Prevalence of hyperoxaluria in idiopathic calcium oxalate kidney stone disease

Urinary excretion of oxalate, calcium and urate has been investigated in 88 patients affected by idiopathic calcium oxalate stone disease and in 20 normal subjects. Of these ions, only oxalate was found significantly higher in stone formers. Defining hyperoxaluria as urinary oxalate excretion greater than 2 SD above normal, 50% of stone-forming people were found to be hyperoxaluric. When stone formers were classified in normo- and hyperoxaluric, the prevalence of hypercalciuria, hyperuricuria, family history of stone disease and recurrencies in stone formation was the same in both groups. It is concluded that hyperoxaluria is a frequent finding in finding in idiopathic calcium oxalate renal stone disease.     

Relationship between supersaturation and calcium oxalate crystallization in normals and idiopathic calcium oxalate stone formers

BACKGROUND: In an earlier study on recurrent CaOx stone formers with no detectable abnormalities, we found that the urine of these subjects had a lower tolerance to oxalate load than controls and that the removal of urinary macromolecules with a molecular weight greater than 10,000 D improved their tolerance to oxalate. METHODS: The effects on CaOx crystallization of reduced urinary supersaturation of calcium oxalate (CaOx), induced by night water load, were studied in 12 normal males and in 15 male OxCa stone formers who were free from urinary metabolic abnormalities. The effect of the macromolecules, purified and retrieved from the natural and diluted urine, were analyzed in a metastable solution of CaOx. RESULTS: The water load caused an increase in urine volume (from 307 +/- 111 to 572 +/- 322 ml/8 hr, P = 0.014 in normal subjects, and from 266 +/- 92 to 518 +/- 208 ml/8 hr, P = 0.001 in the stone formers) and a concomitant reduction of the relative CaOx supersaturation (from 8.7 +/- 2.5 to 5.1 +/- 2.5 ml/8 hr, P = 0.001 in normal subjects, and from 10.4 +/- 3.5 to 5.0 +/- 2.7 ml/8 hr, P = 0.001 in the stone formers). The decrease in CaOx supersaturation was accompanied by an increase of the permissible increment in oxalate, both in normal subjects (from 43.8 +/- 10.1 to 67.2 +/- 30. 3 mg/liter, P = 0.018) and in the stone formers (from 25.7 +/- 9.4 to 43.7 +/- 17.1 mg/liter, P = 0.0001), without any significant variations of the upper limit of metastability for CaOx (from 21.6 +/- 5.3 to 20.5 +/- 4.2 mg/liter in normal subjects, and from 18.7 +/- 4.5 to 17.1 +/- 3.7 mg/liter in the stone formers). The inhibitory effect of urinary macromolecules with molecular weight greater than 10,000 Daltons did not undergo any change when the latter were recovered from concentrated or diluted urine, either in normal subjects or in the stone formers. CONCLUSIONS: Reduced CaOx supersaturation by means of water load has a protective effect with regards to CaOx crystallization in subjects who do not present any of the common urinary stone risk factors.     

Lowering urinary oxalate excretion to decrease calcium oxalate stone disease

Dietary modifications should be considered as a first line approach in the treatment of idiopathic calcium oxalate nephrolithiasis. The amounts of oxalate and calcium consumed in the diet are significant factors in the development of the disease due to their impact on urinary oxalate excretion. There are a number of strategies that can be employed to reduce oxalate excretion. The consumption of oxalate-rich foods should be avoided and calcium intake adjusted to 1000–1200 mg/day. To encourage compliance it should be emphasized to patients that they be vigilant with this diet as a deviation in any meal or snack could potentially result in significant stone growth. The evidence underlying these two modifications is outlined and other strategies to reduce urinary oxalate excretion are reviewed.     

Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease

Oxalate excretion was measured in healthy subjects and idiopathic calcium stone-formers on dietary regimens which differed in the type and amount of protein allowed; 24-h urine collections were obtained from 41 practising vegetarians and 40 normal persons on a free, mixed, "mediterranean" diet. Twenty idiopathic calcium stone-formers were also studied while on two low calcium, low oxalate diets which differed in that animal protein was high in one and restricted in the other. Vegetarians had higher urinary oxalate levels than controls and although the calcium levels were markedly lower, urinary saturation with calcium/oxalate was significantly higher. This mild hypercalciuria was interpreted as being secondary to both a higher intake and increased fractional intestinal absorption of oxalate. Changing calcium stone-formers from a high to a low animal protein intake produced a significant decrease in calcium excretion but there was no variation in urinary oxalate. As a result, the decrease in calcium oxalate saturation was only marginal and not significant. It was concluded that dietary animal protein has a minimal effect on oxalate excretion. Mild hyperoxaluria of idiopathic calcium stone disease is likely to be intestinal in origin. Calcium stone-formers should be advised to avoid an excess of animal protein but the risks of a vegetable-rich diet should also be borne in mind.     

