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Dissolution of Renal Calculus with Allopurinol: A Case Report
Vol. 100, Oct. Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1968 by The Williams & Wilkins Co.
DISSOLUTION OF RENAL CALCULUS WITH ALLOPURINOL: A CASE REPORT JOHN T. HARBAUGH Two excellent articles have recently documented the efficacy of allopurinol, 1 , 2 a xanthine oxidase inhibitor, 3 to lower the serum and urinary levels of uric acid, with prevention of further formation of uric acid stones during the period of treatment. The case herein reported demonstrates the dissolution of a large and partially opaque, apparent calculus in the renal pelvis following 3 months of oral administration of)llopurinol. CASE REPORT
A 71-year-old man was admitted to St. Cloud Hospital, No. 199270, on October 29, 1966 for investigation of gross hematuria. The patient had been feeling well and had had no urinary symptoms. For 2 weeks he had been taking a sulfonamide prescribed by the referring physician; for 7 years he had taken a tablespoon of cod-liver oil a day for arthritis. A left inguinal herniorrhaphy had been performed in 1961, and an ulcer of the esophagus (?) had been diagnosed in 1959. The patient had passed kidney stones spontaneously in 1950, 1958 and 1963. He had never been catheterized, never had a cystoscopy and never had a urinary tract infection. The stone passed in 1963 had been recovered and saved: it was sent to the hospital laboratory for analysis, revealing uric acid composition. He thought he had arthritis of the hands and neck, but gave no history of gout. The patient appeared healthy, was in no apparent distress, was slightly obese and had mild osteoarthritic changes in the hands. There was no tenderness of the abdomen or back. External genitalia were normal. On palpation the prostate Accepted for publication November 24, 1967. Read at annual meeting of North Central Section, American Urological Association, Inc., Cleveland, Ohio, September 27-30, 1967. 1 Alexander, S. and Brendler, IL: Treatment of uric acid urolithiasis with allopurinol: a xanthine oxidase inhibitor. J. Urol., 97: 340-343, 1967. 2 Anderson, E. E., Rundles, R. W., Silberman, H. R. and Metz, E. N.: Allopurinol control of hypernricosuria: a new concept in the prevention of uric acid stones. J. Urol., 97: 344-347, 1967. 3 Goodman, L. S. and Gilman, A.: The Pharmacological Basis of Therapeutics. New York: MacMillan Co., p. 1371, 3rd edit., 1965.
was slightly enlarged, non-tender and benign. Residual urine was 5 ml. The urine was grossly bloody on admission, but subsequently cleared. Urine culture showed no growth. Serum calcium was 9.7 mg. per cent; serum phosphorus was 2.7 mg. per cent; serum uric acid was 4.7 mg. and blood urea nitrogen was 18 mg. per cent. The urine was negative for cystine and gave an acid reaction. Complete blood count and prothrombin time were normal. The erythrocyte sedimentation rate was 29 ml. per hour. An excretory urogram was obtained on admission (fig. 1, A_). Preliminary x-ray film of the kidneys, ureters and bladder (KUB) showed a faint opacity overlying the tip of the twelfth rib on the left side, better demonstrated 2 days later (fig. 1, B). There was prompt fnnction bilaterally without stasis, but incomplete filling. On October 31 intubation urethroscopy done under spinal anesthesia revealed no lesions. The prostate was small and non-obstructing. The bladder appeared normal and efflux bilaterally was clear. Prelirninary KUB x-ray film exposure was made. A No. 8 French Braasch bulb catheter was used to engage each ureteral orifice, and bilateral retrograde ureteropyelograms were made, using 15 ml. 40 per cent skiodan. Both renal pelves exhibited pyelolymphatic backflow. An air pyelogram was then made on the left, demonstrating a large filling defect of the lower major infundibulum and calyces, apparently by a calculus with very faint opacity (fig. 1, C). The patient was discharged from the hospital the following day on forced fluids and sodium bicarbonate, 10 grains, 4 times a day. He was followed closely in the office, and he managed to maintain an alkaline urine. On December 21 he was started on allopurinol, 100 mg. orally, 3 times daily. He continued to force fluids, contiirned the bicarbonate and tolerated the allopurinol without complaint. Office urinalysis at times showed scattered urate crystals, and at times a degree of microhematuria, but no further episodes of gross hematuria occurred. On March 27, 1967 the patient was readmitted to the hospital for repeat cystoscopy and retrograde pyelograms. A KUB x-ray film showed no 412
DISSOLUTION OF RENAL CALCULUS WITH ALLOPURINOL
Fm. 1. A_, excretory nrog;ram shows slight calcinm stippling overlving somewhat Lnlbons left lower calyx. _B, KUB x-ray film shows faint opacity overlying tip of left tw.elfth rib. C, retrograde pyelogram with air contrast shows rather large partial staghoru stone in left lower infnndibulnm and calyx.
