Urine composition in patients with urolithiasis during treatment with magnesium oxide

Summary Fifteen patients with recurrent renal stone formation were treated with 400 mg magnesium oxide daily. Urine composition was analyzed before the start of treatment and after 6–12 months. The urinary excretion of magnesium before and during treatment was 321±120 (mean ±SD) and 409±140 mmol per mol creatinine respectively, a difference that was not statistically significant. Urinary calcium increased from 473±186 to 662±213 mmol per mol creatinine (p<0.05). All patients who increased their excretion of magnesium also increased the urinary output of calcium and, as a result of this, the calcium/magnesium-quotients were unaffected by the treatment. No significant effect was observed on urine oxalate excretion. Serum concentrations of calcium, magnesium and urate all remained at the pre-treatment level. From the results obtained in this study, magnesium oxide in this dosage cannot be recommended for use in treatment of patients with urolithiasis.     

Risk factors of calcium stone formation in patients with primary Sjögren's syndrome

Distal renal tubular acidosis (dRTA), which occurs in patients with primary Sjögren's syndrome (SS), is a risk factor for the development of urolithiasis. Twenty-seven patients with SS were evaluated with respect to biochemical risk factors of calcium stone formation. Sixteen had no history of urolithiasis (group 1) whereas 11 had such a history (group 2). The stone composition was known for seven of the patients, and calcium phosphate was the major stone constituent in all of them. dRTA was present in all patients in group 2, and in 7 of the 16 patients in group 1. Hypocitraturia was common inboth groups, and the urinary excretion of citrate did not differ between the two groups. There was a higher urinary excretion of calcium and urate in group 2 and this group also had a higher urine volume. The risk of forming a urine supersaturated with calcium oxalate (CaOx) expressed in terms of AP(CaOx)index(s), which is an approximate estimate of the ion-activity product of CaOx calculated for a 24-h urine volume of 1500 ml, was higher in stone formers. A similarly derived estimate of the ion-activity product of calcium phosphate, AP(CaP)index(s), was calculated for a urine pH of 7. Although AP(CaP)index(s) was not significantly higher in group 2, there was a good correlation between AP(CaP)index(s) and AP(CaOx)index(s). We conclude that the urine composition in patients with SS, dRTA and urolithiasis is similar to that of other stone-forming patients with dRTA, and recurrence preventive therapy can be designed as for these patients.     

A study on the cause of urolithiasis of the upper urinary tract--clinical study of risk factors in the formation of stones in the upper urinary tract

Various risk factors and inhibitors of the stone formation of the upper urinary tract have been pointed out in urine. We examined the amount of daily excretion of several important risk factors (calcium, phosphorus, urate and oxalate) and inhibitors (magnesium and citrate) in the urine of 21 healthy males, 13 male single stone formeks and recurrent and/or multiple stone formers before and after taking the regular diet which contains 500 mg of calcium and 1,000 mg of phosphorus a day. The daily excretion of calcium, phosphorus and magnesium indicated no significant differences among the 3 groups. The excretion of oxalate in urine for 24 hours was significantly decreased in the stone formers after taking the regular diet. The urinary excretion of the urate per body surface area in the stone formers was significantly higher than that in the healthy control. The amount of the excretion of the citrate in urine in the recurrent and/or multiple stone formers was significantly lower than that in the other 2 groups. Many patients of the recurrent and/or multiple urinary stones had more than two abnormal values of above-mentioned risk factors and inhibitors. These results suggest that the causes of the formation of the upper urinary stone were not single but multiple and that the dietary advice to these patients was important against the recurrence of the urolithiasis.     

Effect of magnesium on calcium oxalate urolithiasis

Previous studies have shown that hypomagnesuria induced by magnesium deficient diet causes calcium oxalate crystal deposition in renal tubules of hyperoxaluric rats and administration of magnesium to these rats results in prevention of calcium oxalate crystallization in their kidneys. Based on these studies magnesium was claimed to be beneficial for calcium oxalate stone patients. However, hypomagnesuria is not a common phenomenon. To better understand the role of magnesium as an inhibitor of calcium oxalate crystallization in urine, we studied the effect of magnesium on calcium oxalate urolithiasis in rats on a regular diet and a hyperoxaluric protocol. Excess magnesium was administered to male rats on regular diet and a lithogenic protocol. Magnesium administration to hyperoxaluric rats did not result in significant changes in urinary excretion of calcium or oxalate or in calcium oxalate relative supersaturation. Urinary excretion of citrate was also not significantly altered. Some animals from both groups, those on magnesium therapy and those not on magnesium therapy had crystals deposited in their renal tubules. We conclude that excess magnesium has no significant effect on calcium oxalate urolithiasis in normomagnesuric conditions.     

