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The chemical analysis of an urolith is often interpreted as "stone's composition". However, it must be taken into consideration, that in most cases, only a fragment of the stone has been sent to the laboratory. In some recurrent patients, stone compositions either vary considerably between episodes or the analytical result obtained from the stone fragment does not fit with the data of e.g. current 24 h-urinalysis or urinary pH-records. The question arises, whether this outcome may be the result of an improper stone sampling scheme. On a simple layered 2D-stone model composed of two mineral phases it is shown, how the choice of a stone fragment process may influence the result of "stone composition". Depending on the initial position of fragment within the whole stone, the respective calculated analyses can relevantly differ from the whole stone composition as well as strongly between two fragments. Even under the simplified conditions of a 2D-2-component-model "grown" under defined conditions, the differences between the analyses of the different specimens taken from a stone are in part remarkable. The more it can be argued that these differences increase if a real 3D-urolith is investigated. Further sampling biases may evolve and increase the problem of proper sampling:, e.g., if an urolith's more resistant parts remain intact while ESWL or laser-based stone fragmentation ("dusting"), the weak parts became fully disintegrated and removed from the body as fine-grained sludge-the stone's fine fraction is lost although its composition may carry important information on the stone's pathogenesis. Consequently, a "stone analysis" only obtained from the harder remains reveals an incomplete result, a fact that in principle limits its clinical interpretation. Choice of stone fragment is crucial. The extent of the uncertainty of an analysis resulting from potential selection biases should not be underestimated. Thus, sampling should be considered as an important part of the processes of quality assurance and management. Errors made at this early stage of diagnosis finding will affect the analytical result and thus influence the clarification of the underlying pathomechanism. This can lead to an improper metaphylactic strategy potentially causing recurrent stone formation which otherwise would have been prevented. A decision scheme for analysis of urinary stones removed using endoscopic methods is suggested.

A multitude of differently composed biomedical polymers has been researched for many years for their distinctive ease of production and wide range of applications. New technologies and new material characteristics have always evolved accordingly. The lumina of biomedical polymer tubes such as catheters, intravenous tubes, and biomedical microfluidic channels do not necessarily show the required biocompatibility and desired functionality. In such cases, the products are provided with additional inner liner or coatings to achieve the desired specific properties. Specific adjustments, for example, low friction coefficient, low gas diffusion resistance, wear resistance, and hydrophobicity, are key properties which are in focus for the improvement of biomedical surfaces. In this pilot study, a technical method was developed to deposit parylene-AF4 on the inner surface of silicone tubes with aspect ratios exceeding 78:1. Uncoated and parylene-AF4-coated silicone tubes were investigated in respect to the aforementioned physical properties. Compared to the uncoated tubes, the parylene-coated tubes showed superior quality with respect to friction coefficient, gas diffusivity as well as wear resistance. It could be demonstrated that the new technical approach is suitable to parylene-coat the inner surfaces of tubes with high aspect ratios thereby achieving conformal coatings.

Nach einer erfolgreichen Steinentfernung sind die Rezidivraten bei fehlender Metaphylaxe bedenklich hoch. Um eine effektive Rezidivprophylaxe einzuleiten, ist die individuelle ambulante Stoffwechselabklarung in Kombination mit Steinanalytik und Urindiagnostik derzeit die beste und kostengunstigste Methode.

The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on 24-hour urine collection. We studied whether the Bonn Risk Index could be measured in spot urine samples and which part of the day is most suitable for this purpose.We collected total and fractionated 24-hour urine (in a 6-hour nocturnal portion and 9 consecutive 2-hour diurnal samples) in 42 children and adolescents with calcium oxalate urolithiasis and 46 controls. Bonn Risk Index values determined from each of the urine fractions were compared to those obtained from related 24-hour urine collections.Both groups exhibited similar circadian patterns of Bonn Risk Index values. Median Bonn Risk Index for the nighttime portion of urine in the stone group was 1.4 times higher than that obtained from the total 24-hour urine. The morning hours between 08:00 and 10:00 showed the peak lithogenic risk, and this fraction had the highest sensitivity and selectivity regarding discrimination between stone formers and healthy subjects. The afternoon hours demonstrated lower and less fluctuating crystallization risk. Despite diurnal fluctuations in Bonn Risk Index, there was still a well-defined cutoff between the groups.Bonn Risk Index determined from urine samples collected between 08:00 and 10:00 appears optimal in separating stone formers from healthy subjects, and appears as useful as the value determined from 24-hour urine collection. Investigation of this diurnal sample simplifies diagnosis in pediatric stone disease without loss of clinical information.

Emotional stress is associated with e.g. increased hormone release, high blood-sugar level and blood pressure. Stress clearly affects metabolism. Whether chronic stress exposure leads to altered urinary compositions with increased risk of CaOx; urolithiasis was examined by investigating the relation between stress burden and urine composition. 29 controls (CG), 29 CaOx stone formers (SF), and 28 patients with chronic inflammatory bowel diseases (CIBD) were advised to avoid unfavorable aliment. Any urolithiasis-related medications were stopped. At day 5, a 24-h urine was collected and comprehensive urinalysis performed. AP (CaOx) index was calculated. Subjects completed a questionnaire designed to measure perceived stress ("Trier-Inventory-of-Chronic-Stress"). Mean AP (CaOx) in CG, SF and CIBD amount to 0.8 (+/-0.3), 1.2 (+/-0.7), and 1.9 (+/-1.2), respectively. Increased AP (CaOx) in SF is mainly attributed to an increased effect of calcium and oxalate, whereas in CIBD this is additionally caused by a reduced effect of citrate, magnesium and volume. Stress dimensions are correlated to any investigated urinary parameter with an absolute value of ror = 0.600; some correlations are statistically significant: whereas in SF only one combination, "lack of social recognition" versus calcium, shows significance, in CIBD various combinations are significantly related. In particular, sodium excretion increases with stress. In CG, some stress dimensions are directly related to citrate; with increasing stress, protection against CaOx crystallization tends to increase. It could be shown that stress load and urinary composition are related by statistical means. The observed metabolic stress response patterns in urinary compositions are different for the distinct groups, thereby, reflecting a conclusive picture. This is in particular in CIBD, for which a link between stress and inflammatory activity and between inflammatory activity and altered urinary composition is well established.

Purpose: The Bonn Risk Index has been used to evaluate the risk of urinary calcium oxalate stone formation. According to the original method, risk should be determined based on a 200 ml urine sample taken from a 24-hour collection. We evaluated whether the Bonn Risk Index can also be effectively determined in small urine samples. Materials and Methods: We studied 190 children and adolescents with nocturia and calcium oxalate urolithiasis. Initially Bonn Risk Index was determined according to the original method of Laube. Subsequently Bonn Risk Index was calculated using a computer program controlling a specially designed system to define the time point of induced crystallization based on consecutive urine samples of 1.5, 2.0 and 3.0 ml. Results: No significant differences were found in Bonn Risk Index between values obtained from 200 ml samples and those based on the micromethod with urine samples of 2 and 3 ml. Conclusions: Assessment of risk of urinary calcium oxalate stone formation with Bonn Risk Index in small urine volumes, based on prototype equipment controlled by specialized computer software, is comparable to the original method. This finding facilitates the procedure and improves Bonn Risk Index determination in children.

