Racial Differences in Risk Factors for Kidney Stone Formation.

BACKGROUND AND OBJECTIVES: Incidence of kidney stone disease is rising. It is not known whether mechanisms of stone formation differ across racial groups. Our objective was to identify differing lithogenic risk factors across racial groups in idiopathic nephrolithiasis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective cohort study evaluating metabolic risk factors in black and age-matched white idiopathic stone formers at our tertiary referral center. We compared serum and urine metabolic risk factors pre- and post-treatment across racial groups using analysis of covariance. Generalized linear modeling was used to build regression models for risk of stone formation in both groups. RESULTS: Among 117 black and 172 white stone formers, urine volume was lower in black stone formers (1.4±0.8 versus 2.0±0.8 L/d, P<0.001). Urine calcium was lower in black stone formers (116±70 versus 217±115 mg/d, P<0.001). Supersaturations for calcium oxalate were similar among the groups, whereas calcium phosphate supersaturation was higher in white stone formers, and uric acid supersaturation was higher in black stone formers. Electrolyte free water clearance was significantly lower in black stone formers (207±780 versus 435±759 ml/d, P=0.02). In the subgroup of 77 black patients and 107 white patients with post-treatment evaluations, urine volume rose significantly and similarly in both groups. Urine sodium was unchanged in whites but increased in blacks by 40 mmol/d (95% confidence interval, 32 to 48 mmol/d). Electrolyte free water clearance remained lower in black stone formers (385±891 versus 706±893 ml/d, P=0.02). Post-treatment supersaturations were similar across the groups except for calcium phosphate, which improved with treatment in whites. CONCLUSIONS: Black stone formers have lower 24-hour urine calcium excretion and urine volume. Increases in urine volume with treatment were associated with increased solute, but not free water, excretion in black stone formers.

Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.

Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

Socioeconomic Disparities in the Acute Management of Stone Disease in the United States.

INTRODUCTION: Patients admitted to the hospital with an acute, noninfected episode of urolithiasis are candidates for medical expulsive therapy, ureteral stent placement, or upfront ureteroscopy (URS). We sought to assess socioeconomic factors influencing treatment decisions in managing urolithiasis and to determine differences in outcomes based on treatment modality. MATERIALS AND METHODS: The Healthcare Cost and Utilization Project State Inpatient Database, State Ambulatory Surgery and Services Database, and State Emergency Department Database for California from 2007 to 2011 and for Florida from 2009 to 2014 were utilized. Patients who were admitted to the hospital with a primary diagnosis of kidney or ureteral stone were identified. The initial treatment modality utilized was assessed and factors that influenced that decision were analyzed. Multivariate logistic regression model was fit to determine factors independently associated with upfront URS. Lastly, outcomes of noninfected patients who underwent stent alone vs URS were compared. RESULTS: We identified 146,199 patients who had an inpatient admission with urolithiasis. Overall, 45% of patients had no intervention at the time of their evaluation. Of the 55% of patients who underwent surgical intervention, 42% underwent stent alone, 44% underwent upfront URS, 1% had a PCN tube placement, 8% underwent extracorporeal shockwave lithotripsy, while 5% underwent PCNL. On multivariate logistic regression model, minorities, younger patients, publicly uninsured patients, more comorbid patients, those admitted on the weekends, and those admitted to an academic institution had significantly lower odds of undergoing upfront URS. Secondary analysis demonstrated clinical and economic advantages of upfront URS vs stent alone in eligible patients. CONCLUSION: Upfront URS is an overlooked procedure that has clinical and cost-saving implications. Unfortunately, minorities, publicly insured patients, and those admitted on the weekend are less likely to undergo upfront URS, a disparity that should be addressed by urologist.

Common Variants in ALPL Gene Contribute to the Risk of Kidney Stones in the Han Chinese Population.

OBJECTIVE: Kidney stone formation is a complex disorder that likely results from both dietary and genetic factors. A recent study identified an association between the risk of kidney stones and polymorphisms in the ALPL gene, but the study needs replication. To confirm whether the ALPL gene is universally associated with kidney stones, the present study further investigated polymorphisms of the ALPL gene in a Han Chinese population. METHODS: A total of 331 kidney stone patients and 553 unrelated healthy controls were included in the present case-control study. We conducted genetic analyses to detect the association of 19 tagging single nucleotide polymorphisms (SNPs) with kidney stones. In addition, we examined the relations between targeted SNP(s) and several clinical characteristics of kidney stones in the patients. RESULTS: Genetic association analyses using logistic regression models identified one ALPL SNP, rs1256328, which was significantly associated with the kidney stone disease status (OR = 1.52, p = 0.0009). No significant results were obtained through association tests between genotypes of this SNP and the various clinical characteristics of kidney stone patients. CONCLUSION: The ALPL SNP, rs1256328, was identified as being significantly associated with kidney stone disease status in a large Chinese Han cohort. Our study replicated a previous genome-wide association study that was conducted in an Icelandic population.

