Pediatric Urinary Stone Disease in the United States: The Urologic Diseases in America Project.

OBJECTIVE: To examine the recent epidemiology of pediatric urinary stone disease (USD) in the United States. METHODS: We utilized the 2004-2016 Optum© Clinformatics® Data Mart database, a de-identified adjudicated administrative health claims database that includes 15-18 million individuals covered annually by commercial insurance in all 50 US states. The analysis included 12,739,125 children aged 0-18 years. We calculated annual rates of USD, ambulatory visits, and procedures, and the prevalence of prescription fills. RESULTS: The 2005-2016 USD rate was 59.5 cases per 100,000 person-years. The annual rate rose gradually from 2005 to a peak of 65.2 cases per 100,000 person-years in 2011. The USD rate increased with increasing age, and was highest among females compared to males, non-Hispanic Whites compared to other race/ethnic groups, and those residing in the South compared to other geographic regions. The overall 2005-2016 rate in the 120 days following a USD episode was 1.9 for ambulatory visits, 0.24 for surgical procedures, and 1.1 for imaging procedures. Ureteroscopy was the most common surgical procedure and CT scan was the most common imaging procedures, although ultrasound utilization increased over time. Medications were filled in 46.9% of cases, and use was lowest among males (43.1%), Asians (34.8%), and in the Northeast (34.3%). Opiate agonists were the most prevalent prescription (39.9%). CONCLUSION: Our study provides one of the most comprehensive examinations of pediatric USD to date, demonstrating shifting rates and treatment patterns over time, as well as differences by age, gender, race/ethnicity, and geographic region.

Payer Type, Race/Ethnicity, and the Timing of Surgical Management of Urinary Stone Disease.

PURPOSE: Surgery for upper tract urinary stone disease is often reserved for symptomatic patients and those whose stone does not spontaneously pass after a trial of passage. Our objective was to determine whether payer type or race/ethnicity is associated with the timeliness of kidney stone surgery. MATERIALS AND METHODS: A population-based cohort study was conducted using the California Office of Statewide Health Planning and Development dataset from 2010 to 2012. We identified patients who were discharged from an emergency department (ED) with a stone diagnosis and who subsequently underwent a stone surgery. Primary outcome was time from ED discharge to urinary stone surgery in days. Secondary outcomes included potential harms resulting from delayed stone surgery. RESULTS: Over the study period, 15,193 patients met the inclusion criteria. Median time from ED discharge to stone surgery was 28 days. On multivariable analysis patients with Medicaid, Medicare, and self-pay coverage experienced adjusted mean increases of 46%, 42%, and 60% in time to surgery, respectively, when compared with those with private insurance. In addition, patients of Black and Hispanic race/ethnicity, respectively, experienced adjusted mean increases of 36% and 20% in time to surgery relative to their White counterparts. Before a stone surgery, underinsured patients were more likely to revisit an ED three or more times, undergo two or more CT imaging studies, and receive upper urinary tract decompression. CONCLUSIONS: Underinsured and minority patients are more likely to experience a longer time to stone surgery after presenting to an ED and experience potential harm from this delay.

Composition of urinary tract stones formed by children in two populations in the Uyghur region of China.

BACKGROUND: To retrospectively compare the composition of urinary tract stones formed by Uyghur children from the southern (Kashgar) and northern (Urumchi) parts of the Xinjiang region. METHODS: The chemical composition of urinary tract calculi formed by 855 Uyghur children from the two regions in Xinjiang (366 Kashgar and 489 Urumchi) was compared retrospectively. Stone composition was determined by infrared spectroscopy. Factors that might have been of relevance for the findings such as age, gender, stone location and geographic region were also considered. RESULTS: Kashgar children were younger than Urumchi children (2.8 ± 2.7 vs. 4.3 ± 3.7 years, p < 0.001). Although ammonium urate was the dominant stone component in the whole population, calcium oxalate was most common in children from Urumchi. The mean occurrence of ammonium urate, calcium oxalate and uric acid differed significantly between stones formed by Kashgar and Urumchi children (52.5% vs. 29.2%, 18.9% vs. 29.4%, 12.3% vs. 20.9%; respectively, p < 0.001). Renal stones were less frequently recorded in Kashgar children than in Urumchi children (65.8% vs. 91.6%, p < 0.001). Interestingly, bladder stones were more common in children from Kashgar (28.4% vs. 3.7%; p < 0.001). CONCLUSION: Uyghur children from the southern part of Xinjiang apparently had a more serious form of stone disease than children from the northern part and the occurrence of stones dominated by ammonium urate stones was extremely high in children from the southern part of the region.