Oxalate transport and calcium oxalate renal stone disease

Hyperoxaluria is considered to play a crucial role in calcium oxalate (CaOx) renal stone disease. The amount of oxalate excreted into the urine depends on intestinal absorption, endogenous production, renal clearance and renal tubular transport. Since a primary disorder has not been found so far in most CaOx stone formers and since oxalate is freely filtered at the glomerulus, most studies are presently focussed on alterations in epithelial oxalate transport pathways. Oxalate can be transported across an epithelium by the paracellular (passive) and transcellular (active) pathway. Oxalate transport across cellular membranes is mediated by anion-exchange transport proteins. A defect in the structure of these transport proteins could explain augmented transcellular oxalate transport. Little is known about the physiological regulation of oxalate transport. In this review cellular transport systems for oxalate will be summarized with special attention for the progress that has been made to study oxalate transport in a model of cultured renal tubule cells. Better understanding of the physiological processes that are involved in oxalate transport could yield information on the basis of which it might be possible to design new approaches for an effective treatment of CaOx stone disease.     

Plasma oxalate concentration in calcium oxalate stone formers

A sensitive, simplified method for plasma oxalate determination by gas chromatography is described. After deproteinizing the plasma with 3N HC1 and 20% sulfosalicylic acid, the oxalate was methylated, extracted and analysed by gas chromatography. This method has three advantages i.e., smaller sample size (plasma 5.0 ml), rapidity (takes less than 3 hours) and accuracy. The recovery rate of oxalate added to plasma was 91.42 +/- 11.31% (SD) and the coefficient of variation of replicate determinations was 4.18%. The minimum detectable concentration of oxalate was 0.3 micrograms/ml (oxalate peak was higher than 5 mm). The mean oxalate concentration under fasting conditions from 16 healthy subjects was 1.37 +/- 0.39 micrograms/ml (SD), while that from 31 calcium oxalate stone formers was 1.45 +/- 0.39 micrograms/ml (SD). There was no significant difference in plasma oxalate concentration between the two groups. The dietary influence of oxalate on plasma and urinary oxalate was investigated in 5 healthy subjects and 5 calcium oxalate stone formers. When 100 g spinach (total oxalate 545.5 mg, soluble oxalate 381.5 mg) was given, the increase of plasma oxalate concentration was more prominent in stone formers; in stone formers it increased to 142% of control value at 2 hours (p less than 0.05) after spinach loading, to 163% at 4 hour (p less than 0.01) and to 232% at 6 hours (p less than 0.01); while in healthy subjects increased to 119% at 2 hours (ns) after loading, to 144% at 4 hours (p less than 0.05) and only to 167% at 6 hours (p less than 0.01). Urinary oxalate excretion increased promptly between 1 and 2 hours after loading in both groups, reaching peak levels between 2 and 4 hours after loading in healthy subjects and between 4 and 6 hours or later in stone formers. The mean renal clearance of oxalate was 18.0 ml/min in 6 healthy subjects and 19.0 ml/min in 4 calcium oxalate stone formers. There was no significant difference in oxalate clearance between the two groups. The mean ratio of oxalate/creatinine clearance was 0.22 for stone formers, which was equal to that for healthy subjects.     

A porcine model of calcium oxalate kidney stone disease

PURPOSE: The pig has been extensively used in biomedical research because of the similarities in organ structure and function to humans. It is desirable to have an animal model of oxaluria and urolithiasis with physiological, anatomical and nutritional characteristics that more closely resemble those of man. In this study we determined if feeding pigs trans-4-hydroxy-l-proline (HP) increased urine oxalate levels and if it would serve as a model for human hyperoxaluria and stone disease. MATERIALS AND METHODS: Male Yorkshire-Durox cross-bred pigs were fed HP for up to 20 days. Urine was periodically collected and analyzed for oxalate levels and the presence of crystalluria. After 20 days of feeding the kidneys were removed and examined grossly and microscopically for indications of injury, crystal deposition and stone formation. RESULTS: Feeding pigs 10% HP (weight per weight HP/food) produced hyperoxaluria, which reached a maximum and leveled off by day 6. Urine oxalate remained near this level until the study ended at 20 days regardless of the further increase in HP to 20% of the weight of the food. When the kidneys were removed and grossly examined, calcium oxalate encrustations were observed on multiple papillary tips. Histopathological observation of the papillary tissue showed tissue injury and crystal deposition. CONCLUSIONS: Pigs fed HP have hyperoxaluria and calcium oxalate crystalluria, and calcium oxalate papillary deposits form that may be precursors of kidney stones. The use of the pig as a model of human hyperoxaluria and stone formation should prove ideal for studies of these human diseases.     

Factors influencing the course of calcium oxalate stone disease.

