Untersuchungen zur Bestimmung und Verteilung des Calciumoxalat-Harnsteinbildungsrisikos innerhalb dreier Generationen einer Familie

Neben umweltbedingten und erworbenen Risikofaktoren kann, wie bereits mehrfach vermutet wurde, auch die genetische Prädisposition einer Person einen entscheidenden Einfluss auf die Wahrscheinlichkeit der Ausbildung einer Urolithiasis haben. Allerdings steht erst seit kurzem mit dem BONN-Risk-Index eine geeignete Methode zur Verfügung, mit der in einem Screening bei mehreren Familienmitgliedern eines Steinbildners das individuelle Steinbildungsrisiko bestimmt werden kann. Mit dieser Methode wurde hier erstmals die Vererbung dieser Disposition am Beispiel einer Familie untersucht. In dieser Familie leidet die väterliche Seite (Großvater und Vater) seit mindestens zwei Generationen unter Calciumoxalat (CaOx)-Urolithiasis, während von der mütterlichen Seite und der jüngsten Generation keine Fälle bekannt waren. Insgesamt wurden von sieben Personen aus drei Generationen der Familie Urin und Blut auf für die Ausbildung einer Urolithiasis relevante Parameter analysiert. Die erhaltenen umfangreichen Daten dienten als Basis für die Ermittlung des individuellen Kristallisationsrisikos der einzelnen Personen mit Hilfe des BONN-Risk-Index und zusätzlich des Computerprogramms EQUIL. Es konnte gezeigt werden, dass alle Personen jeweils einer von zwei Gruppen mit sehr unterschiedlichem Risikoniveau zuzuordnen sind und dass eine der Personen der jüngsten Generation ein bisher nicht erkanntes stark erhöhtes Risiko für eine Harnsteinbildung geerbt hat. Daraufhin durchgeführte Ultraschalluntersuchungen der Nieren bestätigten den Verdacht. Damit erwies sich das mit relativ geringem Aufwand durchzuführende Verfahren BONN-Risk-Index als gut geeignet für die Identifizierung eines erhöhten CaOx-Urolithiasis-Risikos, insbesondere auch für Mitglieder einer Familie mit genetischer Prädisposition.Apart from environmental and acquired risk factors, a person's genetic predisposition - as supposed before - may play an important part on the probability of the onset of urolithiasis. However only with the recently developed BONN-Risk-Index there is now availability of an appropriate method to screen family members of a person suffering from urolithiasis in order to determine the individual crystallization risk of each one. For the first time the inheritance of this predisposition was examined by using this method with a certain family. The paternal line in this family 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. Therefore we analysed parameters in blood and urine, which were relevant with respect to urolithiasis, of seven persons belonging to three generations of the family. The BONN-Risk-Index and the computer program EQUIL were applied on the extensive data in order to determine the individual crystallization risk of each family member. We clearly verified the existence of two groups of different risk within the family and showed that one of the siblings of the youngest generation has inherited a high risk for stone formation which was unknown until now. Therefore we performed ultrasound examinations of the kidneys which confirmed our assumption. In conclusion the BONN-Risk-Index was shown to be an appropriate method, which is performed without high efforts, to identify an increased risk for CaOx-Urolithiasis generally and especially for persons within families possessing a genetic predisposition

Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

Background: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. Design: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Results: Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. Conclusions: This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified

Metabolic diagnosis and medical prevention of calcium nephrolithiasis and its systemic manifestations: a consensus statement

Background: Recently published guidelines on the medical management of renal stone disease did not address relevant topics in the field of idiopathic calcium nephrolithiasis, which are important also for clinical research. Design: A steering committee identified 27 questions, which were proposed to a faculty of 44 experts in nephrolithiasis and allied fields. A systematic review of the literature was conducted and 5216 potentially relevant articles were selected; from these, 407 articles were deemed to provide useful scientific information. The Faculty, divided into working groups, analysed the relevant literature. Preliminary statements developed by each group were exhaustively discussed in plenary sessions and approved. Results: Statements were developed to inform clinicians on the identification of secondary forms of calcium nephrolithiasis and systemic complications; on the definition of idiopathic calcium nephrolithiasis; on the use of urinary tests of crystallization and of surgical observations during stone treatment in the management of these patients; on the identification of patients warranting preventive measures; on the role of fluid and nutritional measures and of drugs to prevent recurrent episodes of stones; and finally, on the cooperation between the urologist and nephrologist in the renal stone patients. Conclusions: This document has addressed idiopathic calcium nephrolithiasis from the perspective of a disease that can associate with systemic disorders, emphasizing the interplay needed between urologists and nephrologists. It is complementary to the American Urological Association and European Association of Urology guidelines. Future areas for research are identified.info:eu-repo/semantics/publishedVersio