Fm. 2. A_, plain x-ray film reveals that previously noted faint opacity overlying tip of left twelfth rib is no longer present. B, left retrograde pyelogram reveals that previously noted filling defect in left lower infundibulmn and calyx is no longer seen. C, retrograde pyelogram with air contrast reveals DO evidenee of staghorn calculus.
evidence of previous opacity (fig. 2, , 1). Left retrograde pyelogram showed no evidence of previous filling defect (fig. 2, B), nor did the air pyelogram (fig. 2, G). DISCUSSIOK
It 1s well known that uric acid (and cystine and calcium oxalate) Rtones form in an acid urine. The medical management of such stones emphasizes the advantages of alkalinization of the urine and forced fluid intake. 4 Creevy has '1 Schreiner. G. E.: Miscellaneous renal disorders. In: Cecil-Loeb Textbook of Medicine. Edited bv P B. Beeson and W. McDermott. Philadelphia: W. B. Rannders Co., p. 859, 11th edit., 19(\:3.
shown that with protracted use (years) 8Uch a regimen may actually cause the complete dissolution of stones, provided the pretreatment urine culture is sterile. 5 Vermeulen and Fried reported 2 cases of partial dissolution of rernd pelvis stone during alkalinization of the urine, confirmed by operative recovery of stone (one uric acid, one mixed uric acid and calcium oxalate). 6 As recently as 1960, however, Suby expressed his disappointment with the attempted 5 Creevy, C. D.: Outline of Urology.New York: McGrnw-Hill Book Co., p. 240, 1964. 'Vermeulen, C. W. and Fried, F. A.: Observations on dissolution of uric acid calculi. J. Urn!., 94: 293-296, 1965.
414
HARBAUGH
dissolution of uric acid (or cystine or calcium oxalate) renal stones, even by direct and continuous irrigation with alkaline solutions. He expressed little optimism for dissolution of established stones by oral therapy.7 In contradistinction, McCrea and Van Buskirk have demonstrated the successful dissolution of secondary stones (calcium-magnesium-ammonium-phosphate complex), which have even been reported to disintegrate spontaneously within 3 months. 8 The stone in the present case report appeared to be slightly opaque, indicating either deposition of cystine or calcium components in addition to uric acid or that the stone was not uric acid but an early calcium phosphate (or other mixed) secondary stone or a primary calcium oxalate stone. The fact that this patient had a previous diagnosis of ulcer of the esophagus made elsewhere in 1959 and had been treated for a time (several months) with antiacids and, in addition, had medicated himself with large doses of codliver oil, does not exclude this latter possibility, nor can one completely exclude hyperparathyroidism. Against a calcium oxalate stone, however, was the faintness of the opacity and the dissolution of the calculus within a relatively 7 Suby, H. I.: Medical management of urinary calculi by retrograde instillation of drugs. In: Treatment of Urinary Lithiasis. Edited by A. J. Butt. Springfield, Illinois: Charles C. Thomas, pp. 465--476, 1960. 8 McCrea, L. E. and Van Buskirk, K. E.: Spontaneous disintegration of staghorn calculus due to recumbency. J. Urol., 66: 640-644, 1951.
short time. Against a secondary stone are these facts: 1) the patient has repeatedly passed stones, one of which was uric acid; 2) uric acid crystals have repeatedly been demonstrated in the urine; 3) the urine was acid and sterile; 4) there was a negative history for urinary tract infections, instrumentation or periods of prolonged recumbency; 5) the dissolution of the calculus with alkalinization of the urine and allopurinol therapy. One concludes, therefore, that this opacity represented a uric acid stone with calcium components. With the advent of allopurinol it has now become possible to decrease or prevent the formation of uric acid, to decrease the concentration of this purine in serum and urine and to prevent formation of uric acid stones. The present case report suggests that the use of this drug may cause the dissolution of established uric acid stones. SUMMARY
A case is presented in which allopurinol given orally for 3 months, together with forced fluid intake and alkalinization of the urine, caused the dissolution of a calculus in the renal pelvis. The calculus appeared slightly opaque to roentgen examination, indicating that the stone was of mixed composition. It is suggested that allopurinol be tried in other types of renal lithiasis.
