Although surgical interventions effectively manage symptomatic stones, recurrence rates remain high, with 30–50% of patients experiencing a repeat stone episode or surgery within five years. Despite its prevalence, the precise mechanisms underlying stone formation remain poorly understood. Understanding these mechanisms is essential to prevent recurrence and to guide effective therapeutic strategies.
In 1937, Alexander Randall published “The Origin and Growth of Renal Calculi,” in which he reported small, calcified deposits now known as Randall’s plaque (RP) on the renal papilla that act as niduses for kidney stone formation. These interstitial calcium phosphate deposits have been shown to anchor CaOx stones to papillae in idiopathic stone formers. Studies, including work by Evan et al. (2003), have echoed Randall’s findings that RP may originate in the basement membranes of the renal tubules. Disruption of the papillary epithelium may expose these interstitial plaques to calyceal urine, facilitating CaOx crystallization and overgrowth on RP.
Image Source: Evan AP. Physiopathology and etiology of stone formation in the kidney and the urinary tract. Pediatr Nephrol. 2010; 25(5): 831-41. doi: 10.1007/s00467-009-1116-y.
Our study analyzed eighteen stones from nine patients, and all of these stones demonstrated evidence of RP. Stones were collected during percutaneous nephrolithotomy and/or ureteroscopy procedures. Imaging and compositional analyses included stereoscopic microscopy, micro-computed tomography (micro CT), scanning electron microscopy (SEM), and energy-dispersive spectroscopy (EDS). Micro CT analysis identified RP in all stones, typically as a whitish gray mineral contrasting with the darker grayish calcium oxalate monohydrate (COM) overgrowth. SEM revealed regions of RP as tubular mineralized structures with size and shape that are consistent with thin loops, collecting ducts, ducts of Bellini, or vasa recta, supporting prior hypotheses regarding RP origin. EDS analyses confirmed that RP was composed of calcium and phosphorus, consistent with apatite, while the overlying stone growth was consistently calcium oxalate monohydrate (COM).
Seven stones were manually sectioned to examine internal RP architecture. In three of these seven, monosodium urate monohydrate (MSU) crystals were observed intercalated with RP. EDS analysis confirmed MSU presence, showing needle-like structures positive for sodium (Na) and nitrogen (N), suggesting that urate deposition may precede RP formation in a subset of cases. This observation raises the possibility of a gouty nephropathy-like phenotype in certain stone formers, potentially influenced by urinary pH shifts, though further studies are needed to test this hypothesis.
Our work supports previous findings about RP morphology and origin, while the unexpected finding of MSU crystals further expands our understanding of RP stone formation, highlighting the possibility that various mineral species may contribute to early plaque development in some patients. Further work with advanced molecular technology is necessary to elucidate and validate the mechanisms contributing to the deposition of MSU crystals in the papilla and to inform targeted preventive and therapeutic strategies for kidney stone disease.
Written by: Victor Hugo Canela, PhD,1,2,3 Antonia Costa-Bauzá, PhD,3 Felix Grases, PhD,3 Tarek M. El-Achkar, MD,1,4 James E. Lingeman, MD,5 James C. Williams Jr., PhD,1
- Department of Anatomy, Cell Biology and Physiology, Indiana University School of Medicine, Indianapolis, IN
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, Butler University, Indianapolis, IN
- Renal Lithiasis and Pathological Calcification Group, Research Institute of Health Sciences (IUNICS), University of the Balearic Islands, Palma, Spain.
- Department of Medicine, Division of Nephrology, Indiana School of Medicine, Indianapolis, IN
- Department of Urology, Indiana University School of Medicine, Indianapolis, IN