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RE: THE ASSOCIATION OF AN INCREASED URINARY CALCIUM-TO-CREATININE RATIO, AND ASYMPTOMATIC GROSS AND MICROSCOPIC HEMATURIA IN CHILDREN
0022-5347/02/1685-2126/0 THE JOURNAL OF UROLOGY® Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC.®
Vol. 168, 2126 –2135, November 2002 Printed in U.S.A.
Letters to the Editor cause and effect relationship, between hypercalciuria and any of the aforementioned conditions.
RE: THE ASSOCIATION OF AN INCREASED URINARY CALCIUM-TO-CREATININE RATIO, AND ASYMPTOMATIC GROSS AND MICROSCOPIC HEMATURIA IN CHILDREN
Respectfully, P. R. Dodds Section of Urology Department of Surgery Norwalk Hospital Norwalk, Connecticut 06850 and
D. J. Parekh, J. C. Pope, IV, M. C. Adams and J. W. Brock, III J Urol, 167: 272–274, 2002 To the Editor. The authors report that 30% of children evaluated at their hospital with otherwise unexplained hematuria were found to have hypercalciuria as defined by a urinary calcium-tocreatinine ratio of 0.2 or greater. This number is contrasted with a prevalence of hypercalciuria (referred to by the authors as “incidence”) of 2.9% to 6.2% in asymptomatic children as previously reported by Heiliczer1 and Moore2 et al. The implication of this statistical comparison is that hypercalciuria is more common than expected by chance in children with hematuria. Despite the observation that hematuria spontaneously resolved in most children without treatment of the hypercalciuria, the authors conclude that hypercalciuria “may have a significant etiological role” in hematuria. The authors do not prove a positive statistical correlation between hypercalciuria and hematuria because the validity of the reported prevalence in asymptomatic children and in those with hematuria is uncertain. The prevalence of hypercalciuria in asymptomatic children cited by the authors is inappropriate to the analysis because it is unknown whether the distribution of urinary calcium excretion in asymptomatic children from the patient referral base is the same as that from the predominantly black clinic population studied by Moore et al.2 Reported normal values for urinary calcium excretion vary widely in different studies, suggesting that the quantity of urinary calcium excretion is specific to the study.1 The disparate values used to define hypercalciuria probably reflect differences in the race and diet of the subjects studied, the methodology of collecting and analyzing samples, and the arbitrary statistical standard chosen to define the upper limit of normal. In a study we conducted of asymptomatic ambulatory subjects in Norwalk, Connecticut 22% of white children (13 of 60) on an unrestricted diet would be considered hypercalciuric based on a urinary calcium-to-creatinine ratio of 0.2 or greater from a single 24-hour urine collection, while none of the 15 black children had a calcium-to-creatinine ratio greater than 0.13. The unstated assumption of Parekh et al that the prevalence of hypercalciuria in asymptomatic children is transferable from 1 study or 1 population to another appears invalid. We have observed, as have others, that because of test to test variability a subject may demonstrate hypercalciuria on 1 urine sample but not another. The importance of this observation is that repetitive testing, in essence “looking for hypercalciuria,” will yield a higher prevalence, which can be thought of as a cumulative or period prevalence. Parekh et al do not exclude the possibility that they are comparing a period prevalence of hypercalciuria in children with hematuria to a point prevalence in asymptomatic children. The prevalence of hypercalciuria reported by the authors in children with hematuria is suspect because it is based only on those patients who were chosen, for unstated reasons, for urinary calcium testing. Lastly, it seems possible that some of the children evaluated for hematuria were preselected for referral because of known hypercalciuria. The authors call attention to the extensive literature asserting that hypercalciuria is an established cause of diverse pediatric urological problems, including hematuria, pyuria, proteinuria, dysuria, daytime incontinence, enuresis, the urgency-frequency syndrome, suprapubic and flank pain, and even chronic urinary tract infections. However, it is important to note that they do not cite any article that rigorously demonstrates a positive statistical correlation, let alone a
J. H. Dodds Public Health Program Health Professions Division Nova Southeastern University Fort Lauderdale, Florida 33328 1. Heiliczer, J. D., Canonigo, B. B., Bishof, N. A. and Moore, E. S.: Noncalculi urinary tract disorders secondary to idiopathic hypercalciuria in children. Pediatr Clin North Am, 34: 711, 1987 2. Moore, E. S., Coe, F. L., McMann, B. J. and Favus, M. J.: Idiopathic hypercalciuria in children: prevalence and metabolic characteristics. J Pediatr, 92: 906, 1978
