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Endourology
Urological Survey
Urolithiasis/Endourology Genotype-Phenotype Correlation in Primary Hyperoxaluria Type 1: The p.Gly170Arg AGXT Mutation is Associated With a Better Outcome J. Harambat, S. Fargue, C. Acquaviva, M. F. Gagnadoux, F. Janssen, A. Liutkus, C. Mourani, M. A. Macher, D. Abramowicz, C. Legendre, A. Durrbach, M. Tsimaratos, H. Nivet, E. Girardin, A. M. Schott, M. O. Rolland and P. Cochat Service de Pediatrie, Centre de Reference des Maladies Renales Rares du Sud-Ouest, Centre Hospitalier Universitaire, Bordeaux and Service de Pediatrie, Centre de Reference des Maladies Renales Rares and Inserm U820, Hospices Civils de Lyon and Universite de Lyon, Lyon, France Kidney Int 2009; 77: 443– 449.
We sought to ascertain the long-term outcome and genotype-phenotype correlations available for primary hyperoxaluria type 1 in a large retrospective cohort study. We examined the clinical history of 155 patients (129 families primarily from Western Europe, North Africa, or the Middle East) as well as the enzymatic or genetic diagnosis. The median age at first symptom was 4 years, and at diagnosis 7.7 years, at which time 43% had reached end-stage renal disease. Presentations included: (1) early nephrocalcinosis and infantile renal failure, (2) recurrent urolithiasis and progressive renal failure diagnosed during childhood, (3) late onset with occasional stone passage diagnosed in adulthood, (4) diagnosis occurring on post-transplantation recurrence, and (5) family screening. The cumulative patient survival was 95, 86, and 74% at ages 10, 30, and 50 years, respectively, with the cumulative renal survival of 81, 59, 41, and 10% at ages 10, 20, 30, and 50 years, respectively; 72 patients had undergone a total of 97 transplantations. Among the 136 patients with DNA analysis, the most common mutation was p.Gly170Arg (allelic frequency 21.5%), with a median age at end-stage renal disease of 47 years for homozygotes, 35 years for heterozygotes, and 21 years for other mutations. Our results underscore the severe prognosis of primary hyperoxaluria type 1 and the necessity for early diagnosis and treatment, as well as confirm a better prognosis of the p.Gly170Arg mutation. Editorial Comment: Primary hyperoxaluria type 1 is a rare, monogenic, autosomal recessive disease that is due to either absence or defective production of the hepatic peroxisomal enzyme alanine glyoxylate aminotransferase. This enzyme derives glyoxylate from oxalate synthesis. Those afflicted with this disorder are at high risk for renal failure. These investigators demonstrated that the latter may be influenced by the mutations that are associated with this disorder. Dean Assimos, M.D.
0022-5347/10/1835-1873/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
Vol. 183, 1873-1879, May 2010 Printed in U.S.A. DOI:10.1016/j.juro.2010.01.067
www.jurology.com
1873
1874
UROLITHIASIS/ENDOUROLOGY
Association of Interleukin-18 Gene Polymorphisms With Calcium Oxalate Kidney Stone Disease K. C. Lai, W. Y. Lin, K. M. Man, C. H. Tsai, H. Y. Chen, F. J. Tsai, F. J. Chen, H. Y. Chen, H. P. Liu, T. J. Ho, P. H. Huang, P. L. Liu, F. Y. Lin, J. L. Shen, J. T. Liu, Y. H. Chen and W. C. Chen Department of Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan Scand J Urol Nephrol 2009; 44: 20 –26.
