Fragility of brushite stones in shock wave lithotripsy: absence of correlation with computerized tomography visible structure.

PURPOSE: Brushite stones were imaged in vitro and then broken with shock wave lithotripsy to assess whether stone fragility correlates with internal stone structure visible on helical computerized tomography. MATERIALS AND METHODS: A total of 52 brushite calculi were scanned by micro computerized tomography, weighed, hydrated and placed in a radiological phantom. Stones were scanned using a Philips® Brilliance iCT 256 system and images were evaluated for the visibility of internal structural features. The calculi were then treated with shock wave lithotripsy in vitro. The number of shock waves needed to break each stone to completion was recorded. RESULTS: The number of shock waves needed to break each stone normalized to stone weight did not differ by HU value (p = 0.84) or by computerized tomography visible structures that could be identified consistently by all observers (p = 0.053). Stone fragility correlated highly with stone density and brushite content (each p <0.001). Calculi of almost pure brushite required the most shock waves to break. When all observations of computerized tomography visible structures were used for analysis by logistic fit, computerized tomography visible structure predicted increased stone fragility with an overall area under the ROC curve of 0.64. CONCLUSIONS: The shock wave lithotripsy fragility of brushite stones did not correlate with internal structure discernible on helical computerized tomography. However, fragility did correlate with stone density and increasing brushite mineral content, consistent with clinical experience with patients with brushite calculi. Thus, current diagnostic computerized tomography technology does not provide a means to predict when brushite stones will break well using shock wave lithotripsy.

Inaccurate reporting of mineral composition by commercial stone analysis laboratories: implications for infection and metabolic stones.

PURPOSE: We determined the accuracy of stone composition analysis at commercial laboratories. MATERIALS AND METHODS: A total of 25 human renal stones with infrared spectroscopy determined composition were fragmented into aliquots and studied with micro computerized tomography to ensure fragment similarity. Representative fragments of each stone were submitted to 5 commercial stone laboratories for blinded analysis. RESULTS: All laboratories agreed on the composition of 6 pure stones. Only 2 of 4 stones (50%) known to contain struvite were identified as struvite at all laboratories. Struvite was reported as a component by some laboratories for 4 stones previously determined not to contain struvite. Overall there was disagreement regarding struvite in 6 stones (24%). For 9 calcium oxalate stones all laboratories reported some mixture of calcium oxalate but the quantity of subtypes differed significantly among laboratories. In 6 apatite containing stones apatite was missed by the laboratories in 20% of samples. None of the laboratories identified atazanavir in a stone containing that antiviral drug. One laboratory reported protein in every sample while all others reported it in only 1. Nomenclature for apatite differed among laboratories with 1 reporting apatite as carbonate apatite and never hydroxyapatite, another never reporting carbonate apatite and always reporting hydroxyapatite, and a third reporting carbonate apatite as apatite with calcium carbonate. CONCLUSIONS: Commercial laboratories reliably recognize pure calculi. However, variability in the reporting of mixed calculi suggests a problem with the accuracy of stone analysis results. There is also a lack of standard nomenclature used by laboratories.

Noninvasive differentiation of uric acid versus non-uric acid kidney stones using dual-energy CT.

RATIONALE AND OBJECTIVES: To determine the accuracy and sensitivity for dual-energy computed tomography (DECT) discrimination of uric acid (UA) stones from other (non-UA) renal stones in a commercially implemented product. MATERIALS AND METHODS: Forty human renal stones comprising uric acid (n=16), hydroxyapatite (n=8), calcium oxalate (n=8), and cystine (n=8) were inserted in four porcine kidneys (10 each) and placed inside a 32-cm water tank anterior to a cadaver spine. Spiral dual-energy scans were obtained on a dual-source, 64-slice computed tomography (CT) system using a clinical protocol and automatic exposure control. Scanning was performed at two different collimations (0.6 mm and 1.2 mm) and within three phantom sizes (medium, large, and extra large) resulting in a total of six image datasets. These datasets were analyzed using the dual-energy software tool available on the CT system for both accuracy (number of stones correctly classified as either UA or non-UA) and sensitivity (for UA stones). Stone characterization was correlated with micro-CT. RESULTS: For the medium and large phantom sizes, the DECT technique demonstrated 100% accuracy (40/40), regardless of collimation. For the extra large phantom size and the 0.6-mm collimation (resulting in the noisiest dataset), three (two cystine and one small UA) stones could not be classified (93% accuracy and 94% sensitivity). For the extra large phantom size and the 1.2-mm collimation, the dual-energy tool failed to identify two small UA stones (95% accuracy and 88% sensitivity). CONCLUSIONS: In an anthropomorphic phantom model, dual-energy CT can accurately discriminate uric acid stones from other stone types.

