Vol. 116, December Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
A CASE OF URIC ACID RENAL STONE WITH HYPOURICEMIA CAUSED BY TUBULAR REABSORPTIVE DEFECT OF URIC ACID KAZUKI KAWABE, TAKEO MURAYAMA
AND
IEO AKAOKA
From the Urology Section, Sanraku Hospital and Departments of Urology and Internal Medicine and Physical Therapy, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
ABSTRACT
A 60-year-old man had a uric acid stone in the kidney and laboratory findings of hypouricemia ( l, 1 mg, per 100 ml.) and increased uric acid clearance (43 ml. per minute per 1,73 m. 2 ). Clearance of uric acid exceeded the, endogenous creatinine clearance after administration of pyrazinamide, an inhibitor of renal tubular secretion of uric acid. It was suggested that our patient had a complete defective mechanism for uric acid reabsorption, resulting in hyperuricuria and the formation of the uric acid stone. infiltration in the pelvic mucosa and interstitial connective tissue. This finding was consistent with mild interstitial nephritis. The calculus was a pure uric acid stone. Postoperatively, hypouricemia persisted (1.1 to 0.7 mg. per 100 ml.). The values of urinary excretion of uric acid ranged from 0.7 to 1.6 gm. per day, depending on the food eaten. Uric acid clearance was 43 ml. per minute per 1.73 perm. 2 of body surface area and creatinine clearance was 88.8 ml. per minute per 1.73 m. 2
A significant number of patients with uric acid calculi have neither hyperuricemia nor increased urinary excretion of uric acid, whereas those with hyperuricuria have an increased risk of stone formation. 1 However, uric acid nephrolithiasis associated with hyperuricuria owing to an inherent defect of reabsorption of uric acid is unusual. 1 We present a rare case of uric acid stone of the kidney, probably caused by a defective mechanism for tubular reabsorption of uric acid. CASE REPORT
METHODS
A 60-year-old man was admitted to our hospital on September 3, 1974 for the evaluation of microscopic hematuria, which had been detected by another physician 2 years previously. There was no pertinent medical or family history. Physical examination revealed a well developed man in apparent good health. Blood pressure was 146/86 mm. Hg on admission to the hospital. Body weight was 62 kg. and height was 170 cm. Routine blood cell counts were not remarkable. The most striking abnormal laboratory finding was a low level of serum uric acid at 1.1 mg. per 100 ml. All other values of serum chemistry studies were within normal limits: blood urea nitrogen 11.6 mg. per 100 ml., creatinine 1.0 mg. per 100 ml., sodium 145 mEq. per 1., potassium 3.5 mEq. per I., chloride 108 mEq. per I., calcium 9.2 mg. per 100 ml. and inorganic phosphorus 2.4 mg. per 100 ml. Serum copper was 97 µg. per 100 ml. and serum ceruloplasmin was 28 mg. per 100 ml. The serum protein was 7.0 gm. per 100 ml., with a normal pattern on electrophoresis. Plasma renin activity was 0.7 ng. per ml. per hour on a regular diet. Routine urinalysis showed a pH of 5.0 to 6.1, average 5.5, and was negative for protein and sugar. There were 20 to 30 red blood cells per high power field and many amorphous crystals in the urinary sediments. The urinary pattern of amino acid by resin column chromatography showed no abnormalities and urinary cytology was negative. Fasting glucose level was 88 mg. per 100 ml. Roentgenograms of the chest and bones were normal. A scout film of the kidneys, ureters and bladder was negative for any calcified lesions. Excretory urography revealed a filling defect, suggesting a renal stone in the lower calix of the left kidney but a small caliceal tumor could not be denied com2letely at this stage. Left partial nephrectomy was done and a caliceal stone was removed on September 5. A small amount of delayed hematuria was noted 14 days postoperatively but otherwise convalescence was uneventful. Microscopic examination of the removed kidney tissue disclosed moderate lymphocyte