OBJECTIVE: To assess the influence of previous stone formation, urine and stone composition on the further course of the disease in recurrent calcium stone formers without pharmacological treatment. METHOD: The course of the disease was analysed during a prospective follow-up period by means of Kaplan-Meier estimates. At the start of follow-up the patients were subgrouped with regard to their previous history of stone formation expressed as stone age index (SAI = 100 x number of stones/age), urine composition, stone composition, and sex. In 223 of the patients was it possible to calculate AP(CaOx) index(s), a standardized estimate of the ion-activity product of calcium oxalate. RESULTS: The 446 patients (329 men, 117 women) who were considered representative of an average population of recurrent calcium stone formers, had a 5-year recurrence risk of approximately 50%. Patients with an SAI <2 had a lower recurrence risk than those with an SAI >2 and a corresponding difference was recorded between patients with SAI levels <5 and >5. Furthermore, female patients had a lower risk of new stone formation than male patients. Patients with an AP(CaOx) index(s) of 1.5 or more had a significantly higher recurrence risk than those with a lower index, a difference that was most pronounced in female stone formers. A slightly higher risk of recurrent stone formation during the follow-up period could also be related to the presence of calcium phosphate in the stone, a high AP(CaP) index(s) (a standardized estimate of the ion-activity product of calcium phosphate) and a low concentration of citrate. CONCLUSION: AP(CaOx) index(s) and SAI were the most obvious predictors of the recurrence risk and these two variables, together with information on the sex distribution, might be useful for deriving an expected recurrence risk at a defined point of time in a group of recurrent stone formers. Such an estimate can be valuable for conclusions on the efficacy of different stone-preventive treatments when an appropriate control group is lacking.     

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.     

Serum,urinary and stone zinc,iron, magnesium and copper levels in idiopathic calcium oxalate stone patients

Many theories have been put forward to explain the mechanism of stone formation and growth. The aim of this study was to investigate the urinary, serum and stone levels of zinc, iron, magnesium, and copper in patients with calcium oxalate stones and to investigate urinary and serum element levels in healthy controls and to find a possible connection between the elements and calcium oxalate stone formation. A total of 104 patients with calcium oxalate stones ranging in age from 3 to 79 years (mean 44.0 ± 18.1) and 77 healthy controls ranging in age from 18 to 77 (mean 44.2 ± 17.9) were included in this study. The mean urinary iron and copper levels in stone patients were significantly higher than healthy controls (P = 0.000). The mean urinary zinc and magnesium levels in healthy controls were significantly higher than stone patients (P = 0.000). There was no significant difference in the serum levels of magnesium and copper in stone patients and healthy controls. Serum zinc and iron level were significantly high in healthy controls as compared to stone patients. Each stone had all 4 elements. Zn and Mg have inhibitory effect on calcium oxalate stone formation. Fe and Cu could be promotor of the calcium oxalate stone formation.     

Drug dosage protocol for calcium oxalate stone

In earlier studies, we have confirmed that in most patients with calcium oxalate stone formation, a combination of allopurinol and pyridoxine is best suited for treatment and prevention of the stone forming process. The objective of this study is to identify the most effective directed medical treatment of urinary stones. The drug dose adjustment was based on clinical, radiological, biochemical, and microscopic parameters. 444 patients with proved calcium oxalate stone disease who were getting a combination of allopurinol and pyridoxine for a minimum period of 36 months were enrolled in this prospective study. The dosage schedule of these patients was recorded. Dosage adjustment was made depending upon the various clinical, biochemical, microscopic, and radiological changes during the study period. The dosage schedules were in six categories, namely very high dose chemotherapy (VHDC), i.e. allopurinol 600 mg/day and pyridoxine 240 mg/day, high-dose chemotherapy (HDC), i.e. allopurinol 300 mg/day and pyridoxine 120 mg/day, moderate dose prophylaxis (MDP), i.e. allopurinol 200 mg/day and pyridoxine 80 mg/day, low-dose prophylaxis (LDP), i.e. allopurinol 100 mg/day and pyridoxine 40 mg/day, and very low-dose prophylaxis (VLDP), i.e. allopurinol 50 mg/day and pyridoxine 20 mg/day and intermittent VLDP, wherein the VLDP was given on alternate months and still later at longer intervals. The temporary risk was assessed at each visit and dosage adjustment was made. The effect of the intervention was assessed during the next visit. All the patients involved in the study needed dose adjustment. The following schedules were initiated: VHDC (12) 3.5%, HDC (103) 23.2%, MDP (78) 17.57%, or LDP (251) 56.53%. Patients who defaulted for more than a month were excluded from the study. During each visit for follow up, all patients were advised change over of dose depending upon the clinical situation at the time of review. Patients on VHDC were advised reduction to lower doses systematically. On passage of stones, the dose was immediately reduced to LDP in all situations unless prevented by the presence of significant crystalluria or severe pain. All patients on MDP had reduction of dose to LDP subsequently. Patients started on LDP needed elevation in dose in 63 (16.8%) to HDC and 23 patients (12.87%) to MDP. Dose of 247 patients could be reduced to VLDP (55.63%) and later on to intermittent VLDP 85 (19.14%). 74 (16.7%) patients continued to be on LDP throughout the period of study. It is concluded that in managing the stone patient, the clinical, radiological, microscopic and biochemical parameters should be taken into consideration in deciding the reduction/increase in the dose of drugs. The principle of giving chemotherapy/chemoprophylaxis should be to administer the least number of drugs in the least dosage depending upon the requirement of the disease.     