Objective: The interleukin-18 (IL-18) encoding gene has three common single-nucleotide polymorphisms at -607C/A, -137G/C and ⫹105A/C, which have been reported to be associated with several diseases. The aim of this study is to test whether IL-18 polymorphisms could act as genetic markers for renal stone disease. Material and Methods: A control group of 104 healthy subjects, and 272 patients with recurrent calcium oxalate stones were examined. Polymerase chain reaction-based restriction endonuclease analysis was used to detect IL-18 polymorphisms. Results: The patient and control groups differed significantly in genotypic expression of the IL-18 ⫹105A/C polymorphism. The prevalence of the A/C ⫹ C/C genotypes in the patients was higher than that in the controls. The allelic frequency of IL-18 ⫹105A/C differed significantly between the patients and the controls. The odds ratio (OR) of the A/C heterozygote of IL-18 ⫹105A/C associated with urolithiasis was 2.772. The OR of the A/C ⫹ C/C genotypes of IL-18 ⫹105A/C associated with urolithiasis was 3.097. The OR per copy of the C allele of IL-18 ⫹105A/C associated with urolithiasis was 4.143. There were also significant differences in the prevalence of genotype IL-18 ⫺137G/C polymorphisms between the patients and controls. The distribution of the G/G homozygote in the patients was higher than that in the controls. There was no significant difference in genotype and allelic frequency at the IL-18 ⫺607C/A polymorphism between patients and control subjects. Conclusion: The results indicate that IL-18 ⫹105A/C polymorphisms may play a role in the development of urolithiasis.
Fetuin-A Gene Polymorphism in Patients With Calcium Oxalate Stone Disease H. Aksoy, Y. Aksoy, N. Ozturk, H. R. Aydin, A. K. Yildirim and F. Akcay Department of Biochemistry, Ataturk University Medical School, Erzurum, Turkey Urology 2009; Epub ahead of print.
Objectives: To evaluate the association of fetuin-A polymorphisms with calcium oxalate nephrolithiasis. Fetuin-A is a circulating calcium-regulatory glycoprotein that inhibits extraosseous calcification. Methods: Fetuin-A c.742C ⬎ T and c.766C ⬎ G polymorphisms were investigated in 103 patients with calcium oxalate nephrolithiasis and 73 age- and gender-matched healthy volunteers, using polymerase chain reaction-restriction fragment length polymorphism techniques. Additionally, we compared serum fetuin-A levels in the 2 groups. Results: A statistically significant difference was observed between the control and patient groups (chi(2) test, P ⫽ .003) for the genotype of fetuin-A c.766C ⬎ G polymorphism. The odds ratio (95% confidence interval) for the CG genotype in those at risk of stone disease was 4.2 (1.73–10.28). The frequency distribution for fetuin-A c.742C ⬎ T polymorphism was not statistically different in stone patients and controls (P ⫽ .77). Serum mean fetuin-A concentration was significantly lower in the patients (710.38 ⫾ 156.42 mug/mL) than in the controls (810.89 ⫾ 173.43 mug/mL, P ⫽ .0001). In the patient group (but not in the control group), subjects carrying fetuin-A genotype 1 had significantly higher serum fetuin-A concentrations than the group carrying fetuin-A genotype 2–1 (P ⫽ .001). Conclusions: These results reveal that the patients with fetuin-A c.766C ⬎ G gene polymorphism may be at higher risk for renal calcium oxalate stone formation. Editorial Comment: Idiopathic calcium oxalate stone formation is a multifactorial disease influenced by genetic and environmental factors. While an association with these polymorphisms and recurrent calcium oxalate kidney stone formation was demonstrated in these studies, causation was not established. The latter will require more in-depth investigations. Dean Assimos, M.D.
UROLITHIASIS/ENDOUROLOGY
1875
Relationship Between Body Mass Index and Quantitative 24-Hour Urine Chemistries in Patients With Nephrolithiasis B. H. Eisner, M. L. Eisenberg and M. L. Stoller Department of Urology, Massachusetts General Hospital, Boston, Massachusetts Urology 2009; Epub ahead of print.