The Comparison of Urinary Stones Between She Minority and Han Nationality in East Fujian, China.

BACKGROUND: The purpose of the study was to compare the incidence of urinary stones of She minority and Han nationality and analyze the composition of urinary stones. METHODS: The study was performed in 381 cases with 181 She minority and 200 Han nationality. The composition of stones was mainly analyzed by infrared absorption spectrum. The incidence of urinary stones at different ages, different gender and different parts was compared between She minority and Han nationality. RESULTS: The urinary stone incidence of males was about twice as high as in women in She minority and Han nationality, and the incidence reached its maximum between the ages of 41 and 60, but the incidence decreased after 60 years of age. The distribution characteristics of urethra stones between She minority and Han nationality showed a significant difference (p < 0.05). The differences of carbonate apatite and struvite in male and female were statistically significant between She minority and Han nationality (p < 0.05). The level of Ca2+ and HPO42- in serum showed significant difference between She minority and Han nationality (p < 0.05). CONCLUSIONS: According to these results, we put forward corresponding preventive measures of urinary stones in She minority.

Difference in urinary stone composition between Uyghur and Han children with urolithiasis.

The Objective of this study is to analyze the difference in renal stone composition between Uyghur and Han children with urolithiasis in China and possible reasons. From May 2011 to September 2013, we analyzed the stone compositions of 274 Chinese children with urolithiasis, including 151 Uyghur children from Xinjiang Province and 123 Han children from Guangdong Province. All the stone components were determined by Infrared spectroscopy and the main components were recorded. We also evaluated the data, including age, gender and geographic region of the patients. The mean age of Uyghur children was less than Han children (5.3 ± 4.2 vs 8.6 ± 5.7 years, p < 0.001). Calcium oxalate (CaOx) was the main stone composition in both Uyghur (35.1 %) and Han (64.2 %) children, but was more common in Han children (p < 0.0001). Cystine stone was also more abundant in Han children (8.9 % vs 0.7 %, p = 0.001). While, both uric acid (20.5 % vs 3.3 %, p < 0.0001) and magnesium ammonium phosphate (16.6 % vs 2.5 %, p < 0.0001) stones were more common in Uyghur. Interestingly, the significant differences in stone composition between the two groups were only observed in males. When the pediatric patients were further divided into three age groups which were 0-5, 6-12 and >12, the prevalence of calcium oxalate stones increased with age in both groups and was higher in Han children at each age level. The compositions of urinary stones were significantly different between Uyghur and Han children with urolithiasis, factors such as diet habit, life style, genetic diversity, environmental and medical conditions may all contribute to the variances.

Component analysis of 251 cases of urinary calculi in Uigurs and Han in Xingjiang.

OBJECTIVE: To explore the relationship between urolithiasis and related factors by chemical analysis of urolithic components in the urine and serum of Uigurs and Han in Xingjiang. MATERIALS AND METHODS: A series of 251 inpatients' urinary calculi (Uigurs: 148; Han: 103) were qualitatively chemically analyzed. Their serum and urine biochemistry was determined using an automatic biochemical machine. RESULTS: There are significant differences between the Uigurs and the Han (p<0.05) in the ratio of reoccurrence of urinary calculi, age and region; calcium oxalate has the highest concentration (Uigurs: 75.68%; Han: 60.78%). There are significant differences (p<0.05) in serum phosphate (HPO42-) levels, urine specific gravity and uric acid, with the Uigurs having higher levels than that of the Han. CONCLUSIONS: 1. Differences in distributions of urolithic components between Uigurs and Han in Xingjiang are not significant; 2. The ratios of reoccurrence and ages are significantly different. The children and youth of Uigurs have higher rates of occurrence than the Han. There are notable differences in serum HPO42-, urine specific gravity, and uric acid between Uigurs and the Han. The ratio of Uigurs is notably higher than that of the Han. All these differences may result from differences in race, dietary habits, and physical activity.

Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis.

Renal hypouricemia (RHUC) is a heterogeneous inherited disorder characterized by impaired tubular uric acid (UA) transport with severe complications, such as acute kidney injury (AKI). Type 1 is caused by a loss-of-function mutation in the SLC22A12 gene (URAT1), type 2 in the SLC2A9 gene (GLUT9). This article describes three Czech families with RHUC type 1. The serum UA in the probands was 0.9, 1.1 and 0.5 mg/dl and expressed as an increase in the fractional excretion of UA (48, 43 and 39%). The sequencing analysis of SLC22A12 revealed three novel variants: p.G366R, p.T467M and a deletion p.L415_G417del. A detailed metabolic investigation in proband C for progressive visual failure supported suspicion of neuronal ceroid lipofuscinosis type 7 conditioned by the mutation in the MFSD8 gene. Functional studies showed significantly decreased urate uptake and a mis-localized URAT1 signal in p.G366R, p.L415_G417del and p.T467M. Furthermore, colocalization studies showed accumulation of URAT1 protein in the endoplasmic reticulum. The findings suggest that loss-of-function mutations cause RHUC via loss of UA absorption partly by protein misfolding. However, they do not necessarily lead to AKI and a possible genotype-phenotype correlation was not proposed. Furthermore, results confirm an uneven geographical and ethnic distribution of SLC22A12 variants; the p.L415_G417del mutation predominates in the Roma ethnic group in the Czech Republic.

Clinical characteristics of obstructive uropathy associated with rotavirus gastroenteritis in Japan.

AIMS: Rotavirus gastroenteritis is severe and often results in dehydration and pre-renal azotemia. However, we have encountered four children with acute obstructive uropathy associated with acute rotavirus gastroenteritis, and several similar cases have been reported. Therefore, the aim of the present study was to clarify the epidemiology and clinical features of acute obstructive uropathy associated with acute rotavirus gastroenteritis in Japanese children. PATIENTS AND METHODS: We sent questionnaires to all members of the Japanese Society for Nephrology and all authors who had published case reports of this disease in Japan, inquiring about patient age at diagnosis, sex, the type of stones, laboratory data and other factors. RESULTS: 21 reported patients were evaluable, ranging from 0.4 to 3 years. The sex distribution showed a strong male prevalence. Oliguria had appeared about 7 days after the onset of gastroenteritis. Most of the patients showed hyperuricemia and hyponatremia. The stones consisted mainly of ammonium acid urate. The patients were discharged with normal renal function. CONCLUSION: Although obstructive uropathy associated with rotavirus gastroenteritis is very rare, this disease condition should be explored when anuria is refractory to sufficient fluid replacement therapy or when oliguria persists despite recovery of the gastrointestinal symptoms.

Ultrasound of urinary system and urinary screening in 14 256 asymptomatic children in China.

AIM: The aim of this study is to assess the characteristics of urinary system diseases and the role of the ultrasound screening and urinalysis screening for chronic kidney disease (CKD) in asymptomatic children in China. METHODS: Between September 2008 and November 2008, 14 256 children excluding those with obvious symptoms and signs were enrolled in our study. All the subjects accepted ultrasound and urinary screening. A case-control study was performed to evaluate the relative risk of having stones in those children exposed to melamine formula. RESULTS: Of the enrolled children, 6.10% (869 of 14 256) showed abnormalities, of which 409 (2.87%) were established by ultrasound, 572 (4.01%) by urinalysis and 112 (0.79%) by both ultrasound screening and urinalysis. The abnormalities included congenital anomalies of kidney and urinary tract, urinary stones and/or hydronephrosis, leucocyturia and haematuria and/or proteinuria. Children exposed to melamine formula were 5.17 times as likely to have kidney stones as children exposed to no-melamine formula (95% confidence interval, 3.28-8.14; P < 0.001); the probability of kidney stones in melamine-fed infants were 6.28 times as likely as those no melamine-fed (95% confidence interval, 3.71-10.65; P < 0.001). CONCLUSION: Ultrasonography and urinalysis could complement each other and play important roles in the early diagnosis of anomalies of the urinary system, but urinalysis is a more cost-effective screening tool for CKD in children in China. Exposure to melamine-contaminated formula associated with urinary stones, especially in infants, was significantly higher than the control group.

