Renal stone disease: a commentary on the nature and significance of Randall's plaque.

Abstract

In this short follow-up commentary to the recent minireview on renal stone disease by Johri et al. [1], we seek to clarify one aspect of their review that is covered only briefly: current theories of kidney stone formation, including a physicochemical pathway driven by the supersaturation level of dissolved salts in the urine, intratubular crystal adhesion [2], and the Randall's plaque theory for calcium oxalate kidney stone formation and growth [3,4]. Much confusion exists in the literature regarding these theories; in particular it is often assumed that Randall's plaques are connected in some way with adhesion of crystals to tubular epithelial cells. However, Randall proposed no such adhesion of crystals in his original theory, and recent data collected in human stone formers have supported Randall's ideas. Thus, we now need to think of human stone formation in more than one category: The formation of some types of stones clearly involves the adhesion of crystals to the luminal surface of renal tubules, but the formation of stones on Randall's plaques does not involve crystal adhesion to epithelial cells. Finally, it may be that some stones form in the absence of Randall's plaques and also without crystal adhesion as an essential mechanism of stone formation. To better understand these three main potential pathways for stone formation [5], we have produced an illustration (fig. ​(fig.1)1) that depicts the site of initial mineralization along the nephron/renal pelvis, and the final location of the developing stone for each pathway. The three pathways are labeled: ‘free-particle’ stone formation, stone formation on a plug (sometimes referred to as the ‘fixed-particle’ model), and Randall's plaque. In this short paper we will confine our discussion to the Randall's plaque hypothesis and touch only briefly on the other two theories. To give a historical perspective to Randall's plaque hypothesis, we will begin by reviewing his original observations and then link them to our own more recent findings. Fig. 1 Models of renal stone formation (see text for details). Observations Made by Randall It was Randall who reasoned from clinical observations in his own clinical practice of stone disease that: (1) there must be an initiating lesion that precedes the formation of a primary renal calculus, and (2) that such an initiating lesion was to be looked for on the renal papilla. It was from these seemingly self-evident facts as a guide that Randall first studied 265 naturally voided stones for the presence of a mural attachment site. In 106, or 40%, of the 265 stones he examined, he found a visible facet on the surface of the stone that was of a different color from the rest of the stone. In his mind this finding strongly supported his original hypothesis that an initiating lesion was required for stone formation. Therefore, Randall decided to obtain direct evidence to test his hypothesis by examining human kidneys, and particularly the renal papilla, for evidence of a mural attachment site. Using a hand lens, Randall [4] examined 1,154 pairs of kidneys obtained at autopsy and found calcium deposits on the renal papilla in 227 (19.6%) individuals, and a primary renal calculus in 65 of them. From his visual inspection, the papillary lesion appeared creamy colored and located beneath the urothelium. Histological examination of such a lesion site revealed deposits of calcium salts, termed Randall's plaque or papillary lesion type 1, in the interstitial tissues of the papilla near segments of the nephron (fig. ​(fig.1c).1c). Chemical analysis of these deposits suggested the mineral composition to be calcium phosphate. No deposits were found in the nephron lumen as an intratubular plug, nor was there any evidence of inflammation. Randall also discovered sites of black material (a small stone) overlying a region of interstitial plaque. In two cases, Randall was able to embed the stone-plaque complex and section the specimen for light microscope analysis. The stone (black material) was continuous with the interstitial plaque, with no evidence of a urothelial covering or barrier between the two mineral sites. Mineral analysis of the stone detected calcium oxalate, whereas the interstitial plaque material was composed of calcium phosphate. Thus, Randall viewed stone formation as beginning with the deposition of calcium phosphate in the interstitial tissues of the renal papilla; this lesion, though buried in the renal papilla, eventually loses its epithelial covering to become bathed in calyceal urine. By acting as a ‘foreign body’, the exposed plaque material becomes the nidus on which a different urinary salt can crystallize to form a new (surface) calculus (fig. ​(fig.1c1c).