Urinary citrate in kidney stone disease

BACKGROUNDS: Hypocitraturia, or low urinary citrate excretion is known as a risk for nephrolithiasis. Though urinary citrate excretion is basically determined by acid-base balance, metabolic acidosis is not always manifest in urinary stone patients with hypocitraturia. From our stone clinic data, we estimated the incidence of hypocitraturia and addressed its causes in the absence of obvious acid-base imbalance. METHODS: We selected 310 stone patients in whom 24-hour urine chemistry was examined on regular diets on 2 or more occasions during follow-up. Totally, 1361 specimens were analyzed in them. RESULTS: In the male subjects, the average urinary citrate excretion was 450.9 +/- 284.4 mg/ day, whereas in the female, 536.5 +/- 305.9 mg/day (p < 0.0001). Eventually, hypocitraturia was found in 119 of the 310 patients (38.4 %). Of 222 with calcium stones, 70 (31.5 %) had hypocitraturia. In 32 of those, potential causes of hypocitraturia were identified, but in the rest, no apparent cause was found. In the latter, the net gastrointestinal alkali absorption was calculated from the 24-hour urine chemical data, and it was lower in those with hypocitraturia than in the normal control (9.2 vs. 34.4). CONCLUSION: It was suggested that defective gastrointestinal alkali absorption may be involved in hypocitraturia of calcium stone patients.     

防石合剂对草酸钙肾结石ESWL术后尿骨桥蛋白影响的临床研究

目的:观察防石合剂对草酸钙肾结石体外冲击波碎石(ESWL)术后尿骨桥蛋白(OPN)的影响,探讨防石合剂预防草酸钙肾结石的作用机制。方法:将100例草酸钙肾结石患者随机分为对照组(50例)和药物组(50例)。药物组服用防石合剂,每次33mL,每日3次;对照组不服任何药物。观察2组患者服药前及服药后1、4周尿OPN、尿钙、尿草酸、血肌酐及尿素氮水平。结果:草酸钙肾结石患者ESWL术后尿OPN水平明显降低,防石合剂能显著增加草酸钙肾结石患者尿OPN水平(P<0.01),且与对照组比较有显著性差异(P<0.01);服药后血肌酐及尿素氮水平正常,未发现有肾毒性。结论:防石合剂可以升高尿中OPN浓度,抑制草酸钙结石形成,从而预防草酸钙肾结石ESWL术后患者结石复发。     

Renal calcium conservation in recurrent stone-formers with idiopathic hypercalciuria

Urinary excretions of calcium and cyclic AMP were studied in male recurrent stone-formers after an overnight fast and following an oral calcium load. The results from eight patients with established hypercalciuria (greater than 7.5 mmol Ca/24 h) were compared with those from eight age matched normocalciuric stone-formers. The urinary calcium/creatinine ratio was higher in the hypercalciuric group both when fasting and calcium loaded whilst their urinary cyclic AMP was lower in both 24-h and calcium-loaded collections. Five of the eight hypercalciuric patients exhibited an increased urinary calcium/creatinine ratio whilst fasting. These findings support the view that renal calcium wasting, in association with suppression of parathyroid activity, is common among men with idiopathic hypercalciuria. Dietary calcium restriction may lead to bone loss in patients with obligatory renal calcium wasting and enteric adsorption is rarely applicable to the treatment of stone disease. Therefore, the demonstration of a high fasting urinary calcium/creatinine ratio is a strong indication for therapeutic agents which act to suppress renal calcium loss to treat hypercalciuria.     

Mechanism of action of xipamide and its classification as a "low ceiling diuretic". Pharmacodynamic-pharmacokinetic studies in healthy volunteers and in kidney and liver patients