Various clearance studies were done postoperatively while the patient was on a low purine diet for a week before and during the study. Uric acid was determined by the enzymatic method. Renal clearance of uric acid (Cur) was measured before and after the oral administration of 3.0 gm. pyrazinamide, as proposed by Steele and Rieselbach, 2 except that the endogenous creatinine clearance (Ccr) was used instead of inulin clearance (C,n), Uric acid clearance also was determined after the oral administration of 1.5 gm. probenecid, a uricosuric agent. Incorporation of glycine 15 N into urinary uric acid was measured by the method of Benedict and associates. 3 A single oral dose of 0.1 gm. per kg. body weight glycine 15 N was administered and 24-hour urine samples were collected for 7 days. Urinary oxypurines (xanthine plus hypoxanthine) were determined by the method of Jorgensen and Poulsen. 4
Accepted for publication March 26, 1976. 690
RESULTS
Plasma uric acid concentrations in our patient ranged from 0.50 to 0.59 mg. per 100 ml. Urinary excretion of uric acid was 516 mg. per 24 hours, averaged from 7 measurements with the patient placed on the low purine diet. The mean uric acid clearance was 69.8 ml. per minute per 1.73 m. 2 body surface area, which was approximately equal to the endogenous creatinine clearance. Since normal Cur is 4 to 14 ml. per minute 5 that of our patient was markedly high. Results of the pyrazinamide suppression test in the patient and in 2 normal controls are summarized in table 1. In our patient Cur and the ratio of Cur to Ccr were markedly elevated (normal Cur to C,n equal to 0.098 plus or minus 0.011) 2 in the control period, with mean values of 64.6 ml. per minute and 1.04, respectively, and the values were slightly increased after the administration of pyrazinamide. According to Steele and Rieselbach 2 the maximum decrease in UurV per Ccc represents the tubular secretion of uric acid (TSur), which was 5.90 minus 4.45 equaled 1.45 µg. per ml. Because the calculated normal value of TSur at the Sur of 0.5
691
HYPOURICEMIA AND URIC ACID RENAL STONE TABLE
1. Clearance of creatinine and uric acid in patient and 2 control subjects with use of 3.0 gm. pyrazinamide*
Patient KY: Control period Pyrazinamide period
Control subject IA: Control period
Pyrazinamide period
Serum Urate Concentration (mg./100 ml.)
C" (ml./min.)
1 2 3 4 5 6
0.59 0.55 0.34 0.21 0.25 0.34
65.7 58.3 71.3 58.3 65.4 57.3
1 2 3 4 5
4.19 4.19 4.19 4.19 4.19 4.19
2.60 2.68 2.76 2.77 2.51 3.35
6
Control subject TN: Control period
1 2 3 4 5
Pyrazinamide period
6
Cu, (ml./min.)
Cu,/Ccc (%)
Uu,V /Ccc (µg./ml.)
68.7 60.6 106.9 150.0 115.9 99.4
104.5 103.9 149.9 257.2 177.3 173.6
6.13 5.66 5.02 5.40 4.45 5.82
110.4 101.2 75.4 79.6 108.1 118.9
14.4 12.8 10.7 7.7 2.1 1.6
13.1 12.6 14.2 9.7 2.0 1.4
5.48 5.28 5.94 4.06 0.82 0.57
114.6 127.7 112.0 107.5 93.3 103.3
12.6 9.7 8.6 5.7 2.4 1.2
8.3 7.6 7.6 5.3 2.6
2.26 2.03 2.11 1.48 0.64 0.38
1.1
* Not corrected for body surface area.
TABLE
Control period
2. Clearance of uric acid in patient with use of 1.5 gm. probenecid Serum Urate Concentration (mg./100 ml.)
C" (ml./min.)
Cu, (ml./min.)
Cu,./Ccc (%)
Uu,.V/Ccc (µg./ml.)
