A cohort study showing correspondence of low wall shear stress and cephalic arch stenosis in brachiocephalic arteriovenous fistula access.

BACKGROUND: A brachiocephalic fistula is frequently placed for hemodialysis; unfortunately, cephalic arch stenosis commonly develops, leading to failure. We hypothesized that a contribution to brachiocephalic fistula failure is low wall shear stress resulting in neointimal hyperplasia leading to venous stenosis. The objective of this investigation is to determine correspondence of low wall shear stress and the development of cephalic arch stenosis. METHODS: Forty subjects receiving hemodialysis with a primary brachiocephalic fistula access were followed from time of placement for 3 years or until cephalic arch stenosis. Venogram, Doppler, and viscosity were performed at time of fistula maturation, annually for 3 years or to time of cephalic arch stenosis. Computational hemodynamics modeling was performed to determine location and percent low wall shear stress in the arch. The relationship between wall shear stress at time of maturation and location of cephalic arch stenosis were estimated by correlating computational modeling and quadrant location of cephalic arch stenosis. RESULTS: In total, 32 subjects developed cephalic arch stenosis with 26 displaying correspondence between location of low wall shear stress at time of maturation and subsequent cephalic arch stenosis, whereas 6 subjects did not (p = 0.0015). Most subjects with correspondence had low wall shear stress areas evident in greater than 20% of the arch (p = 0.0006). Low wall shear stress was associated with a higher risk of cephalic arch stenosis in the 23-to-45 age group (p = 0.0029). CONCLUSIONS: The presence and magnitude of low wall shear stress in the cephalic arch is a factor associated with development of cephalic arch stenosis in patients with brachiocephalic fistula. Attenuation of low wall shear stress at time of maturation may help prevent the development of cephalic arch stenosis which is difficult to treat once it develops.

Asymmetric dimethylarginine and whole blood viscosity in renal failure.

BACKGROUND: Renal failure is a disease with accelerated atherosclerosis beginning with endothelial cell dysfunction. Factors affecting endothelial cell dysfunction include whole blood viscosity (WBV) and asymmetric dimethylarginine (ADMA). The relationship in controls and renal failure was determined. METHODS: 51 subjects, 20 controls, 11 renal transplant recipients, 10 chronic kidney disease and 10 end-stage renal disease patients had blood samples drawn for WBV, Hematocrit, and ADMA. WBV was measured at various shear rates from 10 s(-1) to 780 s(-1) at 37 °C. Hematocrit using CritSpin, and ADMA was assayed using an ELISA method. The significance between groups was compared by boxplots and analysis of variance. Linear relationships were shown by regression lines and correlation coefficients. RESULTS: ADMA was elevated in all groups with renal failure when compared to controls (p < 0.05). Control subjects showed a positive correlation between ADMA and WBV, while those who received a renal transplant had a negative correlation (p < 0.05). The difference in ADMA comparing pre-dialysis to post-dialysis conditions was positive (p < 0.05). CONCLUSIONS: The positive relationship between WBV and ADMA in controls is a novel finding and allows for comparison with other groups. This relationship is dramatically altered in renal failure.

Association of urinary pH with body weight in nephrolithiasis.

BACKGROUND: The prevalence of kidney stone disease in the United States is progressively increasing, paralleling the growing rate of obesity. Uric acid nephrolithiasis, a condition associated with a low urinary pH, has been linked to obesity and insulin resistance. Based on these observations, we hypothesized that urinary pH may be inversely associated to body weight in nephrolithiasis. METHODS: Data were retrieved from 4883 patients with nephrolithiasis who underwent ambulatory evaluation at two established stone clinics in Dallas and Chicago. The patients collected 24-hour urine samples on an outpatient basis, while avoiding any drug that could alter urinary pH. Patients were divided in increasing sextiles of body weight, and urinary pH was adjusted for urinary creatinine and for age. RESULTS: Urinary pH had a strong, graded inverse association with body weight. Urinary creatinine and age were both found to be significant covariates of urinary pH, while gender was not a significant independent variable after adjustment for urinary creatinine. Mean 24-hour urinary pH, adjusted for age and urinary creatinine, were 6.09, 6.04, 6.01, 5.99, 5.97, and 5.91 for sextiles of body weight in increasing order from Dallas (P for linear trend <0.0001), and 6.18, 6.10, 6.04, 6.02, 5.97, and 5.88 for the sextiles from Chicago (P for linear trend <0.0001). CONCLUSION: We conclude that urinary pH is inversely related to body weight among patients with stones. The results confirm the previously proposed scheme that obesity may sometimes cause uric acid nephrolithiasis by producing excessively acid urine due to insulin resistance.

Outcome of metabolic evaluation and medical treatment for calcium nephrolithiasis in a private urological practice.

PURPOSE: We determine if medications that have been proven effective for kidney stone prevention in prospective controlled trials can reduce kidney stone recurrence in a private practice of urology better than life-style advice, including hydration. MATERIALS AND METHODS: Between July 1, 1995 and December 31, 1996, 203 patients with stones received care from 1 private practice. Physicians chose to evaluate these patients metabolically based on clinical judgement. Thiazide, potassium citrate and allopurinol are recognized in this study as active treatments, and drug treatment intervals were calculated. Relapse and recurrent stones were counted as those stones manifesting after the initial index event. A stone was called a relapse stone if its date was included in the active treatment interval. RESULTS: The association between use of active therapy and ordering of metabolic evaluation was highly significant. Using survival tables, we separately considered all patients and only those who had formed more than 1 stone. For both populations active treatment reduced stone recurrence significantly more than diet advice and hydration. CONCLUSIONS: Medications validated in trials and guided by metabolic evaluation lower stone recurrence when used in a private practice setting as they do in trials.