Xipamide (CAS 14293-44-8) shows structural features comparable with the thiazide- as well as the class of loop diuretics. According to earlier findings this diuretic, in contrast to the thiazides, should not decrease the glomerular filtration rate (GFR) and be effective even in patients with advanced renal failure. Therefore recently the question, which class of diuretics xipamide should be related to, has been increasingly discussed. In order to solve this issue, the diuretic effect of xipamide was assessed in healthy volunteers once without and once under strict water and salt restriction. Additionally, changes in GFR were monitored by means of measurement of the creatinine clearance. Kinetic parameters were determined in plasma and urine; further, in patients with liver cirrhosis, renal elimination kinetics of the diuretic were correlated with the concentration of direct plasma bilirubin, as a marker of cholestasis, at the beginning of a treatment with xipamide, 40 mg qd. The investigations proved that xipamide, like a typical thiazide diuretic, gives rise to a temporary decrease in GFR of about 30 %, provided the renin-angiotensin-aldosterone system of the volunteer is activated by previous salt and water restriction. Xipamide leads to an increase of K+ and Mg2+ excretion, but to a decrease of Ca2+ excretion in urine, a charactaristical feature of the thiazide-like diuretics. The correlation between Na+ excretion and drug excreted in urine over time showed a functional graph that is characteristic for a "low ceiling" thiazide diuretic. In patients with renal failure FE(Na) was increased when related to the GFR-adjusted drug excretion rate, whereas it was diminished in conditions with decreased effective circulating volume like in liver cirrhosis with ascites. It could be shown that the elimination kinetics of xipamide are determined by renal drug clearance, which proportionally decreases with GFR. In patients with liver failure, a decrease of non-renal drug clearance went along with an increase in urinary drug excretion. The amount of drug excreted in urine (Ae) proportionally increased with the concentration of the patients' direct plasma bilirubin. Thus, from a pharmacological as well as clinical point of view xipamide acts like a thiazide diuretic. As could be shown for other thiazides some time ago, xipamide is effective not only in patients with cardiovascular diseases, but also in those with advanced renal failure.     

The influence of hydrochlorothiazide and tripamide on serum and urinary amylase

Pancreatitis and asymptomatic elevations of serum amylase have been reported after therapy with thiazide diuretics. In the current study, the effects of hydrochlorothiazide and tripamide treatment on serum and urinary amylase excretion were investigated in 12 hypertensive volunteers. Two patients developed modest elevations of the serum amylase above the normal range after 12 weeks of treatment with hydrochlorothiazide 50 mg daily, but the mean serum amylase did not change. Hydrochlorothiazide did not produce a statistically significant increase in urinary amylase excretion but did reduce the ratio of salivary amylase/creatinine clearance in a two-hour urine collection. Tripamide 10 mg daily had no effect on serum or urinary amylase.     

The effects of substituting frusemide for a thiazide diuretic in the drug regimens of patients with essential hypertension

Summary Eighteen patients with mild to moderate hypertension on a drug regimen which included a thiazide diuretic had the latter substituted by frusemide for twelve weeks after an initial two-week placebo wash-out period. Blood pressure and heart rate and a number of plasma and urinary biochemical indices were measured. Significant findings included a reduction in standing blood pressure and an elevation of plasma sodium, potassium, chloride, osmolarity, creatinine and alkaline phosphatase levels at the end of the twelve week frusemide phase relative to the values on the thiazide. However the means for all the biochemical indices remained within the normal laboratory reference limits. In the 24-hour urinary studies, no significant findings emerged, apart from an elevated calcium. The foregoing suggest that frusemide is an effective component of an anti-hypertensive drug regimen and that in a dose of 40 mg/day it produces no detectable perturbations of plasma electrolytes. The significance of the enhanced levels of urinary calcium excretion in conjunction with the augmented plasma alkaline phosphatase is unclear.     

Urine saturation and promoter/inhibitor parameters and ratios in renal stone disease caused by ceftriaxone

During ceftriaxone treatment of subdural empyema caused by Streptococcus intermedius urinary and biliary stones were noticed. Increased levels of urinary calcium excretion were detected during ongoing treatment in comparison with 2 months check-up. There were no significant changes in the promoter/inhibitor urolithiasis parameters, oxalate, citrate, urate, cistine, glycosaminoglycans or their ratios. Urine saturation was calculated using EQUIL 2 computer programme (calcium oxalate, brushite) and it was normal. Probable trigger for the ceftriaxone/calcium hydroxy carbonate phosphate mixture of stones was a critical boost of solubility products caused by ceftriaxone treatment and phospnate urine content with a subsequent large-scale spontaneous precipitation of crystals.     

