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Endourology
Urological Survey
Urolithiasis/Endourology 24-H Uric Acid Excretion and the Risk of Kidney Stones G. C. Curhan and E. N. Taylor Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Kidney Int 2008; 73: 489 – 496.
There is uncertainty about the relation between 24-h urinary uric acid excretion and the risk of calcium oxalate nephrolithiasis. In addition, the risk associated with different levels of other urinary factors needs clarification. We performed a cross-sectional study of 24-h urine excretion and the risk of kidney stone formation in 3350 men and women, of whom 2237 had a history of nephrolithiasis. After adjusting for other urinary factors, urinary uric acid had a significant inverse association with stone formation in men, a marginal inverse association with risk in younger women, and no association in older women. The risk of stone formation in men and women significantly rose with increasing urine calcium and oxalate, and significantly decreased with increasing citrate and urine volume, with the change in risk beginning below the traditional normal thresholds. Other urinary factors were also associated with risk, but this varied by age and gender. Our study does not support the prevailing belief that higher urine uric acid excretion increases the risk for calcium oxalate stone formation. In addition, the current definitions of normal levels for urinary factors need to be re-evaluated. Editorial Comment: The 24-hour urine test is routinely used to profile phenotypic risks of stone formation in patients afflicted with nephrolithiasis. Curhan and Taylor performed a cross-sectional study of 3 large epidemiological cohorts to determine if the analytes measured could predict stone risk. They demonstrated that the risk of stone formation was positively correlated with calcium and oxalate excretion, and negatively correlated with citrate excretion in all 3 cohorts. Interestingly, the stone risk increased at values that would be considered in the normal range. They found no correlation with stone risk and uric acid excretion. This study raises the question of whether the thresholds should be changed for the institution of selective medical therapy for stone prevention. The uric acid findings are consistent with a study in which there were no differences in uric acid excretion between stone formers and healthy controls when both cohorts consumed standardized diets.1 The main evidence that uric acid excretion may have a role in calcium oxalate stone formation is from a randomized prospective trial in which administration of allopurinol to patients with isolated hyperuricosuria resulted in a decreased rate of stone activity.2 Perhaps the benefits of allopurinol therapy are independent of urinary uric acid reduction. Dean Assimos, M.D. 1. Pais VM Jr, Holmes RP and Assimos DG: Effect of dietary control of urinary uric acid excretion in calcium oxalate stone formers and non-stone-forming controls. J Endourol 2007; 21: 232. 2. Ettinger B, Tang A, Citron JT, Livermore B and Williams T: Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med 1986; 315: 1386.
0022-5347/09/1814-1721/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 181, 1721-1724, April 2009 Printed in U.S.A. DOI:10.1016/j.juro.2008.12.039
www.jurology.com
1721
1722
UROLITHIASIS/ENDOUROLOGY
Fructose Consumption and the Risk of Kidney Stones E. N. Taylor and G. C. Curhan Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Kidney Int 2008; 73: 207–212.
Fructose consumption has markedly increased over the past decades. This intake may increase the urinary excretion of calcium, oxalate, uric acid, and other factors associated with kidney stone risk. We prospectively examined the relationship between fructose intake and incident kidney stones in the Nurses’ Health Study I (NHS I) (93,730 older women), the Nurses’ Health Study II (NHS II) (101,824 younger women), and the Health Professionals Follow-up Study (45,984 men). Food frequency questionnaires were used to assess free fructose and sucrose intake every 4 years. Total-fructose intake was calculated as free fructose plus half the intake of sucrose, and expressed as percentage of total energy. Cox proportional hazard regressions were adjusted for age, body mass index (BMI), thiazide use, caloric intake, and other dietary factors. We documented 4902 incident kidney stones during a combined 48 years of follow-up. The multivariate relative risks of kidney stones significantly increased for participants in the highest compared to the lowest quintile of total-fructose intake for all three study groups. Free-fructose intake was also associated with increased risk. Non-fructose carbohydrates were not associated with increased risk in any cohort. Our study suggests that fructose intake is independently associated with an increased risk of incident kidney stones.
Determinants of 24-Hour Urinary Oxalate Excretion E. N. Taylor and G. C. Curhan Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Clin J Am Soc Nephrol 2008; 3: 1453–1460.
