Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis.

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73-0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66-0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55-0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00-2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72-1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68-1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86-2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70-1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.

Genetic polymorphism (rs6776158) in CaSR gene is associated with risk of nephrolithiasis in Chinese population.

The objective of this study is to find about the association between calcium-sensing receptor (CaSR) genetic variants and susceptibility to nephrolithiasis in the Chinese Han population.This hospital-based case-control study included 319 nephrolithiasis cases and 378 healthy controls subjects. Two SNPs in CaSR were genotyped using the TaqMan assay.We found that subjects carrying the G allele of rs6776158 (AG and GG) had significantly higher risk of nephrolithiasis compared to the AA genotype (P = .015 and .009, respectively).Our results indicate that rs6776158 polymorphism that might elevate the risk of nephrolithiasis in the Chinese population.

rs11567842 SNP in SLC13A2 gene associates with hypocitraturia in Thai patients with nephrolithiasis.

Hypocitraturia is a profound risk for kidney stone formation and recurrence. Sodium-dicarboxylate cotransporter-1 (NaDC-1) is a main transporter responsible for citrate reabsorption in renal proximal tubules. To investigate an association of sodium-dicarboxylate cotransporter-1 (NaDC-1) polymorphism with hypocitraturia in Thai patients with nephrolithiasis (NL). Exonic SNPs in NaDC-1 were screened in peripheral blood DNA of 13 NL patients. The rs11567842 (A/G) variant was found and further genotyped in 145 NL patients and 115 non-stone forming controls. NL patients had significantly lower level of urinary citrate than the controls. Based on logistic regression, hypocitraturia was significantly associated with urinary stone formation (adjusted OR 8.34, 95% CI 4.63-15.04). Significant association of urinary citrate level with rs11567842 genotype was found only in the NL group. NL patients with GG genotype had significantly higher urinary citrate than those with AA and AG genotypes. GG carrying patients had significantly reduced risk for hypocitraturia (adjusted OR 0.15; 95% CI 0.05-0.48, AA as reference). In selected 15 calcium oxalate stone patients, AA carriers had significantly higher intrarenal NaDC-1 mRNA than GG and AG carriers. Homozygous GG of rs11567842 SNP in NaDC-1 gene was a protective genotype for hypocitraturia in kidney stone patients. The findings suggested that patients with AA genotypes were more susceptible to hypocitraturia than those with GG, hence carrying a higher risk for kidney stone recurrence.

Different effects of γ-linolenic acid (GLA) supplementation on plasma and red blood cell phospholipid fatty acid composition and calcium oxalate kidney stone risk factors in healthy subjects from two race groups with different risk profiles pose questions about the GLA-arachidonic acid-oxaluria metabolic pathway: pilot study.

Fatty acid (FA) composition of phospholipids in plasma and red blood cells (RBC) can influence calciuria, oxaluria and renal stone formation. In this regard, the ratio of arachidonic acid (AA) and its precursor linoleic acid (LA) appears to be important. Administration of γ-linolenic acid (GLA) has been shown to increase the concentration of dihomo-gamma linoleic acid (DGLA) relative to AA indicating that it may attenuate biosynthesis of the latter. Such effects have not been investigated in race groups having difference stone occurrence rates. Black (B) and white (W) healthy males ingested capsules containing linoleic acid (LA) and GLA, for 30 days. Plasma and RBC total phospholipid (TPL) FA profiles, serum and 24 h urine biomarkers of hypercalciuria and urinary stone risk factors were determined on days 0 and 30. Data were tested for statistical significance using GraphPadInstat version 3.02. Concentration and percentage content of DGLA in plasma TPL increased in W but not in B. Arachidonic acid (AA) did not change in either group. There was no change in calcium excretion in either group but oxalate and citrate excretion increased in W. We suggest that elongation of GLA to DGLA may occur more rapidly than desaturation of DGLA to AA in W and that depressed activity of the enzyme elongase may occur in B. Calciuric and citraturic effects may be dependent on the quantity of LA or on the mass ratio of LA/GLA in the FA supplement. Questions about the mooted DGLA-AA-oxaluria pathway arise. We speculate that there exists a potential for using GLA as a conservative treatment for hypocitraturia. The observation of different responses in B and W indicates that such differences may play a role in stone formation and prevention.

Calcium-Sensing Receptor Genetic Polymorphisms and Risk of Developing Nephrolithiasis in a Chinese Population.