钙敏感受体及紧密连接蛋白-14在草酸钙结石大鼠肾组织中的表达及意义

【摘要】目的 初步探讨钙敏感受体（CaSR）和紧密连接蛋白（Claudin）-14在肾草酸钙结石大鼠肾组织中的表达及意义。方法 30只雄性SD大鼠随机分为对照组和结石组各15只,采用1%乙二醇和2%氯化铵每日2mL灌胃诱导制作大鼠肾草酸钙结石模型。免疫组织化学检测CaSR蛋白表达;RT-PCR检测Claudin-14mRNA表达;West? ern-Blotting分别检测CaSR和Claudin-14蛋白表达;全自动生化分析仪检测2组大鼠肾功能、血及尿生化指标。结果 光镜下结石组有大量结石结晶形成,血清肌肝（Cr）、尿素氮（BUN）、24h尿钙及尿量较对照组升高（P＜0.01）,2 组间血钙、尿pH差异无统计学意义。结石组Claudin-14mRNA及CaSR蛋白表达较对照组升高（P＜0.01）,Claudin- 14蛋白在结石组大鼠肾组织中呈特异性高表达,对照组未检测到Claudin-14蛋白表达;结石组大鼠肾组织中CaSR 和Claudin-14蛋白表达呈正相关,同时,CaSR、Claudin-14蛋白表达与24h尿钙排泄量也呈正相关。结论 CaSR和 Claudin-14表达增高可通过增加尿钙排泄量,进而参与结石的形成。     

柠檬乌梅提取液预防肾草酸钙结石作用机制的研究

目的:本文旨在通过研究柠檬乌梅提取液对预防肾草酸钙结石产生的协同效应及其作用机制,为进一步研究和临床预防和治疗肾结石的应用提供理论基础。方法:将50只大鼠（体质量200～250 g）按随机数字表法分为5组,A组（对照组）、B组（成石组）、C组（柠檬提取液组）、D组（乌梅提取液组）、E组（柠檬乌梅提取液组）,造模和加药处...     

Accuracy of two-hour urine urea nitrogen determinations in critically ill patients

The accuracy of two-hour versus 24-hour urine urea nitrogen (UUN) determinations in critically ill patients was compared. A 24-hour urine collection for UUN determinations was obtained each day for five days in 20 patients who had been receiving parenteral nutrition at a constant rate for at least 36 hours. For each patient, the UUN value obtained from a two-hour sample was projected using the actual 24-hour urine output to determine an estimated daily UUN excretion. Creatinine clearance determinations were performed to evaluate the effects of impaired renal function on the correlation of two-hour and 24-hour UUN excretion. A significant correlation (r = 0.889) was found between the two-hour and 24-hour UUN excretions. However, in three patients with creatinine clearances less than 30 ml/min and two patients with gram-negative sepsis, correlations between two-hour and 24-hour UUN excretion were poor. Total urine volumes in the 20 patients varied considerably but did not affect the correlation between UUN determinations. A two-hour UUN determination may be a valuable tool for monitoring the nutritional status of critically ill patients. The rate of intravenous nutrition must be kept constant, however, to minimize diurnal variations in nitrogen excretion. Conditions such a shock, sepsis, or acute renal failure may limit the use of a shorter urine collection period for urea nitrogen determination.     

Urine oxalate levels in a New Zealand reference population and renal stone formers

Increasing attention is being given to oxalate as a risk factor in urinary calcium stone disease. The accuracy of some methods for measuring urine oxalate is uncertain. Using gas chromatography urine oxalate levels were 0.36 +/- 0.02 and 0.31 +/- 0.02 (mmol/24 h +/- 1 SEM) for men and women respectively of a reference population. In recurrent stone formers urinary oxalate was 0.43 +/- 0.03 in males and 0.38 +/- 0.04 for females whilst solitary stone forming females excreted only 0.31 +/- 0.04 mmol/24 h. The difference between males and females of the reference population was significant (p less than 0.05) as was the difference between reference males and male stone formers.     

Antilithiatic effect of Asparagus racemosus Willd on ethylene glycol-induced lithiasis in male albino Wistar rats

The ethanolic extract of Asparagus racemosus Willd. was evaluated for its inhibitory potential on lithiasis (stone formation), induced by oral administration of 0.75% ethylene glycolated water to adult male albino Wistar rats for 28 days. The ionic chemistry of urine was altered by ethylene glycol, which elevated the urinary concentration of crucial ions viz. calcium, oxalate, and phosphate, thereby contributing to renal stone formation. The ethanolic extract, however, significantly (p < 0.05) reduced the elevated level of these ions in urine. Also, it elevated the urinary concentration of magnesium, which is considered as one of the inhibitors of crystallization. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced, following treatment with the extract. The histopathological findings also showed signs of improvement after treatment with the extract. All these observations provided the basis for the conclusion that this plant extract inhibits stone formation induced by ethylene glycol treatment.     

