The primary stone event: A new hypothesis involving a vascular etiology

Purpose: We detail a new hypothesis regarding a vascular phenomenon as the primary event in the formation of urolithiasis. Materials and Methods: A complete MEDLINE search was performed to examine the existing literature regarding the etiology of nephrolithiasis. In addition, urinary calculi were retrieved from 11 patients undergoing percutaneous nephrolithotomy and analyzed for total and esterified cholesterol content. Results: A review of the literature on stone disease revealed many factors inconsistent with the current paradigm of the initiation of nephrolithiasis. These arguments can be based and classified on epidemiological, clinical, physiological, anatomical, and molecular data. In our stone analysis free and esterified cholesterol were found in varying quantities between 0.058 and 2.258 mug/mg stone and 0.012 and 0.777 mug/mg stone, respectively. Esterified cholesterol was found to comprise 75% of total serum cholesterol. In urinary stones esterified cholesterol accounted for 14% to 16% of total cholesterol and the esterified-to-free cholesterol ratio appeared to be related to stone composition. Conclusions: Numerous inconsistencies exist between current theories of the initial event in nephrolithiasis formation and empirical observational data on stone disease. Our review of the literature and our study of the cholesterol content of renal stones support a new theory regarding the initial stone forming event. We base this novel hypothesis on multiple epidemiological, physiological, anatomical and clinical observations. Further studies are required to confirm this hypothesis and its clinical usefulness.