0.50 0.59 0.46 0.34 0.46
78.6 62.8 56.9 59.7 58.3
80.1 68.3 81.6 95.2 67.0
101.9 108.8 143.3 159.5 114.9
5.13 6.39 6.60 5.34 5.30
1 2
Pro benecid period
3 4 5
before and after administration of probenecid were 5.76 and 5.75 µg. per ml. on the average, respectively. The cumulative 15 N concentration in urinary uric acid during the 7 days after oral administration of glycine 15N was 0.11 per cent in the patient and 0.10 per cent in a normal control subject (see figure). These values were within the normal limits proposed by Benedict and associates. 3 Urinary oxypurine excretion was 14.9 mg. per day (normal 5 to 25 mg. per day). 4
0.15
.g :::,
~
0.10
C
·;: :::,
0
DISCUSSION
1J
Abnormally low serum urate concentrations (less than 2 mg. per 100 ml.) are rare in man. 5 ' • The incidence of such hypouricemia in numerous measurements was found to be approximately 1 per cent. 5 Hypouricemia was caused either by diminished production of uric acid or by increased excretion of uric acid. Hypouricemia occurring in decreased production of uric acid is best known in xanthinuria, a congenital defect of xanthine oxidase or in administration of allopurinol, a xanthine oxidase inhibitor. Hypouricemia owing to accelerated excretion of uric acid is seen in various disorders, such as Fanconi's syndrome, Wilson's disease and Hartnup's disease. In these instances the uric acid clearance is increased in contrast to the cases of diminished production of uric acid. There are generalized defects of tubular transport, evidenced by amino-aciduria and hyperphosphaturia in Fanconi's syndrome or carcinoma of the lung. 5 Mild hypouricemia also is presented in early pregnancy and at the time of salt loading, probably caused by increased uric acid clearance. 7 Our case does not have the aforementioned characteristics but resembles the cases reported by Praetorius and Kirk, 8
E Q)
1ii 0
C.
0 ()
0.05
.!:
0
2
3
4
5
6
7 days
Cumulative excretion of uric acid "N after administration of glycine "N.
mg. per 100 ml. was 0.413 Pur1. 359 equaled 0.12 µg. per ml., tubular secretion of uric acid was considered elevated. Data of the probenecid administration test are summarized in table 2. The mean ratios of Cur to Ccr before and after oral administration of 1.5 gm. probenecid were 1.05 and 1.39, respectively. The uric acid excretion indexes (U ur V per Cc,)
692
KAWABE, MURAYAMA AND AKAOKA
Greene and associates,• and Khachadurian and Arslanian, 10 in which the uric acid clearance was markedly increased. Praetorius and Kirk's patient showed a marked uric acid clearance exceeding the inulin clearance by 46 per cent but there were no data available concerning the pyrazinamide suppression test. In fact, there have been some cases in which the uric acid clearance is markedly increased but is blocked by pyrazina, mide. 2, u, ,2 In our case, as well as the patients of Greene and associates• and of Khachadurian and Arslanian, 10 the uric acid clearance was not diminished by pyrazinamide. In our patient the uric acid clearance was markedly elevated nearly equal to the glomerular filtration rate and unaffected by pyrazinamide. These results suggested the complete block of tubular reabsorption of uric acid. In addition, the rate of the tubular secretion of uric acid was elevated, considering the low serum concentration. Administration of probenecid did not affect the uric acid clearance, 13 which meant the maximal uricosuric state was operating in this patient. Accordingly, the accelerated uric acid excretion induced the extremely low urate concentration in the patient, especially when he was placed on a low purine diet. Increased production of purines was not excluded from the data on the incorporation rate of glycine 15N into urinary uric acid but the possibility is slight. Uric acid stone formation has not been raported in this type of renal lesion. Hyperuricuria noted when the patient was on regular food facilitated the urate deposition in acid urine and in the presence of other predisposing factors. 1 In conclusion, our case may have had a complete defect of uric acid reabsorption and a possible hypersecretion of uric acid, which resulted in occasional high concentration of urinary uric acid and in a renal stone of uric acid.
REFERENCES 1. Gutman, A. B. and Yii, T. F.: Uric acid nephrolithiasis. Amer. J.