Comparison of renal function and metabolic abnormalities of cystine stone patients and calcium oxalate stone patients in China

Purpose

To compare renal function and metabolic abnormalities of cystine stone patients and calcium oxalate stone patients in China.

Methods

Between 2008 and 2011, thirty cystine stone patients were involved in our study, and an equal number of age- and gender pair-matched patients with calcium oxalate stones. Non-stone forming individuals were elected as controls. The evaluation included blood chemistry studies and 24-h urine collection in both groups of patients.

Results

The cystine stone patients had higher mean values of serum blood urea nitrogen, urate and creatinine levels than patients in other two groups. With respect to urine risk factors, cystine stone patients had higher urinary citrate and lower urinary oxalate and creatinine than calcium oxalate stone patients. When compared to non-stone forming individuals, cystine stone patients had higher urinary urate excretion and lower urinary creatinine excretion. Metabolic abnormalities could be demonstrated in 80 % of the cystine stone patients and in 100 % of the calcium oxalate stone patients. We also compared urine risk factors among cystine stone patients with different urine cystine excretion (<1 mmol/24 h, 1–2 mmol/24 h and >2 mmol/24 h). No significant difference was found in urine risk factors among three groups.

Conclusions

This study suggested that cystine stone patients were at greater risk for the loss of renal function than calcium oxalate stone patients, but the risk of the formation of calcium oxalate stones was lower. Our results also indicated that urinary cystine had little or no impact on the excretion of urine chemistries in cystine stone patients.     

Estimated levels of supersaturation with calcium phosphate and calcium oxalate in the distal tubule

Approximate estimates of the ion-acitivity products of calcium phosphate and calcium oxalate in distal tubular urine were derived from the 16-h urinary excretion of calcium, oxalate, citrate, magnesium and phosphate. Urine variables were obtained from 96 normal subjects and 277 calcium stone formers and the calculations were carried out with iterative approximation using the EQUIL2 program. With respect to other ions of importance for the ion-activity products, the urine was assumed to have a fixed composition with pH 6.45. Significantly higher ion-activity products of both calcium phosphate and calcium oxalate were recorded in stone formers. It was concluded that diurnal variations in urine composition and pH might result in peaks of calcium phosphate supersaturation in distal tubular urine whereby a crystallization can occur. In association with abnormalities in terms of promotion and inhibition of calcium salt crystallization, such a precipitation can be of importance for the subsequent formation of calcium renal stones.     

Effects of jejunoileal bypass on oxalate and mineral metabolism in rats.

OBJECTIVE--To reassess the effects of jejunoileal bypass on the gastrointestinal absorption and bone metabolism of certain minerals in rats, and to see if jejunoileal bypass in rats was a suitable model in which to study formation of calcium oxalate renal stones. DESIGN--Controlled study. SETTING--Division of Experimental Surgery, University of Erlangen, Germany. MATERIAL--43 male Sprague-Dawley rats. INTERVENTION--23 rate underwent jejunoileal bypass, and 20 laparotomy, with transsection and anastomosis of the jejunum and ileotomy and suture (sham operation). RESULTS--Rats that had undergone jejunoileal bypass ate less and gained less weight than those that had had sham operations. Absorption of calcium and phosphorus from the intestine was impaired, but that of magnesium was unchanged. Absorption of oxalate from the small intestine was unchanged, but that from the colon was increased. There were no signs of hyperoxaluria or urolithiasis. Serum mineral homeostasis was not affected by jejunoileal bypass nor were bone volume, density, or mineral concentrations. Serum concentrations of parathyroid hormone and 1,25-dihydroxycholecalciferol remained low, suggesting that jejunoileal bypass might have induced some calcium flux towards the vascular space. CONCLUSIONS--Jejunoileal bypass halts weight increase in rats; the model may be helpful in elucidating associations between enteric factors and calciotropic hormones, and several metabolic features that are altered by jejunoileal bypass in man are not altered in rats.     