OBJECTIVE: To evaluate the association between calcium-sensing receptor (CaSR) Arg990Gly (rs1042636, A > G), Ala986Ser (rs1801725, G > T) polymorphisms, and urolithiasis risk. METHODS: Polymorphisms mentioned above were genotyped in a hospital-based case-control study of 615 patients diagnosed with nephrolithiasis and 315 kidney stone-free controls in a Chinese population using the SNaPshot method. RESULTS: The results indicated a significantly increased risk associated with CaSR Arg990Gly GG genotypes (OR 1.64, 95% CI 1.08-2.50) compared with the AA genotype. The CaSR Arg990Gly G carriers (AG/GG) had an adjusted OR (95% CI) of 1.45 (1.04-2.03, p = 0.021) compared with the wild genotype in the dominant model. In the stratified analyses, the risk remained for the subgroup of patients with age >48, never smokers and patients with hypertension and calcium oxalate stones (OR 1.78, 95% CI 1.02-3.09; OR 1.54, 95% CI 1.03-2.30; OR 2.83, 95% CI 1.32-6.07; OR 1.60, 95% CI 1.12-2.28, respectively). CONCLUSION: Our results provide evidences that the CaSR Arg990Gly polymorphism is associated with the risk of nephrolithiasis development in a Chinese population.

Glycaemia and phosphatemia after oral glucose and maltitol ingestion in subjects from two different race groups: preliminary evidence of inter-race differences in metabolism and possible implications for urinary stone disease.

PURPOSE: Glucose (Glu) and maltitol (Mal) ingestion affect calciuria and phosphaturia. Renal phosphate leak involving hypophosphatemia is thought to be a mechanism. Inter-race differences in carbohydrate metabolism are known. We investigated the effects of Glu and Mal ingestion on glycaemia and phosphatemia in subjects from two race groups to better understand potential implications for nephrolithiasis. METHODS: Healthy black (B) (n = 8) and white (W) (n = 8) males followed a self-selected standardized diet for 7 days and a strictly controlled standardized diet on Day 8. After an overnight fast, subjects provided blood samples prior to and 30 min after ingestion of a randomly assigned solution of Glu or Mal. Blood Glu and serum phosphate were measured. Protocols were swapped after a 1-week washout period. RESULTS: Following Glu ingestion, glycaemia increased significantly in W (4.8 vs 6.2 mmol/l) but not in B (4.7 vs 5.3 mmol/l) while phosphatemia decreased significantly in B (1.16 vs 1.01 mmol/l) but not in W (1.24 vs 1.15 mmol/l). After Mal ingestion, glycaemia increased significantly in B (4.7 vs 5.2 mmol/l) but not in W (4.6 vs 5.9 mmol/l), while phosphatemia decreased significantly in W (1.24 vs 1.18 mmol/l) but not in B (1.17 vs 1.06 mmol/l). CONCLUSIONS: Our results suggest that enzymes which regulate glycolysis may be less active in B than in W, or expression of renal transcellular Glu transporters may be relatively inhibited in B. Effects on phosphatemia are carbohydrate- and race-dependent, thereby prohibiting speculation of a general algorithm linking these variables. Inter-race differences in metabolic handling of carbohydrates might impact on respective nephrolithiasis risk factors in such groups.

Annual Incidence of Nephrolithiasis among Children and Adults in South Carolina from 1997 to 2012.

BACKGROUND AND OBJECTIVES: The prevalence of nephrolithiasis in the United States has increased substantially, but recent changes in incidence with respect to age, sex, and race are not well characterized. This study examined temporal trends in the annual incidence and cumulative risk of nephrolithiasis among children and adults living in South Carolina over a 16-year period. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a population-based, repeated cross-sectional study using the US Census and South Carolina Medical Encounter data, which capture all emergency department visits, surgeries, and admissions in the state. The annual incidence of nephrolithiasis in South Carolina from 1997 to 2012 was estimated, and linear mixed models were used to estimate incidence rate ratios for age, sex, and racial groups. The cumulative risk of nephrolithiasis during childhood and over the lifetime was estimated for males and females in 1997 and 2012. RESULTS: Among an at-risk population of 4,625,364 people, 152,925 unique patients received emergency, inpatient, or surgical care for nephrolithiasis. Between 1997 and 2012, the mean annual incidence of nephrolithiasis increased 1% annually from 206 to 239 per 100,000 persons. Among age groups, the greatest increase was observed among 15-19 year olds, in whom incidence increased 26% per 5 years (incidence rate ratio, 1.26; 95% confidence interval, 1.22 to 1.29). Adjusting for age and race, incidence increased 15% per 5 years among females (incidence rate ratio, 1.15; 95% confidence interval, 1.14 to 1.16) but remained stable for males. The incidence among blacks increased 15% more per 5 years compared with whites (incidence rate ratio, 1.15; 95% confidence interval, 1.14 to 1.17). These changes in incidence resulted in doubling of the risk of nephrolithiasis during childhood and a 45% increase in the lifetime risk of nephrolithiasis for women over the study period. CONCLUSIONS: The incidence of kidney stones has increased among young patients, particularly women, and blacks.

