Oral potassium citrate treatment for idiopathic hypocitruria in children with calcium urolithiasis

PURPOSE :We evaluated the clinical and laboratory outcome of oral potassium citrate treatment in children with idiopathic hypocitruria and calcium stones. MATERIALS AND METHODS: The charts of 64 children 1 to 15 years old with hypocitruria and calcium stones (median age 7.2) treated with oral potassium citrate were reviewed. Evaluation parameters were tolerability, adverse reactions, metabolic profile and stone recurrence. RESULTS: No serious adverse reaction due to potassium citrate administration was recorded. Normal citrate excretion was restored in all patients. After treatment median urinary citrate daily plus or minus SD increased from 197 +/- 72 to 632 +/- 218 mg./1.73 m.2 (p <0.001) and mean urinary pH increased from 5.3 +/- 0.3 to 6.2 +/- 0.7 (p <0.01). Mean calcium excretion decreased from 3.5 +/- 2.7 to 2.5 +/- 2.7 mg./kg. (p <0.05). At an average followup of 22 months (range 3 to 67) the recurrence rate in the group overall was 0.07 per patient-year. The previous recurrence rate of 0.32 per patient-year in the 20 children with a history of recurrent stone disease decreased to 0.17 per patient-year after treatment. None of the 44 initial stone formers had recurrent stones. CONCLUSIONS: Our results show the safety and efficacy of oral potassium citrate treatment for restoring normal urinary citrate and suggest a preventive effect for recurrent calcium stone disease in children with hypocitruria and calcium stones.     

Prophylaxis in idiopathic calcium urolithiasis

Summary The most important measure in the prophylaxis of idiopathic calcium urolithiasis is dietary advice. Patients should be kept to a high-fluid intake, increasing their diuresis by at least 0.51. The mineral content of drinking water seems to be of minor importance, but the liquid should be low in carbohydrates and oxalate. The intake of animal proteins should be reduced to no more than five meals with meat, fish or poultry per week. Excesses of oxalate-rich food must be avoided. The daily intake of calcium in dairy products should be in the range of 800–1200 mg. Sodium and refined carbohydrates should be moderately restricted. Medical treatment is indicated only in cases of recurrence under the appropriate diet. Selective treatment according to urinary chemical composition is favoured; alkali citrate, thiazides, allopurinol, and pyridoxine are of major interest.     

Citrate and recurrent idiopathic calcium urolithiasis

Summary In idiopathic recurrent calcium urolithiasis (RCU) in men (n=37) the metabolic effects of oral tripotassium citrate (PC) were investigated in a longitudinal field study. The patients were either normo- (n=22) or hypocitraturic (n=15). Laboratory examinations were performed before, and after 3, 6, and more than 12 months of medication. Acceptance of PC was poor, mainly because of the salty taste of the tablet preparation chosen, and a number of participants dropped out of the study. In the remaining participants, compliance was acceptable when evaluated on the basis of urinary potassium and undesired side effects did not occur. In the short term (up to 3 months), PC evoked compensated metabolic alkalosis (pH and citrate in urine increased; blood gases remained normal), a drop in urinary calcium, together with increasing oxaluria, hydroxyapatite supersaturation, and calcium phosphate crystalluria. In the long term (>12 months) PC urinary pH and citrate dissociated, in that pH returned to pretreatment baseline values, whereas citrate stayed at high levels. In normocitraturics but not in hypocitraturics, urinary urea and sodium in creased with PC. Hypocitraturics appeared to be less sensitive to the effects of PC, as reflected by the relatively small rise in urinary pH and citrate, and they maintained higher mean levels of indicators of bone metabolism (osteocalcin, alkaline phosphatase, hydroxyproline) despite continuous administration of PC. It was concluded that although the PC tablet preparation was effective it may not be an ideal anti-stone drug treatment in the long term and that, especially in hypocitraturiecs, the intrinsic metabolic defect of RCU may not be sufficiently well controlled.     