Med., 45: 756, 1968. 2. Steele, T. H. and Rieselbach, R. E.: The renal mechanism for urate homeostasis in normal man. Amer. J. Med., 43: 868, 1967. 3. Benedict, J. D., Roche, M., Yii, T. F., Bien, E. J., Gutman, A. B. and Stepten, B., Jr.: Incorporation of glycine nitrogen into uric acid in normal and gouty man. Metabolism, 1: 3, 1952. 4. J!,irgensen, S. and Poulsen, H.: Enzymic determination of hypoxanthine and xanthine in human plasma and urine. Acta Pharmacol. Toxicol., 11: 223, 1955. 5. Ramsdell, C. M. and Kelley, W. N.: The clinical significance of hypouricemia. Ann. Intern. Med., 78: 239, 1973. 6. Van Peenen, H.J.: Causes ofhypouricemia. Ann. Intern. Med., 78: 977, 1973. 7. Holmes, E.W., Kelley, W. N. and Wyngaaden, J.B.: The kidney and uric acid excretion in man. Kidney Int., 2: 115, 1972. 8. Praetorius, E. and Kirk, J. E.: Hypouricemia: with evidence for tubular elimination of uric acid. J. Lab. Clin. Med., 38: 865, 1950. 9. Greene, M. L., Marcus, R., Aurbach, G. D., Kazam, E. S. and Seegmiller, J. E.: Hypouricemia due to isolated renal tubular defect. Dalmatian dog mutation in man. Amer. J. Med., 53: 361, 1972. 10. Khachadurian, A. K. and Arslanian, M. J.: Hypouricemia due to renal uricosuria. A case study. Ann. Intern. Med., 78: 547, 1973. 11. Bennett, J. S., Bond, J., Singer, I. and Gottlieb, A. J.: Hypouricemia in Hodgkin's disease. Ann. Intern. Med., 76: 751, 1972. 12. Sperling, 0., Weinberger, A., Oliver, I., Liberman, U. A. and De Vries, A.: Hypouricemia, hypercalciuria, and decreased bone density: a hereditary syndrome. Ann. Intern. Med., 80: 482, 1974. 13. Akaoka, I., Nishizawa, T., Yano, E., Takeuchi, A., Nishida, Y., Yoshimura, T. and Horiuchi, Y.: Familial hypouricemia due to renal tubular defect of urate transport. Ann. Clin. Res., 7: 318, 1975.
THE JOURNAL OF UROLOGY
Copyright© 1976 by The Williams & Wilkins Co.
A CASE OF URIC ACID RENAL STONE WITH HYPOURICEMIA CAUSED BY TUBULAR REABSORPTIVE DEFECT OF URIC ACID KAZUKI KAWABE, TAKEO MURAYAMA
AND
IEO AKAOKA
From the Urology Section, Sanraku Hospital and Departments of Urology and Internal Medicine and Physical Therapy, Faculty of Medicine, the University of Tokyo, Tokyo, Japan
ABSTRACT
A 60-year-old man had a uric acid stone in the kidney and laboratory findings of hypouricemia ( l, 1 mg, per 100 ml.) and increased uric acid clearance (43 ml. per minute per 1,73 m. 2 ). Clearance of uric acid exceeded the, endogenous creatinine clearance after administration of pyrazinamide, an inhibitor of renal tubular secretion of uric acid. It was suggested that our patient had a complete defective mechanism for uric acid reabsorption, resulting in hyperuricuria and the formation of the uric acid stone. infiltration in the pelvic mucosa and interstitial connective tissue. This finding was consistent with mild interstitial nephritis. The calculus was a pure uric acid stone. Postoperatively, hypouricemia persisted (1.1 to 0.7 mg. per 100 ml.). The values of urinary excretion of uric acid ranged from 0.7 to 1.6 gm. per day, depending on the food eaten. Uric acid clearance was 43 ml. per minute per 1.73 perm. 2 of body surface area and creatinine clearance was 88.8 ml. per minute per 1.73 m. 2
A significant number of patients with uric acid calculi have neither hyperuricemia nor increased urinary excretion of uric acid, whereas those with hyperuricuria have an increased risk of stone formation. 1 However, uric acid nephrolithiasis associated with hyperuricuria owing to an inherent defect of reabsorption of uric acid is unusual. 1 We present a rare case of uric acid stone of the kidney, probably caused by a defective mechanism for tubular reabsorption of uric acid. CASE REPORT
METHODS