Investigação de nefrolitíase no Oeste do Paraná / Investigation of nephrolithiasis in the West of Paraná

INTRODUÇÃO: Nefrolitíase é comum e tem alta taxa de recorrência. OBJETIVOS: Avaliar a prevalência das principais alterações metabólicas e anatômicas e a análise química do cálculo encontrado em pacientes com nefrolitíase na região Oeste do Paraná. MÉTODOS: Foi realizado um estudo retrospectivo em 681 pacientes adultos com nefrolitíase. A investigação laboratorial incluiu pelo menos duas amostras de urina de 24 horas, com dosagens de cálcio, ácido úrico, citrato, oxalato, sódio e creatinina; cistinúria qualitativa, pH urinário após 12 horas de jejum e restrição hídrica, urocultura e análise química do cálculo, quando disponível. Técnicas de imagem renal incluíram pelo menos ultrassonografia e urografia excretora. RESULTADOS: As alterações metabólicas mais frequentemente encontradas foram: hipercalciúria (51,8 por cento), hiperuricosúria (27,6 por cento) e hipocitratúria (23,5 por cento). A análise química dos cálculos mostrou oxalato de cálcio em 85,7 por cento dos casos. As alterações anatômicas mais frequentes foram: cisto renal, duplicação pieloureteral e obstrução da junção pieloureteral. CONCLUSÕES: Este trabalho serviu de base para o conhecimento das características de pacientes com nefrolitíase na região Oeste do Paraná.

INTRODUCTION: Nephrolithiasis is com>mon and has a high rate of recurrence. OBJECTIVES: To assess the prevalence of the main metabolic and anatomical changes and the chemical analysis of stone found in patients with nephrolithiasis in the West region of Paraná. METHODS: Retrospective study with 681 adult patients with nephrolithiasis. The laboratory investigation included at least two samples of 24-hour urine test with doses of calcium, uric acid, citrate, oxalate, sodium and creatinine; qualitative cystinuria, urinary pH following 12-hour fast and water restriction, urine culture and chemical analysis, when the stones were available. Renal imaging techniques included at least renal ultrasound and excretory urogram. RESULTS: The metabolic changes most frequently found were: hypercalciuria (51.8 percent), hyperuricosuria (27.6 percent), and hypocitraturia (23.5 percent). Chemical analysis of stones showed calcium oxa late in 85.7 percent of the cases. The most frequently anatomical changes were renal cyst, duplicated ureter, and ureteropelvic junction obstruction. CONCLUSIONS: This paper served as a base for knowing the characteristics of patients with nephrolithiasis in the West area of Paraná.

Comparison of quality of life between hemodialysis patients waiting and not waiting for kidney transplant from a poor region of Brazil / Comparação da qualidade de vida entre pacientes em hemodiálise aguardando e não aguardando transplante renal em uma região pobre do Brasil

INTRODUCTION: There are few data about the quality of life (QOL) level among patients undergoing hemodialysis (HD) and not eligible for kidney transplant. OBJECTIVE: The QOL level was compared between HD patients waiting and not waiting for kidney transplant. METHODS: We included 161 end-stage renal disease patients undergoing HD, during April, 2009. All patients were older than 18 years old, had been on HD at least three months, and had no previous transplantation. To measure QOL, the SF-36 was used. We also collected data about death and transplants in the 12 months after April, 2009. QOL scores were compared by analysis of variance with covariates. RESULTS: Patients not awaiting transplantation were older (53.7 versus 36.3 years old; p < 0.001), more often had diabetes (15.8 versus 4.7 percent; p = 0.032) and hypertension (35.5 versus 12.9 percent; p < 0.001), and had no lupus (0 versus 4.7 percent; p = 0.001). They also presented lower creatinine levels (11.5 versus 13.5 mg/dL; p = 0.001) and were submitted to a lower dose of dialysis, estimated by Kt/V (1.6 versus 2.0; p = 0.026). Patients not awaiting transplant died more often in the following 12 months (21.1 versus 5.9 percent; p = 0.005). Adjusted mean scores were lower among patients not awaiting transplant regarding six dimensions of QOL: functional capacity (42.0 versus 53.4; p = 0.022), physical limitation (29.9 versus 49.2; p = 0.030); pain (45.0 versus 64.0; p = 0.003), social aspects (56.3 versus 75.9; p = 0.003), emotional aspects (45.1 versus 79.0; p = 0.001), and mental health (50.1 versus 64.3; p = 0.004). CONCLUSIONS: Patients undergoing HD and not awaiting transplant are at risk of poor QOL level, mainly regarding role-emotional and role-physical aspects. We recommend psychological approaches and physical rehabilitation for this group of patients.

