Jan 27, 1977 - Normocalciuric and hypercalciuric patients with idiopathic recurrent calcium nephrolithiasis were compared with healthy individuals without ...
Idiopathic calcium nephrolithiasis. 2. Differences between hypercalciuric and normocalciuric persons with recurrent kidney stone formation and persons without such a history D.R. WILSON, MD, FRCP[C]; G. PYLYPCHUK,* MD, FRCP[C]; U. EHRIG,t MD, FRCP[C]
Normocalciuric and hypercalciuric patients with idiopathic recurrent calcium nephrolithiasis were compared with healthy individuals without such a history to examine the factors that predispose normocalciuric patients to stone formation. The urine calcium excretion rate was higher in the normocalciuric patients than in the control subjects (227 v. 183 mg/24 h; P < 0.01), but the urine calcium concentration was not significantly different. The urine magnesium and citrate excretion rates and concentrations were lower in the normocalciuric patients than in the control subjects (P < 0.001), while the urine uric acid and oxalate excretion rates and concentrations and the urine saturation with brushite (CaHPO4 .2H20) were not significantly different. These results suggest the importance of slight increases in the urine calcium excretion rate together with decreased urine magnesium and citrate excretion rates in normocalciuric persons with recurrent calcium stone formation. The urine of the hypercalciuric patients was more highly saturated with brushite than the urine of the normocalciuric patients and the control subjects, and the excretion rates of uric acid and oxalate were increased in the hypercalciuric patients. The hypercalciuric patients had a higher urine creatinine excretion rate than the normocalciuric patients and a higher daily urine volume than the control subjects, which suggests that differences in lean body mass or fluid and food intake, or both, may be important determinants of these differences in crystalloid excretion. As in the normocalciuric patients, the urine citrate excretion rate and concentration were. decreased in the hypercalciuric patients compared with the control subjects. From the department of medicine, University of Toronto Presented in part at the 46th annual meeting of the Royal College of Physicians and Surgeons of Canada, Toronto, Jan. 27, 1977 *Present address: Phoenix House, 22620th St. E, Saskatoon, Sask. tPresent address: Pentucket Medical Associates, Haverhill, Mass., USA Reprint requests to: Dr. D.R. Wilson, Division of nephrology, College wing, Rm. 3-218, Toronto General Hospital, Toronto, Ont. M5G 1L7 666
Des patients normocalciuriques et hypercalciuriques souffrant de lithiase renale calcique idiopathique recidivante ont ete compares a des individus sains n'ayant pas de tels antecedents af in d'examiner les facteurs qui predisposent des patients normocalciuriques A Ia formation de calculs. Le taux d'excretion urinaire du calcium etait plus grande chez les patients normocalciuriques que chez les temoins (227 contre 183 mg/24 h; P < 0.01) mais Ia concentration urinaire en calcium n'etait pas significativement differente. Les taux d'excretion et les concentrations urinaires du magnesium et du citrate etaient plus faibles chez les patients normocalciuriques que chez les temoins (P < 0.001) alors que les taux d'excretion et les concentrations urinaires de l'acide urique et de l'oxalate, et Ia saturation de l'urine avec le phosphate bicalcique (brushite) (CaHPO4 .2H20) n'etaient pas significativement differentes. Ces resultats suggerent l'importance de modestes augmentations des taux d'excre. tion urinaire du calcium, ainsi que d'une diminution des taux d'excr6tion urinaire du magnesium et du citrate chez les personnes qui ont Ia formation de calculs calciques recurrents. L'urine des patients hypercalciuriques etait plus fortement saturee avec le phosphate bicalcique que celle des patients normocalciuriques et des temoins, et les taux d'excr6tion de l'acide urique et de l'oxalate etaient augmentes chez les patients hyper. calciuriques. Les patients hypercalci. uriques montraient un taux d'excretion urinaire de Ia creatinine plus grand que celui des patients normocalciuriques et un volume urinaire quotidien sup6rieur A celui des t6moins, ce qui suggere que des differences dans Ia masse maigre de lorganisme ou dans lapport de liquide ou de nourriture peuvent Atre des determinants importants de ces differences. Tout comme chez les patients normocalciuriques, le taux d'excr6tion et Ia concentration urinaires du citrate etaient diminues chez les patients hypercalciuriques comparativement aux sujets temoins.
