Ignite Creation Date:
2024-05-05 @ 11:53 AM
Last Modification Date:
2024-10-26 @ 9:16 AM
Study NCT ID:
NCT00169754
Status:
COMPLETED
Last Update Posted:
2008-09-17
First Post:
2005-09-09
Brief Title:
Attached Stone Project Do Calcium Oxalate Renal Calculi Originate From Randalls Plaque
Sponsor:
Indiana Kidney Stone Institute
Organization:
Indiana Kidney Stone Institute
Study Overview
Official Title:
Do Calcium Oxalate Renal Calculi Originate From Randalls Plaque
Status:
COMPLETED
Status Verified Date:
2008-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Urolithiasis is a common condition in the United States and is associated with significant morbidity and even mortality The most commonly occurring urinary calculi are comprised of calcium oxalate salts and until recently the pathogenesis of calcium oxalate calculi was poorly understood New evidence however suggests that the development of calcium oxalate calculi may be intimately associated with hydroxyapatite HA plaque also known as Randalls plaque which is located on the renal papillae The investigators have previously demonstrated that Randalls plaque originates in the thin ascending limb of the loop of Henle and they have shown that Randalls plaque is composed of HA Evan Lingeman et al 2003 As well the amount of Randalls plaque correlates with elevated levels of urinary calcium and decreased urinary volume risk factors for the formation of calcium oxalate calculi Kuo Lingeman et al 2003 In the course of these previous studies the investigators have anecdotally noted that calcium oxalate stones are often found attached to Randalls plaque an observation that others have reported as well Prien 1949 Carr 1954 Cifuentes Delatte Minon-Cifuentes et al 1987 However there has been no in-vivo rigorous documentation of this attached stone relationship Attached calculi represent an important point in the pathogenesis of calcium oxalate calculi as they correspond to a moment in time where there is a continuum between the HA plaque of Randall and the calcium oxalate stone thus linking the origin of plaque with the development of stone A better understanding of the phenomenon of attached calculi will lead to a better understanding of how and why calcium oxalate stones form which may ultimately direct future interventions to attenuate stone activity
Detailed Description:
Urolithiasis is a very common condition in the United States with an estimated prevalence of 117 by age 70 Furthermore it has been associated with considerable patient morbidity and occasional mortality Stamatelou Francis et al 2003 Direct costs associated with the treatment of renal calculi are enormous as over 600000 stone related medical procedures are performed annually in the United States shock wave lithotripsy SWL ureteroscopy URS percutaneous nephrolithotomy PERC stone removal ureteral stents and stone basketing source Boston Scientific Corporation Although the last two decades have seen considerable advances in less invasive techniques for the treatment of symptomatic stone episodes as well as progress in mitigating the risks of new stone formation our knowledge of the inciting lesion in human urolithiasis remains rudimentary and much debated
Until recently the sequence of events that leads to the formation of urinary calculi were poorly understood most fundamentally due to the lack of appropriate in-vivo data Earlier theories of calculogenesis proposed that stones could result from tubular epithelial injury due to oxalate toxicity a lack of urinary inhibitors of crystal formation or crystal epitaxy on a pre-existing nidus Khan Finlayson et al 1979 Theoretical work on free and fixed particle growth indicated that a transit time from the collecting duct to the bladder of only 10 minutes provided insufficient time for a crystal to grow to a clinically meaningful size Jonassen Cooney et al 1999 Morphological classification of the directional growth of calculi supported the necessity for a fixed point of origin in the absence of obstruction Hinman 1979 These observations suggested that most stones must initiate from a fixed point or nidus in the collecting system or renal papilla
One such nidus first described more than sixty years ago by Alexander Randall was proposed to be the originating lesion for the formation of calcium oxalate stones Randall 1936 Randall 1937 Randall 1940 In microscopic studies of renal papilla obtained at necropsy he demonstrated the presence of 2-3mm lesions in 196 of patients that were composed of calcium phosphate and devoid of evidence of inflammation Adherent to this in 65 of 1514 pairs of kidneys he identified nascent stones composed of calcium oxalate and calcium phosphate When these stones reached sufficient size he hypothesized that they would break free taking with them the underlying plaque In subsequent work 256 voided or removed calculi were examined and 106 gave visible evidence of mural attachment Randall 1940 Later microradiographic studies would confirm the presence of plaque in a papillary location that could be co-localized with stone Carr 1954 Unfortunately all earlier studies of stone pathogenesis have suffered from lack of definition of clear clinical stone-forming phenotypes
There are intriguing reports to support Randalls and our hypothesis that stones originate from a fixed plaque composed of HA Earlier microscopic studies of stone structure demonstrated the presence of concavities on small stones compatible with a point of mural attachment and indicated that apatite may be present at the attachment point Rosenow 1940 Prien 1949 In an early x-ray diffraction and crystallographic study of 10000 urinary calculi Herring noted that HA was frequently found as the nucleus of calcium oxalate monohydrate usually as a small discoid plaque which was felt to resemble Randalls plaque Herring 1962 Later Chambers performed an electron probe analysis of 115 small renal calculi Of 92 predominantly calcium oxalate stones he was able to identify small central areas of HA usually 10-200 microns in diameter in 70 Chambers Hodgkinson et al 1972 Using scanning electron microscopy and x-ray dispersive energy Cifuentes Delatte found that 63 of 87 passed calcium oxalate stones had evidence of plaque Cifuentes Delatte Minon-Cifuentes et al 1985 Observation of uncalcified tubular lumens found in conjunction with these plaques suggested an interstitial papillary tip origin of this material Cifuentes Delatte Minon-Cifuentes et al 1987