Background and Objectives: Higher levels of urinary oxalate substantially increase the risk of calcium oxalate kidney stones. However, the determinants of urinary oxalate excretion are unclear. The objective was to examine the impact of dietary factors, age, body size, diabetes, and urinary factors on 24-h urinary oxalate. Design, Setting, Participants, and Measurements: We conducted a crosssectional study of 3348 stone forming and non-stone-forming participants in the Health Professionals Follow-up Study (men), the Nurses’ Health Study (older women), and the Nurses’ Health Study II (younger women). Results: Median urinary oxalate was 39 mg/d in men, 27 mg/d in older women, and 26 mg/d in younger women. Participants in the highest quartile of dietary oxalate excreted 1.7 mg/d more urinary oxalate than participants in the lowest quartile (P trend 0.001). The relation between dietary and urinary oxalate was similar in individuals with and without nephrolithiasis. Participants consuming 1000 mg/d or more of vitamin C excreted 6.8 mg/d more urinary oxalate than participants consuming ⬍90 mg/d (P trend ⬍ 0.001). Body mass index, total fructose intake, and 24-h urinary potassium, magnesium, and phosphorus levels also were positively associated with urinary oxalate. Calcium intake and age were inversely associated with urinary oxalate. After adjustment for body size, participants with diabetes excreted 2.0 mg/d more urinary oxalate than those without diabetes (P ⬍ 0.01). Conclusions: The impact of dietary oxalate on urinary oxalate appears to be small. Further investigation of factors influencing urinary oxalate may lead to new approaches to prevent calcium kidney stones. Editorial Comment: Stone formation is usually caused by environmental and genetic factors. Diet is considered the most important environmental influence. Much has been learned about diet and stone risk from the prospective studies of 3 large epidemiological cohorts—Nurses’ Health Study I, Nurses’ Health Study II and the Health Professionals Follow-Up Study. Taylor and Curhan report that fructose consumption was associated with stone risk in all 3 of these cohorts. In a subsequent study of the same cohorts these investigators reported that increasing body mass and fructose consumption were positively correlated to oxalate consumption. Metabolic studies in humans and in vivo studies in rats have revealed that fructose intake
UROLITHIASIS/ENDOUROLOGY
1723
may promote calcium and oxalate excretion, and insulin resistance. Fructose consumption has significantly increased during the last 3 decades, and this increase parallels the obesity epidemic in the United States in adults and children. Americans are addicted to high fructose corn syrup—nectar for the waistline as well as renal colic. Dean Assimos, M.D.
Evidence for Increased Postprandial Distal Nephron Calcium Delivery in Hypercalciuric Stone-Forming Patients E. M. Worcester, F. L. Coe, A. P. Evan, K. J. Bergsland, J. H. Parks, L. R. Willis, D. L. Clark and D. L. Gillen Department of Medicine, University of Chicago School of Medicine, Chicago, Illinois Am J Physiol Renal Physiol 2008; 295: F1286 –F1294.
A main mechanism of idiopathic hypercalciuria (IH) in calcium stone forming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using 14 one hour measurements of the clearances of sodium, calcium and endogenous lithium during a three meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normals. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ; but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque. Editorial Comment: A significant number of stone formers have hypercalciuria. Increased gastrointestinal absorption of calcium has been thought to be the driving factor. These investigators, who performed carefully controlled metabolic studies in normal subjects and idiopathic calcium oxalate stone formers, demonstrated that the kidney also contributes to increased calcium excretion. This increase occurs at both ends of the nephron, with decreased reabsorption of calcium in the proximal tubule as well as the distal nephron. Further definition of the mechanisms of these responses may permit development of better pharmacological agents for reducing calcium excretion and perhaps Randall’s plaque. Dean Assimos, M.D.
Urolithiasis/Endourology 24-H Uric Acid Excretion and the Risk of Kidney Stones G. C. Curhan and E. N. Taylor Renal Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Kidney Int 2008; 73: 489 – 496.
