Oxypurines, protein, glucose and the functional state of blood vasculature are markers of renal calcium stone-forming processes? Observations in men with idiopathic recurrent calcium urolithiasis.
In idiopathic calcium urolithiasis the relationships between oxypurines, accompanying proteins and glucose in urine and plasma, and the associated metabolic activity (MA) are unknown. To establish whether MA is related to these parameters and to calcium oxalate crystallization, or whether it reflects a reaction of metabolism to systemic insults was the major goal of the work. One hundred fifty one males were studied in three trials: trial 1 (n=130 patients) and trial 2 (n=24 patients) were cross-sectional; trial 3 included 11 patients and 14 controls). Mean age was 46 years (trials 1 and 2) and 29 years (trial 3). In trial 1 the stratification was based on the median urinary oxypurine excretion, in trial 2 on the median plasma oxypurine concentration (below or above: Low and High subgroups). No dietary restrictions were imposed, but standardized ambulatory laboratory testing was carried out. MA was quantitated by a score. Established analytical methods were used, except for oxypurine measurement which was done by high performance liquid chromatography. Patients with kidney stones tended to be overweight (body mass index >25 kg/(m)2) and to have fasting hyperglycemia. In trial 1 severe oxypurinuria, and especially severe xanthinuria, was associated with an increase in urinary pH, creatinine clearance, proteins, uric acid, malonedialdehyde (indicator of lipid peroxidation), systolic blood pressure, and with a decrease in plasma uric acid (synonymous with a decrease of antioxidant capacity). Tubular reabsorption of proteins and stone-forming substances was diminished but MA remained unchanged despite slightly increased calcium oxalate crystal growth. In trial 2 high adenosine and xanthine coincided with elevated systolic and diastolic blood pressure, high uric acid with high urinary malonedialdehyde, high summed oxypurines minus uric acid with an increase of diastolic blood pressure, glycemia and MA; urinary nitrate (indicator of systemic vasodilation) was unchanged. In trial 3 patients' oxypurinemia and proteinuria were normal, but body mass index, glycemia and insulinemia were increased. Urinary total protein, albumin and non-albumin proteins were positively predicted (multivariate regression analysis) by urinary xanthine, glucose and pH (trial 1); MA was positively (trial 3) or negatively (trial 2) predicted by urinary total protein. In calcium urolithiasis, a disorder of affluence, 1) oxypurinuria and proteinuria and oxypurinemia and MA appear causally linked, presumably via oxidant/antioxidant imbalance-induced renal tissue damage; 2) urinary proteins may act as inhibitors or promoters of stone-forming processes; 3) a stone-initiating role of impaired vasodilatation is conjectural; 4) overweight, obesity, mild glucosuria and hyperdynamic blood circulation are regular signs.
Manoharan
Mahimaidos
M
Mineral Metabolism and Endocrine Research Laboratory, Department of Surgery, University of Erlangen, Germany.
Schwille
Paul O
PO
D000328:Adult; D000367:Age Factors; D000368:Aged; D001786:Blood Glucose / Q000032:analysis*; D001808:Blood Vessels / Q000473:pathology*; D001835:Body Weight; D002129:Calcium Oxalate / Q000378:metabolism; D002624:Chemistry, Clinical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019271:Hypoxanthine / Q000652:urine; D007669:Kidney Calculi / Q000175:diagnosis* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000175:diagnosis; D011687:Purines / Q000097:blood*; D013997:Time Factors; D019820:Xanthine / Q000652:urine
D001786:Blood Glucose; D011687:Purines; D019820:Xanthine; D002129:Calcium Oxalate; D019271:Hypoxanthine