We have noted that when endoscopically examining the renal papillae of patients undergoing PERC oftentimes stones attached to renal papillae are encountered We have collected three attached stones from three separate patients who were undergoing PERC The stones were analyzed with a Micro CT device and 3-D reconstruction with identification of mineral components was performed The stones all showed multiple mineral components including calcium oxalate apatite and probable regions of poorly mineralized matrix Although the significance of these various components in varying amounts is not yet well understood it is apparent that even at early stages of stone formation multiple minerals in complex arrangement are present in papilla-attached stones It will be only through a rigorous prospectively designed protocol that the significance of attached renal calculi will be understood By demonstrating that renal calculi in a population of common calcium oxalate stone formers originate from an HA plaque we would link in a substantive way the origin of plaque with the subsequent development of stone
Until recently the sequence of events that leads to the formation of urinary calculi were poorly understood most fundamentally due to the lack of appropriate in-vivo data Earlier theories of calculogenesis proposed that stones could result from tubular epithelial injury due to oxalate toxicity a lack of urinary inhibitors of crystal formation or crystal epitaxy on a pre-existing nidus Khan Finlayson et al 1979 Theoretical work on free and fixed particle growth indicated that a transit time from the collecting duct to the bladder of only 10 minutes provided insufficient time for a crystal to grow to a clinically meaningful size Jonassen Cooney et al 1999 Morphological classification of the directional growth of calculi supported the necessity for a fixed point of origin in the absence of obstruction Hinman 1979 These observations suggested that most stones must initiate from a fixed point or nidus in the collecting system or renal papilla
One such nidus first described more than sixty years ago by Alexander Randall was proposed to be the originating lesion for the formation of calcium oxalate stones Randall 1936 Randall 1937 Randall 1940 In microscopic studies of renal papilla obtained at necropsy he demonstrated the presence of 2-3mm lesions in 196 of patients that were composed of calcium phosphate and devoid of evidence of inflammation Adherent to this in 65 of 1514 pairs of kidneys he identified nascent stones composed of calcium oxalate and calcium phosphate When these stones reached sufficient size he hypothesized that they would break free taking with them the underlying plaque In subsequent work 256 voided or removed calculi were examined and 106 gave visible evidence of mural attachment Randall 1940 Later microradiographic studies would confirm the presence of plaque in a papillary location that could be co-localized with stone Carr 1954 Unfortunately all earlier studies of stone pathogenesis have suffered from lack of definition of clear clinical stone-forming phenotypes
There are intriguing reports to support Randalls and our hypothesis that stones originate from a fixed plaque composed of HA Earlier microscopic studies of stone structure demonstrated the presence of concavities on small stones compatible with a point of mural attachment and indicated that apatite may be present at the attachment point Rosenow 1940 Prien 1949 In an early x-ray diffraction and crystallographic study of 10000 urinary calculi Herring noted that HA was frequently found as the nucleus of calcium oxalate monohydrate usually as a small discoid plaque which was felt to resemble Randalls plaque Herring 1962 Later Chambers performed an electron probe analysis of 115 small renal calculi Of 92 predominantly calcium oxalate stones he was able to identify small central areas of HA usually 10-200 microns in diameter in 70 Chambers Hodgkinson et al 1972 Using scanning electron microscopy and x-ray dispersive energy Cifuentes Delatte found that 63 of 87 passed calcium oxalate stones had evidence of plaque Cifuentes Delatte Minon-Cifuentes et al 1985 Observation of uncalcified tubular lumens found in conjunction with these plaques suggested an interstitial papillary tip origin of this material Cifuentes Delatte Minon-Cifuentes et al 1987
We have noted that when endoscopically examining the renal papillae of patients undergoing PERC oftentimes stones attached to renal papillae are encountered We have collected three attached stones from three separate patients who were undergoing PERC The stones were analyzed with a Micro CT device and 3-D reconstruction with identification of mineral components was performed The stones all showed multiple mineral components including calcium oxalate apatite and probable regions of poorly mineralized matrix Although the significance of these various components in varying amounts is not yet well understood it is apparent that even at early stages of stone formation multiple minerals in complex arrangement are present in papilla-attached stones It will be only through a rigorous prospectively designed protocol that the significance of attached renal calculi will be understood By demonstrating that renal calculi in a population of common calcium oxalate stone formers originate from an HA plaque we would link in a substantive way the origin of plaque with the subsequent development of stone
Study Oversight
Has Oversight DMC:
None
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None
Is a FDA Regulated Device?:
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Is an Unapproved Device?:
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Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None