Management of pediatric urolithiasis in Pakistan: experience with 1,440 children

PURPOSE: We evaluated the efficacy and safety of different modalities for pediatric urolithiasis in a developing country in 2 eras, namely before and after the advent of minimally invasive surgery. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,440 children younger than 14 years treated with various modalities during a 14-year period. From 1987 to 1995, 486 and 50 patients were treated with open surgery, and extracorporeal shock wave lithotripsy (ESWL, Dornier Medical Systems, Inc., Marietta, Georgia) and minimally invasive methods, respectively. Between 1996 and 2000, 518 and 386 children were treated with surgery and minimally invasive methods, respectively. RESULTS: Of the 1,440 children 795 (55.2%) had renal, 198 (13.8%) had ureteral and 447 (31%) had bladder calculi. Of the renal stones 556 (70%), 177 (22%) and 62 (7.8%) were treated with open surgery, ESWL and percutaneous nephrolithotomy, respectively. Of the ureteral calculi 85 (43%), 37 (18.6%) and 76 (38%) were managed by ESWL, ureterorenoscopy and open surgery, respectively. Of the bladder calculi 307 (68%), 77 (17.2%) and 63 (14%) were treated with open vesicolithotomy, transurethral pneumatic cystolithotripsy and ESWL, respectively. The renal stone clearance rate was 98% after open surgery, 84% after ESWL and 68% after percutaneous nephrolithotomy monotherapy at 3 months of followup. Similarly the ureteral stone-free rate was 54% after ESWL and 86.9% after ureterorenoscopy. Of the patients with bladder calculi 48% and 93% become stone-free after ESWL and transurethral pneumatic cystolithotripsy, respectively. CONCLUSIONS: The use of ESWL, percutaneous nephrolithotomy and ureterorenoscopy has resulted in treating a large number of children with a short hospital stay and early return to school. Open surgery is reserved only for complex stones.     

Metabolic features and renal outcomes of urolithiasis in children

Aim: The incidence of pediatric urolithiasis has increased over the last century because of dietary changes, metabolic abnormalities, climate change, and genitourinary abnormalities. Data on pediatric urolithiasis in non-endemic countries are limited. The aim of this study was to evaluate the clinical findings and metabolic etiology of urolithiasis in Korean children. Material and methods: The medical records of 73 Korean children who were newly diagnosed with urolithiasis from January 2010 to December 2013 were retrospectively analyzed. Evaluation of metabolic risk factors, including hypercalciuria, hyperuricosuria, hypomagnesuria, hyperoxaluria, and hypocitraturia, required analysis of 24-h urine specimens or, alternatively, for infants and toddlers, the solute-creatinine ratio in spot urine. Results: The male-to-female ratio of the included patients was 1.3:1. The median age at diagnosis was 10.1 years, and the patients were divided into two age groups with pre-school-age children (n?=?27, 37.0%) and school-age children (n?=?46, 63.0%). While flank pain was more common in school-age children, incidentally detected or urinary tract infection (UTI)-associated urolithiasis was more common in pre-school-age children. Eight patients (11.0%) had renal function deterioration associated with urolithiasis, and three patients (4.1%) progressed to chronic kidney disease. Metabolic abnormalities according to urine chemistry were found in 30 patients (41.1%), including hypercalciuria in 21.9%, hyperuricosuria in 11.0%, hypomagnesuria in 4.1%, hyperoxaluria in 1.4%, hypocitraturia in 1.4%, and cystinuria in 1.4%. Conclusion: We suggest that school-age children with renal colic and pre-school-age children with UTI should be evaluated for urolithiasis. Additionally, the evaluation for metabolic risk factors is important in order to prevent recurrence and renal insufficiency.     

尿路结石术前应用抗菌药物治疗的指征是什么?

感染是尿路结石常见的并发症之一.感染性尿液可渗入肾实质内,破坏正常的肾组织而引起肾功能受损,甚至导致肾功能丧失.细菌及内毒素进入血液可发生脓毒血症甚至感染性休克,危及患者生命.对于细菌感染或具感染风险的患者,如果术前使用抗生素有效控制尿路感染,并且能够保持手术时血液及肾盂内一定的药物浓度,可以降低碎石时肾盂内的细菌负荷,减少细菌入血机会,预防感染进一步扩散和加重.目前多数指南对于尿路结石术前应用抗菌药物的指征,仅局限于已经存在尿路感染的患者,作者就这一问题进行进一步探讨.     