A 60-year-old man was admitted to our hospital on September 3, 1974 for the evaluation of microscopic hematuria, which had been detected by another physician 2 years previously. There was no pertinent medical or family history. Physical examination revealed a well developed man in apparent good health. Blood pressure was 146/86 mm. Hg on admission to the hospital. Body weight was 62 kg. and height was 170 cm. Routine blood cell counts were not remarkable. The most striking abnormal laboratory finding was a low level of serum uric acid at 1.1 mg. per 100 ml. All other values of serum chemistry studies were within normal limits: blood urea nitrogen 11.6 mg. per 100 ml., creatinine 1.0 mg. per 100 ml., sodium 145 mEq. per 1., potassium 3.5 mEq. per I., chloride 108 mEq. per I., calcium 9.2 mg. per 100 ml. and inorganic phosphorus 2.4 mg. per 100 ml. Serum copper was 97 µg. per 100 ml. and serum ceruloplasmin was 28 mg. per 100 ml. The serum protein was 7.0 gm. per 100 ml., with a normal pattern on electrophoresis. Plasma renin activity was 0.7 ng. per ml. per hour on a regular diet. Routine urinalysis showed a pH of 5.0 to 6.1, average 5.5, and was negative for protein and sugar. There were 20 to 30 red blood cells per high power field and many amorphous crystals in the urinary sediments. The urinary pattern of amino acid by resin column chromatography showed no abnormalities and urinary cytology was negative. Fasting glucose level was 88 mg. per 100 ml. Roentgenograms of the chest and bones were normal. A scout film of the kidneys, ureters and bladder was negative for any calcified lesions. Excretory urography revealed a filling defect, suggesting a renal stone in the lower calix of the left kidney but a small caliceal tumor could not be denied com2letely at this stage. Left partial nephrectomy was done and a caliceal stone was removed on September 5. A small amount of delayed hematuria was noted 14 days postoperatively but otherwise convalescence was uneventful. Microscopic examination of the removed kidney tissue disclosed moderate lymphocyte
Various clearance studies were done postoperatively while the patient was on a low purine diet for a week before and during the study. Uric acid was determined by the enzymatic method. Renal clearance of uric acid (Cur) was measured before and after the oral administration of 3.0 gm. pyrazinamide, as proposed by Steele and Rieselbach, 2 except that the endogenous creatinine clearance (Ccr) was used instead of inulin clearance (C,n), Uric acid clearance also was determined after the oral administration of 1.5 gm. probenecid, a uricosuric agent. Incorporation of glycine 15 N into urinary uric acid was measured by the method of Benedict and associates. 3 A single oral dose of 0.1 gm. per kg. body weight glycine 15 N was administered and 24-hour urine samples were collected for 7 days. Urinary oxypurines (xanthine plus hypoxanthine) were determined by the method of Jorgensen and Poulsen. 4
Accepted for publication March 26, 1976. 690
RESULTS
Plasma uric acid concentrations in our patient ranged from 0.50 to 0.59 mg. per 100 ml. Urinary excretion of uric acid was 516 mg. per 24 hours, averaged from 7 measurements with the patient placed on the low purine diet. The mean uric acid clearance was 69.8 ml. per minute per 1.73 m. 2 body surface area, which was approximately equal to the endogenous creatinine clearance. Since normal Cur is 4 to 14 ml. per minute 5 that of our patient was markedly high. Results of the pyrazinamide suppression test in the patient and in 2 normal controls are summarized in table 1. In our patient Cur and the ratio of Cur to Ccr were markedly elevated (normal Cur to C,n equal to 0.098 plus or minus 0.011) 2 in the control period, with mean values of 64.6 ml. per minute and 1.04, respectively, and the values were slightly increased after the administration of pyrazinamide. According to Steele and Rieselbach 2 the maximum decrease in UurV per Ccc represents the tubular secretion of uric acid (TSur), which was 5.90 minus 4.45 equaled 1.45 µg. per ml. Because the calculated normal value of TSur at the Sur of 0.5
691
HYPOURICEMIA AND URIC ACID RENAL STONE TABLE
1. Clearance of creatinine and uric acid in patient and 2 control subjects with use of 3.0 gm. pyrazinamide*
Patient KY: Control period Pyrazinamide period
Control subject IA: Control period
Pyrazinamide period
Serum Urate Concentration (mg./100 ml.)
