Are there seasonal variations in renal colic in uric acid stone formers in Germany?

PURPOSE: Seasonal variations in renal colic have been described by many authors for different countries worldwide. In most studies, there was no differentiation with regard to stone composition. Recently, we demonstrated that there was no seasonal variation in renal colic and urine chemistry for calcium oxalate stone formers in Germany. As we have many uric acid stone formers (UASFs) in our region, we were interested in learning the situation of this type of stone. METHODS: We studied 286 consecutive UASFs with symptoms of renal colic. We divided them into four groups according to the quarters of the year. For stone analysis, X-ray diffraction/polarizing microscopy was used. Additionally, the following general parameters were examined in all patients: age, BMI, blood pressure, stone frequency, diabetes mellitus; blood: creatinine, glucose, uric acid, calcium, sodium and potassium; urine: pH, volume, calcium, uric acid, citrate, ammonia, and urea. Using the statistical program Prism 5 (GraphPad Software, San Diego, USA), significant differences between the four groups were calculated by the Kruskal-Wallis test. RESULTS: We observed significantly more UASFs with renal colic in the third and fourth quarters of the year. This is in contrast to our findings in calcium oxalate patients. However, there was no variation in metabolic parameters. CONCLUSION: The reasons are unclear; different temperatures are not a sufficient explanation, as one quarter is in the warm season and the other one is in the cold season. Unfortunately, no data have been reported in the literature thus far. Further studies are required to better understand these findings.

[Therapy of cystitis with nitroxoline-NitroxWin : Prospective, multicenter, non-interventional study and microbiological resistance surveillance]. / Therapie der Zystitis mit Nitroxolin ­ NitroxWin : Prospektive, multizentrische, nicht-interventionelle Studie und mikrobiologische Untersuchungen zur Resistenzsituation.

BACKGROUND: According to German AWMF S3 guideline nitroxoline is recommended as one of the first-choice antibiotics for treatment of acute uncomplicated cystitis (UC) in women. Under real-world conditions the clinical efficacy of nitroxoline should be checked in a noninterventional, prospective and multicenter study (NIS) and the prevalence of nitroxoline resistance in E. coli be monitored. MATERIALS AND METHODS: Female patients with UC treated with nitroxoline (recommended dosage 250 mg tid for 5 days) were included by urologists, general practitioners (GPs), and internists in family medicine throughout Germany from April-December 2022 and followed for 21-28 days. The diagnosis and course of therapy were judged by the Acute Cystitis Symptom Score (ACSS) questionnaire and laboratory investigations (leukocyturia etc). Separately, a nationwide resistance surveillance was performed during 2019-2020 in collaboration with 23 laboratories to collect urinary E. coli isolates and test their susceptibility to nitroxoline. RESULTS: Of the 316 patients with mean (SD) age of 57.2 (±20.4 [median 62.5]) years who were included in the NIS, 193/248 (86.3%) in the per-protocol group and in 193/263 (81.44%) in the intention-to-treat group were clinically successful. Furthermore, 96% of the patients rated the tolerability of nitroxoline as "very good" or "good". All 272 E. coli isolates tested were susceptible to nitroxoline. CONCLUSIONS: Nitroxoline showed very good clinical results in the NIS, and 100% of the tested E. coli urine isolates were susceptible to nitroxoline. Nitroxoline can still be recommended as one of the first-choice antibiotics for treatment of UC in women.

Overweight, insulin resistance and blood pressure (parameters of the metabolic syndrome) in uric acid urolithiasis.