Intestinal oxalate absorption is higher in idiopathic calcium oxalate stone formers than in healthy controls: measurements with the [(13)C2]oxalate absorption test

PURPOSE: We assessed the importance of oxalate hyperabsorption for idiopathic calcium oxalate urolithiasis, oxalate absorption in healthy volunteers and recurrent calcium oxalate stone formers was compared. MATERIALS AND METHODS: The [(13)C2]oxalate absorption test, a standardized, radioactivity-free test, was performed. On 2 days 24-hour urine was collected and an identical standard diet containing 800 mg Ca daily was maintained. On the morning of day 2 a capsule containing 0.37 mmol sodium [(13)C2]oxalate was ingested. A total of 120 healthy volunteers (60 women and 60 men) and 120 patients (30 women and 90 men) with idiopathic CaOx urolithiasis (60% or greater CaOx) were tested. RESULTS: Mean intestinal oxalate absorption in the volunteers was 8.0 +/- 4.4%, and in the patients was 10.2 +/- 5.2% (p <0.001). There was no significant difference in mean absorption values between men and women within both groups. A high overlap between the absorption values of volunteers and patients was found. Only in the patient group did absorption values greater than 20% occur. Oxalate absorption correlated with oxalate excretion in the patients, r = 0.529 (p <0.01) and in the volunteers, r = 0.307 (p <0.01). CONCLUSIONS: In high oxalate absorbers dietary oxalate has a significant role in oxalate excretion and, therefore, increases the risk of calcium oxalate stone formation.     

Role of the diurnal variation of urinary pH and urinary calcium in urolithiasis: A study in outpatients

BACKGROUND: We previously reported that the urinary excretion of calcium and the diurnal variation of urinary pH were important for stone formation in hospitalized inpatients with hospital standard diet. Because almost all urinary stones are formed in outpatients with ambulatory free diet, it is essential to investigate these factors in outpatients. METHODS: We examined the urinary excretion of calcium, oxalate, uric acid, phosphate and magnesium in 96 male outpatients and 142 male inpatients. We also studied the relationship between the stone composition and the diurnal variation of urinary pH in 32 male outpatients (five uric acid stones (UA), 13 pure calcium oxalate stones (CaOX) and 14 mixed calcium oxalate and calcium phosphate stones (CaOX-CaP)) and 53 male inpatients (nine UA, 15 CaOX and 29 CaOX-CaP). RESULTS: There was a significant difference in the urinary excretion of calcium among outpatients with UA, CaOX and CaOX-CaP (133 +/- 96 vs 219 +/- 97 vs 268 +/- 102 mg per day, P < 0.05). In outpatients with UA, urinary pH was constantly low throughout the entire day. In contrast, outpatients with CaOX and those with CaOX-CaP had diurnal variation of urinary pH that was low in the early morning, followed by elevation in the daytime and was lowered in the night. The pHs in the early morning, afternoon and night were significantly higher in outpatients with CaOX-CaP than in those with CaOX. CONCLUSION: The diurnal variation of urinary pH and the urinary calcium are important for stone formation.     

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.     

Decreased renal expression of the putative calcium oxalate inhibitor Tamm-Horsfall protein in the ethylene glycol rat model of calcium oxalate urolithiasis