Variability of protein content in calcium oxalate monohydrate stones.

BACKGROUND AND PURPOSE: Urinary stones are heterogeneous in their fragility to lithotripter shockwaves. As a first step in gaining a better understanding of the role of matrix in stone fragility, we measured extractible protein in calcium oxalate monohydrate (COM) stones that were extensively characterized by micro-computed tomography (micro CT). MATERIALS AND METHODS: Stones were scanned using micro CT (Scanco mCT20, 34 microm). They were ground, and the protein extracted using four methods: 0.25M EDTA, 2% SDS reducing buffer, 9M urea buffer, and 10% acetic acid. Protein was measured using NanoOrange. The SDS extracts were also examined using polyacrylamide electrophoresis (PAGE). RESULTS: Extracted protein was highest with the SDS or urea methods (0.28% +/- 0.13% and 0.24% +/- 0.11%, respectively) and lower using the EDTA method (0.17% +/- 0.05%; P < 0.02). Acetic acid extracted little protein (0.006 +/- 0.002%; P < 0.001). Individual stones were significantly different in extractability of protein by the different methods, and SDS-PAGE revealed different protein patterns for individual stones. Extracted protein did not correlate with X-ray-lucent void percentage, which ranged from 0.06% to 2.8% of stone volume, or with apatite content. CONCLUSIONS: Extractible stone-matrix protein differs for individual COM stones, and yield is dependent on the extraction method. The presence of X-ray-lucent voids or minor amounts of apatite in stones did not correlate with protein content. The amounts of protein recovered were much lower than reported by Boyce, showing that these methods extracted only a fraction of the protein bound up in the stones. The results suggest that none of the methods tested will be useful for helping to answer the question of whether matrix content differs among stones of differing fragility to lithotripter shockwaves.

Calcium oxalate calculi found attached to the renal papilla: Preliminary evidence for early mechanisms in stone formation.

BACKGROUND: Calculi are commonly found attached to the renal papilla in calcium oxalate (CaOx) stone formers, but the mechanisms by which stones form in this manner are not well established. MATERIALS AND METHODS: Data are presented from three attached stones collected from different patients. Stone morphology and composition were determined using micro computed tomography (CT) and infrared microspectrometry. RESULTS: One of the stones was composed of CaOx with a peripheral region of apatite, such as might have come from a Randall's plaque. Another stone was covered with large CaOx crystals but contained at least two layers of apatite, with no apatite regions exposed at the surface. The third stone contained CaOx with inclusions of apatite and more apatite on its surface, along with a substantial volume of poorly mineralized material that could not be identified. CONCLUSIONS: The complexity of these stones and their differing morphologies do not by themselves allow inference of the mechanism of stone formation. Future work will require the careful documentation of attached stones on the papilla, as well as study of the papilla after the stone has been removed, before it can be determined whether such diverse CaOx stones originate from the same or different underlying etiologies.

Stability of the infection marker struvite in urinary stone samples.

BACKGROUND AND PURPOSE: Struvite in kidney stones is an important marker for infection. In kidney stone samples, struvite is known to be prone to chemical breakdown, but no data exist on the stability of samples stored in dry form. The objective of this study was to examine stability of struvite under increasingly poor conditions of storage. MATERIALS AND METHODS: Samples of struvite kidney stones were broken to obtain 38 pieces averaging 67 mg in weight, and these were randomized into four storage conditions: Airtight containers stored in the dark, open containers in the dark, open containers in ambient light, and open containers at elevated temperature (40°C). Pieces were left for 6 months, and then analyzed for changes using micro CT and Fourier transform infrared spectroscopy (FT-IR). RESULTS: Initial samples proved to be struvite, indicating no transformation in the large specimens that had been stored in airtight containers in the dark for more than 6 years before this study. Pieces of struvite taken from these large specimens appeared unchanged by micro CT and FT-IR after being stored in closed containers for 6 months, but 8 of 9 pieces in open containers showed the presence of newberyite in surface layers, as did 10 of 10 pieces in open containers out in ambient light. All pieces stored at 40°C showed transformation of struvite, with 60% of the pieces showing the presence of amorphous phosphates, indicating complete breakdown of struvite in the surface layers of the pieces. CONCLUSION: We conclude that struvite in dry kidney stone samples is stable when the specimens are stored in airtight containers at room temperature, even after several years.