Overweight, arterial hypertension and disturbances of the carbohydrate metabolism are important parameters of the metabolic syndrome (MS). The most important factor regarding renal pathophysiology is insulin resistance resulting in alterations of urine acidification and low urine pH. Since low urine pH is the main risk factor for uric acid urolithiasis (UAU), UAU may be regarded as a renal manifestation of the MS. So far, there are only few data on the prevalence of parameters of the MS in UAU patients especially with regard to the severity of the disease and recurrence rate, respectively. The objective of this study was to know more about the prevalence of different parameters of the MS and their importance for the natural history of this type of renal stone disease using a total number of 167 consecutive patients with pure UA stones. Stone analysis was performed by polarization microscopy and X-ray diffraction. The following parameters were measured: age, sex, systolic and diastolic arterial blood pressure (RRs and RRd), number of stone episodes, diabetes mellitus (DM); serum: creatinine, calcium, sodium, potassium, uric acid, glucose; urine: pH-profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. The following results were obtained (means ± standard deviations): age 61 ± 13 years, BMI 30 ± 6 kg/m(2), BP 147/84 ± 22/13 mmHg, number of stone episodes 1.8 ± 1.2, DM 32%; serum: creatinine 1.3 ± 0.6 mg/dl, glucose 136 ± 52 mg/dl, UA 6.3 ± 1.8 mg/dl, calcium 2.4 ± 1.3 mmol/l, sodium 134 ± 18 mmol/l, potassium 4.1 ± 0.4 mmol/l; urine: pH 5.87 ± 0.27, volume 2.4 ± 1.1 l/d, calcium 3.5 ± 2.5 mmol/d, UA 3.9 ± 2.4 mmol/d, citrate 1.3 ± 1.1 mmol/d, ammonia 41 ± 26 mmol/d, urea 390 ± 176 mmol/d. A significant positive correlation could be found for BMI and urea excretion, BMI correlated negatively with RRs and RRd. There was no significant correlation between BMI, urine pH, citrate, ammonia and UA in serum and urine. Undue acidity and hyperuricosuria were found in two-thirds of the UAU patients, increased urea excretion and decreased excretion of ammonia in less than 25%, Hyperuricemia in 37%. There was no significant correlation between the number of stone episodes and any other parameter studied. Overweight, arterial hypertension and DM as parameters of the MS are frequent in many patients with UAU. However, these parameters do explain the pathogenesis in two-thirds of the patients. The severity of the disease and the recurrence are not influenced by the presence of these metabolic parameters. Therefore, MS is no prognostic factor in UAU.

Urinary stone formers with hypocitraturia and 'normal' urinary pH are at high risk for recurrence.

BACKGROUND: Citrate is one of the most important inhibitors in urolithiasis. Hypocitraturia is a common risk factor in stone formers. Citrate excretion is regulated - amongst others - by acidosis and protein intake. A considerable number of stone formers, however, show hypocitraturia in the presence of normal urine pH levels. This is potentially due to defects in the renal tubular citrate carriers (NaDC 1 and 3) which may be genetically determined. PATIENTS AND METHODS: 350 consecutive stone formers were examined. Exclusion criteria were urinary tract infection, hypokalemia, and steatorrhea. The following parameters were measured: serum: creatinine, calcium, potassium, and uric acid; urine: pH profiles, citrate, calcium, uric acid, ammonia, urea, and creatinine. RESULTS: 83/350 patients were hypocitraturic (48 males, 35 females). 14/83 had low urine pH (≤ 6), 69/83 showed normal levels (>6). In the latter group there was a significantly higher recurrence rate (23 vs. 9%). The two groups were not different in serum parameters apart from uric acid. In urine, only pH and calcium (males) were significantly lower in the first group. Citrate did not correlate with urine pH and creatinine in the hypocitraturia-normal pH group, only with calcium in both sexes and urea and ammonia in females. In the hypocitraturia-low pH patients, there was no significant correlation between citrate and any other parameter tested. CONCLUSIONS: Hypocitraturia with normal urine pH is an entity indicating a high risk for recurrence. Since there was no correlation between citrate and pH, urea and ammonia, respectively, citrate excretion is not regulated in these patients as usual. There may be a link to calcium excretion. Potentially, these patients have defects in the renal tubular citrate carriers which may be genetically determined. Genetic examinations should be performed to elucidate a potential genetic disorder in hypocitraturia-normal pH stone formers.

Clinical significance of uric acid dihydrate in urinary stones.

Uric acid crystallizes as an anhydrous compound (UAA), a dihydrate (UAD) or a mixture of both. A monohydrate form is very rare. About 20% of uric acid stones contain a significant amount (≥20%) UAD. It is believed that UAD crystallizes under highly acidic conditions (urine pH ≤ 5.0). Up to now, metabolic data on patients with UAD stones have not been reported in the literature. One hundred and fifty patients with pure uric acid calculi were studied. Stone analysis was performed using X-ray diffraction. According to the stone analysis, they were divided in two groups: 1. UAD (≥20% UAD), 2. UAA (<20% UAD). In all patients the following parameters were examined: age, sex, number of recurrences, body mass index (BMI); blood: creatinine, uric acid, calcium, sodium, and potassium; urine: pH-profiles, volume, calcium, uric acid, citrate, ammonia, and urea. Group 1 (≥20% UAD) consisted of 33 patients and group 2 (<20% UAD) of 117 patients. Between these groups, there was a significant difference concerning the number of recurrences, the urine volume, and the urinary excretion of calcium. Patients with ≥20% dihydrate had a mean BMI of 31.6 ± 7.5, a mean number of recurrences of 0.24 ± 0.44, an urine volume of 2.6 ± 0.8 l/24 h, and a calcium excretion of 4.5 ± 2.2 mmol/24 h, whereas those with <20% dihydrate had BMI of 29.9 ± 5.0, 1.10 ± 1.42 recurrences, urine volume of 2.3 ± 1.2 l/24 h, and calcium excretion of 3.2 ± 2.4 mmol/24 h. All the other parameters tested were not significantly different. For the first time, our study shows metabolic data in uric acid patients with a significant amount of UAD. The comparison between this group and those patients with <20% UAD revealed that the first group is less prone to develop recurrences. This is a relevant difference concerning the necessity of metaphylactic measures. We could not confirm in patients with dihydrate if the urinary pH is more acid than in those with insignificant amounts of dihydrate. The higher 24-h urine volume, the higher excretion of calcium, and the higher BMI in the UAD group may be of pathophysiological relevance and requires further attention.