PURPOSE: Tamm-Horsfall protein is believed to inhibit calcium oxalate crystallization, aggregation or adhesion to the renal epithelium. We determined whether ethylene glycol induced urolithiasis changes the expression of renal and urinary Tamm-Horsfall protein. For comparison the expression of another calcium oxalate inhibitor, osteopontin, was also analyzed. MATERIALS AND METHODS: Male rats were treated with 0.75% ethylene glycol plus an AIN-76 diet (Dyets, Bethlehem Pennsylvania) (ethylene glycol group) or standard rat chow and water (control group) for up to 8 weeks (6 per group for 8 weeks and 3 per group for 3 days to 6 weeks). Kidneys and urine (8 weeks only) were harvested and analyzed by Northern and Western blot analysis, and immunohistochemistry. RESULTS: Tamm-Horsfall protein message and protein (membrane bound form) were decreased, while those of osteopontin were increased in the kidneys of rats treated with ethylene glycol for 8 weeks. As judged by immunochemistry Tamm-Horsfall protein and osteopontin were consistently present in a few tubules in rats in the ethylene glycol and control groups, respectively. In urine expression of the free form of Tamm-Horsfall protein (approximately 75 kDa.) was decreased but detectable in ethylene glycol treated rats. Although readily detected in tissue, osteopontin was not detected in the urine of control or ethylene glycol treated rats. In the time course experiment Tamm-Horsfall protein did not decrease until 4 weeks, when calcium oxalate crystals were detectable in the kidneys of treated rats. In contrast, osteopontin was increased, although inconsistently, beginning at 3 days. CONCLUSIONS: Unlike other calcium oxalate inhibitors, such as osteopontin, renal message and protein for Tamm-Horsfall protein was decreased in ethylene glycol treated rats. Tamm-Horsfall protein expression did not decrease until aggregates of crystals had been deposited in the kidneys, while osteopontin expression began to increase almost immediately. Comparisons of the data on kidneys and urine obtained by RNA or protein blot analysis and immunochemistry underscore the need to examine tissue and urine by multiple techniques to obtain the most accurate assessment of how protein expression is changed by a given treatment.     

Environmental factors in the pathophysiology of recurrent idiopathic calcium urolithiasis (RCU), with emphasis on nutrition

Summary A number of environmental factors are under discussion as possibly implicated in the etiology of RCU. On the basis of data in the literature and our own results, we attempted a critical weighing up of the possible contributions of climate, pollution, stress, nutrition in general and especially oxalate and minerals in the nutrition. It was concluded that there is a need for more in-depth research into the response of the body to challenges from the environment, in particular nutrition.     

Therapeutic action of citrate in urolithiasis explained by chemical speciation: increase in pH is the determinant factor.

BACKGROUND: The therapeutic action of citrate in the management of calcium oxalate urolithiasis has been attributed to the depletion of free calcium ions by complexation of the latter by citrate itself. However, little attention has been given to the nature of such complexes and the chemical conditions which control their formation because it is very difficult to measure them in solution. We therefore modelled the theoretical formation of these complexes in urine following administration of a citrate-containing preparation, using a powerful speciation program, JESS (Joint Expert Speciation System), which has been widely used to model metal-ligand equilibria in biological systems but which has hitherto not been applied in urolithiasis research. This program has an extensive database of thermodynamic constants and is able to calculate mixed ligand speciation. METHODS: Urine data obtained before and after citrate administration in four groups of subjects (male and female normals and stone formers) were used as input for JESS to calculate the speciation of calcium, citrate and oxalate. The program was also used to examine the effects of varying different urinary components on the nature and concentration of the various species. RESULTS: The speciation predicted the formation of a key calcium-citrate-phosphate species (previously unreported in urolithiasis research), which accounts for a significant percentage of the complexation of the free calcium. Moreover, the formation of this complex was found to be dependent on an increase in urinary pH rather than on an increase in urinary citrate concentration per se. CONCLUSION: The therapeutic action of citrate in the management of calcium oxalate urolithiasis is due to the formation of a pH dependent calcium-citrate-phosphate complex which reduces the concentration of the free calcium ion species, thereby reducing the risk of stone formation.     

Determination of the calcium oxalate crystallization risk from urine samples: the BONN Risk Index in comparison to other risk formulas