Protein content of human apatite and brushite kidney stones: significant correlation with morphologic measures.

Apatite and brushite kidney stones share calcium and phosphate as their main inorganic components. We tested the hypothesis that these stone types differ in the amount of proteins present in the stones. Intact stones were intensively analyzed by microcomputed tomography (micro CT) for both morphology (including the volume of voids, i.e., space devoid of X-ray dense material) and mineral type. To extract all proteins present in kidney stones in soluble form we developed a three-step extraction procedure using the ground stone powder. Apatite stones had significantly higher levels of total protein content and void volume compared to brushite stones. The void volume was highly correlated with the total protein contents in all stones (r2 = 0.61, P < 0.0001), and brushite stones contained significantly fewer void regions and proteins than did apatite stones (3.2 +/- 4.5% voids for brushite vs. 10.8 +/- 11.2% for apatite, P < 0.005; 4.1 +/- 1.6% protein for brushite vs. 6.0 +/- 2.4% for apatite, P < 0.03). Morphological observations other than void volume did not correlate with protein content of stones, and neither did the presence or absence of minor mineral components. Our results show that protein content of brushite and apatite stones is higher than that was previously thought, and also suggest that micro CT-visible void regions are related to the presence of protein.

Using Helical CT to Predict Stone Fragility in Shock Wave Lithotripsy (SWL).

Great variability exists in the response of urinary stones to SWL, and this is true even for stones composed of the same mineral. Efforts have been made to predict stone fragility to shock waves using computed tomography (CT) patient images, but most work to date has focused on the use of stone CT number (i.e., Hounsfield units). This is an easy number to measure on a patient stone, but its value depends on a number of factors, including the relationship of the size of the stone to the resolution (i.e., the slicewidth) of the CT scan. Studies that have shown a relationship between stone CT number and failure in SWL are reviewed, and all are shown to suffer from error due to stone size, which was not accounted for in the use of Hounsfield unit values. Preliminary data are then presented for a study of calcium oxalate monohydrate (COM) stones, in which stone structure-rather than simple CT number values-is shown to correlate with fragility to shock waves. COM stones that were observed to have structure by micro CT (e.g., voids, apatite regions, unusual shapes) broke to completion in about half the number of shock waves required for COM stones that were observed to be homogeneous in structure by CT. This result suggests another direction for the use of CT in predicting success of SWL: the use of CT to view stone structure, rather than simply measuring stone CT number. Viewing stone structure by CT requires the use of different viewing windows than those typically used for examining patient scans, but much research to date indicates that stone structure can be observed in the clinical setting. Future clinical studies will need to be done to verify the relationship between stone structure observed by CT and stone fragility in SWL.

CT visible internal stone structure, but not Hounsfield unit value, of calcium oxalate monohydrate (COM) calculi predicts lithotripsy fragility in vitro.

Calcium oxalate monohydrate (COM) stones are often resistant to breakage using shock wave (SW) lithotripsy. It would be useful to identify by computed tomography (CT) those COM stones that are susceptible to SW's. For this study, 47 COM stones (4-10 mm in diameter) were scanned with micro CT to verify composition and also for assessment of heterogeneity (presence of pronounced lobulation, voids, or apatite inclusions) by blinded observers. Stones were then placed in water and scanned using 64-channel helical CT. As with micro CT, heterogeneity was assessed by blinded observers, using high-bone viewing windows. Then stones were broken in a lithotripter (Dornier Doli-50) over 2 mm mesh, and SW's counted. Results showed that classification of stones using micro CT was highly repeatable among observers (kappa = 0.81), and also predictive of stone fragility. Stones graded as homogeneous required 1,874 +/- 821 SW/g for comminution, while stones with visible structure required half as many SW/g, 912 +/- 678. Similarly, when stones were graded by appearance on helical CT, classification was repeatable (kappa = 0.40), and homogeneous stones required more SW's for comminution than did heterogeneous stones (1,702 +/- 993 SW/g, compared to 907 +/- 773). Stone fragility normalized to stone size did not correlate with Hounsfield units (P = 0.85). In conclusion, COM stones of homogeneous structure require almost twice as many SW's to comminute than stones of similar mineral composition that exhibit internal structural features that are visible by CT. This suggests that stone fragility in patients could be predicted using pre-treatment CT imaging. The findings also show that Hounsfield unit values of COM stones did not correlate with stone fragility. Thus, it is stone morphology, rather than X-ray attenuation, which correlates with fragility to SW's in this common stone type.