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Dissolution of Cystine Calculi by Pelviocaliceal Irrigation with B-Penicillamine
0022-534 7/80 /1246-0895$02.00 /0
Vol. 124, December
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1980 by The Williams & Wilkins Co.
Case Reports DISSOLUTION OF CYSTINE CALCULI BY PELVIOCALICEAL IRRIGATION WITH D-PENICILLAMINE H. STARK*
AND
A. SAVIR
From the Pediatric Nephrology Unit and Department of Urology, Beilinson Medical Center, Petah Tiqva and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
ABSTRACT
We report on a cystinuric patient in whom unilateral hydronephrosis developed as a result of massive renal stone formation owing to non-compliance of systemic penicillamine therapy. At operation a large number of calculi could not be removed for technical reasons. After successful in vitro dissolution of 1 calculus using a 0.5 per cent solution of D-penicillamine at pH 8.0 the same solution was used to irrigate the renal collecting system via a nephrostomy tube. After 2 months of daily irrigations, which were decreased to 2 times a week for another 2 months, all the stones appeared radiographically to have disappeared. At followup 2 years after removal of the nephrostomy tube the patient is on regular systemic therapy with no evidence of residual or recurrent stone formation. Although the use of D-penicillamine has revolutionized the treatment of cystinuria rare patients are still· encountered in whom the systelnic administration of this drug is contraindicated or ineffective. Herein we describe a child in whom prolonged D-penicillamine therapy and an operation had failed to remove numerous cystine calculi filling the pelviocaliceal system of 1 kidney. Direct irrigation of the pelviocaliceal system via a nephrostomy tube using an alkaline solution of D-penicillamine resulted in the dissolution and expulsion of all calculi. CASE REPORT
A 2½-year-old girl was seen in 1965 for recurrent urinary tract infection and bilateral staghorn calculi (fig. 1). Diagnosis was cystinuria based on the finding of typical crystals in the urinary sediment, a positive cyanide nitroprusside test and high concentrations of cystine, lysine, arginine and ornithine on 2dimensional chromatography of the urine. The father and a brother also had cystinuria. To avoid an operation 1.2 gm. D-penicillamine were given daily in divided doses as well as urinary alkalization. A plain radiogram of the abdomen after 2 years of therapy demonstrated a single medium-sized calculus in the left renal pelvis and a small calculus in the right kidney (fig. 2). The stone in the left kidney was removed surgically in 1969 and consisted entirely of calcium oxalate without a trace of cystine. Because of the mother's illness and subsequent death the treatment and clinic attendance of the child from 1970 were most erratic. In 1972 plain radiograms of the abdomen revealed a number of calculi in the right kidney. Despite an increase in the dosage of D-penicillamine to 1.8 gm. daily and because of the irregular therapy and followup, the calculi in the right kidney increased in size and number during the next 3 years. In January 1976 the patient, who was now 13 years old, suffered an attack of severe right loin pain. Radiologically, the entire pelvis and caliceal system of the right kidney were filled with calculi. Excretory urography (IVP) Accepted for publication March 21, 1980. • Requests for reprints: Pediatric Nephrology Unit, Beilinson Medical Center, Petah Tiqva, Israel. 895
demonstrated severe hydronephrosis. At operation a large number of calculi were removed, although numerous stones were left behind owing to technical difficulties involved in their extraction from the caliceal system (fig. 3). Chemical analysis showed the calculi to consist of cystine and small amounts of calcium oxalate. Because of our previous failure with standard therapy in this patient the continued presence of calculi was believed to jeopardize seriously the future of this kidney. Thus, we considered the possibility of attempting to dissolve the calculi by the local instillation of a D-penicillamine solution, using the nephrostomy tube that had been left indwelling postoperatively. To test the feasibility of such therapy an experiment was done first, aimed at dissolving the patient's own calculi in vitro. In vitro experiment. A 0.5 per cent solution of D-penicillamine was chosen for irrigation, since we believed that it represented a concentration approximately 2 to 3 times that expected in the urine while the patient received 2 gm. D-penicillamine orally daily. A large calculus that was removed from the patient's kidney was cut into 2 portions. Each portion was placed in a 10 ml. beaker and irrigated continuously at room temperature by means of an intravenous set and a constant infusion pump. The irrigating solution for 1 beaker was 0.5 per cent Dpenicillamine in isotonic saline brought to pH 8.0 with sodium hydroxide. The second beaker contained isotonic saline, also at pH 8.0. The rate of flow was approximately 0.5 ml. per minute. The calculi were removed at 2-day intervals, dried with filter paper and weighed. The results clearly demonstrated dissolution of the stone irrigated with penicillamine, which decreased in weight by approximately 9 mg. (or 1. 7 per cent of the original weight) per day, compared to a negligible decrease in weight for the stone irrigated with saline (fig. 4). In vivo therapy. Because of the favorable results of the in vitro experiment we used a solution of 0.5 per cent D-penicillamine at pH 8.0 for direct lavage of the pelviocaliceal system via the nephrostomy tube in the patient. To minimize the effects of dilution by the urine 1.8 gm. D-penicillamine also was administered orally daily as well as a solution of sodium and potassium citrate (Eisenberg solution) in quantities required to
