Urinary phosphate excretion in the pathophysiology of idiopathic recurrent calcium urolithiasis: hormonal interactions and lipid metabolism.
Previous work in younger males with recurrent idiopathic calcium urolithiasis (RCU) demonstrated inappropriately high postprandial phosphaturia, hyperinsulinemia and insulin resistance, but normal glycemia. To investigate further whether these abnormalities occur also in RCU patients with a mean age corresponding to the life period with peak formation of calcium-containing stones, two trials were carried out in 155 males of comparable age and body mass index. All participants underwent a standardized laboratory examination, including collection of urine and blood before and following a test meal rich in carbohydrate and calcium but low in phosphorus. In trial 1, comprising control subjects (n = 12, mean age 42 years) and RCU patients (n = 24, mean age 41 years), phosphate (Pi) excretion and fractional Pi excretion in postprandial urine of controls did not change compared with the values in fasting urine, but were significantly increased in RCU, despite the fact that there was almost equal suppression of serum parathyroid hormone (PTH) and increase in serum calcitonin. Postprandially, RCU patients were hyperinsulinemic but still normoglycemic versus controls. In trial 2, carried out in unclassified (in terms of calciuria) RCU patients (n = 119, mean age 40 years) only, the post-load Pi-uria was similar in magnitude to Pi-uria of RCU patients in trial 1; increased postprandial Pi-uria was a phenomenon also of normocalciuria but was slightly more pronounced in hypercalciuria, while changes in calcium phosphate (brushite) and calcium oxalate supersaturation of urine were unrelated to calciuria. In RCU patients, but not controls, there was a tendency toward higher urinary glucose in post-load as compared with fasting urine. When urinary Pi and fractional Pi excretion in trial 2 were considered as dependent variables in multivariate regression analysis, they appeared unrelated to age, but positively associated with postprandial glycemia as the best predictor, followed by insulinemia, insulin resistance, to a lesser degree fasting serum PTH and the metabolic activity of stone disease, negatively associated with blood total lipids and very low density lipoprotein (VLDL) cholesterol. It was concluded that RCU males (1) show low Pi-uria during fasting but impaired renal Pi conservation in response to a mixed meal, a situation carrying the risk of Pi deficiency over the long term; (2) represent a population developing hyperPi-uria despite suppressed PTH; (3) exhibit insulin resistance but are still able to maintain normoglycemia at the expense of hyperinsulinemia. It is suggested that calcium-containing renal stones are related to impaired Pi and glucose translocation across cell membranes, and that the role of lipids in this setting deserves further investigation.
Schwille
P O
PO
University Hospital, Department of Surgery, Erlangen, Germany.
Herrmann
U
U
Schmiedl
A
A
Kissler
H
H
Wipplinger
J
J
Manoharan
M
M
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D002118:Calcium / Q000737:chemistry*; D003430:Cross-Sectional Studies; D005215:Fasting; D006728:Hormones / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000652:urine*; D019518:Postprandial Period; D012008:Recurrence; D014545:Urinary Calculi / Q000097:blood* / Q000737:chemistry / Q000652:urine*
D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D008055:Lipids; D010710:Phosphates; D002118:Calcium