Urinary stone formation has been evolved to a widespread disease during the last years. The reason for the formation of urinary stones are little crystals, mostly composed of calcium oxalate, which are formed in human kidneys. The early diagnosis of the risk for urinary stone formation of patients can be determined by the “Bonn-Risk-Index” method based on the potentiometric detection of the Ca2+-ion concentration and an optical determination of the triggered crystallisation of calcium oxalate in unprocessed urine. In this work, miniaturised capacitive field-effect EMIS (electrolyte-membrane-insulator-semiconductor) sensors have been developed for the determination of the Ca2+-ion concentration in human native urine. The Ca2+-sensitive EMIS sensors have been systematically characterised by impedance spectroscopy, capacitance–voltage and constant–capacitance method in terms of sensitivity, signal stability and response time in both CaCl2 solutions and in native urine. The obtained results demonstrate the suitability of EMIS sensors for the measurement of the Ca2+-ion concentration in native urine of patients.

Der „klassische Infektstein“ Struvit bildet sich als Folge der Stoffwechselaktivitaten ureasepositiver Bakterien aus alkalischem Urin mit pH-Werten >7,5. Dank verbesserter Infektdiagnostik und antibiotischer Therapie ist in den westlichen Industrienationen, trotz steigender Gesamthaufigkeit der Urolithiasis, der Infektstein auf dem Ruckzug. Nicht selten ist der Struvit mit anderen Mineralphasen vergesellschaftet. Diese akzessorischen Mineralphasen konnen auf weitere, nicht infektassoziierte, Ursachen der Steinbildung hinweisen. Eine Analyse des Mineralisats ist daher immer angezeigt. Die Struvitsteine als auch die Struvitinkrustationen auf Harnwegsimplantaten sind durch ein schnelles Wachstum gekennzeichnet. Der mit dem raschen Wachstum verbundene Einschluss ureasepositiver Bakterien macht den sich im Korper befindlichen Stein zu einer standigen Quelle rezidivierender Harnwegsinfekte. Gemas der DGU-Leitlinien „Urolithiasis“ fuhrt die Diagnose „Infektstein“ zur Einordnung des Patienten in die Hochrisikogruppe. Eine komplette Steinsanierung bei Vermeidung des Zuruckbleibens jeglichen Debris und eine besondere Metaphylaxestrategie sind notig, um eine erfolgreiche Therapie einleiten zu konnen.

Formation of crystalline bacterial biofilms (encrustations) on urological implants remains a major complication in patient care. Recently, it was shown that amorphous carbon (a-C:H) coatings deposited on polyurethane (PU) stents provide a distinct reduction in biofilm formation with an effect more pronounced in-vivo than in-vitro. To investigate the underlying mechanisms, the influence of surface properties on the encrustation tendency of plasma coated and uncoated PU tubes was tested in an extended in-vitro model with protein-spiked artificial urine and urease. In the presence of albumin the formation of hollow crystalline spheres was observed mainly on uncoated PU. We suggest that evolving gas bubbles influence protein adherence and attachment of crystalline bacterial biofilm to the implant surfaces.

Purpose: Usually, hampered urine flow and failing of Seldinger technique leads to the explanation “obstructed ureteral stent” with no further clarification where exactly the obstructions are located. If stent obstruction is caused by intra-luminal biofilm and/or crystal deposits, the need of biofilm reducing coatings on the stent's inside has to be discussed. Materials and Methods: We investigated 59 stents from patients in whom acute hydronephrosis and/or acute pyelonephritis required stent replacement and/or usage of Seldinger technique failed. The stents were investigated by X-ray and, after longitudinal cutting, by light-microscopy for occurrence of obstructing material. Results: The inside of 25% of the samples was lined with a thick film composed of blood clots and tiny non-aggregated crystals. Only in these samples X-ray investigation showed a positive result for massive inner encrustations, which in fact may be responsible for stent occlusion. 48% of the stents contained few small domains composed of blood clots and crystals. 27% of the stent samples showed no alteration. Conclusions: 75% of the “obstructed” stents showed no significant inner deposits. Obstruction of urine transport and failure of Seldinger technique occurred due to other reasons. Thus, coating of the stent's inner surface may be overrated. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008

Ureteral stents are placed between kidney and bladder to ensure urine transport, e.g. in case of tumor-related obstruction. In-vitro and in-vivo studies on amorphous carbon (a-C:H) coated ureteral stents revealed significant reduction of biofilm formation, increasing complication-free indwelling times. Additionally, facile handling and less painful replacement procedure were reported. This study investigates the friction behavior of a-C:H coatings on ureteral stents as a possible cause for the observed advantages. Differently composed films were deposited on polyurethane tubes, using rf-PECVD with acetylene as the main precursor gas. The friction coefficients of the coatings were determined in an ex-vivo model using porcine liver as phantom material and saline solution as lubricant. Uncoated references, hospital-standard stents and a-C:H coated stents show comparable friction coefficients. Claimed benefits of commercially available hydrophilic stents suggest a strong influence of the surface wettability on the friction behavior. However, only small differences between the differently wettable a-C:H films were observed.

Biofilm formation on urological stents remains a major complication in patient care. The study focuses on the ability of different plasma-deposited amorphous carbon coatings (a-C:H) to inhibit encrustation and to reduce implant-related side effects. Film forming particle flux was controlled by variation of precursor gases, pressure and RF-power resulting in different electrochemical and topological surface properties. Optical contact angle measurements were performed to determine the surface free energies of the films. Investigations on crystal adhesion and biofilm formation were performed in vitro and in vivo. Encrustation tendency was remarkably reduced by a-C:H. Compared to commercial stents, the indwelling time could be distinctly prolonged as the implanted stents remained biofilm-free.

Background Current discussions about biofilm formation focus on the solid/liquid interface between a medical device and body fluids. Yet it has been shown that gas bubbles (GB) can stably form on ureteral stents in artificial urine and that their fate depends on the stent's surface properties. The liquid/gas interface constitutes an adhesion site for precipitating salts as well as hydrophobic organic molecules. Materials and methods The surface wettability of polyurethane stents is varied by coating with amorphous hydrogenated carbon (a-C:H). GB and crystalline biofilm formation on the stents are investigated in a novel encrustation device which avoids gravitation- or sample-position-related influences on the results. Results Bigger and more stable GB form on hydrophobic stents than on hydrophilic, coated stents. Appearance and amount of crystalline deposits differ significantly between the surfaces. With decreasing wettability the number of hollow crystalline spheres and the mass of precipitate increase. Conclusions On hydrophobic surfaces, stable GB increase precipitation of salts and become incorporated in the growing encrustation layer in vitro. In contrast, GB quickly lift off from hydrophilic surfaces taking part of the precipitate with them. This self-cleaning mechanism slows down the encrustation process. A similar effect may explain the prolonged complication-free indwelling time of amorphous-carbon coated stents in vivo.