There is uncertainty about the relation between 24-h urinary uric acid excretion and the risk of calcium oxalate nephrolithiasis. In addition, the risk associated with different levels of other urinary factors needs clarification. We performed a cross-sectional study of 24-h urine excretion and the risk of kidney stone formation in 3350 men and women, of whom 2237 had a history of nephrolithiasis. After adjusting for other urinary factors, urinary uric acid had a significant inverse association with stone formation in men, a marginal inverse association with risk in younger women, and no association in older women. The risk of stone formation in men and women significantly rose with increasing urine calcium and oxalate, and significantly decreased with increasing citrate and urine volume, with the change in risk beginning below the traditional normal thresholds. Other urinary factors were also associated with risk, but this varied by age and gender. Our study does not support the prevailing belief that higher urine uric acid excretion increases the risk for calcium oxalate stone formation. In addition, the current definitions of normal levels for urinary factors need to be re-evaluated. Editorial Comment: The 24-hour urine test is routinely used to profile phenotypic risks of stone formation in patients afflicted with nephrolithiasis. Curhan and Taylor performed a cross-sectional study of 3 large epidemiological cohorts to determine if the analytes measured could predict stone risk. They demonstrated that the risk of stone formation was positively correlated with calcium and oxalate excretion, and negatively correlated with citrate excretion in all 3 cohorts. Interestingly, the stone risk increased at values that would be considered in the normal range. They found no correlation with stone risk and uric acid excretion. This study raises the question of whether the thresholds should be changed for the institution of selective medical therapy for stone prevention. The uric acid findings are consistent with a study in which there were no differences in uric acid excretion between stone formers and healthy controls when both cohorts consumed standardized diets.1 The main evidence that uric acid excretion may have a role in calcium oxalate stone formation is from a randomized prospective trial in which administration of allopurinol to patients with isolated hyperuricosuria resulted in a decreased rate of stone activity.2 Perhaps the benefits of allopurinol therapy are independent of urinary uric acid reduction. Dean Assimos, M.D. 1. Pais VM Jr, Holmes RP and Assimos DG: Effect of dietary control of urinary uric acid excretion in calcium oxalate stone formers and non-stone-forming controls. J Endourol 2007; 21: 232. 2. Ettinger B, Tang A, Citron JT, Livermore B and Williams T: Randomized trial of allopurinol in the prevention of calcium oxalate calculi. N Engl J Med 1986; 315: 1386.
0022-5347/09/1814-1721/0 THE JOURNAL OF UROLOGY® Copyright © 2009 by AMERICAN UROLOGICAL ASSOCIATION
Vol. 181, 1721-1724, April 2009 Printed in U.S.A. DOI:10.1016/j.juro.2008.12.039
www.jurology.com
1721
1722
UROLITHIASIS/ENDOUROLOGY
Fructose Consumption and the Risk of Kidney Stones E. N. Taylor and G. C. Curhan Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Kidney Int 2008; 73: 207–212.
Fructose consumption has markedly increased over the past decades. This intake may increase the urinary excretion of calcium, oxalate, uric acid, and other factors associated with kidney stone risk. We prospectively examined the relationship between fructose intake and incident kidney stones in the Nurses’ Health Study I (NHS I) (93,730 older women), the Nurses’ Health Study II (NHS II) (101,824 younger women), and the Health Professionals Follow-up Study (45,984 men). Food frequency questionnaires were used to assess free fructose and sucrose intake every 4 years. Total-fructose intake was calculated as free fructose plus half the intake of sucrose, and expressed as percentage of total energy. Cox proportional hazard regressions were adjusted for age, body mass index (BMI), thiazide use, caloric intake, and other dietary factors. We documented 4902 incident kidney stones during a combined 48 years of follow-up. The multivariate relative risks of kidney stones significantly increased for participants in the highest compared to the lowest quintile of total-fructose intake for all three study groups. Free-fructose intake was also associated with increased risk. Non-fructose carbohydrates were not associated with increased risk in any cohort. Our study suggests that fructose intake is independently associated with an increased risk of incident kidney stones.
Determinants of 24-Hour Urinary Oxalate Excretion E. N. Taylor and G. C. Curhan Renal Division and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts Clin J Am Soc Nephrol 2008; 3: 1453–1460.