HIPK2 polymorphisms rs2058265, rs6464214, and rs7456421 were associated with kidney stone disease in Chinese males not females.

BACKGROUND AND AIM: Recent studies have shown that genetic factors are involved in the development of kidney stone disease (KSD). A case-control association analysis was performed to investigate the association between homeodomain-interacting protein kinase 2 (HIPK2; OMIM *606868) polymorphisms and KSD. METHODS: A total of 890 KSD patients and 920 healthy subjects were analyzed. Polymorphisms were genotyped using SNPscanTM high-throughput SNP classification technology. The genotypic and allelic frequencies in KSD patients and healthy individuals were analyzed using a Chi-square test. RESULTS: The genotype and allele distributions of the three polymorphisms (rs2058265, rs6464214, and rs7456421 in HIPK2) displayed strong associations with KSD in males (rs2058265: odds ratio [OR] 2.480,95%confidence interval [CI] 1.205-5.106, p = 0.014; rs6464214: OR 2.466, 95%CI 1.198-5.078, p = 0.014; rs7456421: OR 2.846, 95%CI 1.362-5.947, p = 0.005; perallele: r2058265T, OR 1.357, 95%CI 1.073-1.715, p = 0.011; rs6464214G, OR 1.340, 95%CI 1.060-1.693, p = 0.014; rs7456421C, OR 1.356, 95%CI 1.073-1.713, p = 0.011). Patients carrying the T allele of rs2058265, the G allele of rs6464214, or the C allele of rs7456421 showed higher systolic blood pressure, creatinine, and uric acid levels compared with wild-genotype individuals after adjusting for age, gender, and body mass index (p < 0.005). CONCLUSION: The association of HIPK2 gene polymorphisms with KSD was only observed in males but not in females. HIPK2 gene polymorphisms were also involved in the changes of KSD-related metabolic traits.

Urolithiasis analysis in a multiethnic population at a tertiary hospital in Nairobi, Kenya.

BACKGROUND: Urolithiasis is a global problem whose incidence is reported to be on the rise across the world. Previously, urolithiasis was reported as being rare among the indigenous African population but recent data suggest otherwise. This study reviewed the demographic and clinical characteristics of patients with urolithiasis seen at the Aga Khan University hospital Nairobi (AKUHN) as well as the chemical composition of the stones and the modalities of therapy used. METHODS: This was a retrospective study which utilized patients' clinical and laboratory records from 2013 to 2014. Sixty-seven symptomatic patients with confirmed urolithiasis formed the study. This study aimed to describe the clinical characteristics of patients, modalities of treatment as well as the chemical composition of renal stones from patients diagnosed and managed for urolithiasis during a duration spanning 17 months. Wet chemistry was utilized for analyzing the chemical composition of the urinary calculi. Data on age, sex, symptoms, radiological investigations done, location of the calculi, chemical composition of calculi and therapeutic procedures instituted were extracted and analyzed. RESULTS: Ages ranged from 3 to 87 years with a median of 42; males were the majority (79%) and the commonest presenting symptoms were flank pain (91%) and dysuria (19%). The majority of the stones were located in the ureters (46%) and at the pelvi-ureteric junction (25%). A statistically significant difference in frequency of lodgment at the pelvi-ureteric site between males and females was noted. However, the number of female patients in this study was small and studies with larger numbers of female participants are required to confirm this observation. All stones contained calcium and oxalate, often as the only constituents (72%). In the remainder of the stones, other constituents such bicarbonate, ammonium, phosphorous, magnesium, uric acid and cystine occurred in varying combinations with calcium oxalate. Laser lithotripsy was the most performed therapeutic procedure (77.6%). CONCLUSIONS: Males formed the majority of patient with urolithiasis. Overall, most of the calculi were located in the ureters except in women where the pelviureteric location was commoner. Stones containing calcium oxalate only were predominant across the age groups and in both sexes. Lithotripsy was the commonest mode of management.

Association of kidney stones with atherosclerotic cardiovascular disease among adults in the United States: Considerations by race-ethnicity.

