Metabolic risk factors in children with kidney stone disease

The evaluation of metabolic risk factor in children with renal stone disease is the basis of medical treatment aimed at preventing recurrent stone events and the growth of preexisting calculi. In this retrospective study, we evaluated the metabolic risk factors and clinical and family histories of 90 children with kidney stone disease who had been referred to our institution and subjected to clinical tests using a standardized protocol. The mean age of our pediatric patients was 10.7 years, and the male:female ratio was 1.14:1.0. Biochemical abnormalities were found in 84.4% of all cases. A single urine metabolic risk factor was present in 52.2% (n = 47) of the patients, and multiple risk factors were present in the remaining 31.1% (n = 28). Idiopathic hypercalciuria (alone or in combination) and hypocitraturia (alone or in combination) were the most frequent risk factors identified in 40 and 37.8% of these patients, respectively. Renal colic or unspecified abdominal pain were the most frequent forms of presentation (76.9%), with 97.5% of stones located in the upper urinary tract. In most patients, stone disease was confirmed by renal ultrasonography (77%). A positive family history in first-degree and second-degree relatives was found in 46.2 and 32.5% of the cases, respectively. We conclude that specific urine metabolic risk factors are found in most children with kidney stones and that hypocitraturia is as frequent as hypercalciuria. Very often there is a positive family history of renal stone disease in first- and second-degree relatives.     

Idiopathic hypercalciuria in infants with renal stones

In children older than 2 years, hypercalciuria is the most common metabolic cause of renal stones. In infants, its prevalence is not well established. Since 1990, we observed five infants in whom renal stones or microcalculi were diagnosed between the age of 5 and 19 months. One of them was lost to follow up. In the present report, we describe the four patients who underwent metabolic evaluation and in whom idiopathic hypercalciuria (IH) was diagnosed. We conclude that IH is a frequent cause of microcalculi and renal stones in infants, and a screen for this condition is warranted in this age group.     

Cystinuria in childhood and adolescence: recommendations for diagnosis, treatment, and follow-up

Cystinuria, an autosomal-recessive disorder of a renal tubular amino acid transporter, is the cause of about 10% of all kidney stones observed in children. Different genetic characteristics are not represented by different phenotypes. The stones are formed of cystine, which is relatively insoluble at the physiological pH of urine. Without any preventive measures, the patients will suffer from recurrent stone formation throughout their life. Even with medical management, long-term outcome is poor due to insufficient efficacy and low patient compliance. Many patients suffer from renal insufficiency as a result of recurrent stone formation and repeated interventions. However, regular follow-up and optimal pharmacotherapy significantly increase stone-free intervals. Medical management is mainly based on hyperhydration and urine alkalinization. Sulfhydryl agents such as tiopronin can be added. Recurrent stone formation necessitates repeated urological interventions. These mostly minimally invasive procedures carry the risk of impairment of renal function. In adults, extracorporeal shockwave lithotripsy (SWL) as well as intracorporeal lithotripsy is often unsuccessful. However, in children SWL shows excellent results for cystine stones. In cases with large stone burden, percutaneous nephrolithotripsy (PNL) or even open surgical nephrolithotomy are preferred. This review discusses the underlying pathogenetic mechanisms and provides guidance for the diagnosis, therapy, and management of cystinuria following the recommendations of the International Cystinuria Consortium and the European Association of Urology.     

Urolithiasis in pregnancy

Urolithiasis is the most common cause of urological-related abdominal pain in pregnant women after urinary tract infection. The disease is not uncommon during pregnancy occurring in 1/200 to 1/2,000 women, which is not different from the incidence reported in the nonpregnant female population of reproductive age. During pregnancy, the frequency of stone localization is twice as higher in the ureter than in the renal pelvis or calyx, but there is no difference between the left and right kidney or ureter. Urinary stones during pregnancy are composed mainly of calcium phosphate (hydroxyapatite) in 74% of cases and calcium oxalate in the remaining 26% (Ross et al., Urol Res 36:99–102, 2008). In conclusion, urolithiasis during pregnancy can be serious, causing preterm labor in up to 40% of affected women. The pathogenesis, diagnosis, and management are analyzed.     