INTRODUÇÃO: Há pouca informação acerca do nível de qualidade de vida (QV) entre pacientes em hemodiálise (HD) não-elegíveis para transplante renal. OBJETIVO: Foi comparado o nível de QV entre pacientes em HD inscritos e não-inscritos na lista de espera para transplante renal. MÉTODOS: Foram incluídos 161 pacientes portadores de doença renal crônica terminal, mantidos em HD durante abril de 2009, com mais de 18 anos, mais de três meses em HD e sem realização de transplante prévio. Para medida de QV, utilizou-se o SF-36. Também foram coletados dados sobre óbito e transplante ocorridos nos 12 meses seguintes a abril de 2009. As pontuações de QV foram comparadas pela análise de variância com covariáveis. RESULTADOS: Pacientes que não aguardavam transplante eram mais velhos (53,7 versus 36,3 anos; p < 0,001), tinham mais diabetes (15,8 versus 4,7 por cento; p = 0,032) e hipertensão (35,5 versus 12,9 por cento; p < 0,001) e não apresentavam lúpus (0 versus 4,7 por cento; p = 0,001). Esses pacientes também apresentavam creatinina mais baixa (11,5 versus 13,5 mg/dL; p = 0,001) e eram submetidos a menor dose de diálise, estimada pelo Kt/V (1,6 versus 2,0; p = 0,026). Pacientes que não aguardavam transplante evoluíram mais frequentemente para óbito no período de 12 meses (21,1 versus 5,9 por cento; p = 0,005). As médias ajustadas das pontuações foram mais baixas entre os pacientes que não aguardavam transplante em seis dimensões da QV: capacidade funcional (42,0 versus 53,4; p = 0,022); limitação por aspectos físicos (29,9 versus 49,2; p = 0,030); dor (45,0 versus 64,0; p = 0,003); aspectos sociais (56,3 versus 75,9; p = 0,003); limitação por aspectos emocionais (45,1 versus 79,0; p = 0,001) e saúde mental (50,1 versus 64,3; p = 0,004). CONCLUSÕES: Pacientes em HD que não aguardam transplante estão em risco de vivenciar baixa QV, principalmente no que se refere à limitação por aspectos emocionais e físicos...

Demographic, dietary, and urinary factors and 24-h urinary calcium excretion.

BACKGROUND AND OBJECTIVES: Higher urinary calcium is a risk factor for nephrolithiasis. This study delineated associations between demographic, dietary, and urinary factors and 24-h urinary calcium. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Cross-sectional studies were conducted of 2201 stone formers (SF) and 1167 nonstone formers (NSF) in the Health Professionals Follow-up Study (men) and Nurses' Health Studies I and II (older and younger women). RESULTS: Median urinary calcium was 182 mg/d in men, 182 mg/d in older women, and 192 mg/d in younger women. Compared with NSF, urinary calcium as a fraction of calcium intake was 33 to 38% higher in SF (P values < or =0.01). In regression analyses, participants were combined because associations with urinary calcium were similar in each cohort and in SF and NSF. After multivariate adjustment, participants in the highest quartile of calcium intake excreted 18 mg/d more urinary calcium than those in the lowest (P trend =0.01). Caffeine and family history of nephrolithiasis were positively associated, whereas urinary potassium, thiazides, gout, and age were inversely associated, with urinary calcium. After multivariate adjustment, participants in the highest quartiles of urinary magnesium, sodium, sulfate, citrate, phosphorus, and volume excreted 71 mg/d, 37 mg/d, 44 mg/d, 61 mg/d, 37 mg/d, and 24 mg/d more urinary calcium, respectively, than participants in the lowest (P values trend < or =0.01). CONCLUSIONS: Intestinal calcium absorption and/or negative calcium balance is greater in SF than NSF. Higher calcium intakes at levels typically observed in free-living individuals are associated with only small increases in urinary calcium.