BACKGROUND: There is a paucity of research examining the relationship between kidney stones and risk of cardiovascular disease while considering individuals of different race-ethnicities. PURPOSE: The purpose of this study was to examine the association between history of kidney stones and increased odds of atherosclerotic cardiovascular disease (via the Pooled Cohort Equations) across race-ethnicity groups. METHODS: 5571 participants aged 40-79 from the 2007-2012 cycles of the NHANES were used for this study. A history of kidney stones was collected from survey data. Predicted odds of having a 10-year atherosclerotic cardiovascular disease (ASCVD) event was assessed from the Pooled Cohort Equations. RESULTS: After adjustments, having kidney stones was not associated with an increase odds of having an ASCVD event within the next 10-years (OR 1.03; 95% CI: 0.58-1.82, P=0.91). However, among non-Hispanic blacks, those with kidney stones had a 2.24 increased odds (OR 2.24; 95% CI: 1.08-4.66; P=0.03) of having an ASCVD event within the next 10-years when compared to non-Hispanic blacks with no history of a kidney stone. CONCLUSION: Kidney stones were associated with 10-year risk of a future ASCVD event among non-Hispanic blacks.

Renal calculi: trends in the utilization of shockwave lithotripsy and ureteroscopy.

INTRODUCTION: To assess trends in the usage of extracorporeal shockwave lithotripsy (SWL) and ureteroscopy (URS) in the treatment of renal calculi. MATERIALS AND METHODS: An analysis of the 5% Medicare Public Use Files (years 2001, 2004, 2007 and 2010) was performed to evaluate changes in the use of SWL and URS to treat renal calculi. Patients were identified using ICD-9 (cm) and CPT codes. Statistical analyses, including the Fisher, 2 tests, and multivariate logistic regression analysis were performed using SAS 9.3 (SAS Institute Inc., Cary, NC, USA) and SPSS v20 (IBM Corp., Armonk, NY, USA). RESULTS: The absolute number of patients diagnosed with (+85.1%) and treated for (+31.5%) kidney calculi increased from 2001 to 2010. The ratio of diagnosed/treated patients declined from 15.2% in 2001 to 10.8% in 2010. Whites (OR = 1.27, p < 0.0001), patients in the South (OR = 1.16, p < 0.0001) and those ≤ 84 years of age were more likely to be treated. The utilization of SWL (84.7%) was greater than URS (15.3%), but the utilization of URS increased over time from 8.4% in 2001 to 20.6% of cases by 2010 (p < 0.0001). Treatment via URS was more likely in women (OR = 1.28, p < 0.0001), in patients living outside the South (OR = 1.29-1.45, p ≤ 0.006) and in later years of the study (OR = 2.87, p < 0.0001). CONCLUSIONS: Treatment patterns for renal calculi changed from 2001 to 2010. The usage of URS increased at the cost of SWL. Multiple sociodemographic factors correlated with the likelihood of being treated surgically as well as the choice of the surgical approach.

Prevalence of kidney stones in the United States.

BACKGROUND: The last nationally representative assessment of kidney stone prevalence in the United States occurred in 1994. After a 13-yr hiatus, the National Health and Nutrition Examination Survey (NHANES) reinitiated data collection regarding kidney stone history. OBJECTIVE: Describe the current prevalence of stone disease in the United States, and identify factors associated with a history of kidney stones. DESIGN, SETTING, AND PARTICIPANTS: A cross-sectional analysis of responses to the 2007-2010 NHANES (n=12 110). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Self-reported history of kidney stones. Percent prevalence was calculated and multivariable models were used to identify factors associated with a history of kidney stones. RESULTS AND LIMITATIONS: The prevalence of kidney stones was 8.8% (95% confidence interval [CI], 8.1-9.5). Among men, the prevalence of stones was 10.6% (95% CI, 9.4-11.9), compared with 7.1% (95% CI, 6.4-7.8) among women. Kidney stones were more common among obese than normal-weight individuals (11.2% [95% CI, 10.0-12.3] compared with 6.1% [95% CI, 4.8-7.4], respectively; p<0.001). Black, non-Hispanic and Hispanic individuals were less likely to report a history of stone disease than were white, non-Hispanic individuals (black, non-Hispanic: odds ratio [OR]: 0.37 [95% CI, 0.28-0.49], p<0.001; Hispanic: OR: 0.60 [95% CI, 0.49-0.73], p<0.001). Obesity and diabetes were strongly associated with a history of kidney stones in multivariable models. The cross-sectional survey design limits causal inference regarding potential risk factors for kidney stones. CONCLUSIONS: Kidney stones affect approximately 1 in 11 people in the United States. These data represent a marked increase in stone disease compared with the NHANES III cohort, particularly in black, non-Hispanic and Hispanic individuals. Diet and lifestyle factors likely play an important role in the changing epidemiology of kidney stones.