儿童特发性高钙尿症与家族泌尿系结石的关系

我们采用目前国际上通用的筛查高钙尿症的方法，检测５７０名７～１４岁儿童，发现尿钙与尿肌肝（Ｃａ／Ｃｒ）比值呈偏态分布，中位值为０．０８１，第９５百分位值为０．２６，对尿Ｃａ／Ｃｒ比值大于０，２６的３１名儿童，测定２４小时尿钙定量，其中１６例２４小时尿钙大于４ｍｇ／ｋｇ，可确诊为特发性高钙尿症（ＩｄｉｏｐａｔｈｉｃＨｙｐｅｒｃａｌｃｉｕｒｉａ，ＩＨ），本组儿童ＩＨ检出率为２．８％，对此１６例经口服钙负荷测试，发现其中１１例是吸收型（ａＩＨ），４例为肾型（ｒＩＨ）。禁食时尿Ｃａ／Ｃｒ比值为０．１１７±０．０５３，服钙后增至０．３４２±０．０９２，较服钙前有非常显著升高。１６例ＩＨ家族调查发现，９名有泌尿系结石家族史，提示ＩＨ与家族泌尿系结石和本地区泌尿系结石发病有密切关系。     

Urolithiasis in enterocystoplasties

The incidence of stones in patients with enterocystoplasty is reported as 12–52.5%. Most patients will have multiple physical factors such as immobility, need for self catheterisation and poor urine drainage, so that it is not certain that an intestinal reservoir is the cause of stones on its own. There is little or no evidence that mucus is an aetiological factor. Foreign bodies in the reservoir, such as staples, increase the risk of stone formation from 13% to 43%. Stones require surgical removal. Minimally invasive techniques may be used for small stones. A low velocity disintegrator is required so that fragments are not propelled into the intestinal mucosa. Stones are infective in origin in 86% of cases, but 14% are sterile. Metabolic screen shows that 80% of patients have risk factors for at least three different types of stone. All patients have raised pH (mean 6.93) and hypocitraturia. Raised serum and urinary calcium, hyperoxaluria and hyperuricosuria are found in up to 33% of patients.     

Hematuria associated with hypercalciuria and hyperuricosuria: a practical approach

Hematuria is one of the most common urinary abnormalities found in children. When hypercalciuria was identified as a potential etiology of painless hematuria, many questions arose concerning the general importance of this observation. Subsequently, increased uric acid excretion also has been purported to cause hematuria in children. This review traces the history of these observations and describes the clinical characteristics of the clinical syndrome of hematuria associated with hypercalciuria and hyperuricosuria. Diagnostic criteria of excessive urinary excretion of calcium and uric acid are reviewed; differences in urinary calcium and uric acid excretion between infants and older children are emphasized. Aside from urolithiasis, few long-term consequences from hypercalciuria or hyperurcosuria have been identified, although some debate exists concerning the effect of chronic hypercalciuria upon bone mineralization.     

Urolithiasis,inhibitors and promoters

Summary The aim of this work is to evaluate the role and importance of inhibitors and promoters in urolithiasis. Carrying in mind theoretical considerations, we conclude that in urolithogenic processes, inhibitors and promoters could only play a decisive role in the idiopathic oxalocalcic urolithiasis. We classify the idiopathic oxalocalcic stone-formers into three main groups, considering inhibitory and promoting factors. It is shown that such classification is in good agreement with the clinical results observed in a group of 88 idiopathic oxalocalcic stone-formers.     

Coexistence of VATER association and recurrent urolithiasis: a case report

VATER association is diagnosed by the combined presence of at least three of the following features: vertebral anomalies, anal atresia, tracheo-esophageal fistula and/or esophageal atresia, radial ray anomalies, and renal anomalies (53%). Urolithiasis has not been reported in this syndrome. A 4-month old girl presented because of irritability, and the presence of stones in the diapers. Physical examination revealed anal atresia for which colostomy was performed in the newborn period. The diagnosis of VATER association was established by the additional findings of hemivertebrae, sacral dysgenesis, and horseshoe kidney which was partly non-functional. Urinary pH was repeatedly below 6. An excreted stone consisted of pure uric acid. Metabolic investigations detected no specific pathology in purine metabolism. Urolithiasis did not recur after reconstructive anal and anorecto-vaginoplasty, implying that it was a consequence of colostomy and/or of the underlying renal anomaly. We suggest that after colostomy patients with VATER association should be followed for possible urate stones, e.g. by regular screening of urinary pH. Received May 20, 1997; received in revised form August 6, 1997; accepted August 12, 1997     

