Idiopathic Recurrent Calcium Urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or
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EUROPEAN JOURNAL OF MEDICAL RESEARCH
Eur J Med Res (2009) 14: 378-392
September 1, 2009 © I. Holzapfel Publishers 2009
IDIOPATHIC RECURRENT CALCIUM UROLITHIASIS (IRCU): VARIATION OF FASTING URINARY PROTEIN IS A WINDOW TO PATHOPHYSIOLOGY OR SIMPLE CONSEQUENCE OF RENAL STONES IN SITU? A TRIPARTITE STUDY IN MALE PATIENTS PROVIDING INSIGHT INTO OXIDATIVE METABOLISM AS POSSIBLE DRIVING FORCE TOWARDS ALTERATION OF URINE COMPOSITION, CALCIUM SALT CRYSTALLIZATION AND STONE FORMATION* P. O. Schwille, A. Schmiedl, J. Wipplinger
Mineral Metabolism and Endocrine Research Laboratory, Departments of Surgery and Urology, University of Erlangen-Nürnberg, Germany
Abstract Background: In IRCU it is uncertain whether variation of urinary protein, especially non-albumin protein (NAlb-P), is due to the presence of stones or reflects alteration of oxidative metabolism. Aims: To validate in a tripartite cross-sectional study of 187 ambulatory male patients, undergoing a standardized laboratory programme, whether stones impact on N-Alb-P or the state of oxidative metabolism interferes with IRCU pathophysiology. Methods: In part 1 the strata low and high of fasting urinary excretion rate per 2 h of N-Alb-P, malonedialdehyde, hypoxanthine, xanthine, pH and other urine components were compared, and association with renal stones in situ evaluated; in part 2 the co-variation of oxidatively modulated environment, fasting urinary pH, calcium (Ca) salt crystallization risk and the number of patients with stones in situ was examined; in part 3, the nucleation of Ca oxalate and Ca phosphate was tested in undiluted postprandial urine of patients and related to the state of oxidative metabolism. Results: In part 1, N-Alb-P excretion >4.3 mg was associated with increase of blood pressure, excretion of total protein, hypoxanthine (a marker of tissue hypoxia), malonedialdehyde (a marker of lipid peroxidation), sodium, magnesium, citrate, uric acid, volume, pH, and increase of renal fractional excretion of both NAlb-P and uric acid; when stones were present, urinary pH was elevated but other parameters were unaffected. Significant predictors of N-Alb-P excretion were malonedialdehyde, fractional N-Alb-P and hypoxanthine. In part 2, urine pH >6.14 was associated with unchanged blood pressure and plasma vasopressin, increase of blood pH, urinary volume, malonedialde-
hyde, fractional excretion of N-Alb-P, uric acid, Ca phosphate, but not Ca oxalate, supersaturation; this spectrum was accompanied by decrease of concentration of urinary total and free magnesium, total and complexed citrate, plasma uric acid (in humans the major circulating antioxidant) and insulin; the number of stone-bearing patients was increased. Significant predictors of urine pH were body mass index, plasma insulin and uric acid (negative), and urinary xanthine (positive). In part 3 low plasma uric acid, not high urinary malonedialdehyde or high ratio malonedialdehyde/uric acid was significantly associated with diminished Ca but not oxalate tolerance, with the first nucleating cry
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