Correlates of kidney stone disease differ by race in a multi-ethnic middle-aged population: the ARIC study.

OBJECTIVE: To identify correlates of kidney stone disease in white and African American men and women in a population-based longitudinal study starting in four US communities, and to assess differences in correlates across racial groups. METHODS: Between 1993 and 1995, 12,161 middle-aged participants of the ARIC Study provided information on history of kidney stone disease. Information on incident kidney stone-related hospitalizations was obtained from ICD codes on hospital discharge records. RESULTS: Kidney stone disease was reported by 12.0% of men and 4.8% of women. After multivariable adjustment, prevalent kidney stone disease was significantly (p<0.05) associated with male gender (PR=2.50), increased serum triglycerides (PR=1.07 per SD increase), diabetes (PR=1.27), gallstone disease (PR=1.54), white race (PR=1.67), and region of residence. Male gender (HR=1.70), diabetes (HR=1.98), and hypertension (HR=1.69) were significantly associated (p<0.05) with incident kidney stone-related hospitalizations (n=94). Race-stratified analyses showed stronger associations of prevalent kidney stone disease with increased triglycerides, older age, and gallstone disease in African Americans compared to whites, whereas male gender showed stronger association in whites (all p-interaction<0.05). CONCLUSION: We identified novel correlates of kidney stone disease (triglycerides, gallstone disease) and risk factor interactions by race (age, male gender, triglycerides, gallstone disease).

Increasing incidence of kidney stones in children evaluated in the emergency department.

OBJECTIVE: To test the hypothesis that there is an increase in the incidence of childhood nephrolithiasis in the state of South Carolina. STUDY DESIGN: We analyzed demographic data from a statewide database on incidence of kidney stones from emergency department data and financial charges. Data were compared with population data from the US Census to control for population growth. RESULTS: There was a significant increase in the incidence of kidney stones in children between 1996 and 2007. The greatest rate of increase was seen in adolescents, pre-adolescents, and Caucasian children. Infants, toddlers, and African-American children did not show significantly increased incidence in the period. Girls show a growing predominance in our population. The amount of money charged for care of children with kidney stones has gone up >4-fold in our state. CONCLUSION: The incidence of kidney stone disease has risen dramatically in the state of South Carolina since 1996. Further studies investigating potential contributing factors are needed to prevent this costly and painful condition.

Renal stone disease in Christchurch, New Zealand. Part 1: presentation and epidemiology.

AIM: To document the modes of presentation and the epidemiology of radiologically diagnosed renal stone disease over a 1-year period in the region of Christchurch, New Zealand. METHOD: Data on the presentation and epidemiology of renal stone disease was prospectively collected in a 1-year cohort of patients who had a new radiological diagnosis of renal stone disease. RESULTS: The incidence of new renal stone diagnoses was 105 per 100,000 per annum. Renal stone disease was more common in men than women, most common in the three decades from 30 to 59 years, and more common in people in trades or machine operating jobs. There was no significant difference in incidence by ethnicity or season. 58% of people presented with stones located in the ureter. Renal stones tended to be larger and were more likely to present incidentally or with haematuria, whilst ureteric stones were smaller and presented more typically with pain. 33% had a personal history of previous renal stone episodes and 20% had a family history of previous stones. CONCLUSIONS: Kidney stone disease is a significant health condition that affects people of predominantly working ages and men more than women. Both personal and family history are significant risk factors. Patients presenting with pain are more likely to have stones located in the ureter. Renal stones are more likely to present with haematuria or incidentally.

Characterization of human kidney stones using micro-PIXE and RBS: a comparative study between two different populations.

The micro-PIXE and RBS techniques are used to investigate the matrix as well as the trace elemental composition of calcium-rich human tissues on a microscopic scale. This paper deals with the spatial distribution of trace metals in hard human tissues such as kidney stone concretions, undertaken at the nuclear microprobe (NMP) facility. Relevant information about ion beam techniques used for material characterization will be discussed. Mapping correlation between different trace metals to extract information related to micro-regions composition will be illustrated with an application using proton energies of 1.5 and 3.0 MeV and applied to a comparative study for human kidney stone concretions nucleation region analysis from two different population groups (Sudan and South Africa).

Urinary phosphorus rather than urinary calcium possibly increases renal stone formation in a sample of Asian Indian, male stone-formers.

