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Re: Clinical Significance of Uric Acid Dihydrate in Urinary Stones
Urological Survey
Urolithiasis/Endourology Evidence for Net Renal Tubule Oxalate Secretion in Patients With Calcium Kidney Stones K. J. Bergsland, A. L. Zisman, J. R. Asplin, E. M. Worcester and F. L. Coe Department of Medicine, Section of Nephrology, University of Chicago, Chicago, Illinois Am J Physiol Renal Physiol 2010; Epub ahead of print.
Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normals, and 2 bariatric stone formers (BSF) during a one-day General Clinical Research Center protocol utilizing a low oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was greater than 1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared to none of the controls (p ⬍0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normals with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range. Editorial Comment: These investigators further confirmed that renal oxalate secretion occurs. A limitation is that diets leading into these experiments were not controlled. An assessment of response to a more robust oxalate intake is warranted. The underlying mechanisms for secretion need to be defined. Dean Assimos, M.D.
Re: Clinical Significance of Uric Acid Dihydrate in Urinary Stones W. L. Strohmaier, J. Seilnacht and G. Schubert Department of Urology and Paediatric Urology, RegioMed Kliniken, Klinikum Coburg, Coburg, Germany Urol Res 2010; Epub ahead of print.
Uric acid crystallizes as an anhydrous compound (UAA), a dihydrate (UAD) or a mixture of both. A monohydrate form is very rare. About 20% of uric acid stones contain a significant amount (ⱖ20%) UAD. It is believed that UAD crystallizes under highly acidic conditions (urine pH ⱕ 5.0). Up to now, metabolic data on patients with UAD stones have not been reported in the literature. One hundred and fifty patients with pure uric acid calculi were studied. Stone analysis was performed using X-ray diffraction. According to the stone analysis, they were divided in two groups: 1. UAD (ⱖ20% UAD), 2. UAA (⬍20% UAD). In all patients the following parameters were examined: age, sex, number of recurrences, body mass index (BMI); blood: creatinine, uric acid, calcium, sodium, and potassium; urine: pH-profiles, volume, calcium, uric acid, citrate, ammonia, and urea. Group 1 (ⱖ20% UAD) 0022-5347/11/1855-1747/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
Vol. 185, 1747-1750, May 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.01.049
www.jurology.com
1747
1748
UROLITHIASIS/ENDOUROLOGY
consisted of 33 patients and group 2 (⬍20% UAD) of 117 patients. Between these groups, there was a significant difference concerning the number of recurrences, the urine volume, and the urinary excretion of calcium. Patients with ⱖ20% dihydrate had a mean BMI of 31.6 ⫾ 7.5, a mean number of recurrences of 0.24 ⫾ 0.44, an urine volume of 2.6 ⫾ 0.8 l/24 h, and a calcium excretion of 4.5 ⫾ 2.2 mmol/24 h, whereas those with ⬍20% dihydrate had BMI of 29.9 ⫾ 5.0, 1.10 ⫾ 1.42 recurrences, urine volume of 2.3 ⫾ 1.2 l/24 h, and calcium excretion of 3.2 ⫾ 2.4 mmol/24 h. All the other parameters tested were not significantly different. For the first time, our study shows metabolic data in uric acid patients with a significant amount of UAD. The comparison between this group and those patients with ⬍20% UAD revealed that the first group is less prone to develop recurrences. This is a relevant difference concerning the necessity of metaphylactic measures. We could not confirm in patients with dihydrate if the urinary pH is more acid than in those with insignificant amounts of dihydrate. The higher 24-h urine volume, the higher excretion of calcium, and the higher BMI in the UAD group may be of pathophysiological relevance and requires further attention. Editorial Comment: The authors demonstrate that uric acid stone formers are a heterogeneous group and that this differential may be influenced by the type of uric acid compound that the stones are composed of. They suggest that this information may be used to determine the necessity of medical therapy. However, the “favorable group” is still at risk for recurrence, and medical therapy is fairly straightforward—pH manipulation! Dean Assimos, M.D.
