Lithogenic activity and clinical relevance of lipids extracted from urines and stones of nephrolithiasis patients.

We investigated contents and classes of urinary and stone matrix lipids, and evaluated their clinical relevance in nephrolithiasis patients. Lithogenic role of major lipid classes was explored. Urine (24 h) and stone samples were collected from 47 patients with nephrolithiasis. Control urines were obtained from 29 healthy subjects. Urinary 8-hydroxy-deoxyguanosine (8-OHdG), malondialdehyde (MDA), N-acetyl-ß-glucosaminidase (NAG) activity and total proteins were measured. Total lipids were extracted from centrifuged urines (10,000 rpm, 30 min) and stones by chloroform/methanol method. Major classes of lipids were identified using multi-one-dimensional thin-layer chromatography (MOD-TLC). Influence of each lipid class purified from stone matrices on stone formation was evaluated using crystallization and crystal aggregation assays. Urinary NAG activity and 8-OHdG were significantly elevated in nephrolithiasis patients. Total lipids in centrifuged urines of the patients were not significantly different from that of controls. In nephrolithiasis, urinary excretion of total lipids was linearly correlated to urinary MDA, 8-OHdG, NAG activity and total proteins. Lipid contents in stone matrices varied among stone types. Uric acid stone contained lower amount of total lipids than calcium oxalate and magnesium ammonium phosphate stones. MOD-TLC lipid chromatograms of healthy urines, nephrolithiasis urines and stone matrices were obviously different. Triacylglyceride was abundant in urines, but scarcely found in stone matrices. Stone matrices were rich in glycolipids and high-polar lipids (phospholipids/gangliosides). Partially purified glycolipids significantly induced crystal aggregation while cholesterol was a significant inducer of both crystal formation and agglomeration. In conclusion, total lipids in centrifuged urines did not differ between nephrolithiasis and healthy subjects. Our finding suggests that the significant sources of lipids in patients' urine may be large lipids-containing particles, which are removed in centrifuged urines. However, urinary lipid excretion in nephrolithiasis patients was associated with the extent of oxidative stress and renal tubular injury. Triacylglyceride was abundant in urines, but rarely incorporated into stones. Glycolipids were principal lipid constituents in stone matrices and functioned as crystal aggregator. Cholesterol purified from stone matrices bared crystal nucleating and aggregating activities.

Safety and efficacy of a prolonged-release formulation of alfuzosin 10 mg once daily in patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia.

OBJECTIVE: Assess safety and efficacy of 10-mg prolonged-release alfuzosin (Xatral XL) in benign prostatic hyperplasia (BPH) patients with lower urinary tract symptoms (LUTS). MATERIAL AND METHOD: A multicenter observational study looking at safety by adverse events (AEs) incidence, efficacy by changes in International Prostate Symptom Score (I-PSS), quality of life index (QOL), sexual function using Danish Prostate Symptom Score (DAN-PSS sex), and flow rates. Patients were allocated to receive alfuzosin (Xatral XL) 10 mg once daily tablet along with a meal for 6 months. Patients were assessed at 3 months and 6 months. RESULTS: In 118 males, 22% had AEs (most common was dizziness). Ten patients discontinued the treatment. Of those patients, five had serious AEs, which only one was related to the study. At month 6, there were improvements from baseline in mean I-PSS (-9.3, p < 0.001), in QOL index (-2.96, p < 0.001), in symptom (-0.72, p < 0.05) and bothersome (-1.13, p < 0.01) subscores on DAN-PSS sex, and in mean flow rate (0.92, p < 0.01). Approximately 74% patients improved within two weeks. There was one case of Acute urinary retention (AUR), which none required surgery. CONCLUSION: A 10-mg prolonged-release alfuzosin safely and rapidly relieves LUTS and maintains improvement. It also improves BPH-associated sexual dysfunction.