Cystinuria: the South Indian experience.

Cystinuria is reportedly a rare condition affecting the stone patients in India. This paper presents the occurrence of cystine-related abnormality in the population of stone patients reporting to the hospitals in South India. Two thousand and eight hundred urine samples from 1,300 patients attending the urinary stone clinic during the period 2004-2008 were assessed for cystinuria by performing the nitroprusside test on the early morning urine and random samples on the day of attendance. Urinary deposits were also studied in all the patients. Stones retrieved from 800 stone patients were analysed qualitatively and by Fourier Transform infra red (FTIR) spectroscopy. Cystinuria was identified in only three patients. None of these patients showed cystine crystals. Three other patients out of the 1,300 showed presence of cystine crystals in the urine deposit. FTIR spectroscopy of the stones retrieved from the patients showed presence of cystine in 19 out of the 800 stones analysed (2.375%). None of the patients with cystine in the stones had either cystine crystals in the urine or positive nitroprusside test for cystine. All the patients who had positive cystine, cystine crystals or cystine in stone analysis had other biochemical abnormalities. They were medically managed with appropriate biochemical corrective chemotherapy and had control of stone disease process. All the patients were advised purine restriction in the diet. It is concluded from the study that cystinuria is a rare entity in South India. It, however, exists in a small percentage of stone patients. Specific treatment with D-penicillamine was not administered to the patients in view of the high cost, nonavailability and possible toxicity. The patients considered above did not have intractable stone disease which was not amenable to usual modalities of directed medical therapy.

Incidence of upper urinary tract stone during 15 years in Tajima area, Japan: a hospital-based study.

Time trend of incidence of upper urinary tract stone during 15 years was evaluated by hospital-based cohort study in Tajima area, northern part of Hyogo prefecture, Japan, which has only two general hospitals with Department of Urology. Due to isolation in terms of traffic network and geographic circumstances, almost all patients with urinary stone in Tajima area are referred to the two hospitals. During the period 2005-2007, patients of the two hospitals with radiologically proven upper urinary tract stone were included in this study. The survey included the age and gender, location of stones, history of urinary stone, treatment received, and stone composition, if available. Annual incidence of upper urinary tract stone was estimated using the data of population census of Japan 2005 and compared with the data of Tajima during 1991-1993. 1,305 patients were included in this study. Age-adjusted incidence (+/-95% CI) was 157 (+/-22.4) for men, and 57 (+/-12.6) for women, compared with 141 (+/-20.7) for men, and 63 (+/-13.4) for women during 1991-1993. In total, 30.7% of patients received interventional treatment including shock wave lithotripsy, endoscopic lithotripsy and open surgery, whereas 25.3% in 1991-1993. Calcium oxalate/phosphate stone was 89.6%, struvite stone was 4.5%, cystine stone was 1.0%, uric acid stone was 4.0%, and others were 1.0%. In Tajima area, incidence of upper urinary tract stone has not changed during 15 years.

Renal response to lithogenic and anti-lithogenic supplement challenges in a stone-free population group.