Purpose Placement of ureteral stents (DJ-stents) may lead to complications. Inappropriate friction properties of the implant are, inter alia, made responsible for primary injuries, injury-related inflammation and a cascade of consecutive side effects. Hydrophilicity is considered to be related to low friction. The question arises, whether the various products on the market show their respective maximum hydrophilicity directly after unwrapping or a pre-use moistening, as already routinely done with the guide wire, is necessary. Methods The surface wettability of commercial and experimental DJ-stents was determined by water contact angle (WCA) measurements using the sessile drop method. One reference surface and 11 different stent surface types were tested. In order to determine the influence of moistening on the stents’ surface wettability, WCAs were measured twice, with dry, and soaked (30 min, 0.9%-NaCl) specimens. Each sample of a surface type was tested at three different positions to avoid effects of surface heterogeneities. Up to six samples of the same surface type were examined. Results Mean WCAs on fresh and soaked stent surfaces ranged from 75°–103° and 71°–99°. In every case the WCAs on soaked surfaces were lower. On average the WCAs decrease by 7%, the individual decreases differ considerably, from 2 to 16%. For 7/12 of the examined surface types, the decrease in contact angle is statistically significant with p ≤ 0.01. Conclusions DJ-stents freshly unwrapped show less hydrophilic properties compared to DJ-stents soaked in saline. To obtain maximum hydrophilicity at stent placement, DJ-stents should be soaked. The results may advocate a similar approach for other urological equipment.

In the year 2006 urolithiasis was second only to diseases of the prostate as the most frequent diagnosis at urological centers in Germany (1). Urinary stones are polycrystalline concretions occurring in the urinary tract of humans and animals. Like bones and teeth, they are biominerals. While the non-pathological products of biomineralization, formed in genetically determined processes, display a high degree of biological organization, uroliths are a special case. Their formation is governed by pathoanatomical and physicochemical factors (2). Around 97% of urinary stones are found in the kidneys and ureters (kidney stones), the remaining 3% in the urinary bladder and urethra (3). Urinary stones can range in size from micrometers to several centimeters in diameter. They frequently remain unnoticed for long periods before manifesting themselves—often very painfully—or being discovered incidentally on radiography or ultrasound (Figure 1). Figure 1 Starting with pathological processes in the formation of urine, mineralization can occur as high as the renal tubule (a). Crystals just a few micrometers in diameter form further downstream in the urinary tract, preferentially attaching themselves to ... Urinary stones are a symptom of exo- and endogenous factors and are usually of multifactorial origin. Natural passing or surgical removal of the stone does not eliminate the cause, and many patients suffer recurrences (4). Owing to the etiological diversity of urinary stones, many different compositions are found. Calcium oxalate (whewellite, weddellite; prevalence >80%), calcium phosphate (carbonate apatite, 5%), magnesium ammonium phosphate (“infectious stones”; struvite, 5%), and uric acid (13%) are the most commonly occurring biominerals, while cystine, ammonium urate, and brushite are rare (all ≤1%) (5, 6). Changes in lifestyle and improvements in diagnosis have led to growing prevalence and incidence of urinary stones. In Germany, a nationwide survey showed an increase in both incidence (from 0.54% to 1.47%) and prevalence (from 4.0% to 4.7%) between 1979 and 2001 (4). Urolithiasis is thus a widespread disease. Fifty percent of patients suffer at least one recurrence, and 10 to 20% experience three or more further episodes of urolithiasis (4, 6). Prevalence of 12% has been reported in the USA (6). Affluence-related urolithiasis is also on the increase in the emerging economies, due among other reasons to highly calorific diets combined with low levels of exercise. As early as the 12thcentury, Hildegard of Bingen (1098–1179) recognized the connection between rich meals, wine, and urinary stones and urged her contemporaries to modify their diets accordingly (7, 8). In the year 2000, 9.7% of German men but only 5.9% of German women in the age group 50 to 64 years had experienced an episode of urolithiasis. In the past two decades the incidence has risen predominantly between the ages of 40 and 49 years (4, 6, 9). There are differences in sex distribution and among different regions of Germany: uric acid stones are more common in the eastern and southern states, infectious stones in the east of the country (9). Calcium phosphate stones are demonstrated more often in younger patients, while uric acid stones and stones with atypical compositions are more frequent in older individuals (10). Occupation can be a risk factor: among other professions, the risk is elevated in physicians—particularly surgeons (11). Poor fluid balance is one of the factors responsible. The essential factors accounting for variations in the prevalence of urolithiasis include dietary habits, climate, environment, ethnicity, and heredity (Figure 2). Figure 2 The so-called stone belt (red) extends all the way around the world and is characterized by urinary stone prevalence of 10 to 15%. Exogenic risk factors such as nutritional patterns and lifestyles characterized by low levels of physical activity combined with high energy intake from food rich in fats, proteins, carbohydrates, and purines (13, 14) are growing in importance, as are smoking, alcohol abuse, and chronic stress (15). Increasing incidence and prevalence of urolithiasis is therefore expected, especially in Europe and the USA (7).

Although urolithiasis is common in spinal cord injury patients, it is presumed that the predisposing factors for urinary stones in spinal cord injury patients are immobilization-induced hypercalciuria in the initial period after spinal injury and, in later stages, urine infection by urease-producing micro-organisms, e.g.,Proteussp., which cause struvite stones. We describe a patient who sustained C-7 complete tetraplegia in a road traffic accident in 1970, when he was 16 years old. Left ureterolithotomy was performed in 1971 followed by left nephrectomy in 1972. Probably due to adhesions, this patient developed volvulus of the intestine in 1974. As he had complete tetraplegia, he did not feel pain in the abdomen and there was a delay in the diagnosis of volvulus, which led to ischemia of a large segment of the small bowel. All but 1 ft of jejunum and 1 ft of ileum were resected leaving the large bowel intact. In 1998, suprapubic cystostomy was performed. In 2004, this patient developed calculus in the solitary right kidney. Complete stone clearance was achieved by extracorporeal shock wave lithotripsy. Stone analysis: calcium oxalate 60% and calcium phosphate 40%. Metabolic evaluation revealed hyperoxaluria, hypocitraturia, and hypomagnesiuria. Since this patient had hyperoxaluria, the stool was tested forOxalobacter formigenes, a specific oxalate-degrading, anerobic bacterium inhabiting the gastrointestinal tracts of humans; absence of this bacterium appears to be a risk factor for development of hyperoxaluria and, subsequently, calcium oxalate kidney stone disease. DNA from the stool was extracted using the QIAamp DNA stool Mini Kit (Qiagen, Chatsworth, CA). The genomic DNA was amplified by polymerase chain reaction using specific primers for oxc gene (developed by Sidhu and associates). The stool sample tested negative forO. formigenes. The patient was prescribed potassium citrate mixture; he was advised to avoid oxalate-rich food, maintain recommended levels of calcium in his diet, and take live bio-yogurt. Two months later, 24-h urinary oxalate decreased from 0.618 to 0.411 mmol/day; 24-h urine citrate increased from 0.58 to 1.10 mmol/day. Six months later, an oxalate absorption test was performed. The patient swallowed a capsule, soluble in gastric juice, containing 50 mg (0.37 mmol) sodium [13C2]oxalate corresponding to 33.8 mg of [13C2]oxalic acid. The amount of labeled oxalate, excreted in urine, was measured by a gas chromatographic-mass spectrometric assay. Oxalate absorption, expressed as the percentage of the labeled dose recovered in the 24-h urine after dosing, was 8.3% (reference range: 2.3–17.5%). In addition to other conventional measures, oral administration ofO. formigenesor lactic acid bacteria mixture to promote bacterial degradation of oxalate in the gut, and thus combat hyperoxaluria, may play a role in prevention of calcium oxalate kidney stones.