C" (ml./min.)
1 2 3 4 5 6
0.59 0.55 0.34 0.21 0.25 0.34
65.7 58.3 71.3 58.3 65.4 57.3
1 2 3 4 5
4.19 4.19 4.19 4.19 4.19 4.19
2.60 2.68 2.76 2.77 2.51 3.35
6
Control subject TN: Control period
1 2 3 4 5
Pyrazinamide period
6
Cu, (ml./min.)
Cu,/Ccc (%)
Uu,V /Ccc (µg./ml.)
68.7 60.6 106.9 150.0 115.9 99.4
104.5 103.9 149.9 257.2 177.3 173.6
6.13 5.66 5.02 5.40 4.45 5.82
110.4 101.2 75.4 79.6 108.1 118.9
14.4 12.8 10.7 7.7 2.1 1.6
13.1 12.6 14.2 9.7 2.0 1.4
5.48 5.28 5.94 4.06 0.82 0.57
114.6 127.7 112.0 107.5 93.3 103.3
12.6 9.7 8.6 5.7 2.4 1.2
8.3 7.6 7.6 5.3 2.6
2.26 2.03 2.11 1.48 0.64 0.38
1.1
* Not corrected for body surface area.
TABLE
Control period
2. Clearance of uric acid in patient with use of 1.5 gm. probenecid Serum Urate Concentration (mg./100 ml.)
C" (ml./min.)
Cu, (ml./min.)
Cu,./Ccc (%)
Uu,.V/Ccc (µg./ml.)
0.50 0.59 0.46 0.34 0.46
78.6 62.8 56.9 59.7 58.3
80.1 68.3 81.6 95.2 67.0
101.9 108.8 143.3 159.5 114.9
5.13 6.39 6.60 5.34 5.30
1 2
Pro benecid period
3 4 5
before and after administration of probenecid were 5.76 and 5.75 µg. per ml. on the average, respectively. The cumulative 15 N concentration in urinary uric acid during the 7 days after oral administration of glycine 15N was 0.11 per cent in the patient and 0.10 per cent in a normal control subject (see figure). These values were within the normal limits proposed by Benedict and associates. 3 Urinary oxypurine excretion was 14.9 mg. per day (normal 5 to 25 mg. per day). 4
0.15
.g :::,
~
0.10
C
·;: :::,
0
DISCUSSION
1J
Abnormally low serum urate concentrations (less than 2 mg. per 100 ml.) are rare in man. 5 ' • The incidence of such hypouricemia in numerous measurements was found to be approximately 1 per cent. 5 Hypouricemia was caused either by diminished production of uric acid or by increased excretion of uric acid. Hypouricemia occurring in decreased production of uric acid is best known in xanthinuria, a congenital defect of xanthine oxidase or in administration of allopurinol, a xanthine oxidase inhibitor. Hypouricemia owing to accelerated excretion of uric acid is seen in various disorders, such as Fanconi's syndrome, Wilson's disease and Hartnup's disease. In these instances the uric acid clearance is increased in contrast to the cases of diminished production of uric acid. There are generalized defects of tubular transport, evidenced by amino-aciduria and hyperphosphaturia in Fanconi's syndrome or carcinoma of the lung. 5 Mild hypouricemia also is presented in early pregnancy and at the time of salt loading, probably caused by increased uric acid clearance. 7 Our case does not have the aforementioned characteristics but resembles the cases reported by Praetorius and Kirk, 8
E Q)
1ii 0
C.
