been fed the glycolic-acid diet developed marked urinary calculi within four weeks. Rats in the sodium and potassium pyruvate groups had, however, almost no stones in the urinary system. Rats in the bicarbonate and pyruvic-acid groups showed slightly less effect than those in the pyruvate groups. Urinary oxalate excretion was high in all the groups during the experiment. The urinary oxalate concentration was relatively higher in the sodium-pyruvate group, and significantly higher in the potassium-pyruvate group, than in the glycolic-acid group. Urinary citrate excretion was high both in the pyruvate and bicarbonate groups; the urinary citrate concentration was, however, significantly higher in the pyruvate groups than in the bicarbonate groups at the fourth experimental week. The urinary calcium and magnesium concentrations were irrelevant to the diets administered. Therefore, it can be concluded that pyruvate salts inhibit urinary calculi formation, not by decreasing oxalate synthesis, but by increasing the urinary citrate concentration; bicarbonate salts work in the same manner, but a little less effectively.