Reply by Authors. While the aim of our study was to highlight the association between hypercalciuria and hematuria in children, we would agree that the cause and effect of hypercalciuria are poorly defined, as are normal and abnormal laboratory values in all patient populations. Yes, our population in this series consisted of white and black patients but we still believe that a urinary calcium-tocreatinine ratio of less than 0.2 may have a causative role in hematuria. We address the value of random spot urine calcium-tocreatinine ratio being representative of hypercalciuria, with references 9 through 13 in the article providing sufficient evidence to back our claim. We cannot agree or disagree with the comments that there may have been some preselection bias in the patients sent to us for evaluation of hematuria. It is possible that this is the case. However, we do not believe that our noted prevalence (defined as calcium-to-creatinine ratio greater than 0.2) is suspect as all patients with repeat microscopic hematuria were evaluated thoroughly in exactly the same fashion. We understand the difference between period and point prevalence. If our patients had a negative evaluation, they did not undergo multiple analyses for hypercalciuria. We do not believe that that is a significant concern. Clearly, much remains to be learned about hypercalciuria and its natural history, but one way to do so remains to check for it in patients with hematuria. Finally, we were extremely careful in the concluding paragraph to indicate that we do not believe a strong cause and effect relationship exists between hypercalciuria and hematuria. However, hypercalciuria in 30% of cases with hematuria merits attention, especially when managing refractory cases.
To the Editor. In this study the authors examined 96 children with unexplained microscopic hematuria, of whom 30% had hypercalciuria. They did not examine the urine by phase contrast microscopy to determine whether the urinary red blood cells were dysmorphic and, hence, glomerular in origin. This simple test would have indicated more clearly the nature of the underlying diseases and, thus, the significance of the hypercalciuria. Hematuria is common in children, and the red blood cells are usually dysmorphic. The most frequent cause of hematuria is thin basement membrane disease, which is suspected clinically when there is persistent glomerular hematuria, minimal or no proteinuria, normal renal function and no other obvious cause. There is often a family history of hematuria but no history of X-linked Alport’s syndrome, renal failure or inherited deafness.
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Vol. 168, 2126 –2135, November 2002 Printed in U.S.A.
Letters to the Editor cause and effect relationship, between hypercalciuria and any of the aforementioned conditions.
RE: THE ASSOCIATION OF AN INCREASED URINARY CALCIUM-TO-CREATININE RATIO, AND ASYMPTOMATIC GROSS AND MICROSCOPIC HEMATURIA IN CHILDREN
Respectfully, P. R. Dodds Section of Urology Department of Surgery Norwalk Hospital Norwalk, Connecticut 06850 and
D. J. Parekh, J. C. Pope, IV, M. C. Adams and J. W. Brock, III J Urol, 167: 272–274, 2002 To the Editor. The authors report that 30% of children evaluated at their hospital with otherwise unexplained hematuria were found to have hypercalciuria as defined by a urinary calcium-tocreatinine ratio of 0.2 or greater. This number is contrasted with a prevalence of hypercalciuria (referred to by the authors as “incidence”) of 2.9% to 6.2% in asymptomatic children as previously reported by Heiliczer1 and Moore2 et al. The implication of this statistical comparison is that hypercalciuria is more common than expected by chance in children with hematuria. Despite the observation that hematuria spontaneously resolved in most children without treatment of the hypercalciuria, the authors conclude that hypercalciuria “may have a significant etiological role” in hematuria. The authors do not prove a positive statistical correlation between hypercalciuria and hematuria because the validity of the reported prevalence in asymptomatic children and in those with hematuria is uncertain. The prevalence of hypercalciuria in asymptomatic children cited by the authors is inappropriate to the analysis because it is unknown whether the distribution of urinary calcium excretion in asymptomatic children from the patient referral base is the same as that from the predominantly black clinic population studied by Moore et al.2 Reported normal values for urinary calcium excretion vary widely in different studies, suggesting that the quantity of urinary calcium excretion is specific to the study.1 The disparate values used to define hypercalciuria probably reflect differences in the race and diet of the subjects studied, the methodology of collecting and analyzing samples, and the arbitrary statistical standard chosen to define the upper limit of normal. In a study we conducted of asymptomatic ambulatory subjects in Norwalk, Connecticut 