Studies of genetic, gastrointestinal, renal and dietary factors in white and black South African subjects as a possible key to understanding the relative absence of calcium oxalate kidney stone disease in the black population

The incidence of urolithiasis in South Africa's black population is extremely rare «1%) while in the white population it is similar to that of western countries (-15%). The present thesis was aimed at shedding more light on the complex nature of the physicochemical, biochemical and physiological mechanisms in black South Africans which provide this group with a natural protection against urolithiasis in contrast to their white compatriots. Four studies comprise this thesis

Investigation of the in vitro and in vivo effects of some herbal preparations on risk factors for calcium oxalate kidney stone disease

Includes bibliographical references.Several herbal preparations (Folium pyrrosiae , Desmodium styracifolium, Hylocereus trigonus, Phyllanthus niruri, Orthosiphon stamineus and Cystone®) were investigated as potential therapeutic and prophylactic agents for kidney stone disease. These studies were executed in the context of the existence of a virtually stone-free (black) and a stone-prone (white) population group in South Africa, with a view of establishing whether their respective renal responses are different. The independent in vitro effects of six plant extracts were tested on the crystallization characteristics of calcium oxalate (CaOx), the predominant stone-forming salt in urine. These investigations were performed in synthetic urine and real urine collected from healthy black and white South African males and the following parameters were assessed: urine composition; CaOx metastable limit; particle size-volume distribution; 14 [C]-oxalate deposition kinetics; CaOx crystal nucleation, aggregation and growth kinetics; examination of crystalluria by scanning electron microscopy and calculation of various physicochemical risk indices (Bonn Risk Index, Tiselius Risk Index and the relative urinary supersaturation of several stone-forming salts). All plant extracts inhibited one or more of the crystallization processes. Furthermore, crystal-cell binding, another risk factor for stone formation, was investigated in the presence of plant extracts. Madin-Darby canine kidney (MDCK)-I cells were used for this experiment. Crystals (inorganic and urinary) were bound to cells incubated in both aqueous media and real urine. Results showed that plant extracts reduced crystal binding under some but not all conditions. One of the extracts (Folium pyrrosiae) was administered to healthy South African black (n=9) and white (n=9) males in a double-blind placebo-controlled study. No significant effects on urine chemistry were found and there were no significant differences between the race groups post- treatment. Compounds from this herb were isolated and purified by the use of sequential liquid-liquid extractions and gel-permeation chromatography. A novel compound, 5 - (3 -(5,5 -dihydroxy-3- oxopentyl)phenoxy)-2-hydroxy-5H-indene-6-carboxylic acid , was identified using mass spectrometry and nuclear magnetic resonance imaging spectroscopy. The findings in this thesis have contributed to the body of knowledge about kidney stone disease. It has been demonstrated that some herbal preparations may be potentially useful in treating and managing this disease, but further clinical testing is required prior to the implementation of such an approach

Studies of the effects of various lithogenic and antilithogenic dietry supplements on calcium oxalate kidney stone risk factors in South African black and white subjects

Includes bibliographical references.In South Africa, the incidence of urolithiasis in the white population occurs to the same extent as in other western societies. However, in the black population, this disease is extremely rare. Differences in the gastrointestinal and renal handling of several lithogenic and antilithogenic agents in the two ethnic groups have been reported, but the rarity of kidney stone disease in the black group remains a riddle. The studies described in this thesis were undertaken to address aspects of this phenomenon. Carbohydrate and oxalate-containing dietary agents were identified as being of interest since surveys have paradoxically demonstrated that the consumption of these potentially lithogenic substances is significantly higher in the black group. The carbohydrates selected for study were glucose, sorbitol and xylitol, while the oxalatecontaining agents were rhubarb, spinach and an aqueous solution of sodium oxalate itself. Finally, taurine, which has been shown to reduce urinary glycolate and oxalate in animal models, was also selected for investigation in the two population groups. In all studies, similar protocols were adopted. These were approved by the Research and Ethics Committee of the University of Cape Town

Crystallization of calcium oxalate on molecularly imprinted polymer surfaces

Bibliography: leaves 100-114.Calcium oxalate (CaOx) is the most common component of human kidney stones. Heterogeneous nucleation is regarded as the key mechanism in this process. As such, crystallization of this substance has been studied in several different model systems. However, molecular imprinting has not been previously used in this field. In the present study, template crystals of calcium oxalate mono- and di-hydrate (COM and COD respectively) were used to imprint a copolymer of 6-methacrylamidohexanoic acid and divinylbenzene