PURPOSE: Regular risk evaluation and risk monitoring during stone therapy are recommended measures to ensure reduction of recurrence of crystal formation. This strategy optimizes the patient treatment by a more individual approach and decreases expensive over treatment. We evaluated the BONN Risk Index (BRI) through data actualization and evaluation refinement. The BRI was compared with the most common methods of risk evaluation, namely calculation of relative urinary calcium oxalate (CaOx) supersaturation (RS) and of the urine activity product (AP)CaOx index to estimate the urine AP with respect to CaOx. MATERIALS AND METHODS: A total of 201, 12 and 24-hour urine samples were collected from 95 healthy volunteers and from 106 CaOx stone formers. Crystallization experiments following the BRI method were performed. RS and APCaOx were calculated from urinalysis. Data were indexed and individually grouped into 8 classes, and frequency distributions were plotted. A calculation scheme for the BRI based estimation of the statistical probability of a clinically healthy person being a (still nondetected) CaOx stone former is provided. RESULTS: Logarithmically arranged BRI groups from healthy subject and patient data showed Gaussian frequency distributions. Compared with RS and APCaOx BRI allowed optimum distinction between healthy subjects and stone formers. The healthy subject probability of already being a CaOx stone former strongly increased with increasing BRI. CONCLUSIONS: The BRI for evaluating CaOx crystallization risk allows reliable distinction between healthy subjects and CaOx stone formers. Although RS and APCaOx require much more analytical efforts for determination, their results do not show higher reliability.     

Ureteroscopy for the treatment of urolithiasis in children

PURPOSE: Ureteroscopy for treating urolithiasis in prepubertal children has become more common with the advent of smaller instruments. We reviewed our experience with ureteroscopy for urolithiasis in this cohort of patients as well as the literature using this treatment modality in children. MATERIALS AND METHODS: Between 1994 and 2000 we performed 27 ureteroscopic stone extractions in 25 children. Ureteroscopy was done in a manner similar to that in adults. Ureteral dilation was performed when necessary to access the ureter. A stent was placed postoperatively if there was significant ureteral trauma. RESULTS: Of the 25 children 13 were male and 12 were female. Average age was 9.2 years (range 3 to 14). Stones were 2 to 12 mm. in greatest diameter (average 6). Of the 27 procedures the ureteral orifice was dilated before stone treatment in 15 (56%), while in 19 (70%) a stent was placed afterward. No intraoperative and 2 postoperative complications were identified. Overall 92% of the children were rendered stone-free after 1 procedure and 100% were stone-free after 2. CONCLUSIONS: Ureteroscopy for urolithiasis in prepubertal children is safe and effective. Routine ureteral dilation and ureteral stent placement are not always necessary in these patients.     

拉萨地区尿结石发病情况及危险因素的调查研究

目的:通过单中心调查,研究拉萨地区尿结石的发病情况及其危险因素,为本地区尿结石的诊治及预防提供科学依据。方法:对我院确诊为尿结石的362例患者进行问卷调查,对调查因素进行统计分析。结果:362例患者中,尿结石患者男女比例为3.36∶1(279/83),高发年龄段为20~39岁,且以上尿路结石为主;饮水少、高脂肪、高蛋白、高食盐、饮酒是本地区引发尿结石的危险因素。结论:减少饮酒和动物蛋白脂肪的摄入,限制钠盐日摄入量,并合理增加饮水,对本地区泌尿系结石的防治有积极意义。     

Conversion of calcium oxalate to calcium phosphate with recurrent stone episodes

PURPOSE: We have extended our previous observation that the percent occurrence of calcium oxalate stones decreased while that of calcium phosphate stones increased with each new stone event. MATERIALS AND METHODS: The National VA Crystal Identification Center has analyzed veteran patient urinary tract stones from VA hospitals throughout the United States since 1983. We reviewed the composition of 33,198 stones with emphasis on the changes in composition. More than 11,786 stones came from 5,088 recurrent stone formers. Stones were analyzed using high resolution x-ray powder diffraction and Fourier transform infrared spectroscopic techniques. When the stones were investigated as a function of time, it was determined that there was greater variability when samples were more than 30 days apart. RESULTS: The percent occurrence of whewellite, weddelite, apatite, brushite and uric acid in stones increased between 1.0% and 5.9% since our previous study. The percent occurrence of struvite decreased by 2.6%. The percent of calcium oxalate stones decreased while that of calcium phosphate stones increased with each new event. However, the total percent occurrence of all calcium containing stones did not significantly change with recurrent stone events. CONCLUSIONS: Our study suggests a strong trend for the conversion of stone disease from calcium oxalate to calcium phosphate containing stones, which could influence the progression and severity of disease.