896
STARK AND SA VIR
Fm. 1. Plain radiogram of abdomen in 1965
maintain urine pH around 7.5. Repeated urine cultures were negative before commencing lavage and continued so throughout therapy. With a regular intravenous set lavage was started at a rate of 1 1. per day and administered during 3 to 4 hours. When no ill effects were encountered this was increased to 3 L daily administered during 6 to 8 hours. During the following weeks numerous small stones and gravel were passed by the patient, while the number and size of calculi seen radiologically diminished markedly. The patient was discharged from the hospital 2 months after commencing irrigations. Lavage was continued on an ambulatory basis with 3.5 L D-penicillamine solution being infused during 4 to 6 hours twice a week in the evening. Only a single, small dense stone remained in the right kidney 2 months later (fig. 5). Since we thought that this calculus consisted of calcium salts or phosphates we changed the irrigating solution to 1.5 1. hemiacidrin1• 2 twice weekly. After 2 months of this therapy the solitary stone in the right kidney also disappeared. The injection of contrast material via the nephrostomy tube showed no filling defects suggestive of radiotranslucent calculi. At this stage the nephrostomy tube was removed. Throughout the 6-month period of penicillamine irrigation the patient remained free of symptoms, while blood counts, serum chemistry, urine bacteriology and urinalyses remained normal. During the 2½ years since removal of the nephrostomy tube she has remained asymptomatic. Treatment has been continued with 1.8 gm. D-penicillamine orally daily, alkalization to maintain urine pH around 7.0 and a high fluid intake. The patient has been cooperative and adhering well to the therapeutic regimen. No renal calculi have been evident radiologically, while repeated urinalyses have shown no cystine crystals or erythrocytes. Kidney function is normal.
severe side effects, precluding its systemic administration, 2) markedly reduced renal function, limiting excretion into the collecting system by the affected kidney and 3) lack of patient compliance in regular ingestion of the tablets. It was the last factor that was responsible for the therapeutic failure in our patient. Although intrarenal irrigation of cystine calculi does not appear to have been attempted we believe that this should be an efficient way of dissolving cystine calculi. Much higher concentrations could be used than those attainable with systemic therapy. The irrigating solution could be maintained more easily at high pH values. A high flow rate could be maintained readily. Patient cooperation would not be required for drug ingestion or the maintenance of a high fluid intake. A 0.5 per cent solution of D-penicillamine was chosen as representing a concentration approximating 2 to 3 times that expected in the urine of a patient receiving 2 gm. per day systemically, assuming that the drug is entirely excreted unchanged in the urine. The solution was brought to pH 8.0 with the aim of maximizing the rate of solution of cystine at the stone surface5 and the efficacy of penicillamine (which has a pKsH of 7.9), 6 while remaining in a presumably safe pH range. The dissolved cystine is then presumed either to undergo a direct exchange reaction with penicillamine to form the more soluble penicillamine-cysteine disulfide or to undergo first reduction to cysteine, which in turn combines with the penicillamine to form the same mixed disulfide. The rapid removal of free cystine would then favor further solution of cystine from the stone surface. The frequent passage during therapy of numerous small calculi compared to the large size of the stones seen radiographically before treatment suggests that these stones first underwent partial dissolution until small enough to be washed out of
DISCUSSION
Since 19653• 4 it has been shown repeatedly that D-penicillamine therapy is useful not only in the prevention of cystine stone formation but can, when administered orally, actually dissolve existing cystine calculi in the urinary tract. However, the effectiveness of this drug may be limited by 3 factors: 1)
Fm. 2. Plain radiogram of abdomen after systemic penicillamine therapy. Arrow points to single calculus in right kidney.
897
DISSOLUTION OF CYSTINE CALCULI
.___.__..,__,..,._____.,..
0. 75 , - - , - - - - - - - - - ~ - - - - - . - - - - - , - - ,
0.70
--
&
E
pH 8.0
0
Lu
z 0 I-
0.9 % NaCl
e
0.65.
0.5 % D-PENICILLAMINE pH 8.0
C/)
IL.
0
~
0.60
<.!)