Kidney Stones Associate With Increased Risk for Myocardial Infarction A. D. Rule, V. L. Roger, L. J. Melton, III, E. J. Bergstralh, X. Li, P. A. Peyser, A. E. Krambeck and J. C. Lieske Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota J Am Soc Nephrol 2010; 21: 1641–1644.
Kidney stones are a risk factor for chronic kidney disease (CKD), which, in turn, is a risk factor for myocardial infarction (MI). The objective of this study was to determine whether kidney stones associate with an increased risk for MI. We matched 4564 stone formers (1984 through 2003) on age and gender with 10,860 control subjects among residents in Olmsted County, Minnesota. We identified incident MI by diagnostic codes and validated events by chart review through 2006, 2010 We used diagnostic codes to determine incidence of kidney stones and presence of comorbidities (CKD, hypertension, diabetes, obesity, dyslipidemia, gout, alcohol dependence, and tobacco use). During a mean of 9 years of follow– up, stone formers had a 38% (95% confidence interval 7 to 77%) increased risk for MI, which remained at 31% (95% confidence interval 2% to 69%) after adjustment for CKD and other comorbidities. In conclusion, kidney stone formers are at increased risk for MI, and this risk is independent of CKD and other risk factors. Editorial Comment: We can now add coronary artery disease to the list of systemic diseases that are associated with kidney stone formation, which already includes hypertension, diabetes mellitus, osteoporosis and chronic kidney disease. Dean Assimos, M.D.
Urolithiasis/Endourology Evidence for Net Renal Tubule Oxalate Secretion in Patients With Calcium Kidney Stones K. J. Bergsland, A. L. Zisman, J. R. Asplin, E. M. Worcester and F. L. Coe Department of Medicine, Section of Nephrology, University of Chicago, Chicago, Illinois Am J Physiol Renal Physiol 2010; Epub ahead of print.
Little is known about the renal handling of oxalate in patients with idiopathic hypercalciuria (IH). To explore the role of tubular oxalate handling in IH and to evaluate whether differences exist between IH and normal controls, we studied 19 IH subjects, 8 normals, and 2 bariatric stone formers (BSF) during a one-day General Clinical Research Center protocol utilizing a low oxalate diet. Urine and blood samples were collected at 30- to 60-min intervals while subjects were fasting and after they ate three meals providing known amounts of calcium, phosphorus, sodium, protein, oxalate, and calories. Plasma oxalate concentrations and oxalate filtered loads were similar between patients (includes IH and BSF) and controls in both the fasting and fed states. Urinary oxalate excretion was significantly higher in patients vs. controls regardless of feeding state. Fractional excretion of oxalate (FEOx) was greater than 1, suggesting tubular secretion of oxalate, in 6 of 19 IH and both BSF, compared to none of the controls (p ⬍0.00001). Adjusted for water extraction along the nephron, urine oxalate rose more rapidly among patients than normals with increases in plasma oxalate. Our findings identify tubular secretion of oxalate as a key mediator of hyperoxaluria in calcium stone formers, potentially as a means of maintaining plasma oxalate in a tight range. Editorial Comment: These investigators further confirmed that renal oxalate secretion occurs. A limitation is that diets leading into these experiments were not controlled. An assessment of response to a more robust oxalate intake is warranted. The underlying mechanisms for secretion need to be defined. Dean Assimos, M.D.
Re: Clinical Significance of Uric Acid Dihydrate in Urinary Stones W. L. Strohmaier, J. Seilnacht and G. Schubert Department of Urology and Paediatric Urology, RegioMed Kliniken, Klinikum Coburg, Coburg, Germany Urol Res 2010; Epub ahead of print.