尿酸结石与血脂异常的相关性研究及危险因素分析

目的探讨尿酸结石与血脂异常的相关性,分析尿酸结石的致病危险因素。方法回顾性分析苏州大学附属常熟医院2014年1月至2019年10月收治的尿石症患者的病例资料。93例经结石成分分析确诊为尿酸结石患者为尿酸结石组,男77例(82.8%),女16例(17.2%),中位年龄64岁。按性别、年龄等条件匹配选取同时期的草酸钙结石患者321例为草酸钙结石组,男264例(82.2%),女57例(17.8%),平均年龄61岁。选取我院体检的正常非结石人群306例为对照组,男252例(82.4%),女54例(17.6%),平均年龄61岁。3组的年龄和性别比方面差异无统计学意义(P>0.05)。尿酸结石组、草酸钙结石组、对照组体质指数(BMI)分别为(26.21±2.97)、(24.48±1.87)、(23.75±1.36)kg/m2,差异有统计学意义(P<0.01)。记录3组的血尿酸、尿pH值,以及血脂指标:甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C),分析上述指标与结石成分的相关性。将尿酸结石组按照有无高尿酸血症(HUA)分为伴HUA组41例和不伴HUA组52例,并选择对照组内伴HUA的人群共66例(单纯HUA组),比较上述3组的血脂异常情况及尿pH值。采用多因素logistic回归分析尿酸结石形成的独立危险因素。结果尿酸结石组与草酸钙结石组的TG[1.52(1.02,2.78)mmol/L与1.10(0.80,1.76)mmol/L,P=0.001]、高TG血症患病率[31.2%(29/93)与14.0%(45/321),P<0.01]、低HDL-C血症患病率[28.0%(26/93)与40.2%(129/321),P=0.048]、高LDL-C血症患病率[51.6%(48/93)与36.5%(117/321),P=0.031]、血尿酸水平[(422.28±114.15)mmol/L与(335.72±83.32)mmol/L,P<0.01]及尿pH值[5.5(5.0,6.0)与6.0(6.0,6.5),P<0.01]差异有统计学意义。尿酸结石组与对照组的TG[1.52(1.02,2.78)mmol/L与(1.37±0.55)mmol/L,P=0.010]、高TG血症患病率[31.2%(29/93)与4.9%(15/306),P<0.01]、HDL-C水平[1.13(0.96,1.44)mmol/L与(1.42±0.31)mmol/L,P<0.01]、低HDL-C血症患病率[28.0%(26/93)与3.9%(12/306),P<0.01]、血尿酸[(422.28±114.15)mmol/L与(354.33±79.68)mmol/L,P<0.01]及尿pH值[5.5(5.0,6.0)与6.0(5.5,6.0),P<0.01]差异有统计学意义。尿酸结石伴HUA组和不伴HUA组间尿pH值[5.5(5.0,6.0)与6.0(5.5,6.0),P=0.014]差异有统计学意义。尿酸结石伴HUA组与单纯HUA组的高TG血症患病率[31.7%(13/41)与9.1%(6/66),P=0.003]、低HDL-C血症患病率[29.3%(12/41)与13.6%(9/66),P=0.048]差异有统计学意义。多因素logistic回归分析结果显示,肥胖(OR=1.68,P<0.01)、高TG血症(OR=7.37,P=0.002)、低HDL-C血症(OR=10.46,P=0.001)及低尿pH值(OR=0.10,P<0.01)为尿酸结石致病的独立危险因素。结论尿酸结石患者多有血脂代谢异常,肥胖、高TG血症、低HDL-C血症及低尿pH值与尿酸结石的发生密切相关。     

Urolithiasis in childhood

The management of 131 children with urinary calculi is described. Boys out-numbered girls 2:1. Five per cent of the patients had identifiable metabolic causes, while 78 per cent had infected renal lithiasis. With appropriate therapy, stone disease became inactive in 79 per cent of the children. The remaining 21 per cent continued with active disease. Stone formation may be regarded as a solitary complication or one of several manifestations of a large number of underlying disorders. Along with a thorough search for etiologic factors there must be an equally aggressive therapeutic effort. Because the disease is often sporadic, careful long-term follow-up of the patients with active as well as those with inactive stone disease is mandatory.     