Estimation of renal creatinine clearance in patients with unstable serum creatinine concentrations: comparison of multiple methods

The accuracy of different methods of calculating 24-hour creatinine clearance in patients with unstable renal function was compared using simulated data (based on a one-compartment pharmacokinetic model), as well as data from postrenal transplant patients. When creatinine clearance was calculated from the urinary creatinine excretion and a serum creatinine concentration, the use of the midpoint serum creatinine concentration produced the lowest degree of error. Therefore, this method is recommended for routine clinical determination of creatinine clearance in such patients. When the urinary creatinine excretion was unknown, an iteration method produced the lowest degree of error among four methods, and therefore is recommended to estimate creatinine clearance in such patients.     

Minimum urine collection periods for accurate determination of creatinine clearance in critically ill patients

The accuracy of creatinine clearance (CLcr) determinations obtained from urine collections of less than 24 hours duration and the cyclical variation in creatinine excretion were studied in 10 critically ill patients with trauma or postoperative complications. Data from patients who received drugs or had diseases known to influence creatinine production or interfere with assay methods were excluded. Twelve consecutive two-hour urine collections and midpoint blood samples were obtained for each patient. Urine and serum samples were assayed for creatinine content by kinetic and enzymatic methods, respectively. The mean 24-hour CLcr was 110.6 +/- 47.0 mL/min. Clearance values determined from 8- and 12-hour collections were within 20% of the 24-hour CLcr value, and values determined from 14- to 22-hour collections were not significantly different from the 24-hour CLcr value. Mean differences between each 2-hour interval and the 24-hour interval were not significant for the 12 collection intervals. In critically ill trauma or postsurgical patients, the 24-hour CLcr can be estimated from an 8-hour urine collection if a deviation of up to 20% from the 24-hour value is clinically acceptable. No significant cyclical variation in creatinine excretion over 24 hours was found.     

Influence of sodium valproate on sodium and chloride urinary excretion in rats, gender differences

Evidence exists indicating that sodium valproate (VPA) increases diuresis in rats. The chloriuretic and natriuretic effect of VPA has not previously been investigated, so the aim of the present study was to define the peculiarities of 24-hour urinary sodium (Na) and chloride (Cl) excretion in young adult Wistar rats of both genders, and to evaluate the effects of VPA. 24-hour urinary Na, Cl, creatinine and pH levels were measured in 28 control intact Wistar rats and 26 Wistar rats after a single intragastric administration of 300 mg/kg VPA. After VPA administration, 24-hour diuresis and 24-hour diuresis per 100 g of body weight were significantly higher in VPA rats of both genders. 24-hour urine Na and Cl excretion were significantly higher in VPA male and VPA female rats than in gender-matched controls. The 24-hour urinary Cl excretion was found to be significantly higher in VPA male than in VPA female rats. The study data show that VPA, alongside the diuretic effect, enhances Na and Cl excretion with urine. The 24-hour chloriuretic response to VPA in male rats was significantly higher than in female rats. The mechanism of such a gender-related effect is not yet clear.     

糖尿病肾病与踝臂指数的相关性研究

目的分析研究踝臂指数对糖尿病肾病发病率的相关性研究。方法选择2009年8月～2011年8月就诊于内分泌科的糖尿病患者200例,其中100例经尿微量白蛋白排泄量确诊为糖尿病肾病(观察组),另100例为糖尿病无肾病组(对照组),测定两组患者24h尿蛋白定量、尿mALB、肾功能及血钾、血糖、血压、ABI,统计分析ABI与糖尿病肾病的相关性。结果观察组和对照组在24h尿蛋白定量、尿mALB、收缩压、舒张压、血钾上均有显著性差异,ABI同24h尿蛋白定量呈直线相关关系,其Pearson相关系数r=-0.99。结论通过本试验,证实其与ABI的相关性。可以考虑用ABI联合24h尿蛋白作为糖尿病是否并发肾病的评估指标。     

Hydrochlorothiazide versus spironolactone: long-term metabolic modifications in patients with essential hypertension