Calcium stones, which are composed of calcium oxalate or a mixture of calcium phosphate and calcium oxalate, account for approximately
CMA JOURNAL/MARCH 17, 1979/VOL. 120
80% of all renal calculi. In patients with idiopathic calcium nephrolithiasis, increased excretion and concentration of urine calcium are important factors in the supersaturation of the urine with calcium oxalate or calcium phosphate or both, and hence in spontaneous crystal formation or crystal growth in the urine. Hypercalciuria, however, was present in only 45% to 65% of two large groups of patients with calcium nephrolithiasis.1" In the study described in this paper we examined factors that could be important in calcium stone formation when the rate of urine calcium excretion was considered to be normal.
Patients with recurrent idiopathic calcium nephrolithiasis were divided into two groups on the basis of the rate of urine calcium excretion, and the normocalciuric and hypercalciuric patients were compared with each other and with control subjects to determine the factors that predisposed the normocalciuric patients to
calcium stone formation. Patients and methods The 64 patients with recurrent idiopathic calcium nephrolithiasis described in part 1 of this report (which begins on page 658 of this issue of the Journal) were divided into two groups: a hypercalciuric group, consisting of the 33 subjects, including 3 women, who had an average 24-hour urine calcium excretion greater than 300 mg (in men) or 250 mg (in women); and a normocalciuric group, consisting of the remaining 31 patients, including 5 women. The two
groups were compared with the control group of 30 healthy individuals without a history of recurrent calcium nephrolithiasis described in part 1. The chemical methods are documented in part 1. The data were analysed by a computer with the use of Student's t-test.
Results
The urine concentration of crystalbids is probably more important than the excretion rate in determining urine saturation and the tendency to urinary crystal growth and aggregation; therefore, the results are expressed both ways in Table 1. The normocalciuric patients had a significantly greater urine volume and rate of calcium excretion than the control subjects, although the rate of calcium excretion was in the generally accepted range of normal values. The urine calcium concentration was higher in the normocalciuric patients than in the control subjects, but the difference was not significant. The urine magnesium excretion rate and concentration were markedly less in the normocalciuric patients than in the control subjects, as were the urine citrate excretion rate and
concentration. The phosphate, uric acid and oxalate excretion rates were similar in the two groups, while the urine phosphate and uric acid concentrations were decreased in the patients. The hypercalciuric patients had a higher creatinine excretion rate than the normocalciuric patients and a higher urine volume than the control subjects. The urine magnesium excretion rate was considerably higher in the hypercalciuric patients than in the normocalciuric patients and was similar to that of the control subjects, but the urine magnesium concentration was decreased in the hypercalciuric patients, compared with the control subjects, because of the higher urine volume. The uric acid and oxalate excretion rates were higher in the hypercalciuric patients than in the other two groups, but the urine concentrations of these crystalloids
were the same or lower. Both the excretion rate and the concentration of urine citrate were decreased in the hypercalciuric patients as compared with the control subjects. The urine saturation with brushite was not significantly different from normal in the normocalciuric patients, while collagen calcification by urine in vitro was significantly greater than normal (P < 0.05, Table II). Both were significantly greater than normal in the hypercalciuric patients. The excretion rate of urine inhibitors of collagen calcification was much higher in the hypercalciuric patients than in the other two groups, but the concentration of the inhibitors did not differ in the three groups. The relative saturation of the urine with calcium oxalate, calculated from the nomogram of Marshall and Robertson3 with the use of the measured urine calcium and oxalate con-
Table I-Urine crystalloid values in healthy individuals without a history of recurrent idiopathic calcium nephrolithiasis and in normocalciuric and hypercalciuric patients with such a history Mean . 1 standard error (SE) of the mean Urine variable Volume (mL/24 h) Creatinine excretion rate (mg/24 h) Calcium Excretion rate (mg/24 h) Concentration (mmol/L) Magnesium Excretion rate (mg/24 h) Concentration (mmol/L) pH Phosphate Excretion rate (mg/24 h) Concentration (mmol/L) Uric acid Excretion rate (mg/24 h) Concentration (mg/I) Oxalate Excretion rate (mg/24 h) Concentration (mmol/L) Citrate Excretion rate (mg/24 h) Concentration (mg/I) *NS not significant.
Controls (A) (n = 30)
Normocalciuric patients (B) (n = 31)
1266 ± 87 1784 76 183 . 13 3.84 0.21
1582 + 109 1634 ± 65 227 10 4.23 + 0.31 71 ± 4 1.99 + 0.18 6.12 ± 0.07 891 55 21.5 + 1.5 722 + 30 517 ± 39 29 ± 2 0.17 ± 0.03
92 . 4 3.25 ± 0.15 6.21 :I 0.06 913 i 33 26.7 i: 1.7 748 . 22 654 . 40 29 + 1 0.20 :1 0.01 637 ± 34 553 + 37
459 ± 34 318 ± 29
Av.B
P value. Av.C
Bv.C
1797 ± 96 1877 ± 60