Lu
3
0.55
0.50 ..._..___ _ __,__ _ ___._ _ _ _.___ _ __,__, 0
4
8
12
16
DAYS Fm. 4. Experimental in vitro dissolution of calculus removed from patient. Two halves of calculus were irrigated with alkaline D-penicillamine or saline solutions, respectively. Fm. 3. Plain radiogram of abdomen after attempted surgical removal of calculi. Arrows point to groups of calculi in right kidney.
the calices by the irrigating solution. The successful in vitro dissolution of the patient's own calculus using the same penicillamine solution strongly supports this concept. The concomitant supervised oral administration of D-penicillamine may have contributed to the effectiveness of this therapy. However, the relative rapidity of stone dissolution suggests that this factor had only a minor role in the success of the therapeutic regimen. In a study of the physicochemical basis for the use of mixed disulfides in the treatment of cystinuria Eldjarn and Hambraeus attempted to dissolve cystine calculi in vitro using diethylcysteamine.6 They unaccountably concluded that this was not effective, although their reported dissolution rate of 1 mg. of cystine in a 10-minute incubation period would appear to be definitely significant and useful and, in fact, comparable to the magnitude in our study. The dissolution of a ureteral cystine stone by irrigation with tromethamine has been reported recently. 7 The effect is presumably solely the result of the high pH (10.2) of this organic amine buffer and an attempt to dissolve a staghom renal calculus in the same patient was unsuccessful. The removal of cystine calculi in our patient by means of local irrigation with an alkaline D-penicillamine solution suggests that this may be a useful mode of therapy for those rare but unfortunate cystinuric patients in whom systemic therapy is ineffective or contraindicated and total surgical removal of calculi is not feasible or is hazardous. As in all such forms of therapy, irrigation should only be performed in the absence of renal infection and at low pressures. Taking these precautions the irrigating solution we used would not be expected to cause local or systemic reactions. However, changes in the composition of the solution and, in particular, increasing pH and concentration of penicillamine may improve further its effectiveness.
Fm. 5. Plain radiogram of abdomen after 4 months of irrigation with alkaline D-penicillamine. Remaining, dense shadow (arrow) was believed to be that of calcium or phosphate stone.
898
STARK AND SA VIR
REFERENCES 1. Lazebnik, Y., Bechar, L. and Savir, A.: Dissolution of stones in the
urinary tract by renacidin. Harefuah, 63: 457, 1962. 2. Dretler, S. P., Pfister, R. C. and Newhouse, J. H.: Renal-stone dissolution via percutaneous nephrostomy. New Engl. J. Med., 300: 341, 1979. 3. Lotz, M. and Bartter, F. C.: Stone dissolution with D-penicillamine in cystinuria. Brit. Med. J., 2: 1408, 1965. 4. McDonald, J. E: and Henneman, P.H.: Stone dissolution in vivo and control of cystinuria with D-penicillamine. New Engl. J. Med., 273: 578, 1965. 5. Dent, C. E. and Senior, B.: Studies on the treatment of cystinuria. Brit. J. Urol., 27: 317, 1955. 6. Eldjarn, L. and Hambraeus, L.: The rationale of mixed disulphides
in the treatment of cystinuria. Scand. J. Clin. Lab. Invest., 16: 153, 1964. 7. Crissey, M. M. and Gittes, R. F.: Dissolution of cystine ureteral calculus by irrigation with tromethamine. J. Urol., 121: 811, 1979. EDITORIAL COMMENT This is a case report of the successful application of vigorous therapeutic measures to rid a young girl of renal calculi. This also represents another instance of what has become a frequently recognized occurrence, that is the formation of calcareous calculi in a patient with cystinuria.
William C. Thomas, Jr. Department of Medicine Veterans Administration Hospital Gainesville, Florida
Vol. 124, December
THE JOURNAL OF UROLOGY
Printed in U.S.A.
Copyright© 1980 by The Williams & Wilkins Co.
