Is calcium oxalate nucleation in postprandial urine of males with idiopathic recurrent calcium urolithiasis related to calcium phosphate nucleation and the intensity of stone formation? Studies allowing insight into a possible role of urinary free citrate and protein

Abstract

In idiopathic recurrent urolithiasis (IRCU) calcium oxalate and calcium phosphate are components of stones. It is not sufficiently known whether in urine the nucleation (liquid-solid transition) of each salt requires a different environment, if so which environment, and whether there is an impact on stone formation. Nucleation was induced by in vitro addition of oxalate or calcium to post-test meal load whole urine of male stone patients (n=48), showing normal daily and baseline fasting oxaluria. The maximally tolerated (until visible precipitates occur) concentration of oxalate (T-Ox) or calcium (T-Ca) was determined; additionally evaluated were other variables in urine, including total, complexed and free citrate (F-Cit), protein (albumin, non-albumin protein) and the clinical intensity (synonymous metabolic activity; MA) of IRCU. In the first of three trials the accumulation of substances in stone-forming urine was verified (trial-V); in the second (clinical trial 1) two strata of T-Ox (Low, High) were compared; in the third (clinical trial 2) IRCU patients (n=27) and a control group (n=13) were included to clarify whether in stone-forming urine the first crystal formed was calcium oxalate or calcium phosphate, and to identify the state of F-Cit. T-Ox was studied at the original pH (average < 6.0), T-Ca at prefixed pH 6.0; the precipitates were subjected to electron microscopy and element analysis. Trial-V: Among the urinary substances accumulating at the indicated pHs were calcium, oxalate and phosphate, and the crystal-urine ratios were compatible with the nucleation of calcium oxalate, calcium-poor and calcium-rich calcium phosphate; citrate, protein and potassium also accumulated. Clinical trial 1: the two strata exhibited an inverse change of T-Ox and T-Ca, the ratio T-Ox/T-Ca and MA. The initial (before induction of Ox or Ca excess) supersaturation of calcium oxalate and brushite were unchanged, with the difference of proteinuria being borderline. Several correlations were significant (p < or = 0.05): urine pH with citrate and volume, protein with volume and MA, T-Ox with T-Ca and MA. Clinical trial 2: in patients with reduced urine volume and moderate urine calcium excess, the first precipitate appeared to be calcium oxalate, followed by amorphous calcium phosphate. Conversely, when the calcium excess was extreme, calcium-rich hydroxyapatite developed, followed by calcium oxalate; F-Cit, not total and complexed citrate, was decreased in IRCU vs. male controls; F-Cit rose pH-dependently, and the ratio F-Cit at original pH vs. F-Cit at pH 6.0 correlated inversely with the nucleation index T-Ox/T-Ca; MA correlated inversely with the ratio F-Cit at pH 6.0, respectively, original pH, but directly with the urinary albumin/non-albumin protein ratio. In summary 1) to study calcium oxalate and calcium phosphate nucleation in whole urine of IRCU patients is feasible; 2) at this crystallization stage the two substances, dominant in calcium stones, appear intimately linked, 3) in stone-forming urine, calcium phosph...

Idiopathic recurrent calcium urolithiasis (IRCU): variation of fasting urinary protein is a window to pathophysiology or simple consequence of renal stones in situ?

“…The overlap of participants in the present and previous studies, using different strategies and outcomes [1,5,18], was 80 - 95%. As a search for the mechanism(s) underlying ROS production and ROS nature was not in the focus of present work, overproduction of ROS (by cells during hypoxia-induced ATP degradation [19]) was taken as reflected by increase of urinary hypoxanthine, and ROS excess-mediated damage of lipids and lipid-containing cell membranes, other molecules and genes [11,12,20] as reflected by increase of urinary MDA; low plasma uric acid, the dominant antioxidant component of human plasma [5,21], was taken as indicating antioxidant deficiency.…”

“…Note the absence of a P peak. Reproduced from [18] with kind permission of Walter De Gruyter, Berlin, Germany.…”

“…as practiced in our outpatient stone clinic have been described [17]. For the present work the composition of fasting blood and urine and postprandial urine (after intake of a purine- and oxalate-free but Ca-rich and urine acidifying meal of fixed composition [1,18]) was studied. After an overnight fasting period of 12-14 h, diuresis was stimulated in the laboratory by drinking 2 × 300 ml distilled water (generally resulting in urine flow of 1 - 2 ml/min), blood pressure was measured with the patient in a recumbent position, and forearm venous blood withdrawn into heparinized prechilled tubes.…”

“…The morphology and nature of formed solids were documented by scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) elemental analysis (for details, techniques and equipment see ref. [18]).…”

Helper T‐cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques

“…In addition, Schwille et al . found that crystal nucleation in postprandial urine was more accelerated in CaP stones than in CaOx stones . Clinically, CaP stones are considered to score much higher on the HU scale than CaOx stones; that is, CaP stones are much harder and more difficult to break into pieces during surgical treatments.…”