Temporal trends of acute nephrolithiasis in Auckland, New Zealand.

AIM: An increasing amount of evidence suggests that the occurrence of kidney stone disease has increased over the last 50 years. No data analysis on temporal trends in Auckland, New Zealand has ever been performed. The aim of this study was to investigate the changing pattern by age, ethnicity, and gender on stone incidence over a 10-year period. METHODS: Demographic data was collected on all patients who presented with renal colic. Population numbers were provided by the New Zealand ministry of statistics using regular census data. The analysis was performed using Pearson's correlation coefficients and a Poisson regression model. RESULTS: From 1997 to 2007, 17,532 new stones were coded as nephrolithiasis with an age range of 1-97. Disease incidence amongst Auckland residents was greater in 2007 than 1997 (0.131% or 131 per 100,000 population vs 0.102% or 102 per 100,000 population. p=0.012). The male to female ratio changed over time with a greater proportion of females presenting in 2007 than 1997 (0.47 vs 0.41, p<0.05). Pacific, Asian, and Maori incidence increased faster compared to European whilst those from the Middle East were the only group to have a stable rate (0.26% or 260/100,000 per year) over the 10-year period. CONCLUSIONS: Incidence of kidney stone disease in the Auckland region has increased significantly from 1997 to 2007. Different ethnic groups had different rates of change, but all groups showed an increasing incidence over time, with the exception of those from the Middle East. A greater proportion of patients are female than 10 years ago.

Ethnic differences in relative risk of idiopathic calcium nephrolithiasis in North America.

PURPOSE: Data on susceptibility to kidney stone disease are sparse in individuals of nonEuropean ancestry residing in North America. We determined the relative risk of calcium nephrolithiasis among people of different ethnic backgrounds living in the same geographic region. MATERIALS AND METHODS: Using a cross-sectional design 1,128 consecutive patients with idiopathic calcium nephrolithiasis 18 to 50 years old were recruited from a population based Kidney Stone Center in Toronto. Age and gender adjusted odds ratios and 95% confidence intervals were calculated by logistic regression using the 2001 Canada Census population data. RESULTS: Compared to Europeans the relative risk of calcium nephrolithiasis was significantly higher in individuals of Arabic (OR 3.8, 2.7-5.2), West Indian (OR 2.5, 1.8-3.4), West Asian (OR 2.4, 1.7-3.4) and Latin American (OR 1.7, 1.2-2.4) origin, and significantly lower in those of East Asian (OR 0.4, 0.3-0.5) and African (OR 0.7, 0.5-0.9) background. Several ethnic groups had kidney stone risk factors that were significantly different from those of the European group including higher urinary uric acid, urea excretion and estimated protein intake, and lower urinary citrate, potassium, magnesium and phosphate excretion. However, none was consistent with the variation in relative risk of stone disease overall. CONCLUSIONS: The propensity for the development of calcium nephrolithiasis differed markedly among ethnic groups in North America. While environmental factors could not be completely ruled out, this variability may reflect the influence of genetic susceptibility because there was no dominant environmental factor to account for the differences in relative risk of stone disease.

African American ESRD patients have a high pre-dialysis prevalence of kidney stones compared to NHANES III.

If nephrolithiasis (NL) promotes progression to end stage renal disease (ESRD), requiring renal replacement therapy, one might expect a higher prevalence of pre-ESRD stones among ESRD versus non-ESRD subjects. We compared the prevalence of pre-ESRD stones in an African-American (AA) hemodialysis (HD) population to the estimated stone prevalence in a nationally representative cohort of AA persons as obtained by the Third National Health and Nutrition Survey (NHANES III). Face-to-face questionnaires were administered to a sample of 300 AA HD patients undergoing dialysis therapy at the University of Chicago to determine pre-ESRD NL prevalence. All data on pre-ESRD stone prevalence was confirmed by documented medical history, radiology and laboratory findings, where available. Prevalence of pre-ESRD NL in AA HD patients was 8.3% versus 2.8% in the age, race and sex adjusted NHANES III population (P < 0.001). After adjustment for age and sex, it was estimated that the prevalence of pre-ESRD kidney stones among AA HD patients is significantly higher than the prevalence of kidney stones found in the general AA population.