204 Granite Exchange Building, St. Cloud, Minnesota 56301
THE JOURNAL OF UROLOGY
Copyright© 1968 by The Williams & Wilkins Co.
DISSOLUTION OF RENAL CALCULUS WITH ALLOPURINOL: A CASE REPORT JOHN T. HARBAUGH Two excellent articles have recently documented the efficacy of allopurinol, 1 , 2 a xanthine oxidase inhibitor, 3 to lower the serum and urinary levels of uric acid, with prevention of further formation of uric acid stones during the period of treatment. The case herein reported demonstrates the dissolution of a large and partially opaque, apparent calculus in the renal pelvis following 3 months of oral administration of)llopurinol. CASE REPORT
A 71-year-old man was admitted to St. Cloud Hospital, No. 199270, on October 29, 1966 for investigation of gross hematuria. The patient had been feeling well and had had no urinary symptoms. For 2 weeks he had been taking a sulfonamide prescribed by the referring physician; for 7 years he had taken a tablespoon of cod-liver oil a day for arthritis. A left inguinal herniorrhaphy had been performed in 1961, and an ulcer of the esophagus (?) had been diagnosed in 1959. The patient had passed kidney stones spontaneously in 1950, 1958 and 1963. He had never been catheterized, never had a cystoscopy and never had a urinary tract infection. The stone passed in 1963 had been recovered and saved: it was sent to the hospital laboratory for analysis, revealing uric acid composition. He thought he had arthritis of the hands and neck, but gave no history of gout. The patient appeared healthy, was in no apparent distress, was slightly obese and had mild osteoarthritic changes in the hands. There was no tenderness of the abdomen or back. External genitalia were normal. On palpation the prostate Accepted for publication November 24, 1967. Read at annual meeting of North Central Section, American Urological Association, Inc., Cleveland, Ohio, September 27-30, 1967. 1 Alexander, S. and Brendler, IL: Treatment of uric acid urolithiasis with allopurinol: a xanthine oxidase inhibitor. J. Urol., 97: 340-343, 1967. 2 Anderson, E. E., Rundles, R. W., Silberman, H. R. and Metz, E. N.: Allopurinol control of hypernricosuria: a new concept in the prevention of uric acid stones. J. Urol., 97: 344-347, 1967. 3 Goodman, L. S. and Gilman, A.: The Pharmacological Basis of Therapeutics. New York: MacMillan Co., p. 1371, 3rd edit., 1965.
was slightly enlarged, non-tender and benign. Residual urine was 5 ml. The urine was grossly bloody on admission, but subsequently cleared. Urine culture showed no growth. Serum calcium was 9.7 mg. per cent; serum phosphorus was 2.7 mg. per cent; serum uric acid was 4.7 mg. and blood urea nitrogen was 18 mg. per cent. The urine was negative for cystine and gave an acid reaction. Complete blood count and prothrombin time were normal. The erythrocyte sedimentation rate was 29 ml. per hour. An excretory urogram was obtained on admission (fig. 1, A_). Preliminary x-ray film of the kidneys, ureters and bladder (KUB) showed a faint opacity overlying the tip of the twelfth rib on the left side, better demonstrated 2 days later (fig. 1, B). There was prompt fnnction bilaterally without stasis, but incomplete filling. On October 31 intubation urethroscopy done under spinal anesthesia revealed no lesions. The prostate was small and non-obstructing. The bladder appeared normal and efflux bilaterally was clear. Prelirninary KUB x-ray film exposure was made. A No. 8 French Braasch bulb catheter was used to engage each ureteral orifice, and bilateral retrograde ureteropyelograms were made, using 15 ml. 40 per cent skiodan. Both renal pelves exhibited pyelolymphatic backflow. An air pyelogram was then made on the left, demonstrating a large filling defect of the lower major infundibulum and calyces, apparently by a calculus with very faint opacity (fig. 1, C). The patient was discharged from the hospital the following day on forced fluids and sodium bicarbonate, 10 grains, 4 times a day. He was followed closely in the office, and he managed to maintain an alkaline urine. On December 21 he was started on allopurinol, 100 mg. orally, 3 times daily. He continued to force fluids, contiirned the bicarbonate and tolerated the allopurinol without complaint. Office urinalysis at times showed scattered urate crystals, and at times a degree of microhematuria, but no further episodes of gross hematuria occurred. On March 27, 1967 the patient was readmitted to the hospital for repeat cystoscopy and retrograde pyelograms. A KUB x-ray film showed no 412
DISSOLUTION OF RENAL CALCULUS WITH ALLOPURINOL
Fm. 1. A_, excretory nrog;ram shows slight calcinm stippling overlving somewhat Lnlbons left lower calyx. _B, KUB x-ray film shows faint opacity overlying tip of left tw.elfth rib. C, retrograde pyelogram with air contrast shows rather large partial staghoru stone in left lower infnndibulnm and calyx.