Uric acid crystallizes as an anhydrous compound (UAA), a dihydrate (UAD) or a mixture of both. A monohydrate form is very rare. About 20% of uric acid stones contain a significant amount (ⱖ20%) UAD. It is believed that UAD crystallizes under highly acidic conditions (urine pH ⱕ 5.0). Up to now, metabolic data on patients with UAD stones have not been reported in the literature. One hundred and fifty patients with pure uric acid calculi were studied. Stone analysis was performed using X-ray diffraction. According to the stone analysis, they were divided in two groups: 1. UAD (ⱖ20% UAD), 2. UAA (⬍20% UAD). In all patients the following parameters were examined: age, sex, number of recurrences, body mass index (BMI); blood: creatinine, uric acid, calcium, sodium, and potassium; urine: pH-profiles, volume, calcium, uric acid, citrate, ammonia, and urea. Group 1 (ⱖ20% UAD) 0022-5347/11/1855-1747/0 THE JOURNAL OF UROLOGY® © 2011 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
Vol. 185, 1747-1750, May 2011 Printed in U.S.A. DOI:10.1016/j.juro.2011.01.049
www.jurology.com
1747
1748
UROLITHIASIS/ENDOUROLOGY
consisted of 33 patients and group 2 (⬍20% UAD) of 117 patients. Between these groups, there was a significant difference concerning the number of recurrences, the urine volume, and the urinary excretion of calcium. Patients with ⱖ20% dihydrate had a mean BMI of 31.6 ⫾ 7.5, a mean number of recurrences of 0.24 ⫾ 0.44, an urine volume of 2.6 ⫾ 0.8 l/24 h, and a calcium excretion of 4.5 ⫾ 2.2 mmol/24 h, whereas those with ⬍20% dihydrate had BMI of 29.9 ⫾ 5.0, 1.10 ⫾ 1.42 recurrences, urine volume of 2.3 ⫾ 1.2 l/24 h, and calcium excretion of 3.2 ⫾ 2.4 mmol/24 h. All the other parameters tested were not significantly different. For the first time, our study shows metabolic data in uric acid patients with a significant amount of UAD. The comparison between this group and those patients with ⬍20% UAD revealed that the first group is less prone to develop recurrences. This is a relevant difference concerning the necessity of metaphylactic measures. We could not confirm in patients with dihydrate if the urinary pH is more acid than in those with insignificant amounts of dihydrate. The higher 24-h urine volume, the higher excretion of calcium, and the higher BMI in the UAD group may be of pathophysiological relevance and requires further attention. Editorial Comment: The authors demonstrate that uric acid stone formers are a heterogeneous group and that this differential may be influenced by the type of uric acid compound that the stones are composed of. They suggest that this information may be used to determine the necessity of medical therapy. However, the “favorable group” is still at risk for recurrence, and medical therapy is fairly straightforward—pH manipulation! Dean Assimos, M.D.
Kidney Stones Associate With Increased Risk for Myocardial Infarction A. D. Rule, V. L. Roger, L. J. Melton, III, E. J. Bergstralh, X. Li, P. A. Peyser, A. E. Krambeck and J. C. Lieske Division of Nephrology and Hypertension, Department of Medicine, Mayo Clinic, Rochester, Minnesota J Am Soc Nephrol 2010; 21: 1641–1644.
Kidney stones are a risk factor for chronic kidney disease (CKD), which, in turn, is a risk factor for myocardial infarction (MI). The objective of this study was to determine whether kidney stones associate with an increased risk for MI. We matched 4564 stone formers (1984 through 2003) on age and gender with 10,860 control subjects among residents in Olmsted County, Minnesota. We identified incident MI by diagnostic codes and validated events by chart review through 2006, 2010 We used diagnostic codes to determine incidence of kidney stones and presence of comorbidities (CKD, hypertension, diabetes, obesity, dyslipidemia, gout, alcohol dependence, and tobacco use). During a mean of 9 years of follow– up, stone formers had a 38% (95% confidence interval 7 to 77%) increased risk for MI, which remained at 31% (95% confidence interval 2% to 69%) after adjustment for CKD and other comorbidities. In conclusion, kidney stone formers are at increased risk for MI, and this risk is independent of CKD and other risk factors. Editorial Comment: We can now add coronary artery disease to the list of systemic diseases that are associated with kidney stone formation, which already includes hypertension, diabetes mellitus, osteoporosis and chronic kidney disease. Dean Assimos, M.D.