Objectives: To examine the relationship between body mass index and 24-hour urine constituents in a population of stone-forming patients. Methods: A total of 880 patients who presented to a metabolic stone clinic for initial evaluation were analyzed. Patients were stratified by gender and divided into quartiles of body mass index. Associations between body mass index (BMI) and urine parameters were explored using bivariate and multivariate linear regression. Results: On bivariate analysis, increasing body mass index was associated with a significant increase in sodium, calcium, citrate, uric acid, magnesium, calcium oxalate, uric acid, and a decrease in pH in men. In women, it was associated with a significant increase in sodium, uric acid, oxalate, uric acid, and decreasing pH. On multivariate analysis, BMI was associated only with increases in sodium and calcium oxalate and decrease in pH in men. In women, multivariate analysis demonstrated positive association between BMI and urine sodium, creatinine, and phosphate and a negative relationship with urine citrate and sulfate. Conclusions: Increasing body mass index was related to several risk factors for urinary stone disease in this study, including increasing urine sodium and decreasing pH in men and increasing urine uric acid, sodium, and decreasing urine citrate in women. Just as general recommendations for patients with nephrolithiasis include high voided volumes, low dietary sodium, and low animal protein intake, perhaps weight reduction should be included as part of the counseling of stone-formers to optimize 24-hour urine parameters. Editorial Comment: Obesity is an established risk factor for kidney stone formation. The inverse association between BMI and urine pH has previously been demonstrated and is thought to be due to deficient ammonium production in the proximal renal tubule. This mechanism appears to be influenced by insulin resistance. The increased uric acid and sodium excretion are most likely due to dietary indiscretions. While weight loss should be encouraged, it should not be done with carbohydrate restriction and increased animal protein intake (Atkins diet), since this diet is lithogenic. Dean Assimos, M.D.
Multi-Session Retrograde Endoscopic Lithotripsy of Large Renal Calculi in Obese Patients J. C. Wheat, W. W. Roberts and J. S. Wolf, Jr. Department of Urology, University of Michigan Health System, Ann Arbor, Michigan Can J Urol 2009; 16: 4915– 4920.
Objectives: To establish the safety and efficacy of planned multi-session retrograde endoscopic lithotripsy (REL) for the treatment of large renal calculi in the morbidly obese. Methods: We retrospectively reviewed charts of patients who underwent multi-session REL procedures from 2003 to 2008. Inclusion criteria included body mass index ⬎ 35, total linear stone diameter ⬎ 2.0 cm, and patients with a preoperative plan to perform multi-session ureteroscopy. A total of nine patients (six with staghorn calculi) underwent 21 separate procedures. Stone size was measured on preoperative imaging and was defined as length in greatest diameter. Stone free was defined as the complete absence of residual stone on postoperative imaging. Results: Mean body mass index of the patients was 47.8 kg/m2. Mean total linear stone diameter was 3.8 cm. Three of nine patients (33%) were stone free after their final treatment. Mean decrease in stone size from preoperative imaging was 3.3 cm (83%). There were no intraoperative complications. Mean length of follow up was 0.88 years. Conclusions: Multi-session REL is a safe alternative to percutaneous nephrolithotomy (PCNL) in obese patients with very large stones, including staghorn calculi. We recognize that the stone free rate
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UROLITHIASIS/ENDOUROLOGY
in this series is lower than would be expected with REL for smaller stone burdens or with PCNL. Due to the limitations imposed by both the patient’s general medical conditions as well as technical considerations, these patients are left with few options for treatment. Our experience is that management with staged ureteroscopy offers a reduction in stone burden and in some patients a stone free status that provides an acceptable patient outcome. Editorial Comment: The authors report their experiences with ureteroscopic treatment of large renal stones in large patients. Percutaneous nephrostolithotomy remains a viable, effective treatment option for this cohort that is devoid of some of the frustrations of “endoscopic impotence,” which can be experienced by the surgeon using a retrograde approach. Dean Assimos, M.D.
Bone Disease in Medullary Sponge Kidney and Effect of Potassium Citrate Treatment A. Fabris, P. Bernich, C. Abaterusso, N. Marchionna, C. Canciani, A. Nouvenne, M. Zamboni, A. Lupo and G. Gambaro Division of Nephrology, Department of Biomedical and Surgical Sciences, University Hospital of Verona, Verona, Italy Clin J Am Soc Nephrol 2009; 4: 1974 –1979.