Gender differences in seasonal variation of urine stone risk factors.

PURPOSE: We determined whether men and women differ in urine stone risk factors during the 4 seasons of the year. MATERIALS AND METHODS: Measurements from 28,498, 24-hour urines from stone forming patients prior to treatment were analyzed to determine whether monthly variation was significant and whether the sexes differed using ANOVA. Locations of supersaturation maxima were determined. RESULTS: The 2 sexes showed modest sodium depletion in summer with a corresponding decrease in urine calcium but men showed a remarkable decrease in urine volume, causing high calcium oxalate supersaturation. Women had maximum calcium oxalate supersaturation in early winter because of decreasing urine volume and increasing urine calcium excretion. Urine pH was reduced in the 2 sexes during summer but the decrease was far more marked in men, who had a uric acid supersaturation spike. PURPOSE: Overall the sexes differ markedly in the timing of stone risk. Men show a dual summer calcium oxalate and uric acid high risk, while women show a high early winter calcium oxalate high risk.

Thiazide does not affect urine oxalate excretion.

PURPOSE: We assessed the effects of thiazide treatment on urine oxalate excretion in patients with kidney stones. MATERIALS AND METHODS: Of 537 patients (231 women), 209 (81 women) received thiazide for stone prevention. Urine oxalate was measured in 3, 24-hour urines before treatment, and in 1, 24-hour urine after 6 to 12 weeks of treatment. This was an observational cohort and treatment was not randomized. RESULTS: Urine oxalate increased in general. There was no difference in increase with or without thiazide, whether one considered simple t test comparisons or used ANOVA with pretreatment oxalate excretion as a covariate. CONCLUSIONS: Thiazide administration exerts no measurable effect on urine oxalate excretion that can be detected in clinical practice.

Influence of urine pH and citrate concentration on the upper limit of metastability for calcium phosphate.

PURPOSE: We determined the effects on the urine upper limit of metastability for calcium phosphate of citrate concentration and pH, and achievement of the upper limit of metastability by adding calcium or phosphate. MATERIALS AND METHODS: The citrate concentration in aliquots of 24-hour urine samples from normal males without a history of kidney stones was increased. The upper limit of metastability was determined by the point of visible crystal formation, as confirmed by increased optical density at 620 nm. when calcium or pH was increased. In additional experiments the upper limit of metastability was determined by adding calcium or phosphate at pH 5.9 and 6.4. RESULTS: Regardless of how the upper limit of metastability was achieved increasing the citrate concentration increased the former value by about 0.4 units per mM. citrate per l. The upper limit of metastability achieved in a given urine sample by adding phosphate or calcium did not differ. Increasing urine pH increased the upper limit of metastability. CONCLUSIONS: Treatment with alkaline citrate salts may decrease stone formation via an increase in calcium phosphate upper limit of metastability by increasing urine citrate and by directly affecting increased pH.

Changes in urine volume accomplished by physicians treating nephrolithiasis.

PURPOSE: We quantified the changes in urine volume and sodium accomplished in various practice settings and the consequent effects on calcium oxalate supersaturation. MATERIALS AND METHODS: We determined comprehensive urine stone risk factors in 2,877 patients treated in 14 practices, including a university referral center and private sector practices. Changes in urine volume and stone risk factors were measured. RESULTS: In a wide range of practice settings the volume increase was about 0.3 l. daily. Urine sodium excretion increased with volume for unexplained reasons, as did urine calcium excretion. As expected, thiazide lowered calcium excretion but the effect progressively decreased as urine volume increased. Therefore, urine calcium and calcium oxalate supersaturation changes were the result of opposing forces. The net effect was a decrease partly offset by sodium and calcium excretion increases. CONCLUSIONS: Urine volume increments are modest in practice and they are modestly offset by increases in urine sodium due to increased sodium intake. Clinicians should strive for higher volume increases than are currently achieved and be vigilant concerning what seems to be a strong tendency toward a higher sodium intake with more fluids.

Metabolic evaluation of children with urolithiasis: are adult references for supersaturation appropriate?

PURPOSE: We determined the incidence of urinary stone risk factors in pediatric patients with urolithiasis. MATERIALS AND METHODS: Between 1998 and 2001, 71 children with urolithiasis at 2 pediatric institutions underwent metabolic evaluation. The 24-hour urine samples were analyzed outside central laboratory using adult and known pediatric references. Supersaturation and traditional metabolic parameters were determined and compared. RESULTS: All patients had metabolic abnormalities. Calcium related abnormalities were present in 92% of children, calcium oxalate supersaturation was abnormal in 69%, calcium phosphate supersaturation was elevated in 70% and traditional calcium parameters were abnormal in 80%. While 11% of the patients had abnormal calcium phosphate or oxalate supersaturation with normal traditional calcium parameters, 10% had normal calcium oxalate or phosphate supersaturation with abnormal traditional calcium parameters. Low urinary volume was identified in 75% of the children. CONCLUSIONS: Metabolic abnormalities are extremely common in pediatric patients with urolithiasis. Calcium related abnormalities are the most common abnormality. Urinary supersaturation values are complementary to traditional metabolic parameters and may be more sensitive predictors of recurrent stone risk. It is important to establish pediatric reference ranges to interpret these data more accurately.