Integration and utilization of modern technologies in nephrolithiasis research

Abstract

Nephrolithiasis, or stones, is one of the oldest urological diseases, with descriptions and treatment strategies dating back to ancient times. Despite the enormous number of patients affected by stones, a surprising lack of conceptual understanding of many aspects of this disease still exists. This lack of understanding includes mechanisms of stone formation and retention, the clinical relevance of different stone compositions and that of formation patterns and associated pathological features to the overall course of the condition. Fortunately, a number of new tools are available to assist in answering such questions. New renal endoscopes enable kidney visualization in much higher definition than was previously possible, while micro-CT imaging is the optimal technique for assessment of stone microstructure and mineral composition in a nondestructive fashion. Together, these tools have the potential to provide novel insights into the aetiology of stone formation that might unlock new prevention and treatment strategies, and enable more effective management of patients with nephrolithiasis.

Figure 1. Fibre-optic versus digital ureteroscopic images

Images of the renal papilla acquired using a,b | a fibre-optic ureteroscope (KARL STORZ FLEX-X2, KARL STORZ, Tuttlingen, Germany) and c,d | a digital ureteroscope (ACMI/Olympus Invisio DUR-D, Gyrus ACMI, Massachusetts, USA) The enhanced view provided by the digital scope allows superior visualization of the papilla including both an attached stone as well as nascent mineral which might ultimately become a stone or be related to stone formation. The ability to identify such details opens new doors to study associations between papillary appearance and stone disease. Reproduced with permission obtained from Elsevier Ltd © Humphreys, M. R. et al., A new world revealed: early experience with digital ureteroscopy. J. Urol. 179, 970–975 (2008).

Figure 2. Digital ureteroscopic image of a classic renal papilla

The surface of the papilla is entirely smooth, round and conical in shape and no mineral deposition can be observed.

Figure 3. Micro-CT imaging and reconstruction of a stone fragment

a | First, the specimen is imaged using a radiation source and an x-ray camera, with a small degree of rotation accomplished between consecutive images. In the example shown here, the specimen was rotated 0.4° between each image, for a total rotational range of slightly more than 180°. The computer then used this series of radiographic images to reconstruct the 3D structure of the specimen. b | A single reconstructed slice taken through the specimen depicted in part a. c | A portion of the same slice as depicted in part b; note that the regions of transformation of the calcium oxalate dihydrate (COD) to monohydrate (COM) are quite small, in the order of 100 μm in size, but these can be easily observed. Imaging of transformed regions within COD crystals has also previously been described, but only by physically cutting sections of the crystals^,. The COM absorbs radiation with a slightly greater avidity than that of COD, therefore the image could be easily segmented to measure the portion of the stone occupied by COM. d | Segmentation of COM. When all image slices are similarly segmented, the volume percentages of the minerals can be easily calculated. e | Surface rendering of the fragment used in this example, note the clarity with which the polyhedral crystals of COD are shown.

Figure 4. Renal mapping of a right kidney using high-definition renal endoscopy

a | Calyceal location and number is denoted on fluoroscopic imaging. b-d | Endoscopic images of the upper-pole papillae (UP)s 1-3. e-g | Endoscopic images of the interpolar papillae (MP)s. h,i | Endoscopic images of the lower-pole papillae (LP)s. Dilated ducts of Bellini are circled in white, asterisk indicates the presence of a yellow ductal plug, no Randall plaques are visualized.

Figure 5. Common renal papillary abnormalities observed in stone formers

Digital endoscopic images showing the papillary appearance of two different patients. a | Randall plaquesseen commonly in patients that form idiopathic calcium oxalate stones and b | ductal plugs seen commonly in patients who form idiopathic hydroxyapatite stones. In these images Randall plaques and ductal plugs are distinguishable by their colour (white versus yellow, respectively). Arrows indicate the presence of these abnormalities.

Figure 6. Comparisons of stones anchored to papillary tissue in two different ways

a | Digital reconstruction of a calcium oxalate stone that accumulated on a Randall plaque. The colour inset shows a photograph of the stone on mm-grid paper. Surface rendering and sliced stack analyses both reveal the presence of calcium oxalate (grey). The colour of the Randall plaque (white) indicates a high level of radiographic attenuation, reflecting the presence of apatite. Note the sparse and thin distribution of the apatite comprising the plaque itself b | Digital reconstruction of an apatite stone that accumulated on a ductal plug. In this image the apatite ductal plug anchoring the stone to the papilla is more substantial, thicker and denser compared to that of the Randall plaque indicating a distinct mechanism of formation and retention within the kidney at the level of the papilla.

Figure 7. Direct comparison of reconstructions of stones formed on a Randall plaque or on a ductal plug

a | Stone formed on a Randall plaque showing lumina of tubules and/or vessels (as indicated by arrows), demonstrating that this apatite region is interstitial. In Randall plaques, apatite accumulates in the papillary interstitium, without any deposition into tubular lumina. By contrast, the stone formed on a ductal plug. b | conforms to the shape of the dilated duct in which it formed, and shows signs of accretion by layering (as indicated by arrowheads). This ductal plug seems to have been formed from multiple, small spheres of apatite.