Urolithiasis associated with urogenital tuberculosis

Summary Of 628 patients with bacteriologicaly or histologicaly proven urogenital tuberculosis (UGT) treated from 1960 to 1985. 126 patients (20.1%) had additional urinary tract infection and 66 patients (10.5%) developed urolithiasis. In these 66 patients a simultaneous urinary tract infection occured in 29 cases (43.9%). Twenty-eight calculi were analyzed by a combined crystal-optical and x-ray-diffraction method. A high incidence of struvite/carbonate apatite calculi (11/28) as well as of calcium phosphate calculi (6/28) was found. The texture of 15 calculi was investigated on thin sections by polarization microscopy and a high concentration of organic material was found in both calcium oxalate and struvite/carbonate apatite calculi probably due to the specific and nonspecific infection with deposition of cell and protein degradation products.     

Urolithiasis in childhood: current management

During the past 12 years, 62 children with urinary stones have been treated at the Children's Hospital of Philadelphia. The most common presenting symptoms were abdominal or flank pain (45%), recurrent or persistent pyuria (35%), and gross hematuria (21%). Twenty-two patients had associated congenital urologic anomalies. Infection-related struvite stones were most common and were found in 18 children, of whom 15 were found to have anatomic abnormalities. Eighteen of 28 children evaluated for a metabolic cause were found to have an abnormality, most frequently hypercalciuria. No predisposing factors could be found in 16 of the 62 patients. Forty-four (87%) children had upper urinary tract stones. Twelve of 15 bladder stones were in children with a neuropathic bladder and all were related to infection. Treatment was directed to the correction of anatomic and metabolic predisposing causes, as well as to removing the stones. Fifteen patients passed stones ranging in size from 2 to 6 mm. Forty-six surgical procedures were performed in 43 children. Pyelolithotomy and cystolithotomy were the most frequent procedures. There were three residual stones and five recurrences. Of the 29 operations for upper urinary stones reviewed, 17 might today be considered suitable for percutaneous nephrostolithotripsy or extracorporeal shockwave lithotripsy. Possible future stone management will be discussed in light of this analysis.     

Metabolic factors in the causation of urinary tract stones in patients with enterocystoplasties

Stones are a common complication of the storage of urine in intestinal reservoirs. Previous studies have identified predisposing physical characteristics in the reservoirs. Biochemical and dietary factors have been little investigated. Fifteen patients (6 males and 9 females) who had undergone various enterocystoplasty operations and who had subsequently formed either upper or lower urinary tract stones were investigated. The programme has been previously described and included stone, blood and urine analysis and dietary review. Comparison was made with 15 age- and sex-matched idiopathic stone formers with normal bladders. Stones were infective in origin in 86% of cases, and 14% were sterile. Metabolic screen showed that 80% of enterocystoplasty patients had risk factors for at least three different types of stone. All patients had raised pH (mean 6.93) and hypocitraturia. Five had a raised alkaline phosphatase. Raised serum and urinary calcium, hyperoxaluria and hyperuricosuria were found in 33% of patients. Five had a 24-h urine volume below 1.6 l/day. All patients had a high risk index (P _SF) for phosphatic stones and 12 also for calcium oxalate stones. Compared to age-and sex-matched idiopathic stone-formers, the urine had a higher pH, sodium and protein excretion and a lower calcium and citrate excretion. Although the patients were already selected as stone-formers, the data show that metabolic and dietary factors are present. They may be as important in the aetiology of the stones, as the already recognised factors of infection and poor reservoir drainage. Investigation should include such factors, the presence of which may be taken into account in a prophylactic regime.     

Nephrolithiasis in children

A metabolic etiology is the most common cause for pediatric kidney stones. Appropriate evaluation of affected children should include assessment of stone type, if available, and assessment of predisposing factors in all cases. This review discusses the metabolic disorders that lead to nephrolithiasis with respect to the development of calcium, uric acid, struvite, and cystine stones. Environmental and hereditary factors are summarized to provide a guide in the evaluation of pediatric stone formers.