Background and Objectives: In medullary sponge kidney (MSK)-a common malformative renal condition in patients with calcium nephrolithiasis-hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither has the potential effect of potassium citrate administration (CA) on their urinary metabolic risk factors and on bone mineralization. Design, Setting, Participants, & Measurements: These issues were retrospectively analyzed in 75 patients with MSK and primary stone risk factor (PSRF; hypercalciuria, hypocitraturia, hyperuricosuria, and/or hyperoxaluria) on an outpatient basis; 65 received CA (2.9 ⫾ 0.8 g/d), whereas 10 received only general “stone clinic” suggestions. The 24-h urinary excretion of calcium, phosphate, oxalate, uric acid, and citrate; morning urine pH; serum biochemistry; and bone mineral density were investigated at baseline and at the end of follow-up (78 ⫾ 13 and 72 ⫾ 15 mo in groups A and B, respectively). Results: CA led to a significant rise in urinary pH and citrate and decreased urinary calcium and phosphate (all P ⬍ 0.001). Patients with MSK and PSRF had reduced bone density. Bone density improved significantly in the group that was treated with oral CA. Conclusions: Bone disease is very frequent in patients with MSK and concomitant PSRF. Long-term CA improves bone density. The concurrent effects of treatment on PSRF suggest that the subtle acidosis plays a pivotal role in bone disease and hypercalciuria in patients with MSK. Editorial Comment: The association of medullary sponge kidney and renal stone formation is well established. This disorder is a cause of medullary nephrocalcinosis. The diagnosis may not be made as frequently in current practice since the diagnosis is typically established with excretory urography, which is currently a rarely performed imaging test. The prevalence of hypercalciuria in this cohort is high. These investigators found that patients with medullary sponge kidney and hypercalciuria have reduced bone density, something previously demonstrated in idiopathic calcium oxalate stone formers. Bone density improved with the administration of potassium citrate, implying that subtle acidosis may have a role in inducing increased calcium excretion. The limitations of this study are that it is retrospective and controls were not randomly selected. Dean Assimos, M.D.
Urolithiasis/Endourology Genotype-Phenotype Correlation in Primary Hyperoxaluria Type 1: The p.Gly170Arg AGXT Mutation is Associated With a Better Outcome J. Harambat, S. Fargue, C. Acquaviva, M. F. Gagnadoux, F. Janssen, A. Liutkus, C. Mourani, M. A. Macher, D. Abramowicz, C. Legendre, A. Durrbach, M. Tsimaratos, H. Nivet, E. Girardin, A. M. Schott, M. O. Rolland and P. Cochat Service de Pediatrie, Centre de Reference des Maladies Renales Rares du Sud-Ouest, Centre Hospitalier Universitaire, Bordeaux and Service de Pediatrie, Centre de Reference des Maladies Renales Rares and Inserm U820, Hospices Civils de Lyon and Universite de Lyon, Lyon, France Kidney Int 2009; 77: 443– 449.
We sought to ascertain the long-term outcome and genotype-phenotype correlations available for primary hyperoxaluria type 1 in a large retrospective cohort study. We examined the clinical history of 155 patients (129 families primarily from Western Europe, North Africa, or the Middle East) as well as the enzymatic or genetic diagnosis. The median age at first symptom was 4 years, and at diagnosis 7.7 years, at which time 43% had reached end-stage renal disease. Presentations included: (1) early nephrocalcinosis and infantile renal failure, (2) recurrent urolithiasis and progressive renal failure diagnosed during childhood, (3) late onset with occasional stone passage diagnosed in adulthood, (4) diagnosis occurring on post-transplantation recurrence, and (5) family screening. The cumulative patient survival was 95, 86, and 74% at ages 10, 30, and 50 years, respectively, with the cumulative renal survival of 81, 59, 41, and 10% at ages 10, 20, 30, and 50 years, respectively; 72 patients had undergone a total of 97 transplantations. Among the 136 patients with DNA analysis, the most common mutation was p.Gly170Arg (allelic frequency 21.5%), with a median age at end-stage renal disease of 47 years for homozygotes, 35 years for heterozygotes, and 21 years for other mutations. Our results underscore the severe prognosis of primary hyperoxaluria type 1 and the necessity for early diagnosis and treatment, as well as confirm a better prognosis of the p.Gly170Arg mutation. Editorial Comment: Primary hyperoxaluria type 1 is a rare, monogenic, autosomal recessive disease that is due to either absence or defective production of the hepatic peroxisomal enzyme alanine glyoxylate aminotransferase. This enzyme derives glyoxylate from oxalate synthesis. Those afflicted with this disorder are at high risk for renal failure. These investigators demonstrated that the latter may be influenced by the mutations that are associated with this disorder. Dean Assimos, M.D.