Studies on crystalluria in calcium oxalate stone formers

Summary The excretion of calcium oxalate and calcium phosphate crystals was studied in fractionated 24 h urine from 7 men with recurrent calcium oxalate stone disease, both before and during daily administration of 5 mg bendroflumethiazide. Urinary calcium, oxalate, magnesium, citrate, phosphate, pH, and inhibition of calcium oxalate crystal growth rate were analyzed in all samples. Exclusively calcium oxalate crystals were found in 30 per cent of the samples, all with a pH below 6.25, whereas calcium phosphate was the crystal type encountered in urine with a pH above 6.50. Bendroflumethiazide decreased the volume of calcium phosphate but not of calcium oxalate crystals. During the period of observation there was no correlation between calcium oxalate supersaturation and calcium oxalate crystal volume, but a relationship was demonstrated between calcium phosphate supersaturation and calcium phosphate crystal volume.     

Observations on calcium oxalate stone formers.

Biochemical studies were performed on 22 adult patients with idiopathic recurrent calcium oxalate renal stone disease and 23 healthy controls. It was found that urinary glutamic-oxaloacetic acid transaminase (UGOT) and urinary glutamic-pyruvic acid transaminase (UGPT) activity was low and lactate dehydrogenase (LDH) and gamma-glutamyl transferase (gamma-GT) activity was high in the urine of calcium oxalate stone formers. No significant changes were observed in the activity of glutamic-oxaloacetic acid transaminase, glutamic-pyruvic acid transaminase and gamma-GT in their blood but a significant reduction was found in both LDH and alkaline phosphatase activity. It was concluded that the activity of UGOT and UGPT is reduced in patients with kidney stones.     

草酸钙晶体表面结合蛋白质的研究

目的 了解草酸钙晶体表面结合蛋白质在结石形成的过程中的作用。方法 用草酸钙过饱和结晶法制备正常人和草权钙结石患者尿草酸钙晶体表面结合物质（ＣＳＢＳ）,经ＤＥＡＥ－ＳｅｐｈａｒｏｓｅＣＬ－６Ｂ柱层析分离蛋白质和葡胺聚糖,用ＳＤＳ－聚丙烯酰胺凝胶电泳（ＳＤＳ－ＰＡＧＥ）测定蛋白质组成和分子量,用氨基酸自动分析仪测定蛋白质的氨基酸,结果;正常仍ＣＳＢＳ中主要含分子量为３１０００的尿凝血酶原激活肽片段１（     

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.     

维生素D受体基因多态性与草酸钙尿结石的关系

目的　探讨维生素D受体 (VDR)等位基因多态性与草酸钙尿结石之间的关系。　方法　非高钙尿结石患者 15 0例 ,高钙尿结石患者 36例 ,正常对照 90例。采用聚合酶链反应 (PCR)和限制性酶切法研究VDR的Taq1、Apa1、Fok1等位基因多态性与草酸钙尿结石之间的关系。　结果　两个结石组分别与对照组比较 ,VDR的Fok1启动子等位基因多态性分布差异有显著性意义 (P <0 .0 5 )。ff型等位基因 (Fok1等位基因有 2个酶切位点的纯合子出现 2个月条带 )人群中对照组、非高钙尿结石组及高钙尿结石组 2 4h尿钙含量分别为 (0 .0 5 1± 0 .0 0 4 )、(0 .0 74± 0 .0 0 4 )和 (0 .135± 0 .0 11)mmol/kg,FF型人群 3组分别为 (0 .0 31± 0 .0 0 3)、(0 .0 32± 0 .0 0 3)和 (0 .10 8± 0 .0 14 )mmol/kg,差异有显著性意义 (P <0 .0 5 )。Apa1、Taq1的基因多态性分布在各组之间差异无显著性意义 (P >0 .0 5 )。　结论　VDR的启动子Fok1基因多态性可作为鉴别草酸钙尿结石病因的基因标记物 ,ff型等位基因可作为含钙结石危险因素的标志 ,草酸钙尿结石与VDR基因内含子 8(Apa1)及外显子 9(Taq1)多态性无关。