Despite hyperoxalurogenic eating habits relative to white subjects, South African blacks have urinary oxalate excretions, Tiselius risk indices (AP(CaOx)) and calcium oxalate saturations, which do not differ significantly from those of their white counterparts. The present study was undertaken to establish whether the BONN-Risk-Index (BRI) might discriminate between the urines of the two population groups and whether differences might exist in their respective gastrointestinal absorption rates of oxalate. Participants (n = 15 in each group) provided 24 h urines on their free diets for BRI determination. Gastrointestinal oxalate absorption was measured using the [13C2]oxalate absorption test. Results showed that BRI values were significantly lower in black subjects (2.04 vs 4.90, P = 0.034), but that there was no difference in the oxalate absorption between the groups (10.30 vs 9.95%, P = 0.87). These results suggest that South African black subjects handle dietary oxalate more efficaciously than white subjects and that this occurs via some endogenous mechanism, which has not yet been identified or characterized.

Calcium-oxalate crystal deposition in kidney transplant biopsy specimen led us to investigate the impact of calcineurin inhibitor treatment on urinary excretion of lithogenic and stone inhibitory substances in 53 children after successful kidney transplantation (KTx) receiving cyclosporine A (CsA) or tacrolimus. We compared the values obtained with those of 12 patients with recurrent nephrotic syndrome under CsA and of 6 patients with Rasmussen encephalitis (RE) under tacrolimus therapy. Renal ultrasound examinations were repeatedly performed. Hypocitraturia was found in 69% of patients, with KTx patients having a significantly lower urinary citrate excretion than those receiving calcineurin inhibitors for other reasons. Secondly, we found hyperoxaluria in 35% of patients, again especially in those after KTx. No significant difference in urinary substances was seen comparing CsA with tacrolimus treatment. Urolithiasis was found in one and calcium-oxalate crystal deposition in biopsy specimen of three KTx patients. Calcineurin inhibitor treatment can lead to significant hypocitraturia, especially in patients after KTx receiving the highest dose of medication. Hyperoxaluria is primarily the result of a removal of significant body oxalate stores, deposited during dialysis, but may not be suspected as a specific side effect of calcineurin inhibitor therapy. Both findings can increase the risk for urolithiasis or nephrocalcinosis.

Recently, we showed that urine flowing past growing stone material on its way through the urinary tract becomes systematically depleted of its lithogenic substances (1). This effect can be large enough to be clinically relevant (2). However, only the altered urine can be assessed by urine collection, which leads to a urinalysis that does not sufficiently reflect the patient’s true metabolic status. The excessively low concentrations and excretion values of the lithogenic urinary constituents may lead to “optimistic” misinterpretation of the patient’s actual health status and overestimation of treatment success. Apart from geometric and physiologic simplifications, the previously used model assumes that the differential volume function of the kidneys amounts to 50%. Consequently, both the stone-free and the stone-forming kidney contribute equally to the total urine volume. However, even in healthy individuals, the differential function varies by ±6%. Parenchymal defects, such as tumors, renal arteriopathy, and posttraumatic failures, or morphologic abnormalities, such as pyeloureteral junction stenosis and vesico-ureteral-renal reflux, can lead to a dramatic decrease in renal function, causing a reduction in the glomerular filtration rate. Patients suffering from these diseases often present with calcium nephrolithiasis and proteinuria, occasionally with progression to nephrocalcinosis, urinary concentrating defects, and renal insufficiency caused by tubular atrophy, intestinal fibrosis, and glomerulosclerosis. The process of kidney stone formation follows fundamental physical principles such as mass conservation. In a recently introduced model (1), we evaluated the influence of in vivo-growing uroliths on urinary composition. The material from which the stones are formed originates completely from the urine streaming through the kidneys; therefore, the urinary concentrations of the lithogenic components, such as calcium and oxalate, in the excreted urine must be depleted by the mass deposited in the stone(s). As long as no method exists to measure those concentrations in vivo, mathematical models describing the depletion process …

Objectives: Based on a recently introduced mathematical model approach we show that uroliths located in the urinary tract (UT) can substantially deplete the urinary concentrations of lithogenic constituents by continuous growth. Methods: To illustrate the influence of the urinary depletion effect on urinalysis, a "typical" calcium oxalate (CaOx) stone former, presently not stone-free, was investigated. Serum and urine samples were analyzed. Several metabolic tests were performed. Crystallization risk according to the BONN-Risk-Index (BRI) and the relative supersaturation in respect to CaOx (RS CaOx ) were determined. X-ray films taken before and after a period of six months were evaluated in order to estimate stone size and average stone growth rate taken place within that period. Results: Regarding CaOx urolithiasis the urine samples show a pathologically altered pH, a low 24h-citric acid excretion, and a low 24h-urine volume. Neither calcium nor oxalate excretion data reflect values indicating these substances as risk factors. However, BRI and RS CaOx reflect a high crystallization risk. The patient's intestinal oxalate absorption is high. Applying the depletion model, the patient's 24h-urine composition shifts from normooxaluric to hyperoxaluric. Conclusion: In the patient, a hitherto undetected hyperoxaluria is diagnosed when in-vivo stone growth is taken into account. This is a clear indication that the metabolic status can only be evaluated correctly in "stone-free" patients. Any stone material present in the UT must be considered in urinalysis interpretation as the stone-related urinary depletion effect is of high clinical relevance. A helpful nomogram is presented, allowing the estimation of the extent of urinary depletion caused by CaOx uroliths.

Secondary hyperoxaluria is due either to increased intestinal oxalate absorption or to excessive dietary oxalate intake. Certain intestinal diseases like short bowel syndrome, chronic inflammatory bowel disease or cystic fibrosis and other malabsorption syndromes are known to increase the risk of secondary hyperoxaluria. Although the urinary oxalate excretion is usually lower than in primary hyperoxaluria, it may still lead to significant morbidity by recurrent urolithiasis or progressive nephrocalcinosis. A clear distinction between primary and secondary hyperoxalurias is important. As correct classification may be difficult, appropriate diagnostic tools are needed to delineate the metabolic background as a basis for optimal treatment. We developed an individual approach for the evaluation of patients with suspected secondary hyperoxaluria. First, 24 h urines are examined repeatedly for lithogenic (e.g. calcium, oxalate, uric acid) and stone-inhibitory (e.g. citrate, magnesium) substances, and the patients are asked to fill in a dietary survey form. Urinary saturation is calculated using the computer based program EQUIL2, and the BONN-Risk-index is determined. The measurement of plasma oxalate and of urinary glycolate helps to distinguish between primary and secondary hyperoxalurias. If secondary hyperoxaluria is suspected, the stool is examined for Oxalobacter formigenes, an intestinal oxalate degrading bacterium, as lack or absence may lead to increased intestinal oxalate absorption. The last diagnostic step is to study the intestinal oxalate absorption using [13C2]oxalate. Depending on the results, various therapeutic options are available: 1) a diet low in oxalate, but normal or high in calcium, 2) a high fluid intake (>1.5 L/m2/d), 3) medications to increase the urinary solubility, 4) specific therapeutic measures in patients with malabsorption syndromes, depending on the underlying pathology, and 5) intestinal recolonization of Oxalobacter formigenes or the treatment with other oxalate degrading bacteria.