Fm. 2. A_, plain x-ray film reveals that previously noted faint opacity overlying tip of left twelfth rib is no longer present. B, left retrograde pyelogram reveals that previously noted filling defect in left lower infundibulmn and calyx is no longer seen. C, retrograde pyelogram with air contrast reveals DO evidenee of staghorn calculus.
evidence of previous opacity (fig. 2, , 1). Left retrograde pyelogram showed no evidence of previous filling defect (fig. 2, B), nor did the air pyelogram (fig. 2, G). DISCUSSIOK
It 1s well known that uric acid (and cystine and calcium oxalate) Rtones form in an acid urine. The medical management of such stones emphasizes the advantages of alkalinization of the urine and forced fluid intake. 4 Creevy has '1 Schreiner. G. E.: Miscellaneous renal disorders. In: Cecil-Loeb Textbook of Medicine. Edited bv P B. Beeson and W. McDermott. Philadelphia: W. B. Rannders Co., p. 859, 11th edit., 19(\:3.
shown that with protracted use (years) 8Uch a regimen may actually cause the complete dissolution of stones, provided the pretreatment urine culture is sterile. 5 Vermeulen and Fried reported 2 cases of partial dissolution of rernd pelvis stone during alkalinization of the urine, confirmed by operative recovery of stone (one uric acid, one mixed uric acid and calcium oxalate). 6 As recently as 1960, however, Suby expressed his disappointment with the attempted 5 Creevy, C. D.: Outline of Urology.New York: McGrnw-Hill Book Co., p. 240, 1964. 'Vermeulen, C. W. and Fried, F. A.: Observations on dissolution of uric acid calculi. J. Urn!., 94: 293-296, 1965.
414
HARBAUGH
dissolution of uric acid (or cystine or calcium oxalate) renal stones, even by direct and continuous irrigation with alkaline solutions. He expressed little optimism for dissolution of established stones by oral therapy.7 In contradistinction, McCrea and Van Buskirk have demonstrated the successful dissolution of secondary stones (calcium-magnesium-ammonium-phosphate complex), which have even been reported to disintegrate spontaneously within 3 months. 8 The stone in the present case report appeared to be slightly opaque, indicating either deposition of cystine or calcium components in addition to uric acid or that the stone was not uric acid but an early calcium phosphate (or other mixed) secondary stone or a primary calcium oxalate stone. The fact that this patient had a previous diagnosis of ulcer of the esophagus made elsewhere in 1959 and had been treated for a time (several months) with antiacids and, in addition, had medicated himself with large doses of codliver oil, does not exclude this latter possibility, nor can one completely exclude hyperparathyroidism. Against a calcium oxalate stone, however, was the faintness of the opacity and the dissolution of the calculus within a relatively 7 Suby, H. I.: Medical management of urinary calculi by retrograde instillation of drugs. In: Treatment of Urinary Lithiasis. Edited by A. J. Butt. Springfield, Illinois: Charles C. Thomas, pp. 465--476, 1960. 8 McCrea, L. E. and Van Buskirk, K. E.: Spontaneous disintegration of staghorn calculus due to recumbency. J. Urol., 66: 640-644, 1951.
short time. Against a secondary stone are these facts: 1) the patient has repeatedly passed stones, one of which was uric acid; 2) uric acid crystals have repeatedly been demonstrated in the urine; 3) the urine was acid and sterile; 4) there was a negative history for urinary tract infections, instrumentation or periods of prolonged recumbency; 5) the dissolution of the calculus with alkalinization of the urine and allopurinol therapy. One concludes, therefore, that this opacity represented a uric acid stone with calcium components. With the advent of allopurinol it has now become possible to decrease or prevent the formation of uric acid, to decrease the concentration of this purine in serum and urine and to prevent formation of uric acid stones. The present case report suggests that the use of this drug may cause the dissolution of established uric acid stones. SUMMARY
A case is presented in which allopurinol given orally for 3 months, together with forced fluid intake and alkalinization of the urine, caused the dissolution of a calculus in the renal pelvis. The calculus appeared slightly opaque to roentgen examination, indicating that the stone was of mixed composition. It is suggested that allopurinol be tried in other types of renal lithiasis.
204 Granite Exchange Building, St. Cloud, Minnesota 56301