Hyperoxaluria in kidney stone formers treated with modern bariatric surgery

PURPOSE: Nephrolithiasis and renal failure secondary to severe hyperoxaluria were complications of jejunoileal bypass for obesity, leading to the discontinuation of this procedure in the United States in 1980. Bariatric procedures currently in use have not been adequately evaluated for this complication. MATERIALS AND METHODS: We compared 24-hour urine chemistry studies of 132 patients with nephrolithiasis who had undergone bariatric surgery with the urine chemistry studies of patients who had undergone jejunoileal bypass, those with routine kidney stones and normal subjects. The primary aim was to determine if hyperoxaluria developed in patients who underwent bariatric surgery and had kidney stones as had been seen with jejunoileal bypass. RESULTS: Patients who have undergone modern bariatric surgery had an adjusted mean urine oxalate excretion of 83 mg per day compared to 39 mg per day for routine kidney stone formers and 34 mg per day for normal subjects (p <0.001 for both comparisons), but not quite as high as that found in patients treated with jejunoileal bypass (102 mg per day, p <0.001). Urine supersaturation of calcium oxalate, the main driving force for calcium oxalate stone formation, was higher in patients treated with bariatric surgery compared to routine kidney stone formers and normal subjects (p <0.001 for both comparisons). CONCLUSIONS: Hyperoxaluria is the most significant abnormality of urine chemistry studies in patients with kidney stones who have undergone bariatric surgery. Many of these patients have a degree of hyperoxaluria that could lead to kidney failure. Further studies are required to determine the prevalence of this problem in patients who have undergone bariatric surgery.     

The effect of glucose intake on urine saturation with calcium oxalate,calcium phosphate,uric acid and sodium urate

The effect of simple carbohydrate intake on the state of urine saturation was studied in 44 patients with calcium kidney stones and in 28 healthy subjects. Renal excretion of calcium, magnesium and oxalate significantly increased and pH of urine decreased after an intake of 100 g glucose in stone formers and healthy subjects. In the basic conditions (before glucose administration) urine was supersaturated with calcium oxalate in stone formers (median 0.55) and healthy subjects (0.24; p<0.05). Carbohydrate intake caused a significant increase of the degree of urine saturation with calcium oxalate and uric acid. The degree of urine saturation with brushite and sodium urate after glucose administration did not change. These data suggest that excess of simple carbohydrate consumption may increase the degree of urine saturation with some of the compounds important in stone formation.     

Urinary excretion of urate in patients with calcium oxalate stone disease

Summary The diurnal variation in excretion and concentration of urinary urate was studied in 31 patients with calcium oxalate stone disease. Urate excretion was highest during the day-time, decreased in the evening and was low during the night. Meal-related peaks were observed. The concentration of urate reached the highest levels during the morning hours and, attributable to a low pH in morning urine, most samples were at this time super-saturated with respect to uric acid. In addition, many urines appeared to be at high risk of exceeding the uric acid formation product. Concerning the ion-activity product of sodium urate, supersaturated samples were frequently found, but the risk of exceeding the formation product for sodium urate at a normal urate excretion was apparently low.     

Idiopathic hypercalciuria

Summary 24 h urine compositions of male stone formers with idiopathic hypercalciuria prior to treatment were compared with those of male general practitioners without urolithiasis. Urinary urate was slightly higher in the stone formers than in the normals but this was not statistically significant. Furthermore, when results were corrected for the higher creatinine excretions of the stone formers then the reverse was true and statistically significant. All subjects with urinary urate over 7.0 mmol/24h were separately studied. In these groups the normals had higher urate and creatinine excretions than the stone formers but when results were corrected for creatinine the difference in the urate excretions disappeared. In long term follow up studies urinary calcium was lowered by diet and more so by diet supplemented with either Bendrofluazide or cellulose phosphate. Each drug raised urinary oxalate slightly and this was statistically significant, while both drugs together caused an even bigger rise in oxalate excretion. An unexpected finding was a rise in urinary urate with cellulose phosphate.     

Urinary risk factors in calcium oxalate stone disease: comparison of men and women

The daily excretion of calcium, oxalate, uric acid and glycosaminoglycans, the 24-h urinary pH and volume, and the inhibitory effects of the urines on calcium oxalate crystal growth and aggregation, were measured in 44 normal women, 41 normal men, 32 female stone formers and 63 male stone formers. No significant differences could be found between the normal men and women, the male and female stone formers, or between the patients and their normal controls with regard to the excretion of oxalate and glycosaminoglycans, and the urinary pH. The normal women exhibited significantly lower urinary volumes and excreted less calcium per day than did the other subject groups. The excretion of calcium by the female stone formers was indistinguishable from that of both groups of men. The male and female stone formers did not differ from their corresponding control groups with regard to the excretion of urate, but both groups of male subjects had significantly higher daily urate excretions than did either female category. This was attributed to the greater body weights of the men. There were no discernible differences between any of the subject groups with regard to the inhibitory effects of their urines on calcium oxalate crystal growth, but urines from both groups of female subjects demonstrated a significantly greater inhibitory influence on crystal aggregation than did those of the men. It would appear that the relatively low incidence of uninfected calcium oxalate urolithiasis in women compared with men may be attributable to (a) a lower daily calcium excretion and (b) a higher inhibitory activity of their urines towards crystal aggregation.     

