Is magnesium a marker of disordered mineral metabolism in males with idiopathic recurrent calcium urolithiasis? Observations focussing on fasting magnesiuria and magnesiemia, protein and other substances in urine and plasma

Abstract

Mg can theoretically play a role in renal calcium stone formation of IRCU patients, but the status of Mg is uncertain. The aim of this study was to investigate whether in IRCU variation of Mg in fasting urine and plasma is associated with altered urine Ca, Pi, oxalate, Ca/Pi ratio, supersaturation and other factors, the clinical severity of stone disease (metabolic activity; MA) included. This was a cross-sectional study (284 IRCU patients), comprising males with mean age in the fifth decade and unimpaired renal function. Patients had an unrestricted home diet, standardized laboratory procedures, including sample collection (daily and fasting urine, plasma), with classification of patients according to tertiles of fasting Mg-uria, keeping comparable age, the number of patients with renal stones present or absent, and normo- or idiopathic hypercalciuria. MA was scored. We found that the tertile I patients (= referent) exhibited sub-normal fasting Mg excretion (< 4 mg/2 h) and fractional excretion (< 3.5%), in daily urine the lowest Mg and oxalate, but highest Ca excretion rate; compared with tertile III, tertile I patients had significantly lower plasma total (not ultrafiltrable) Mg, blood bicarbonate and pH, and the lowest MA; fasting urinary excretion of Ca and citrate were also low, but urinary Pi, body weight, plasma glucose and insulin were increased. In tertile III not only was Mg-uria (excretion, FE) significantly elevated vs I, but so were urinary pH, excretion of sodium, Ca, potassium, protein (total and non-albumin) and citrate, FE sodium and Ca, the urinary molar ratios Ca/Pi and Mg/Potassium, hydroxyapatite supersaturation, bone resorption markers, and MA; in this environment urinary oxalate and Ca oxalate supersaturation were unchanged, plasma glucose, insulin and parathyroid hormone decreased. The tertile II patients, showing intermediate Mg excretion, also exhibited (vs. I) increase of FE Mg, urinary excretion and FE of sodium and Ca, excretion of protein, citrate and bone markers, the ratios Ca/Pi and Mg/Potassium, and MA. When urinary Ca/Pi was considered as the outcome of disordered metabolism, significant determinants (according to multiple regression analysis) were urinary Pi (negative), Ca and Mg/Potassium (positive); significant determinants of MA, the sum of stone-forming processes, were the urinary concentration of non-albumin protein, Mg/Potassium and sodium (all positive). Among IRCU patients 1) approx. one third is in need of Mg conservation by the kidney, associated with low plasma total Mg, modest metabolic acidosis, a trend towards overweight, high plasma insulin and glucose; 2) low Mg- or acidosis-induced increase of bone resorption may follow, attenuating glycemia and insulinemia but forcing the kidney to functional adaptation, manifesting as a rise of urinary sodium, Mg, Ca, Pi, Ca/Pi, pH and protein, together presumably aggravating MA; 3) larger controlled studies are justified, to decide whether Mg deficiency initiates renal Ca stones, and if urinary Mg loss exaggerates IRCU.