0 ()
0.05
.!:
0
2
3
4
5
6
7 days
Cumulative excretion of uric acid "N after administration of glycine "N.
mg. per 100 ml. was 0.413 Pur1. 359 equaled 0.12 µg. per ml., tubular secretion of uric acid was considered elevated. Data of the probenecid administration test are summarized in table 2. The mean ratios of Cur to Ccr before and after oral administration of 1.5 gm. probenecid were 1.05 and 1.39, respectively. The uric acid excretion indexes (U ur V per Cc,)
692
KAWABE, MURAYAMA AND AKAOKA
Greene and associates,• and Khachadurian and Arslanian, 10 in which the uric acid clearance was markedly increased. Praetorius and Kirk's patient showed a marked uric acid clearance exceeding the inulin clearance by 46 per cent but there were no data available concerning the pyrazinamide suppression test. In fact, there have been some cases in which the uric acid clearance is markedly increased but is blocked by pyrazina, mide. 2, u, ,2 In our case, as well as the patients of Greene and associates• and of Khachadurian and Arslanian, 10 the uric acid clearance was not diminished by pyrazinamide. In our patient the uric acid clearance was markedly elevated nearly equal to the glomerular filtration rate and unaffected by pyrazinamide. These results suggested the complete block of tubular reabsorption of uric acid. In addition, the rate of the tubular secretion of uric acid was elevated, considering the low serum concentration. Administration of probenecid did not affect the uric acid clearance, 13 which meant the maximal uricosuric state was operating in this patient. Accordingly, the accelerated uric acid excretion induced the extremely low urate concentration in the patient, especially when he was placed on a low purine diet. Increased production of purines was not excluded from the data on the incorporation rate of glycine 15N into urinary uric acid but the possibility is slight. Uric acid stone formation has not been raported in this type of renal lesion. Hyperuricuria noted when the patient was on regular food facilitated the urate deposition in acid urine and in the presence of other predisposing factors. 1 In conclusion, our case may have had a complete defect of uric acid reabsorption and a possible hypersecretion of uric acid, which resulted in occasional high concentration of urinary uric acid and in a renal stone of uric acid.
REFERENCES 1. Gutman, A. B. and Yii, T. F.: Uric acid nephrolithiasis. Amer. J.
Med., 45: 756, 1968. 2. Steele, T. H. and Rieselbach, R. E.: The renal mechanism for urate homeostasis in normal man. Amer. J. Med., 43: 868, 1967. 3. Benedict, J. D., Roche, M., Yii, T. F., Bien, E. J., Gutman, A. B. and Stepten, B., Jr.: Incorporation of glycine nitrogen into uric acid in normal and gouty man. Metabolism, 1: 3, 1952. 4. J!,irgensen, S. and Poulsen, H.: Enzymic determination of hypoxanthine and xanthine in human plasma and urine. Acta Pharmacol. Toxicol., 11: 223, 1955. 5. Ramsdell, C. M. and Kelley, W. N.: The clinical significance of hypouricemia. Ann. Intern. Med., 78: 239, 1973. 6. Van Peenen, H.J.: Causes ofhypouricemia. Ann. Intern. Med., 78: 977, 1973. 7. Holmes, E.W., Kelley, W. N. and Wyngaaden, J.B.: The kidney and uric acid excretion in man. Kidney Int., 2: 115, 1972. 8. Praetorius, E. and Kirk, J. E.: Hypouricemia: with evidence for tubular elimination of uric acid. J. Lab. Clin. Med., 38: 865, 1950. 9. Greene, M. L., Marcus, R., Aurbach, G. D., Kazam, E. S. and Seegmiller, J. E.: Hypouricemia due to isolated renal tubular defect. Dalmatian dog mutation in man. Amer. J. Med., 53: 361, 1972. 10. Khachadurian, A. K. and Arslanian, M. J.: Hypouricemia due to renal uricosuria. A case study. Ann. Intern. Med., 78: 547, 1973. 11. Bennett, J. S., Bond, J., Singer, I. and Gottlieb, A. J.: Hypouricemia in Hodgkin's disease. Ann. Intern. Med., 76: 751, 1972. 12. Sperling, 0., Weinberger, A., Oliver, I., Liberman, U. A. and De Vries, A.: Hypouricemia, hypercalciuria, and decreased bone density: a hereditary syndrome. Ann. Intern. Med., 80: 482, 1974. 13. Akaoka, I., Nishizawa, T., Yano, E., Takeuchi, A., Nishida, Y., Yoshimura, T. and Horiuchi, Y.: Familial hypouricemia due to renal tubular defect of urate transport. Ann. Clin. Res., 7: 318, 1975.