Phenotypic expression of primary hyperoxaluria: comparative features of types I and II

BACKGROUND: The primary hyperoxalurias are autosomal recessive disorders resulting from deficiency of hepatic alanine:glyoxylate aminotransferase (PHI) or D-glycerate dehydrogenase/glyoxylate reductase (PHII). Marked hyperoxaluria results in urolithiasis, renal failure, and systemic oxalosis. A direct comparison of PHI and PHII has not previously been available. METHODS: Twelve patients with PHI and eight patients with PHII with an initial creatinine clearance of greater than or equal to 50 mL/min/1.73 m2 underwent similar laboratory evaluation, clinical management, and follow-up. Diagnosis of PHI and PHII was made by hepatic enzyme analysis (N = 11), increased urinary excretion of glycolate or glycerate (N = 7), or complete pyridoxine responsiveness (N = 2). Six PHI and five PHII patients had measurements of calcium oxalate crystalluria, urine supersaturation, and urine inhibition of calcium oxalate crystal formation. RESULTS: PHI and PHII did not differ in age at the onset of symptoms, initial serum creatinine, or plasma oxalate concentration. Urine oxalate excretion rates were higher in PHI (2.19 +/- 0.61 mmol/1.73 m2/24 hours) than PHII (1.61 +/- 0.43, P = 0.04). Urine osmolality, calcium, citrate, and magnesium concentrations were lower in PHI than PHII (P = 0.001, P = 0.019, P = 0.0002, P = 0.03, respectively). Crystalluria scores and calcium oxalate inhibitory activity of the urine did not differ between PHI and PHII. Calcium oxalate supersaturation in the urine was less in PHI (7.3 +/- 1.9) compared with PHII (14.0 +/- 3.3, P = 0.002). During follow-up of 10.3 +/- 9. 6 years in PHI and 18.1 +/- 5.6 years in PHII, stone-forming activity and stone procedures were more frequent in PHI than PHII (P < 0.01 and P = 0.01, respectively). Four of 12 PHI compared with 0 of 8 PHII patients progressed to end-stage renal disease (P = 0.03). CONCLUSION: The severity of disease expression is greater in type I primary hyperoxaluria than in type II. The difference may be due to greater oxalate excretion and lower concentrations of urine citrate and magnesium in patients with PHI compared with PHII.     

Analysis of the urinary risk factors of urolithiasis in healthy children

Since incidence of idiopathic calcium oxalate urolithiasis in children was very low, a study was made to analyze the risk factors of calcium oxalate stone in male volunteers without any episode of urolithiasis. They were divided into four groups, group I: eight years old, group II: 11 years old, group III: 18 to 24 years old, group IV: 41 to 45 years old. Inhibitory activities of urine were significantly higher in groups of children than in groups of adults. However, inhibitory activities of filtered urine, extracted through filters with conserved limit of 25000 of molecular weight, were reduced significantly. Therefore, it was suggested that materials with molecular weight over 25000 participated in the inhibitory activities. Furthermore, the activities of filtered urine of group I were still higher than those of the non-filtered urine in groups of adults. Accordingly it was considered that substances less than 25000 of molecular weight also participated in the inhibitory activities in children. An analysis of uric acid, citrate, magnesium and uronic acid in urine revealed that magnesium excretion volume and magnesium concentration ratio to creatinine were higher in children than in adults. Magnesium seemed to boost the inhibitory activities in children. In the measurement of crystalloid materials, the concentration of calcium was significantly lower in children groups than in groups of adults. It seemed that calcium also takes part in reduction of incidence of urinary stone in children.     

Magnesium excretion and calcium oxalate urolithiasis

One hundred fifty-five recurrent noninfectious calcium oxalate stone formers were evaluated in an effort to assess the importance of magnesium excretion on calcium oxalate stone formation. All patients evaluated had normal urinary magnesium excretion, and any elevation of the calcium/magnesium ratio was related to the presence of hypercalciuria. The findings indicate that magnesium deficiency does not appear to be a significant cause of calcium oxalate urolithiasis. If magnesium supplement is of value in some patients, it is likely related to its inhibitory effect on calcium oxalate crystallization.     