0022-5347/10/1835-1873/0 THE JOURNAL OF UROLOGY® © 2010 by AMERICAN UROLOGICAL ASSOCIATION EDUCATION
AND
RESEARCH, INC.
Vol. 183, 1873-1879, May 2010 Printed in U.S.A. DOI:10.1016/j.juro.2010.01.067
www.jurology.com
1873
1874
UROLITHIASIS/ENDOUROLOGY
Association of Interleukin-18 Gene Polymorphisms With Calcium Oxalate Kidney Stone Disease K. C. Lai, W. Y. Lin, K. M. Man, C. H. Tsai, H. Y. Chen, F. J. Tsai, F. J. Chen, H. Y. Chen, H. P. Liu, T. J. Ho, P. H. Huang, P. L. Liu, F. Y. Lin, J. L. Shen, J. T. Liu, Y. H. Chen and W. C. Chen Department of Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan Scand J Urol Nephrol 2009; 44: 20 –26.
Objective: The interleukin-18 (IL-18) encoding gene has three common single-nucleotide polymorphisms at -607C/A, -137G/C and ⫹105A/C, which have been reported to be associated with several diseases. The aim of this study is to test whether IL-18 polymorphisms could act as genetic markers for renal stone disease. Material and Methods: A control group of 104 healthy subjects, and 272 patients with recurrent calcium oxalate stones were examined. Polymerase chain reaction-based restriction endonuclease analysis was used to detect IL-18 polymorphisms. Results: The patient and control groups differed significantly in genotypic expression of the IL-18 ⫹105A/C polymorphism. The prevalence of the A/C ⫹ C/C genotypes in the patients was higher than that in the controls. The allelic frequency of IL-18 ⫹105A/C differed significantly between the patients and the controls. The odds ratio (OR) of the A/C heterozygote of IL-18 ⫹105A/C associated with urolithiasis was 2.772. The OR of the A/C ⫹ C/C genotypes of IL-18 ⫹105A/C associated with urolithiasis was 3.097. The OR per copy of the C allele of IL-18 ⫹105A/C associated with urolithiasis was 4.143. There were also significant differences in the prevalence of genotype IL-18 ⫺137G/C polymorphisms between the patients and controls. The distribution of the G/G homozygote in the patients was higher than that in the controls. There was no significant difference in genotype and allelic frequency at the IL-18 ⫺607C/A polymorphism between patients and control subjects. Conclusion: The results indicate that IL-18 ⫹105A/C polymorphisms may play a role in the development of urolithiasis.
Fetuin-A Gene Polymorphism in Patients With Calcium Oxalate Stone Disease H. Aksoy, Y. Aksoy, N. Ozturk, H. R. Aydin, A. K. Yildirim and F. Akcay Department of Biochemistry, Ataturk University Medical School, Erzurum, Turkey Urology 2009; Epub ahead of print.