In order to distinguish between normocitraturia and hypocitraturia, the 24 h urine excretion value of citric acid is evaluated in relation to the established limit value of 2.5 mmol/day. We propose changing this widely-used excretion value to a "minimum contribution" of citric acid to the total urine's ionic strength, since the inhibitory effect of citric acid on crystallization depends on citrate anions being available to complex calcium ions or to associate with the crystal surface. A total of 71424 h-urine samples, taken from 74 healthy persons and 58 calcium stone formers, were investigated for pH, citric acid concentration ([CA]), and related relative calcium oxalate supersaturation (RS). Based on the Henderson-Hasselbalch-equation, the individual concentrations of the differently charged citrate anion species in each of the urines were calculated from the urinary pH and [CA]. From the anion concentrations determined, the contribution of the urine's citric acid to the total urine's ionic strength, ISCA, was calculated. Referring to the limit value of 2.5 mmol/day and assuming an average urine volume of 1.5 l/day, a hypothetical concentration limit of 1.67 mmol/l can be obtained. Grouping the samples into "stone-formers" and "non-stone-formers" as well as into three different ranges of RS revealed: (1). that the groups' median [CA]-values were below 1.67 mmol/l, and (2). that [CA] was not inversely associated with the risk of stone formation. Within the pH-range of 5 and 7, the ISCA-values which are related to, for example, [CA]=1.67 mmol/l, vary considerably by a factor of nearly three between 2.48 mmol/l and 6.64 mmol/l. The use of a fixed citric acid excretion level for the distinction of normocitraturia from hypocitraturia does not take into account the different citrate species which actually modify the urine's crystallization behaviour. The proposed ISCA approach takes this fact into consideration. From this parameter, a desirable "minimum impact of citric acid" can be derived. In a first approach, a potential ISCA-limit value, which currently distinguishes between urines indicated by a "normo-protective" impact and those indicated by a "hypo-protective" impact with respect to calcium oxalate precipitation, may be set at 2.48 mmol/l.

Crystal formation reflects the entire composition of the surrounding solution. In case of urolithiasis, induced crystal formation in native urine has led to the development of the Bonn-Risk-Index (BRI), a valuable tool to quantify an individual's risk of calcium oxalate urolithiasis. If the progression of a disease is associated with characteristic changes in the activities of urinary components, this leads to an altered urinary crystallisation capacity. Therefore, the results of induced urinary crystal formation can be used to detect and monitor any disease linked to the altered urinary composition. Since crystal formation inherently takes into account the entire urinary composition, the influence of the disease on individual urinary parameters does not have to be known in order to monitor the consequent pathologic alterations. In this paper, we review the background of urinary crystal formation analysis and describe its established application in urolithiasis monitoring as well as potential further fields of clinical application.

The prevalence of urolithiasis in Germany is 4.7%; its incidence has trebled in the last three decades. The risk of recurrence is 50-80%, depending on the type of stone, unless secondary prevention is instituted. Risk-adapted secondary prevention lowers this risk to 10-15%.This review is based on publications retrieved by a selective search in PubMed using the key words "urolithiasis," "urinary stones," "epidemiology," "lithogenesis," "biominerals," "risk factors," and "diagnosis, therapy, metaphylaxis." These publications were evaluated with the aid of the urolithiasis guideline of the European Association of Urology.Acute renal colic can usually be diagnosed without sophisticated equipment. Stones can be dealt with by a variety of techniques depending on their size and location, including extracorporeal shock-wave lithotripsy, ureterorenoscopy, percutaneous nephrolitholapaxy, and open surgery. Most ureteric stones of diameter up to 5 mm pass spontaneously. 75% of patients have no complications. The basic evaluation needed for secondary prevention can be carried out by any physician on an ambulatory basis. In the 25% of patients who have complications, a more extensive interdisciplinary evaluation of metabolic parameters should be performed in a clinical center for urinary stones.Urolithiasis has many causes and can be treated in many different ways. An extensive metabolic work-up is often necessary for secondary prevention. The various treatment options must be considered for their suitability in each individual patient. Robust data are now available on surgical and interventional methods, but there are as yet no high-quality trials of secondary prevention. Further research should concentrate on the etiology and pathogenesis of urolithiasis.

The mechanisms for the formation of calcium oxalate kidney stones are not well understood. In our urological basic research study, ammonium oxalate was added to sample solutions of CaCl 2 and to artificial urines to induce the formation of calcium oxalate crystals, the most common crystals in the urinary tract. Using an in-line laser-probe we took real-time readings (4 min intervals) of the PSD evolution of particles ranging in size between 0.5 and 250 μm over a period of 1 h. Most particles were between 0.5 and 14 μm in size. The particle-size mode is approximately 2 μm. The time-dependent PSD development depends on the composition of the solution. The in-line laser-probe permits individual analysis of minute particles which fall below the lower coulter counter detection limit. As these particles form the basis of all further processes which alter the particle size, they are of paramount interest in urinary stone research.

In previous papers we introduced the Bonn-Risk Index (BRI) as a new method of evaluating an individual's actual risk of forming calcium oxalate (CaOx). A comparison of our results with the calculated urinary relative supersaturations (RS) with respect to CaOx, showed that samples with similar values of RS can have different values of BRI. We suggested that this may reflect the individual influence of the urinary macromolecular constituents which are not taken into account at the calculation of RS. To estimate the role of macromolecules on the value of BRI, we examined 45 unprepared 24-h urine samples from 24 persons (16 healthy subjects, eight CaOx stone-formers) with respect to BRI, RS, and the concentration of urinary Tamm-Horsfall-protein ([THP]). The crystallization experiments were carried out by the use of a laser-probe. Based on the data of BRI and RS, the effect of THP may shift from a minor promoter in stone-formers and persons "at risk", to an inert urinary constituent in healthy subjects and persons "without risk". However, the observed effects are small and at least in the latter group close to zero.

Am Anfang einer rationellen und erfolgreichen Steinmetaphylaxe steht neben laboranalytischen Untersuchungen von Urin- und Steinproben die ausfuhrliche Anamnese des Patienten. Der Einsatz eines strukturierten Fragebogens erleichtert es hierbei, alle relevanten Risikofaktoren der Steingenese in uberschaubarem Zeitrahmen zu erfassen. Der „Anamnesebogen Harnstein-Vorsorge”, den das Deutsche Harnsteinzentrum entwickelt hat und nun seit einem Jahr einsetzt, hat sich als hilfreiches Instrument erwiesen.

Die zur palliativen Harnableitung eingesetzten Doppel-J-Stents weisen haufig schon nach kurzer Liegezeit starke Inkrustationen auf. Trotz vielfaltiger materialwissenschaftlicher Ansatze konnte die Komplikationsrate nicht merklich gesenkt werden. Im Rahmen eines vom BMBF geforderten interdisziplinaren und translationalen Projekts werden Oberflachen handelsublicher Materialien mit plasmadeponierten amorphen Kohlenstoffschichten so modifiziert, dass sie in vitro deutlich verminderte Inkrustationstendenzen zeigen. Heilversuche mit entsprechend beschichteten Doppel-J-Stents zeigen eine Verstarkung des Effekts in vivo. Die zugrunde liegenden Mechanismen werden derzeit in einem erweiterten In-vitro-Modell untersucht.