OBJECTIVE: In South Africa, urolithiasis is extremely rare in the black population, but is common in the white population. The objective of this study was to investigate the individual effects of 5 different dietary and supplemental challenges (high dietary calcium, calcium supplement, vitamin B6 supplement, L-glutamine supplement, and L-cysteine supplement) on the urinary risk factors for calcium oxalate urolithiasis in subjects from both race groups. DESIGN: Complete Latin Square design. SETTING: University research laboratory. SUBJECTS: Subjects were recruited from the student cohort of the University of Cape Town (10 male subjects from each race group). Selection criteria were no history of renal or metabolic diseases, and no chronic or acute medication. Subjects served as their own controls. INTERVENTION: After 7 days on a self-selected standardized diet, a 24-hour baseline urine sample was collected. A second 24-hour urine sample was collected after 5 days on the prescribed dietary or supplemental challenge. These were analyzed for biochemical and physicochemical risk factors. Additionally, 24-hour dietary recall questionnaires were recorded at baseline and after the 5-day test period, and were analyzed using a food analysis program. Statistical analysis of variance was performed on all of the data. MAIN OUTCOME MEASURES: Urine composition, relative supersaturation of urinary salts, calcium oxalate metastable limit, and Tiselius risk index. RESULTS: None of the protocols altered any of the urinary biochemical or physicochemical risk factors in black subjects. In white subjects, the calcium diet significantly increased urinary potassium (P =.0001) and decreased the relative supersaturation of brushite (P =.035); the calcium supplement significantly decreased the Tiselius risk index (P =.014); vitamin B6 supplement significantly decreased urinary calcium (P =.016), urinary phosphate (P =.027), and the relative supersaturation of brushite (P =.004); L-glutamine supplement significantly decreased relative supersaturation of calcium oxalate (P =.01); L-cystine supplement significantly decreased urinary calcium (P =.031) and the Tiselius risk index (P =.013). CONCLUSIONS: Because none of the challenges had an effect on the urinary risk factors in black subjects, it is speculated that a renal or gastrointestinal homeostatic adjustment occurs in this group, thereby keeping urinary concentration of substances in balance.

Relationship among risk factors for nephrolithiasis, cardiovascular disease, and ethnicity: focus on a law enforcement cohort.

This cross-sectional study determined the prevalence of nephrolithiasis and common cardiovascular disease (CVD) risk factors in a law enforcement officer (LEO) cohort and evaluated the relationship of nephrolithiasis with several CVD risk factors, including the possible effect of ethnicity. Self reported nephrolithiasis and CVD risk factors among currently employed male LEOs from nine states (n = 2,818) were compared to other men in the same states (n = 9,650). Of the LEOs, 6.2% (n = 174) self reported at least one kidney stone (range = 1 to 12, mean 2.3 6 2.1 stones). Twenty five percent of Native American LEOs (n = 7 of 28) self reported a history of stones. In LEOs with a history of nephrolithiasis, overweight defined as body mass index . 25 kg/m2 (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.04, 3.11), hypercholesterolemia (OR = 1.53, 95% CI = 1.09, 2.15), and hypertension (OR = 1.46, 95% CI = 1.02, 2.11) were associated with the disease. These results suggest officers with common CVD risk factors are also at an increased risk for nephrolithiasis. Native American LEOs have a disproportionately higher prevalence of nephrolithiasis than do other ethnic groups.

Urethral calculi: presentation and management.

OBJECTIVE: To determine the occurrence, symptoms, treatment and outcome in patients with urethral stones. PATIENTS AND METHODS: Fifty-one consecutive patients with urethral calculi were assessed prospectively; all were male and one was an infant. RESULTS: Acute retention of urine occurred in 78% of patients, urethral anatomical pathology in 6% and posterior urethral calculi in 88%. The urethral stones, solitary in each patient, consisted of calcium oxalate in 86%, struvite in 6%, mixed stones in 4%, calcium phosphate in 2% and uric acid in 2%. A methodical approach to therapy was used which aimed to clearly define the circumstances in which a given procedure was used, and the resulting success rate. CONCLUSION: The common belief that most urethral calculi in patients in developing countries originate from the bladder does not seem to be generally applicable. Urethral anatomical pathology does not seem to be a necessary condition for most of these calculi.

Unique pattern of urinary tract calculi in Australian Aboriginal children.

Young Aboriginal children in remote regions of tropical and desert Australia are at risk of developing urate stones in their upper urinary tract from an early age. These radiolucent calculi were only recognized with the availability of ultrasound diagnosis and are not associated with anatomic anomalies or abnormal uric acid production/metabolism. Although these stones appear to resolve spontaneously after the weaning period, some result in ureteric obstruction and infection which may lead to renal damage. This pattern of urolithiasis differs from the usual global urolithiasis pattern of either endemic bladder stones in young children in developing countries or predominantly calcium-based stones in upper tracts of older children and adults in affluent industrialized countries, where upper tract urate stones account for only a minority of childhood urinary tract stones. Risk factors for urate stones are low urine output and acidic urine. An association between urolithiasis and carbohydrate intolerance leading to chronic acidosis has been suggested for Aboriginal children, but existing limited evidence does not support this as a major aetiological factor. Although further studies on the epidemiology, natural history and management of these urate stones are needed, we believe the focus should be on improving the known social and environmental risk factors of remote Aboriginal children during the weaning period which contribute to the unacceptably high prevalence of failure to thrive, diarrhoeal disease, environmental enteropathy, iron deficiency and urolithiasis.