The contribution of dietary Ca and P in renal stone formation is debated. Thus, the main objective was to investigate if there were any differences in the dietary, serum and urine values of Ca and P in stone formers (SF) compared with healthy controls (HC). The secondary aim was to analyse if dietary, serum and urine Ca and P correlated. The study enrolled ten patients with renal stones admitted for stone removal and ten healthy controls. Their dietary macronutrients, Ca and P intakes were calculated from 2-d dietary records. On the second day of dietary record 24-h urine was collected and on the third day morning a 5 ml blood sample was collected. Biochemical analyses were conducted for serum and urine Ca, P and uric acid with qualitative renal stone analysis. All the dietary intakes and urine P were significantly higher (P < 0.05) in SF than in HC. Correlation results showed that in SF dietary Ca correlated to serum and urine Ca. No such correlations were seen for P. Additionally, in SF urine Ca correlated to dietary proteins and fats but not to carbohydrates. None of the biochemical values lay outside the normal range of values. The study suggests urine P rather than urine Ca to be probably at work in the formation of renal stones. Limitation of protein intake with normal Ca intakes could provide a suitable measure to avoid renal stone formation.

Sialylation of urinary prothrombin fragment 1 is implicated as a contributory factor in the risk of calcium oxalate kidney stone formation.

Urinary glycoproteins are important inhibitors of calcium oxalate crystallization and adhesion of crystals to renal cells, both of which are key mechanisms in kidney stone formation. This has been attributed to glycosylation of the proteins. In South Africa, the black population rarely form stones (incidence < 1%) compared with the white population (incidence 12-15%). A previous study involving urinary prothrombin fragment 1 from both populations demonstrated superior inhibitory activity associated with the protein from the black group. In the present study, we compared N-linked and O-linked oligosaccharides released from urinary prothrombin fragment 1 isolated from the urine of healthy and stone-forming subjects in both populations to elucidate the relationship between glycosylation and calcium oxalate stone pathogenesis. The O-glycans of both control groups and the N-glycans of the black control samples were significantly more sialylated than those of the white stone-formers. This demonstrates a possible association between low-percentage sialylation and kidney stone disease and provides a potential diagnostic method for a predisposition to kidney stones that could lead to the implementation of a preventative regimen. These results indicate that sialylated glycoforms of urinary prothrombin fragment 1 afford protection against calcium oxalate stone formation, possibly by coating the surface of calcium oxalate crystals. This provides a rationale for the established roles of urinary prothrombin fragment 1, namely reducing the potential for crystal aggregation and inhibiting crystal-cell adhesion by masking the interaction of the calcium ions on the crystal surface with the renal cell surface along the nephron.

Evidence against a contribution of conventional urine risk factors to de novo ESRD renal stones.

BACKGROUND: The authors measured urine and blood stone risk factors in African-American (AA) haemodialysis (HD) patients with new onset of stones during dialysis. METHODS: Patients with nephrolithiasis (NL) newly manifested during dialysis were matched by age, sex and urine output and dialysis duration to AA HD patients without history or symptoms of stones. Two 24 h urine and serum samples were collected and analysed for conventional stone risk factors. RESULTS: Three percent of the patients formed new stones while on HD; none had formed stones prior to end-stage renal disease. Newly onset NL patients had higher urine citrate and lower serum potassium levels than HD patients without stones. CONCLUSION: Usual stone risk factors did not correlate with new stones during dialysis.

Gender Differences among Hispanics and Caucasians in symptomatic presentation of kidney and ureteral stones.

PURPOSE: We determined gender differences in the symptomatic presentation of kidney and ureteral stones among the Hispanic population and compared it with presentation in the Caucasian population. PATIENTS AND METHODS: A retrospective chart review was performed on 443 patients seen in our Emergency Department or Urgent Care Center for symptomatic kidney or ureteral stones over a 5-year period. Demographic information was obtained, including sex, race, age, location of stone, stone size, and type of urologic intervention. Of the 443 patients, 263 (59%) were Hispanic, and 180 (41%) were Caucasian. RESULTS: The male-to-female ratio of the symptomatic patients with kidney stones was 1.48 for both Hispanic and Caucasian patients. The male-to-female ratio for ureteral stones was 1.06 and 2.48 for the Hispanic and Caucasian patients, respectively (P < 0.05). The rate of urologic intervention was similar among Caucasian males and females and Hispanic females (approximately 33%) but significantly lower among Hispanic males (18%). CONCLUSIONS: The relative symptomatic presentation of ureteral stones of men and women among the Hispanic population is nearly 1:1, whereas the ratio in Caucasian men and women approaches the previously reported 2.5:1. No significant racial or sex differences were noted in the symptomatic presentation of kidney stones. In comparison with Hispanic men, Hispanic women undergo significantly more urologic interventions for symptomatic urolithiasis.