The metabolic side effects of thiazide diuretics are believed to be responsible for the failure of thiazide diuretics to reduce cardiovascular morbidity in patients with hypertension. However, the decrease in the incidence of osteoporotic fractures that are associated with thiazide administration may be relevant in elderly patients with arterial hypertension. Spironolactone (SP) appears not to influence the metabolic risk profile of the patient with hypertension, and no studies have examined its effect on calcium metabolism. Therefore, in 22 patients with mild to moderate essential hypertension, the authors performed a parallel, randomized, double-blind, placebo-controlled study that compared the effects on serum urate and lipid, potassium, magnesium, and calcium metabolism of hydrochlorothiazide (HC) (mean [+/- SD] dose, 72 +/- 26 mg/d) and SP (144 +/- 53 mg/d) during a 52-week period. As compared with placebo, HC significantly increased serum urate and total cholesterol concentrations, and decreased serum potassium levels. SP did not affect serum urate or cholesterol levels but increased serum potassium concentrations. Neither diuretic significantly modified magnesium metabolism. Little changes were seen in serum calcium levels during HC or SP treatment, whereas urinary calcium excretion was significantly decreased by HC (mean decrease, 45%; P less than .01) or SP (40%; P less than .01). The authors conclude that SP, in addition to its potassium-sparing properties, has a calcium-sparing effect that may be beneficial for patients in whom reduction of urinary calcium excretion has a therapeutic value.     

Urolithiasis in geriatric patients

OBJECTIVES: We intended to find risk factors for urolitiasis and its recurrence in a geriatric population. PATIENTS AND METHODS: The medical records of 209 elderly stone patients over age 65 were reviewed. They had been regularly seen at our stone clinic for a mean follow-up period of 1385 +/- 1324 days after urolithiasis was diagnosed. RESULTS: The elderly population comprised 9.6 % of all the stone patients followed at the stone clinic. Regarding stone compositions, calcium oxalate and calcium phosphate were most common in the elderly patients (80 %). The incidence of uric acid stones was higher in the elderly patient group than in the younger group (10.7 % vs. 5.1 %; p = 0.0046). Recurrent stones were seen in 18 of the 207 geriatric patients (15.4 %) during the follow-up period. The urinary calcium excretion of the recurrent stone patients was significantly higher than in those without recurrence (293 +/- 138 mg vs. 177 +/- 98 mg/day, p = 0.0035). However, the probability of stone recurrence estimated by Kaplan-Meier curves was as equivalent in the elderly patient group as in the younger group. CONCLUSIONS: Hypercalciuria may also play a part in stone recurrence of geriatric patients.     

Absorption of magnesium from orally administered magnesium sulfate in man

The use of magnesium sulfate (Epsom salt) as a cathartic in patients with impaired renal function can lead to severe toxicity due to hypermagnesemia. Although toxicity is uncommon in healthy subjects, little is known concerning the extent of absorption of magnesium after a cathartic dose of magnesium sulfate. The bioavailability of magnesium following a large oral dose of magnesium sulfate in normal volunteers was examined in the present investigation. Baseline 24-hour urinary excretion rates of magnesium and creatinine were determined over 3 consecutive days in 6 healthy men. The oral administration of 13.9 g (56.5 mmoles) magnesium sulfate U.S.P., in 4 equal hourly increments, resulted in the urinary excretion (corrected for baseline excretion rate) of 4.0 +/- 2.9% (mean +/- SD) of the dose of magnesium during the first 24 hours and 6.9 +/- 7.0% of the dose during a 72-hour interval. Magnesium sulfate administration had no effect on the 24-hour urinary excretion rate of creatinine. The baseline excretion rate of magnesium was significantly correlated with that of creatinine (r = 0.875) and inorganic sulfate (r = 0.921). All of the subjects experienced mild or moderate diarrhea. Therefore, magnesium is absorbed to a limited and variable extent in healthy adults following a cathartic dose of magnesium sulfate.     

浅论非洛地平的药理作用及临床应用

目的观察钙离子拮抗剂非洛地平的药理作用及治疗肾性高血压临床效果。方法选取148例肾性高血压患者均采用口服非洛地平片,2.5mg/次,2次/d,疗程为2个月。治疗后观察患者的血压、血、尿蛋白(β2-MG)、肾功能(BUN、Scr、UA、Ccr、24h尿蛋白定量)、不良反应及服药情况等。结果 148例患者在经过非洛地平治疗后收缩压、舒张压、血肌酐、尿素氮、肌酐清除率、血尿酸、24h尿蛋白定量比较差异均有统计学意义(P<0.05)。结论非洛地平对治疗肾性高血压有良好的效果。