Lithogenic risk factors in normal black volunteers, and black and white recurrent stone formers.

OBJECTIVE: To compare lithogenic risk factors in normal black volunteer men (BN), male black stone formers (BSF) and male white recurrent stone formers (WSF); in addition, the differential diagnoses in the stone formers were compared to determine if the causes of renal stones differed in the two groups. SUBJECTS AND METHODS: The study included 22 BN, 22 consecutive BSF and 122 consecutive WSF seen over a 10-year period. Each subject was assessed by a thorough medical history, dietary analysis and a full serum and urinary biochemical evaluation. RESULTS: Although the WSF were significantly more overweight (P<0.001) and obese (P<0.001) than the BSF, neither group had values significantly different from those of their respective normal populations. There was no significant difference in serum levels of Ca, phosphorus, ionised Ca, calcitriol and alkaline phosphatase in BSF and WSF, but levels of parathyroid hormone tended to be (P<0.1) and calcitriol was significantly higher in BSF than WSF (P<0.03). The BSF urinary excretion levels tended to be more like that of the WSF, with the following pattern present; BN

Lithogenic risk factors in the urine of black and white subjects.

OBJECTIVE: To identify biochemical and dietary factors which may play a role in the low incidence of stone formation in the black South African population. SUBJECTS AND METHODS: The study included 31 semiurbanized black and 29 urbanized white subjects. The protocol and modern laboratory techniques used to assess recurrent stone formers were followed. Urinary sodium, potassium, creatinine, calcium, phosphate and urate levels were measured, and urinary citrate, oxalate and cystine assessed. RESULTS: Black subjects ate a diet significantly higher in sodium (P < 0.04); there was no difference in serum levels but urinary sodium was significantly higher (P < 0.001) in black than in white subjects. Urinary potassium, calcium, citrate, phosphate and cystine were all significantly lower in black than in white subjects (P < 0.001 for the first four and P < 0.03 for cystine). CONCLUSION: Certain intrinsic factors in South African black subjects may account for their lower frequency of stone formation than in white subjects. Of these, the very low urinary calcium, decreased urinary cystine and different interactions between sodium and calcium/cystine are probably important.

Paediatric urolithiasis in a remote Australian aboriginal community.

A retrospective study of Community Health Service patient records revealed 10 cases of urolithiasis in Aboriginal children under 5 years of age in a remote central Australian Aboriginal community over a 4 year period, out of a total under-5 population estimate of 62. The highest attack rate was in the 0-2 age group, where nearly one in 10 children presented per year. All children had significant associated morbidity. Two children underwent pyelolithotomy. Aboriginal children in the remote arid zone study community suffer exceptionally high rates of urolithiasis. Inadequate diet, dehydration and recurrent infectious disease are factors in pathogenesis. Further study may elucidate aetiology, but the implications of these data for improving environmental conditions and health service delivery in Aboriginal communities are urgent.

Racial variation in gender frequency of calcium urolithiasis.

Calcium oxalate stones are known to occur most frequently in the fifth and sixth decades of life and in a male-to-female ratio of approximately 2:1. However, previous data are from predominantly white populations or from multiracial populations that have included patients with infection stones. We reviewed a population of 444 consecutive patients (189 white, 123 black and 132 Hispanic) from 1 urban hospital treated by shock wave lithotripsy for symptomatic renal and ureteral calculi, and added a population of 260 patients treated at a university hospital in Japan. Patients with infection stones and those with uric acid or cystine stones were excluded. We found men to be more commonly afflicted in the white (62%) and Asian (64%) populations but noted a reversal of gender frequency in the black and Hispanic populations, of which women comprised 68% and 60% of the stone population, respectively. We conclude that calcium urolithiasis is more common in women than previously reported, and discuss the possible etiologies.