William G. Robertson

The Cause of Idiopathic Calcium Stone Disease: Hypercalciuria or Hyperoxaluria?

Hypercalciuria is common in patients who form calcium oxalate urinary stones and is considered by many to be the cause of the disorder. This review shows that there is little relationship between either the rate of stone-formation or calcium oxalate crystalluria and the urinary excretion of calcium. There is, however, a strong relationship between these parameters and the urinary excretion of oxalate which is slightly, but significantly, elevated in stone-formers compared with normals. It is concluded that this mind degree of hyperoxaluria may be much more important than hypercalciuria in the genesis of calcium oxalate stones.

Saturation-inhibition index as a measure of the risk of calcium oxalate stone formation in the urinary tract.

Studies were carried out on multiple urine samples from eight patients with recurrent idiopathic calcium oxalate stone formation and eight normal persons to define an index of the risk of forming calcium oxalate stones. Under the same conditions of dietary and fluid intake the urine samples of the patients with stone formation were more supersaturated with calcium oxalate (P less than 0.001) and had lower concentrations of protective inhibitors of crystallization (P less than 0.001) than those of the controls. However, the best separation between the groups was defined by a discriminant line relating inhibitory activity and urine saturation. A measure of the risk of forming large crystals, the saturation-inhibition index, was defined as the distance of each urine from the discriminant line. The patients with stone formation had a significantly higher mean saturation-inhibition index than the controls (P less than 0.001). Both the percentage of large calcium oxalate crystals excreted (P less than 0.001) and the stone episode rate (P less than 0.005) were significantly correlated with the saturation-inhibition index.

Calcium Measurements in Serum and Plasma—Total and Ionized

This article will review the methods currently employed for measuring the concentrations of total and ionized calcium in serum or plasma. As far as total calcium is concerned, various techniques such as atomic absorption spectrometry, spectrophotometry, fluorometry, complexometric titration, and flame photometry will be described and compared. Particular emphasis will be given to the accuracy and precision of each technique. Possible sources of error and interfering agents will be identified and the various procedures for the taking and handling of blood samples evaluated. Inter-laboratory variation in the measurement of calcium will be studied. An assessment will be made of a new reference method for measuring total calcium in serum using isotope-dilution mass spectrometry. The usefulness of the total calcium measurement in clinical medicine will be briefly discussed. Within the last decade the refinement of spectrophotometric techniques and the improvements in ion-selective electrode technology have revolutionized the measurement of ionized calcium in serum, such that it may now be possible to replace total calcium measurements with ionized calcium measurements on a routine basis. The various techniques currently in use for measuring ionized calcium will be described and evaluated. Particular attention will be paid to the preparation of standards, the procedures for taking blood samples, and the handling of the samples prior to and during measurement. An assessment of the relative value of measuring total and ionized calcium will be presented.

When Should Patients with Symptomatic Urinary Stone Disease be Evaluated Metabolically

To determine the optimal time at which to assess the urinary risk factors for calcium stone formation, we followed 11 patients after an episode of acute renal colic with sequential 24-hour urine collections, first in the hospital and then at regular intervals after they were discharged from the hospital. The changes that occurred in the urinary risk factors were compared to those of a control group in which samples were collected during the same interval. The in-hospital 24-hour urine volumes were high but decreased gradually to approach the relatively constant volume of the control group by 3 months. The opposite trend occurred with respect to the 24-hour urinary excretion of calcium. There were no significant changes in the 24-hour urinary pH or excretions of oxalate, uric acid and alcian blue precipitable polyanions. The over-all effect was to cause a progressive increase in the probability of stones forming in the patients. The accurate assessment of the urinary risk factors of calcium stone disease requires at least a 3-month delay following acute renal colic. This delay usually will provide sufficient time for the stone to pass and for the patient to return to the normal dietary and fluid intake.

Phosphate treatment of recurrent calcium stone disease.

A group of 38 male recurrent idiopathic calcium stone formers were treated with oral supplements of orthophosphate (1 g phosphorus extra in the diet per day) and followed at intervals up to 4 years. The urinary excretion of calcium decreased (p less than 0.001) and that of inorganic phosphate increased (p less than 0.001) during treatment. These changes resulted in a small decrease in the supersaturation of urine with respect to calcium oxalate, sufficient to reduce the percentage of urines which exceeded the upper limit of solubility of that salt, and a small increase in the supersaturation of urine with respect to calcium phosphate. The stone episode rate on treatment fell in 35 of the 38 patients from a mean pretreatment value of 0.66 episodes/year to 0.22 episodes/year. The 3 initially most prolific stone formers increased their rate of stone formation during treatment. Plasma biochemistry showed no evidence of parathyroid stimulation.

Treatment of Urinary Tract Stone Disease

Urinary stone disease has a worldwide distribution. In poorer agricultural societies the disease occurs mainly as bladder stone disease in boys; in the more affiuent societies it predominantly affects the upper urinary tract of adults. The incidence of stone disease at present is about 7: I0,000 population/year with wide local and geographical variations. It has progressively increased during this century, such that urinary stones are now one of the most frequent causes of acute surgical admissions in many hospitals. Over the last 20 years, studies from many research centres have identified the various types of stone causing the disease, the main urinary factors responsible for stone formation, and the diseases and environmental factors leading to the urinary abnormalities. With this knowledge has come a more rational approach to the management of the patient with urinary stones, and to the treatment and prevention of the various types of stone disease. Treatment and prevention, however. are still far from satisfactory and continue to challenge the combined efforts of the surgeon. hospital physician. family physician and the patient him/herself, since the disease is usually recurrent and treatment must be maintained throughout the patients life. J. Pathogenesis