22% of white children (13 of 60) on an unrestricted diet would be considered hypercalciuric based on a urinary calcium-to-creatinine ratio of 0.2 or greater from a single 24-hour urine collection, while none of the 15 black children had a calcium-to-creatinine ratio greater than 0.13. The unstated assumption of Parekh et al that the prevalence of hypercalciuria in asymptomatic children is transferable from 1 study or 1 population to another appears invalid. We have observed, as have others, that because of test to test variability a subject may demonstrate hypercalciuria on 1 urine sample but not another. The importance of this observation is that repetitive testing, in essence “looking for hypercalciuria,” will yield a higher prevalence, which can be thought of as a cumulative or period prevalence. Parekh et al do not exclude the possibility that they are comparing a period prevalence of hypercalciuria in children with hematuria to a point prevalence in asymptomatic children. The prevalence of hypercalciuria reported by the authors in children with hematuria is suspect because it is based only on those patients who were chosen, for unstated reasons, for urinary calcium testing. Lastly, it seems possible that some of the children evaluated for hematuria were preselected for referral because of known hypercalciuria. The authors call attention to the extensive literature asserting that hypercalciuria is an established cause of diverse pediatric urological problems, including hematuria, pyuria, proteinuria, dysuria, daytime incontinence, enuresis, the urgency-frequency syndrome, suprapubic and flank pain, and even chronic urinary tract infections. However, it is important to note that they do not cite any article that rigorously demonstrates a positive statistical correlation, let alone a
J. H. Dodds Public Health Program Health Professions Division Nova Southeastern University Fort Lauderdale, Florida 33328 1. Heiliczer, J. D., Canonigo, B. B., Bishof, N. A. and Moore, E. S.: Noncalculi urinary tract disorders secondary to idiopathic hypercalciuria in children. Pediatr Clin North Am, 34: 711, 1987 2. Moore, E. S., Coe, F. L., McMann, B. J. and Favus, M. J.: Idiopathic hypercalciuria in children: prevalence and metabolic characteristics. J Pediatr, 92: 906, 1978
Reply by Authors. While the aim of our study was to highlight the association between hypercalciuria and hematuria in children, we would agree that the cause and effect of hypercalciuria are poorly defined, as are normal and abnormal laboratory values in all patient populations. Yes, our population in this series consisted of white and black patients but we still believe that a urinary calcium-tocreatinine ratio of less than 0.2 may have a causative role in hematuria. We address the value of random spot urine calcium-tocreatinine ratio being representative of hypercalciuria, with references 9 through 13 in the article providing sufficient evidence to back our claim. We cannot agree or disagree with the comments that there may have been some preselection bias in the patients sent to us for evaluation of hematuria. It is possible that this is the case. However, we do not believe that our noted prevalence (defined as calcium-to-creatinine ratio greater than 0.2) is suspect as all patients with repeat microscopic hematuria were evaluated thoroughly in exactly the same fashion. We understand the difference between period and point prevalence. If our patients had a negative evaluation, they did not undergo multiple analyses for hypercalciuria. We do not believe that that is a significant concern. Clearly, much remains to be learned about hypercalciuria and its natural history, but one way to do so remains to check for it in patients with hematuria. Finally, we were extremely careful in the concluding paragraph to indicate that we do not believe a strong cause and effect relationship exists between hypercalciuria and hematuria. However, hypercalciuria in 30% of cases with hematuria merits attention, especially when managing refractory cases.
To the Editor. In this study the authors examined 96 children with unexplained microscopic hematuria, of whom 30% had hypercalciuria. They did not examine the urine by phase contrast microscopy to determine whether the urinary red blood cells were dysmorphic and, hence, glomerular in origin. This simple test would have indicated more clearly the nature of the underlying diseases and, thus, the significance of the hypercalciuria. Hematuria is common in children, and the red blood cells are usually dysmorphic. The most frequent cause of hematuria is thin basement membrane disease, which is suspected clinically when there is persistent glomerular hematuria, minimal or no proteinuria, normal renal function and no other obvious cause. There is often a family history of hematuria but no history of X-linked Alport’s syndrome, renal failure or inherited deafness.
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