Objectives: To evaluate the association of fetuin-A polymorphisms with calcium oxalate nephrolithiasis. Fetuin-A is a circulating calcium-regulatory glycoprotein that inhibits extraosseous calcification. Methods: Fetuin-A c.742C ⬎ T and c.766C ⬎ G polymorphisms were investigated in 103 patients with calcium oxalate nephrolithiasis and 73 age- and gender-matched healthy volunteers, using polymerase chain reaction-restriction fragment length polymorphism techniques. Additionally, we compared serum fetuin-A levels in the 2 groups. Results: A statistically significant difference was observed between the control and patient groups (chi(2) test, P ⫽ .003) for the genotype of fetuin-A c.766C ⬎ G polymorphism. The odds ratio (95% confidence interval) for the CG genotype in those at risk of stone disease was 4.2 (1.73–10.28). The frequency distribution for fetuin-A c.742C ⬎ T polymorphism was not statistically different in stone patients and controls (P ⫽ .77). Serum mean fetuin-A concentration was significantly lower in the patients (710.38 ⫾ 156.42 mug/mL) than in the controls (810.89 ⫾ 173.43 mug/mL, P ⫽ .0001). In the patient group (but not in the control group), subjects carrying fetuin-A genotype 1 had significantly higher serum fetuin-A concentrations than the group carrying fetuin-A genotype 2–1 (P ⫽ .001). Conclusions: These results reveal that the patients with fetuin-A c.766C ⬎ G gene polymorphism may be at higher risk for renal calcium oxalate stone formation. Editorial Comment: Idiopathic calcium oxalate stone formation is a multifactorial disease influenced by genetic and environmental factors. While an association with these polymorphisms and recurrent calcium oxalate kidney stone formation was demonstrated in these studies, causation was not established. The latter will require more in-depth investigations. Dean Assimos, M.D.
UROLITHIASIS/ENDOUROLOGY
1875
Relationship Between Body Mass Index and Quantitative 24-Hour Urine Chemistries in Patients With Nephrolithiasis B. H. Eisner, M. L. Eisenberg and M. L. Stoller Department of Urology, Massachusetts General Hospital, Boston, Massachusetts Urology 2009; Epub ahead of print.
Objectives: To examine the relationship between body mass index and 24-hour urine constituents in a population of stone-forming patients. Methods: A total of 880 patients who presented to a metabolic stone clinic for initial evaluation were analyzed. Patients were stratified by gender and divided into quartiles of body mass index. Associations between body mass index (BMI) and urine parameters were explored using bivariate and multivariate linear regression. Results: On bivariate analysis, increasing body mass index was associated with a significant increase in sodium, calcium, citrate, uric acid, magnesium, calcium oxalate, uric acid, and a decrease in pH in men. In women, it was associated with a significant increase in sodium, uric acid, oxalate, uric acid, and decreasing pH. On multivariate analysis, BMI was associated only with increases in sodium and calcium oxalate and decrease in pH in men. In women, multivariate analysis demonstrated positive association between BMI and urine sodium, creatinine, and phosphate and a negative relationship with urine citrate and sulfate. Conclusions: Increasing body mass index was related to several risk factors for urinary stone disease in this study, including increasing urine sodium and decreasing pH in men and increasing urine uric acid, sodium, and decreasing urine citrate in women. Just as general recommendations for patients with nephrolithiasis include high voided volumes, low dietary sodium, and low animal protein intake, perhaps weight reduction should be included as part of the counseling of stone-formers to optimize 24-hour urine parameters. Editorial Comment: Obesity is an established risk factor for kidney stone formation. The inverse association between BMI and urine pH has previously been demonstrated and is thought to be due to deficient ammonium production in the proximal renal tubule. This mechanism appears to be influenced by insulin resistance. The increased uric acid and sodium excretion are most likely due to dietary indiscretions. While weight loss should be encouraged, it should not be done with carbohydrate restriction and increased animal protein intake (Atkins diet), since this diet is lithogenic. Dean Assimos, M.D.
Multi-Session Retrograde Endoscopic Lithotripsy of Large Renal Calculi in Obese Patients J. C. Wheat, W. W. Roberts and J. S. Wolf, Jr. Department of Urology, University of Michigan Health System, Ann Arbor, Michigan Can J Urol 2009; 16: 4915– 4920.