Geochemical studies have been conducted on the Waratah Fault Zone, a steep, NE-SW-trending brittle fault zone in the southeastern Lachlan Fold Belt, Australia. Strike-slip movement along the fault juxtaposed an Early Devonian turbidite sequence (Liptrap Formation) against heavily veined Early Devonian limestones. The fault zone consists of the faulted Liptrap Formation and faulted limestones, and a fault core composed of a fault-melange zone and strongly brecciated limestones. The fault zone records extensive mineralogical and stable isotope alteration within the deformed turbidites of the Liptrap Formation and within the limestone sequence. For the Liptrap Formation a volume loss of approximately 28% was calculated for the transition from unaltered sediments to the fault-melange zone. The volume loss in the limestone gouge is much higher (60%). The calculated fluid/rock ratios in the limestone sequence, are at least an order of magnitude lower than in the fault-melange zone. Stable isotopic and rare-earth elemental data document the infiltration of near-surface meteoric water, during brittle deformation and alteration of the fault zone. The interaction of fluids with contrasting lithologies led to different alteration processes affecting fault weakening and/or strengthening. The cyclic change between large-scale fluid infiltration due to brittle failure (open system) and fault rock cementation (closed system) may represent a combined conduit-barrier system in the limestone sequence. Within the Liptrap Formation, no cementation took place, as the conditions for quartz precipitation were unsuitable. Hence, the fault system remains open in respect to fluids (conduit system, only). Additionally, the "permanent" fluid infiltration dissolved silica and altered detrital feldspar, resulting in subsequent porosity increase within the fault-melange zone. Our results are consistent with investigations in modern accretionary complexes, where major decollements and subsidiary faults have been shown to be important fluid conduits.

Increased emotional stress in everyday life influences the way of living and metabolism of people living in developed countries. Contemporaneously, the incidence and prevalence of urolithiasis rises. Does a pathogenetically relevant relationship exist between chronic stress burden and permanently altered urinary composition? The influence of chronic stress burden on urine composition and risk of urinary calcium oxalate (CaOx) stone formation was, for the first time, comprehensively investigated in 29 healthy controls (CG), 29 idiopathic CaOx stone formers (SF) and 28 patients suffering from chronic inflammatory bowel disease (CIBD). After 4 days with standardized nutrition, 24-h urine was collected. Extensive urinalysis was performed and APCaOx index calculated. Evaluation of subjective stress level was carried out by using the standardized and well-established questionnaire Trierer Inventar zur Beurteilung von chronischem Stress (TICS). The concentration values of the urinary parameters as well as the APCaOx values were linearly correlated with the stress scores obtained from the different items of the TICS. A significance level p≤0.05 was considered to indicate statistical significance. The mean APCaOx indices amounted to 0.8±0.3 in CG, 1.2±0.7 in SF and 1.9±1.2 in CIBD. The increased APCaOx in SF mainly results from relatively increased Ca and oxalate excretions, whereas in CIBD this also results from reduced urinary excretions of citrate and Mg as well as reduced 24-h urinary volumes. The calculation of linear correlation coefficients between a TICS stress dimension and a concentration value of a urinary parameter or APCaOx results in r values not exceeding 0.600. However, some of these correlations are statistically highly significant. In SF only one combination with Ca was observed, while in CIBD in contrast a number of combinations, in particular including Na, was obtained. In CG direct statistical relationships between stress burden and citrate as well as Mg exist. In this group, increased stress burden is associated with increased inhibitory potential to prevent CaOx stone formation. In the investigated study groups, differently complex relationships between amount of stress burden and risk of CaOx stone formation were observed, however, without obvious physicochemical principle(s). In some individuals, stress can be associated with a significantly stress-related alteration of urinary composition towards increased CaOx stone formation risk. The results obtained from the CIBD group allow for the first time a conclusive link between emotional stress and inflammatory activity on the one hand and inflammatory activity and metabolic risk constellation of CaOx stone formation on the other hand

BACKGROUND Since its first publication in 2000, the BONN-Risk-Index (BRI) has been successfully used to determine the calcium oxalate (CaOx) crystallization risk from urine samples. To date, a BRI-measuring device, the "Urolizer", has been developed, operating automatically and requiring only a minimum of preparation. Two major objectives were pursued: determination of Urolizer precision, and determination of the influence of 24-h urine storage at moderate temperatures on BRI. METHODS 24-h urine samples from 52 CaOx stone-formers were collected. A total of 37 urine samples were used for the investigation of Urolizer precision by performing six independent BRI determinations in series. In total, 30 samples were taken for additional investigation of urine storability. Each sample was measured thrice: directly after collection, after 24-h storage at T=21 degrees C, and after 24-h cooling at T=4 degrees C. Outcomes were statistically tested for identity with regard to the immediately obtained results. RESULTS Repeat measurements for evaluation of Urolizer precision revealed statistical identity of data (p-0.05). 24-h storage of urine at both tested temperatures did not significantly affect BRI (p-0.05). CONCLUSIONS The pilot-run Urolizer shows high analytical reliability. The innovative analysis device may be especially suited for urologists specializing in urolithiasis treatment. The possibility for urine storage at moderate temperatures without loss of analysis quality further demonstrates the applicability of the BRI method.

The BONN Risk Index (BRI) successfully determines the calcium oxalate (CaOx) crystallization risk from urine samples. The BRI is based on a standardized crystallization test performed on native urine. A BRI-measuring device, the "Urolizer", has been developed, operating automatically and requiring only a minimum of preparative efforts. In this study, the Urolizer is evaluated regarding its analytical and diagnostic practicability for metaphylaxis control in the framework of the daily routine of a stone surgery. From 51 CaOx recurrent stone-formers, 24 h urines were collected at the beginning and after 3 months of metaphylaxis. As much as 27 patients were indicated to suffer from "mild hypercalciuria", low urinary pH or hypocitraturia, and 24 patients from "hypercalciuria". The former were treated with alkaline citrate (AC), and the latter with hydrochlorothiazide (HCT). Analyses of urines collected before and during treatment, BRI using the Urolizer, and urinalysis-based risk indices were evaluated. In both patient groups, BRI decreased significantly, while metaphylaxis (P0.001) in the AC group decreased from 1.08 (+/-0.58) to 0.56 (+/-0.39) L(-1) and in the HCT-group from 3.30 (+/-1.15) to 1.60 (+/-0.52) L(-1). In most patients, urinary parameters changed as desired and related risk indices decreased appropriately. The clinical utility of the easy-to-determine BRI is demonstrated. By quantifying the "overall" therapy effect within 15 min, the innovative analysis device may be especially suited for practitioners specializing in urolithiasis treatment.

