Determination of Urinary Calcium-Oxalate Formation Risk with BONN-Risk-Index and EQUIL Applied to a Family Norbert Laube,* ,² Vera Labedzke, ² Stefan Hergarten, ‡ and Albrecht Hesse ² Division of Experimental Urology, Department of Urology, Bonn University, Germany, and Geodynamics and Physics of the Lithosphere, Bonn University, Germany Received November 12, 2001 Apart from environmental and acquired risk factors, a person’s genetic predisposition may have a distinct influence on the probability of the onset of urolithiasis. To investigate the family related development of calcium oxalate, CaOx, crystallization risk, we studied urines from three generations of the same family. The paternal line has been suffering from CaOx-urolithiasis for at least two generations; no case of urolithiasis has been reported from the maternal line and the youngest generation.We applicated the BONN-Risk-Index and the computer program EQUIL to determine the crystallization risk of each family member (n ) 7). We clearly verified by probability calculations of the existence of the two risk groups within the family and showed that one of the siblings of the youngest generation may have inherited the stone-formation risk from its paternal relatives as this person clearly reflects a high risk pattern. INTRODUCTION Pathological crystal formation in the urinary tract is the result of a complex interplay of a number of different physicochemical and biochemical processes; at least one of which must be dysfunctional. A wealth of reasons exist for such a dysfunction. Apart from environmental and acquired (and anatomic) risk factors, a person’s hereditary predisposi- tion may have a distinct influence on the probability of suffering from urolithiasis. In the case of a genetically caused nephrolithiasis, the genetic defect is often transmitted from the parents to their children. 1-2 In around two-thirds of all stone-formers a metabolic disorder can be diagnosed. The other fraction, the so-called idiopathic stone-formers, show concentrations of the lithogenic substances in both blood and urine, 3 which fall within the normal range. Focusing on the most common type of urinary calculi, the salts calcium-oxalate-monohydrate (whewellite) and calcium- oxalate-dihydrate (weddellite), the main risk factors associ- ated with formation are hypercalciuria, hyperoxaluria, and hypocitraturia. These phenomena increase with high impact urinary supersaturation in relation to CaOx. For each of these general factors, a number of subgroups indicating the different origins which are involved in the particular pathogenesis can be distinguished. 4,5 Evidence suggests that, in some subgroups, genetic disorders contribute to the development of urolithiasis through a complex interplay with environmental factors. Only a few of the manifestations are caused by a monogenetic defect; they represent, without exception, severe symptoms with very low prevalence. 6-9 Most types of CaOx stone disease are due to a polygenetic etiology; 10,11 however, in these cases the genetic predisposi- tion alone is not sufficient to cause pathological urinary stone-formation. It is mostly a polygenetic defect in com- bination with unfavorable environmental factors which results in real disease. Idiopathic hypercalciuria, the most common reason for the pathological formation of calcium salts, has been described as reflecting a polygenetic autosomal domi- nant trait 10,12,13 affecting both sexes equally. Comprehensive surveys of this topic have recently been published by Goodman et al. (1995) 10 and Baggio (1999); 14 the latter points to the work still required in order to understand the pathogenesis of nephrolithiasis in detail. In this study, the members of three generations of the same family, from which only the paternal line is affected by a recurrent CaOx-stone disease, were tested for their individual risk to actually form CaOx-stones. The members of the youngest generation are still regarded as “clinically healthy”. The scope of this work is to investigate with examples the CaOx-crystallization risk of the family members and to evaluate whether the paternal line’s risk can also be traced to the youngest generation. In a comparative study we quantified the urinary CaOx crystallization risk of test persons based on both the BONN-Risk-Index approach (BRI) 15 and the value of the urinary relative CaOx-super- saturation (RS CaOx ) computed by the EQUIL-program. 16-18 If an increased formation risk is assigned to the youngest generation, prophylactic measures to protect them from stone formation in the future should be taken. MATERIAL AND METHODS Seven persons representing three generations of a family were tested for their actual risk of forming calcium oxalate crystals. All persons were highly motivated and showed a high compliance. Figure 1 illustrates the family relationship, the individual persons’ status with respect to urolithiasis, and shows the * Corresponding author phone: ++49 (0)228 287 9106; fax: ++49 (0)228 287 6344; e-mail: norbert.laube@ukb.uni-bonn.de. Corresponding author address: Klinik und Poliklinik fu ¨r Urologie, Experimentelle Urologie, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany. ² Division of Experimental Urology, Department of Urology, Bonn University. ‡ Geodynamics and Physics of the Lithosphere, Bonn University. 633 J. Chem. Inf. Comput. Sci. 2002, 42, 633-639 10.1021/ci0102620 CCC: $22.00 © 2002 American Chemical Society Published on Web 04/26/2002