Improved ex vivo training model for percutaneous renal surgery.

Percutaneous endourological procedures require an advanced level of skills. To facilitate the training of the proper technique, some years ago we developed a porcine ex vivo model for training percutaneous endourological procedures. When dilating the percutaneous tract silicone and gelatine were frequently damaged thus inhibiting proper working with the endoscopes. To circumvent these problems we improved our ex vivo model in order to be as close to the clinical situation as possible. The kidney with the ureter was dissected off the retroperitoneal organ package of the freshly slaughtered pigs. The kidneys were put into bags cut into parts of the thoracic/abdominal wall of these pigs. The renal pelvis can be filled with saline to simulate hydronephrosis; stones can be implanted for PCNL. Our new model allows for even better training of all percutaneous endourological procedures (e.g. percutaneous nephrostomy, PCNL, endopyelotomy). Especially puncturing is extremely close to the situation in humans as the porcine thoracic/abdominal wall in principal has the same anatomy as the human one. The new model has been already used with great success in hands-on courses. Concerning "tissue feeling", the anatomic relations and the great variety of procedures that can be trained, it is superior to non-biological models. Nevertheless, it is easily available and inexpensive.

Imaging in pediatric urolithiasis-what's the best choice?

The incidence of urolithiasis increased dramatically during the last decades in adults as well as in children. Today, when a urinary stone is suspected, the imaging modality used most frequently is non-contrast enhanced computed tomography (NCCT). Due to the high sensitivity and specifity, NCCT is regarded as the gold standard. Its major drawback is the high dose of radiation administered with this examination. This is of special concern in children. Children with urinary stones are at high risk for multiple recurrences during their life. NCCT increases the risk for abdominal and pelvic cancer in children significantly. With respect to therapeutic success, however, conventional imaging modalities like ultrasound are not inferior and are without any harm. Therefore, ultrasound is recommended as the primary imaging technique in children by several guidelines. Nevertheless, as could be shown by Tasian et al., ultrasound was the first imaging study in only 24% of children with urolithiasis. NCCT was the modality used most frequently (63%) in the USA between 2003 and 2011. There was a wide regional variation within the USA with highest CT use in the Northwestern and Southern and lowest in the New England states. It is hypothesized that engrained practice patterns and specific local medical resources as well as a lower confidence in ultrasound with its operator dependence are potential reasons. Regarding the fact that ultrasonography is highly reliable in the diagnosis of urolithiasis and is without any harm, it is essential to make all efforts to increase the adherence to the guidelines.

Papillary calcifications: a new prognostic factor in idiopathic calcium oxalate urolithiasis.

Metabolic evaluation is not suitable to forecast the course of the disease in idiopathic calcium oxalate stone formation (iCaOxU). An important pathway in CaOx stone formation is the overgrowth on interstitial apatite papillary plaques. Therefore, we studied whether the extent of such plaques may be used as a prognostic factor in CaOxU. Prospectively, we studied n = 100 patients with iCaOxU. For stone analysis, X-ray diffraction/polarizing microscopy was used. During flexible ureteroscopy and flexible percutaneous nephrolithotomy, all the renal papillae were inspected, counted and the severity of calcifications assessed. A calcification index (CI) was calculated: sum of the No. of papillae × calcification grade (1-3) × No. of calcified/total No. of papillae. Furthermore, the following parameters were examined in all patients: age, sex, BMI, arterial blood pressure, stone episodes, DM; blood: creatinine, glucose, uric acid, calcium, sodium and potassium; urine: pH, volume, calcium, uric acid, citrate, ammonia and urea. Using the statistic programme Prism 5 (GraphPad), summary statistics and non-parametric correlations (Spearman) and their significance were calculated. The CI correlated significantly (r = 0.37; p = 0.012) with the No. of stone episodes. Apart from citrate (r = 0.51; p = 0.002), none of the conventional metabolic parameters correlated significantly with the No. of stone episodes. Paradoxically, the citrate excretion-although citrate being an inhibitor of CaOx stone formation-positively correlated to the recurrence rate. The endoscopic assessment of papillary plaques/calcifications and the calculation of the CI are a more suitable prognostic factor in CaOx than conventional metabolic evaluation.