Bodo B Beck, Norbert Laube, Sandra Habbig, Markus Feldkotter, Jochen WU Fries and Bernd Hoppe Division of Pediatric Nephrology, Department of Pediatrics, University Hospital Cologne, Cologne, Germany; Division of Experimental Urology, Department of Urology, University of Bonn, Bonn, Germany and Department of Pathology, University Hospital Cologne, Cologne, Germany Correspondence: B Hoppe, University Children’s Hospital Cologne, Division of Pediatric Nephrology, Kerpenerstrasse 62, Cologne D-50924, Germany. E-mail: behoppe@t-online.de

During metabolic evaluation stone patients often present with calculi in the urinary tract or are suffering from high frequent formation of small microliths passing routinely the urinary tract. These concrements are presumably in a state of continuous growth. Consequently, the concentrations of the lithogenic components in the voided urine must decrease. Thus, treatment schemes inevitably fail to focus on the true pathogenic urinary composition. Instead, they focus on underestimated concentrations. This can attain high clinical relevance. In recent publications, we introduced a complex physical approach and provided mathematical equations which can be solved analytically. However, to date, solving the equations with a pocket calculator remains cumbersome.Depletion V1.0 was developed to integrate the calculation of the depletion effect into the daily treatment of stone patients. Minimum requirement for Depletion V1.0 is the Java 1.2 platform runtime environment, which is supported on nearly all operation systems including Linux, MacOS X, and Windows. The program can be used directly within a Java-compliant web browser (e.g. Firefox, Mozilla, Internet Explorer) or from the program's storage location. The implemented data base provides stone type relevant parameters. Data input is performed via an easy-to-handle graphical user interface.Results are given as values and interactive plots; computation and update of plots are performed in real time. Result sheets can be exported to platform-independent EPS-format or printed out directly.Depletion V1.0 enables the medical practitioner to obtain an improved interpretation of the stone patient's health status. As input, only one set of easy-to-achieve clinical standard parameters is required. The program will be available from the authors as freeware.

Any catheter material placed in the urinary tract provides a surface for bacterial colonization and, therefore, it is susceptible to encrustation with crystalline bacterial biofilm. Encrustation and blockage by biofilms remain a major complication in patient care. Most patients with indwelling ureteral stents experience irritative symptoms related to these implants and many experience discomfort.Plasma deposited diamond-like amorphous carbon coatings are well-known for their excellent biocompatibility. A low temperature, low pressure plasma enhanced chemical vapor deposition technology was developed especially for coating polymeric medical implants with diamond-like carbon. We investigated the ability of diamond-like carbon to decrease the formation of crystalline bacterial biofilm as well as stent related side effects and discomfort. Diamond-like carbon coated ureteral Double-J stents were tested in vivo.In 10 patients with heavy encrustation, different underlying diseases and a stent removal frequency of less than 6 weeks due to encrustation a total of 26 diamond-like carbon coated stents were successfully tested for their ability to decrease the extent of crystalline biofilm formation. There was a 2,467-day period of experience with diamond-like carbon coated stents. No primarily stent related complications occurred. No crystalline biofilm formation was observed in vivo. Excellent and facile handling, a less painful replacement procedure and high tolerance of application were reported by physicians and patients. Due to low friction the coated stents could be placed and removed much more easily than standard stents. The frequency and severity of symptomatic urinary tract infections were distinctly decreased.Diamond-like carbon coating is a new strategy to improve the surface properties of ureteral stents. This novel surface effectively decreases friction, encrustation tendencies and biofilm formation.

A suitable and advisedly used risk index is an effective tool for improving prevention, therapy monitoring and classification of almost unmanageable amounts of analysis data and diagnoses. In contrast to statistically founded indices, causality-based risk indices can provide a fundamental insight into the mechanisms of the underlying pathology. However, understanding of stone formation as the result of many linked and often non-linear individual processes must be further improved. Only in this way can risk indices be optimized or better ones be developed. We are confident that, with consistent research efforts, science will be able to predict recurrence of stone formation more accurately within the next couple of years.

This review draws the recent state of the art in metabolic diagnosis and metaphylaxis of stone disease. It is the basis for the consensus approval with the other medical societies and institutions in Germany involved in the guideline process of the new "Urolithiasis Guideline". The German Working Committee on Stone Disease reviewed critically the current literature in the field of urolithiasis-including the existing German and EAU-Guidelines as well as the Conference Book of the First International Consultation on Stone Disease. As far as possible the references were rated according to the EBM criteria. On this basis the expert group discussed all pathways and statements regarding the management of stone disease. The present review coincides with the consented guideline draft of the German Working Committee on Stone Disease. Occurrence of stone disease in the western world increases seriously. Modern lifestyle, dietary habits and overweight-problems of the affluent societies-emerge to be the important promoters of the "stone-boom" in the new millennium. This even affects children, whose stone prevalence is otherwise significantly less than that of adults. Criteria for the high risk group of stone formers were clearly defined. A diagnostic standard is formulated for the basic and the elaborate metabolic evaluation of a stone patient. Approximately 75% of all stone patients could anticipate stone recurrence with elementary reorientation of their lifestyle and dietary habits, summarized as general metaphylaxis. About 25% of the stone formers require additional pharmacological intervention to normalize their individual biochemical risk, precisely compiled for each stone type as specific metaphylaxis.

Current treatment options in patients with primary and secondary hyperoxaluria are limited and do not always lead to sufficient reduction in urinary oxalate excretion. Intestinal oxalate degrading bacteria are capable of degrading oxalate to CO(2) and formate, the latter being further metabolized and excreted via the feces. It is speculated, that both endogenously produced, as well as dietary oxalate can be significantly removed via the intestinal tract. Oxalobacter formigenes, an obligate anaerobic microbe normally found in the intestinal tract has one oxalate degrading enzyme, oxalyl-CoA decarboxylase, which is also found in Bifidobacterium lactis. Other bacteria with possible oxalate degrading potency are lactic acid bacteria, as well as Enterococcus faecalis and Eubacterium lentum. However, specific therapeutic studies on humans are scarce and, except for Oxalobacter, data are not congruent. We found the oral application of Oxalobacter successful in patients with primary hyperoxaluria. However, long-term post-treatment follow-up of 1-2 years showed that constant intestinal colonization is not achieved in most patients. In one patient with constant colonization, urinary oxalate excretion normalized over time. Short-term studies with other bacteria such as lactic acid bacteria did not show a specific reduction in urinary oxalate excretion. O. formigenes might be a promising new therapeutic tool in patients with primary and secondary hyperoxaluria.

Purpose: It has been shown that a strong hyperbolic relationship exists between the urinary concentration of free Ca ions ([Ca 2+ ]) and the amount of ammonium oxalate (Ox 2− ) that must be titrated in a standardized procedure to a urine sample to induce CaOx crystallization. The ratio of [Ca 2+ ] to (Ox 2− ) is termed the Bonn Risk Index (BRI). Most data plot around a hyperbola described by the formula, [Ca 2+ ] × (Ox 2− ) = constant. Due to the high relationship between [Ca 2+ ] and (Ox 2− ) one may argue that determining only 1 of the 2 BRI parameters, preferably [Ca 2+ ], is sufficient to describe the urine crystallization risk. Materials and Methods: Based on 195 urine samples taken from CaOx stone formers and healthy subjects we compared the sensitivity and specificity of BRI, and its corresponding [Ca 2+ ] value by calculating ROC curves. Furthermore, ROC curves of the established risk indexes, namely the model value of urinary supersaturation and the model value of the urine activity product, are presented. Results: Our results clearly demonstrate that 1) BRI has the highest sensitivity and specificity of the tested indexes, 2) (Ox 2− ) cannot be reliably predicted from [Ca 2+ ] and 3) determining [Ca 2+ ] alone revealed a meaningful first estimate of urine CaOx crystallization risk according to BRI. Conclusions: To avail ourselves of the high quality of BRI in patient treatment the additional determination of (Ox 2− ) is required.