Background and Objectives: Higher levels of urinary oxalate substantially increase the risk of calcium oxalate kidney stones. However, the determinants of urinary oxalate excretion are unclear. The objective was to examine the impact of dietary factors, age, body size, diabetes, and urinary factors on 24-h urinary oxalate. Design, Setting, Participants, and Measurements: We conducted a crosssectional study of 3348 stone forming and non-stone-forming participants in the Health Professionals Follow-up Study (men), the Nurses’ Health Study (older women), and the Nurses’ Health Study II (younger women). Results: Median urinary oxalate was 39 mg/d in men, 27 mg/d in older women, and 26 mg/d in younger women. Participants in the highest quartile of dietary oxalate excreted 1.7 mg/d more urinary oxalate than participants in the lowest quartile (P trend 0.001). The relation between dietary and urinary oxalate was similar in individuals with and without nephrolithiasis. Participants consuming 1000 mg/d or more of vitamin C excreted 6.8 mg/d more urinary oxalate than participants consuming ⬍90 mg/d (P trend ⬍ 0.001). Body mass index, total fructose intake, and 24-h urinary potassium, magnesium, and phosphorus levels also were positively associated with urinary oxalate. Calcium intake and age were inversely associated with urinary oxalate. After adjustment for body size, participants with diabetes excreted 2.0 mg/d more urinary oxalate than those without diabetes (P ⬍ 0.01). Conclusions: The impact of dietary oxalate on urinary oxalate appears to be small. Further investigation of factors influencing urinary oxalate may lead to new approaches to prevent calcium kidney stones. Editorial Comment: Stone formation is usually caused by environmental and genetic factors. Diet is considered the most important environmental influence. Much has been learned about diet and stone risk from the prospective studies of 3 large epidemiological cohorts—Nurses’ Health Study I, Nurses’ Health Study II and the Health Professionals Follow-Up Study. Taylor and Curhan report that fructose consumption was associated with stone risk in all 3 of these cohorts. In a subsequent study of the same cohorts these investigators reported that increasing body mass and fructose consumption were positively correlated to oxalate consumption. Metabolic studies in humans and in vivo studies in rats have revealed that fructose intake
UROLITHIASIS/ENDOUROLOGY
1723
may promote calcium and oxalate excretion, and insulin resistance. Fructose consumption has significantly increased during the last 3 decades, and this increase parallels the obesity epidemic in the United States in adults and children. Americans are addicted to high fructose corn syrup—nectar for the waistline as well as renal colic. Dean Assimos, M.D.
Evidence for Increased Postprandial Distal Nephron Calcium Delivery in Hypercalciuric Stone-Forming Patients E. M. Worcester, F. L. Coe, A. P. Evan, K. J. Bergsland, J. H. Parks, L. R. Willis, D. L. Clark and D. L. Gillen Department of Medicine, University of Chicago School of Medicine, Chicago, Illinois Am J Physiol Renal Physiol 2008; 295: F1286 –F1294.
A main mechanism of idiopathic hypercalciuria (IH) in calcium stone forming patients (IHSF) is postprandial reduction of renal tubule calcium reabsorption that cannot be explained by selective reduction of serum parathyroid hormone levels; the nephron site(s) responsible are not as yet defined. Using 14 one hour measurements of the clearances of sodium, calcium and endogenous lithium during a three meal day in the University of Chicago General Clinical Research Center, we found reduced postprandial proximal tubule reabsorption of sodium and calcium in IHSF vs. normals. The increased distal sodium delivery is matched by increased distal reabsorption so that urine sodium excretions do not differ; but distal calcium reabsorption does not increase enough to match increased calcium delivery, so hypercalciuria results. In fact, urine calcium excretion and overall renal fractional calcium reabsorption both are high in IHSF vs. normal when adjusted for distal calcium delivery, strongly suggesting a distal as well as proximal reduction of calcium reabsorption. The combination of reduced proximal tubule and distal nephron calcium reabsorption in IHSF is a new finding and indicates that IH involves a complex, presumably genetic, variation of nephron function. The increased calcium delivery into the later nephron may play a role in stone formation via deposition of papillary interstitial apatite plaque. Editorial Comment: A significant number of stone formers have hypercalciuria. Increased gastrointestinal absorption of calcium has been thought to be the driving factor. These investigators, who performed carefully controlled metabolic studies in normal subjects and idiopathic calcium oxalate stone formers, demonstrated that the kidney also contributes to increased calcium excretion. This increase occurs at both ends of the nephron, with decreased reabsorption of calcium in the proximal tubule as well as the distal nephron. Further definition of the mechanisms of these responses may permit development of better pharmacological agents for reducing calcium excretion and perhaps Randall’s plaque. Dean Assimos, M.D.