Economics of stone disease/treatment.

OBJECTIVES: Urolithiasis is a considerable economic burden for health systems, especially in industrialised countries where the incidence of stone disease has increased during the last few decades, and probably will further increase for several reasons. METHODS: The survey was based on investigations in collaboration with a German health insurance company and on a literature search (PubMed, and the author's collection of proceedings of urolithiasis conferences: The keywords included economics, cost, urolithiasis, nephrolithiasis, renal stone disease, metaphylaxis, recurrence) during 1999-2011. In all, 1221 articles were found but only those cited here were sufficient for the purpose of the study. Due to the nature of the subject it is not possible to give levels of evidence, as economic data on stone treatment cannot be obtained with randomised studies. RESULTS: The costs for the treatment and diagnosis of stones vary tremendously among different healthcare systems. Several calculation models showed that metaphylaxis is medically and economically effective when used rationally. Rational metaphylaxis is restricted to patients with a high risk of recurrence (brushite, uric acid, cystine and infected stones, patients with residual fragments after stone treatment and recurrent calcium oxalate stone formers). CONCLUSIONS: For the groups identified, metaphylaxis is cost-effective in almost all healthcare systems, but the cost saved differs. The savings increase even more when adding the economic loss avoided from days off work due to treatment of recurrent stones. In most countries, stone frequency must exceed one stone per patient per year before medical therapy is more cost-effective than dietary measures.

Overweight and obesity: risk factors in calcium oxalate stone disease?

Introduction. Several studies showed an association of overweight and obesity with calcium oxalate stone disease (CaOx). However, there are no sufficient data on the influence of body weight on the course of the disease and the recurrence rate. Patients and Methods. N = 100 consecutive stone formers with pure CaOx were studied. Different parameters were investigated. According to the BMI, patients were divided into three groups: (1) BMI ≤ 25; (2) BMI 25.1-30; (3) BMI > 30. Results. N = 32 patients showed a BMI ≤ 25, n = 42 patients showed a BMI of 25.1-30 and n = 26 patients showed a BMI ≥ 30. The groups differed significantly concerning BMI (by definition), urine pH, and urine citrate. The recurrence rate was not significantly different. Discussion. Our study demonstrated that body weight negatively influences single risk factors in CaOx, but obesity is not a predictor for the risk of recurrence in CaOx.

Ex vivo training model for percutaneous renal surgery.

Percutaneous endourological procedures require an advanced level of skills. To facilitate training in the proper technique, simulators are helpful. Non-biological models, useful for learning the basic steps, do not represent the clinical situation in an ideal way. Recently, we developed a porcine urinary tract model for ureteroscopy. Proceeding from this experience, we developed a further ex vivo model for training percutaneous endourological procedures. The kidney with the ureter is dissected off of the retroperitoneal organ package of freshly slaughtered pigs. It is embedded in silicon. The renal pelvis can be filled with saline to simulate hydronephrosis, stones can be implanted for percutaneous nephrolithotomy. This ex vivo model allows training of all percutaneous endourological procedures (e.g. percutaneous nephrostomy, percutaneous lithotomy, endopyelotomy). It is an ideal way to train these techniques, being superior to non-biological models in terms of "tissue feeling" for anatomic relations, and the great variety of procedures that can be trained. Nevertheless, it is readily available and inexpensive.

Selenium reduces high energy shock wave-induced renal injury in rats.

Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we showed that shock wave-induced renal injury could be ameliorated by selenium. We examined the influence of selenium, a free radical scavenger, in shock wave-induced tubular cell injury in vivo. Male rats were randomly assigned to three groups: 1 control (n= 18), 2 selenium (n = 18), 3 sham treatment (n = 4). Groups 1 and 2 were treated with 500 shock waves on each kidney. Animals assigned to group 3 (sham treatment) received only anesthetics. Selenium (80 microg/kg per 24 h intraperitoneally) was given to the animals in group 2 for 5 days, starting 1 day before shock wave exposure. Urine was collected for 8 h on the day before and immediately, 1, 7 and 28 days after shock wave exposure (SWE) for the measurement of urine volume, N-acetyl-beta-glucosaminidase (NAG), beta-2-microglobulin (beta2 M), and creatinine. Blood was taken from these rats on day 1 after SWE for the determination of creatinine and the calculation of the creatinine clearance (CCr). After SWE, there was a significantly increased diuresis in group 1 and 2. The excretion of NAG and beta2 M was also increased in both groups. These changes were significantly less pronounced in the selenium treated rats. CCr was higher in the selenium group than in the controls. No changes were observed in the sham treated group. These results demonstrate that selenium is able to ameliorate the damaging effects of high energy shock waves on renal tissue not only in vitro, but also in vivo.