The BRI has been shown to discriminate between calcium oxalate stone formers and controls. BRI is the ratio of the concentration of ionized calcium and the amount of oxalate that must be added to 200 ml urine to initiate crystallization. Higher BRI values are predictive of being a stone former and a value of 1.0 has been found to be the cutoff value to distinguish stone formers and controls. It is not easy to present a consistent argument based on the thermodynamics of calcium oxalate crystallization to account for the success of this index. For instance, why should 2 samples sharing the same BRI but with different ionized calcium and oxalate values have the same likelihood of being obtained from a stone former?Using data on 195 samples the distribution and interrelationships of measured variables were examined. They were used to calculate illustrative data with which it was possible to examine the effects of varying the parameters and their relationships.Data simulations identified 3 necessary and sufficient conditions that must be met for BRI to be an effective discriminator between stone former and nonstone former urine samples.The success of BRI can be explained as the natural outcome of there being significantly different distributions (stone formers vs nonstone formers) of the concentration of ionized calcium and the formation product minus activity product difference as well as the correlation between these 2 variables.

Hyperoxaluria has been incriminated to account for the increased incidence of urolithiasis or nephrocalcinosis in patients with cystic fibrosis (CF). Hyperoxaluria presumably is caused by fat malabsorption and the absence of such intestinal oxalate-degrading bacteria as Oxalobacter formigenes. To better elucidate its pathophysiological characteristics, we prospectively studied patients with CF by determining these parameters and performing renal ultrasonography twice yearly.In addition to routine tests in urine (lithogenic and stone-inhibitory substances), the presence of O formigenes was tested in stool, plasma oxalate was measured, and a [13C2]oxalate absorption test was performed in 37 patients with CF aged 5 to 37 years (15 females, 22 males) who were constantly hyperoxaluric before the study.Hyperoxaluria (oxalate, 46 to 141 mg/1.73 m2/24 h [0.51 to 1.57 mmol/1.73 m2/24 h]; normal,45 mg/1.73 m2/24 h [0.5 mmol/1.73 m2/24 h]) was now found in 24 patients (64.8%). Plasma oxalate levels were elevated in 6 patients (7.92 to 19.5 micromol/L; normal, 6.3 +/- 1.1 micromol/L). Oxalobacter species were detected in only 1 patient. Intestinal oxalate absorption was elevated (11.4% to 28.5%; normal,10%) in 23 patients. Hypocitraturia was present in 17 patients (citrate, 0.35 to 2.8 g/1.73 m2/24 h [0.2 to 1.1 mmol/1.73 m2/24 h]; normal female,2.8 mg/1.73 m2/24 h [1.6 mmol/1.73 m2/24 h]; male,3.3 mg/1.73 m2/24 h [1.9 mmol/1.73 m2/24 h]). Urine calcium oxalate saturation was elevated in 17 patients (5.62 to 28.9 relative units; normal female,5.5 relative units; male,6.3 relative units). In 16% of patients, urolithiasis (n = 2) or nephrocalcinosis (n = 4) was diagnosed ultrasonographically.Absorptive hyperoxaluria and hypocitraturia are the main culprits for the increased incidence of urolithiasis and nephrocalcinosis in patients with CF. We advocate high fluid intake, low-oxalate/high-calcium diet, and alkali citrate medication, if necessary. Additional studies are necessary to determine the influence of Oxalobacter species or other oxalate-degrading bacteria on oxalate handling in patients with CF.

Regular calculation of urinary crystallization risk indices in patients suffering from urolithiasis is a recommended measure for treatment adjustment. The more the patient experiences either extensive stone formation or an enhanced recurrence rate, the more important risk index calculations. In patients suffering from primary hyperoxaluria type 1 (PH1), both criteria are met. Different methods of risk determination are known. All strategies for measuring the calcium oxalate (CaOx) crystallization risk of a given urine principally determine this parameter from voided urine. This "bladder urine", however, has possibly passed stone material located in the urinary tract and thus may be depleted in lithogenic components. This is commonly the case for patients with PH1, who mostly experience a massive stone burden or severe nephrocalcinosis. Hence, the question arises as to whether we can adequately determine the crystallization risk in the urine of stone-bearing PH1-patients or not. Based on model calculations, we show that the determination of CaOx formation risk in PH1-patients requires knowledge of the restrictions in risk index interpretation: risk indices calculated from urinalysis (e.g. EQUIL) still indicate, even after strong in vivo stone formation, an enhanced but in fact strongly underestimated risk value. However, the outcome "enhanced" masks the patient's true risk situation. The BONN Risk Index (BRI), in contrast, discloses the process of extreme in vivo crystal formation. As determined, inter alia, from the urinary concentration of free ionized calcium ([Ca(2+)]), BRI approaches abnormally low values, as, in consequence of CaOx - formation, [Ca(2+)] tends to values close to zero. Thus, calculations of urinalysis-based risk indices alone are insufficient strategies for the quantification of a PH1 patient's CaOx crystallization risk.

This study was performed to quantify the effect of a 1-weekfreezer storage of urine on its calcium oxalate crystallization risk. Calcium oxalate is the most common urinary stone material observed in urolithiasis patients in western and affluent countries. The BONN-Risk-Index of calcium oxalate crystallization risk in human urine is determined from a crystallization experiment performed on untreated native urine samples.We tested the influence of a 1-weekfreezing on the BONN-Risk-Index value as well as the effect of the sample freezing on the urinary osmolality. In vitro crystallization experiments in 49 native urine samples from stone-forming and non-stone forming individuals were performed in order to determine their calcium oxalate crystallization risk according to the BONN-Risk-Index approach. Comparison of the results derived from original sample investigations with those obtained from the thawed aliquots by statistical evaluation shows that i) no significant deviation from linearity between both results exists and ii) both results are identical by statistical means. This is valid for both, the BONN-Risk-Index and the osmolality data.The differences in the BONN-Risk-Index results of both procedures of BONN-Risk-Index determination, however, exceed the clinically acceptable difference. Thus, determination of the urinary calcium oxalate crystallization risk from thawed urine samples cannot be recommended.

Regular risk evaluation and risk monitoring during stone therapy are recommended measures to ensure reduction of recurrence of crystal formation. This strategy optimizes the patient treatment by a more individual approach and decreases expensive over treatment. We evaluated the BONN Risk Index (BRI) through data actualization and evaluation refinement. The BRI was compared with the most common methods of risk evaluation, namely calculation of relative urinary calcium oxalate (CaOx) supersaturation (RS) and of the urine activity product (AP)CaOx index to estimate the urine AP with respect to CaOx.A total of 201, 12 and 24-hour urine samples were collected from 95 healthy volunteers and from 106 CaOx stone formers. Crystallization experiments following the BRI method were performed. RS and APCaOx were calculated from urinalysis. Data were indexed and individually grouped into 8 classes, and frequency distributions were plotted. A calculation scheme for the BRI based estimation of the statistical probability of a clinically healthy person being a (still nondetected) CaOx stone former is provided.Logarithmically arranged BRI groups from healthy subject and patient data showed Gaussian frequency distributions. Compared with RS and APCaOx BRI allowed optimum distinction between healthy subjects and stone formers. The healthy subject probability of already being a CaOx stone former strongly increased with increasing BRI.The BRI for evaluating CaOx crystallization risk allows reliable distinction between healthy subjects and CaOx stone formers. Although RS and APCaOx require much more analytical efforts for determination, their results do not show higher reliability.