Pattern of urolithiasis in a general hospital a prospective study

Judging from the abundance of papers published in the medical journals there appears to be a global increase in the incidence of urolithiasis. Urinary excretion of various stone-forming salts in a 24-hour urine specimen is the mainstay of the metabolic workup done in stone-formers. According to the findings patients have been classified into neat categories depending on whether they were hypercalciuric, hyperuriocosuric, etc. As a group their excretion of calcium, oxalate, and urate was not different from the controls. However, they excreted significantly more phosphate and had lower 24-hour urine volumes than the controls.     

Risk factors for urinary calcium oxalate crystals as revealed by their specific enzymatic assay

Calcium oxalate crystal concentrations were assayed by a new highly specific enzymatic method in 1200 urine samples from normal subjects and stone formers. Examination of the crystals was also carried out by light microscopy and urines were analysed for oxalate, calcium, magnesium, citrate, urate, pH and osmolality. A striking positive correlation was established between urinary oxalate concentration and calcium oxalate crystal concentration as well as incidence of calcium oxalate crystals and aggregates seen by microscopy. A less striking relationship, also supported by light microscopy, was found between calcium oxalate crystal concentration and urinary calcium concentration. A small rise in calcium oxalate crystalluria was seen with increasing osmolality, but no relationship found between concentration or urinary urate, citrate or magnesium and that of calcium oxalate crystals. Higher levels of calcium oxalate crystal concentration appeared in alkaline urines in association with calcium phosphates. The dominance of urinary oxalate as a risk factor for calcium oxalate crystalluria is confirmed.     

Uninephrectomy enhances urolithiasis in ethylene glycol treated rats.

Uninephrectomy (uNX) usually induces compensatory hyperfunction of the remaining kidney in an attempt to preserve the homeostasis of body fluid composition. The present study used uninephrectomized Sprague-Dawley rats on a lithogenic diet (0.5% ethylene glycol, EG) to evaluate the influence on urinary stone formation and calcium oxalate crystal deposition of compensatory excretion of lithogenic substances in the remnant kidney. The results showed that there were no urinary stones or calcium oxalate crystal deposits in the intact or uNX rats fed a normal diet. In the EG feeding groups, the incidence of massive (grade 3) crystal deposits was significantly higher in the uNX rats (87.5%) than that in the intact rats (37.5%; P less than 0.05). The incidence of urinary stone formation was also higher in the uNX rats as compared to that of the intact rats, although the difference did not achieve statistical significance. The serum magnesium, phosphorus and creatinine increased significantly, whereas creatinine clearance (CCr), 24-hour urinary excretions of citrate, sodium, potassium and chloride decreased significantly in the uNX rats fed EG. These data indicate that uninephrectomy increases the vulnerability of the contralateral remnant kidney to urolithiasis and crystal deposition when the lithogenic risk factors are present. Furthermore, once the remnant kidney forms urolithiasis or massive calcium oxalate crystal deposits, the renal function is severely compromised.     

Clinical studies on the recurrence of urolithiasis: (1). Influence of diet on urinary excretion of the stone forming constituents

Twenty-four hour urinary excretion of the stone forming constituents, calcium, oxalate, uric acid, phosphate and magnesium were assayed either under the restricted diet (190 stone formers and 52 non-stone formers) or under the ambulatory free diet (93 stone formers and 14 non-stone formers). Under the ambulatory free diet, urinary excretion of calcium, uric acid and magnesium in the male stone formers, and urinary excretion of calcium and magnesium in the female stone formers was significantly higher than that under the restricted diet. Under the restricted diet, no difference in urinary excretion of calcium, oxalate, uric acid or phosphate was noted between the stone formers and non-stone formers. However, urinary magnesium excretion of the stone formers under the restricted diet was significantly lower than that of the non-stone formers. Under the free diet, no difference in urinary excretion of calcium, oxalate, uric acid, phosphate or magnesium was observed between the stone formers and non-stone formers. Also, there was no significant difference in urinary excretion of calcium, oxalate, uric acid, phosphate or magnesium between the unilateral urolithiasis patients without previous stone history and that of the bilateral or recurrent stone formers. We conclude that urinary excretion of calcium, oxalate, uric acid, phosphate and magnesium have no major role in the stone producing mechanism. However, reduction of urinary excretion of calcium, oxalate, uric acid and phosphate and augmentation of urinary excretion of magnesium are mandatory in preventing stone recurrence until a better understanding of the cause of urolithiasis is obtained.