Objectives: To establish the safety and efficacy of planned multi-session retrograde endoscopic lithotripsy (REL) for the treatment of large renal calculi in the morbidly obese. Methods: We retrospectively reviewed charts of patients who underwent multi-session REL procedures from 2003 to 2008. Inclusion criteria included body mass index ⬎ 35, total linear stone diameter ⬎ 2.0 cm, and patients with a preoperative plan to perform multi-session ureteroscopy. A total of nine patients (six with staghorn calculi) underwent 21 separate procedures. Stone size was measured on preoperative imaging and was defined as length in greatest diameter. Stone free was defined as the complete absence of residual stone on postoperative imaging. Results: Mean body mass index of the patients was 47.8 kg/m2. Mean total linear stone diameter was 3.8 cm. Three of nine patients (33%) were stone free after their final treatment. Mean decrease in stone size from preoperative imaging was 3.3 cm (83%). There were no intraoperative complications. Mean length of follow up was 0.88 years. Conclusions: Multi-session REL is a safe alternative to percutaneous nephrolithotomy (PCNL) in obese patients with very large stones, including staghorn calculi. We recognize that the stone free rate
1876
UROLITHIASIS/ENDOUROLOGY
in this series is lower than would be expected with REL for smaller stone burdens or with PCNL. Due to the limitations imposed by both the patient’s general medical conditions as well as technical considerations, these patients are left with few options for treatment. Our experience is that management with staged ureteroscopy offers a reduction in stone burden and in some patients a stone free status that provides an acceptable patient outcome. Editorial Comment: The authors report their experiences with ureteroscopic treatment of large renal stones in large patients. Percutaneous nephrostolithotomy remains a viable, effective treatment option for this cohort that is devoid of some of the frustrations of “endoscopic impotence,” which can be experienced by the surgeon using a retrograde approach. Dean Assimos, M.D.
Bone Disease in Medullary Sponge Kidney and Effect of Potassium Citrate Treatment A. Fabris, P. Bernich, C. Abaterusso, N. Marchionna, C. Canciani, A. Nouvenne, M. Zamboni, A. Lupo and G. Gambaro Division of Nephrology, Department of Biomedical and Surgical Sciences, University Hospital of Verona, Verona, Italy Clin J Am Soc Nephrol 2009; 4: 1974 –1979.
Background and Objectives: In medullary sponge kidney (MSK)-a common malformative renal condition in patients with calcium nephrolithiasis-hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither has the potential effect of potassium citrate administration (CA) on their urinary metabolic risk factors and on bone mineralization. Design, Setting, Participants, & Measurements: These issues were retrospectively analyzed in 75 patients with MSK and primary stone risk factor (PSRF; hypercalciuria, hypocitraturia, hyperuricosuria, and/or hyperoxaluria) on an outpatient basis; 65 received CA (2.9 ⫾ 0.8 g/d), whereas 10 received only general “stone clinic” suggestions. The 24-h urinary excretion of calcium, phosphate, oxalate, uric acid, and citrate; morning urine pH; serum biochemistry; and bone mineral density were investigated at baseline and at the end of follow-up (78 ⫾ 13 and 72 ⫾ 15 mo in groups A and B, respectively). Results: CA led to a significant rise in urinary pH and citrate and decreased urinary calcium and phosphate (all P ⬍ 0.001). Patients with MSK and PSRF had reduced bone density. Bone density improved significantly in the group that was treated with oral CA. Conclusions: Bone disease is very frequent in patients with MSK and concomitant PSRF. Long-term CA improves bone density. The concurrent effects of treatment on PSRF suggest that the subtle acidosis plays a pivotal role in bone disease and hypercalciuria in patients with MSK. Editorial Comment: The association of medullary sponge kidney and renal stone formation is well established. This disorder is a cause of medullary nephrocalcinosis. The diagnosis may not be made as frequently in current practice since the diagnosis is typically established with excretory urography, which is currently a rarely performed imaging test. The prevalence of hypercalciuria in this cohort is high. These investigators found that patients with medullary sponge kidney and hypercalciuria have reduced bone density, something previously demonstrated in idiopathic calcium oxalate stone formers. Bone density improved with the administration of potassium citrate, implying that subtle acidosis may have a role in inducing increased calcium excretion. The limitations of this study are that it is retrospective and controls were not randomly selected. Dean Assimos, M.D.