Case Reports DISSOLUTION OF CYSTINE CALCULI BY PELVIOCALICEAL IRRIGATION WITH D-PENICILLAMINE H. STARK*
AND
A. SAVIR
From the Pediatric Nephrology Unit and Department of Urology, Beilinson Medical Center, Petah Tiqva and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
ABSTRACT
We report on a cystinuric patient in whom unilateral hydronephrosis developed as a result of massive renal stone formation owing to non-compliance of systemic penicillamine therapy. At operation a large number of calculi could not be removed for technical reasons. After successful in vitro dissolution of 1 calculus using a 0.5 per cent solution of D-penicillamine at pH 8.0 the same solution was used to irrigate the renal collecting system via a nephrostomy tube. After 2 months of daily irrigations, which were decreased to 2 times a week for another 2 months, all the stones appeared radiographically to have disappeared. At followup 2 years after removal of the nephrostomy tube the patient is on regular systemic therapy with no evidence of residual or recurrent stone formation. Although the use of D-penicillamine has revolutionized the treatment of cystinuria rare patients are still· encountered in whom the systelnic administration of this drug is contraindicated or ineffective. Herein we describe a child in whom prolonged D-penicillamine therapy and an operation had failed to remove numerous cystine calculi filling the pelviocaliceal system of 1 kidney. Direct irrigation of the pelviocaliceal system via a nephrostomy tube using an alkaline solution of D-penicillamine resulted in the dissolution and expulsion of all calculi. CASE REPORT
A 2½-year-old girl was seen in 1965 for recurrent urinary tract infection and bilateral staghorn calculi (fig. 1). Diagnosis was cystinuria based on the finding of typical crystals in the urinary sediment, a positive cyanide nitroprusside test and high concentrations of cystine, lysine, arginine and ornithine on 2dimensional chromatography of the urine. The father and a brother also had cystinuria. To avoid an operation 1.2 gm. D-penicillamine were given daily in divided doses as well as urinary alkalization. A plain radiogram of the abdomen after 2 years of therapy demonstrated a single medium-sized calculus in the left renal pelvis and a small calculus in the right kidney (fig. 2). The stone in the left kidney was removed surgically in 1969 and consisted entirely of calcium oxalate without a trace of cystine. Because of the mother's illness and subsequent death the treatment and clinic attendance of the child from 1970 were most erratic. In 1972 plain radiograms of the abdomen revealed a number of calculi in the right kidney. Despite an increase in the dosage of D-penicillamine to 1.8 gm. daily and because of the irregular therapy and followup, the calculi in the right kidney increased in size and number during the next 3 years. In January 1976 the patient, who was now 13 years old, suffered an attack of severe right loin pain. Radiologically, the entire pelvis and caliceal system of the right kidney were filled with calculi. Excretory urography (IVP) Accepted for publication March 21, 1980. • Requests for reprints: Pediatric Nephrology Unit, Beilinson Medical Center, Petah Tiqva, Israel. 895
demonstrated severe hydronephrosis. At operation a large number of calculi were removed, although numerous stones were left behind owing to technical difficulties involved in their extraction from the caliceal system (fig. 3). Chemical analysis showed the calculi to consist of cystine and small amounts of calcium oxalate. Because of our previous failure with standard therapy in this patient the continued presence of calculi was believed to jeopardize seriously the future of this kidney. Thus, we considered the possibility of attempting to dissolve the calculi by the local instillation of a D-penicillamine solution, using the nephrostomy tube that had been left indwelling postoperatively. To test the feasibility of such therapy an experiment was done first, aimed at dissolving the patient's own calculi in vitro. In vitro experiment. A 0.5 per cent solution of D-penicillamine was chosen for irrigation, since we believed that it represented a concentration approximately 2 to 3 times that expected in the urine while the patient received 2 gm. D-penicillamine orally daily. A large calculus that was removed from the patient's kidney was cut into 2 portions. Each portion was placed in a 10 ml. beaker and irrigated continuously at room temperature by means of an intravenous set and a constant infusion pump. The irrigating solution for 1 beaker was 0.5 per cent Dpenicillamine in isotonic saline brought to pH 8.0 with sodium hydroxide. The second beaker contained isotonic saline, also at pH 8.0. The rate of flow was approximately 0.5 ml. per minute. The calculi were removed at 2-day intervals, dried with filter paper and weighed. The results clearly demonstrated dissolution of the stone irrigated with penicillamine, which decreased in weight by approximately 9 mg. (or 1. 7 per cent of the original weight) per day, compared to a negligible decrease in weight for the stone irrigated with saline (fig. 4). In vivo therapy. Because of the favorable results of the in vitro experiment we used a solution of 0.5 per cent D-penicillamine at pH 8.0 for direct lavage of the pelviocaliceal system via the nephrostomy tube in the patient. To minimize the effects of dilution by the urine 1.8 gm. D-penicillamine also was administered orally daily as well as a solution of sodium and potassium citrate (Eisenberg solution) in quantities required to
896
STARK AND SA VIR
Fm. 1. Plain radiogram of abdomen in 1965
maintain urine pH around 7.5. Repeated urine cultures were negative before commencing lavage and continued so throughout therapy. With a regular intravenous set lavage was started at a rate of 1 1. per day and administered during 3 to 4 hours. When no ill effects were encountered this was increased to 3 L daily administered during 6 to 8 hours. During the following weeks numerous small stones and gravel were passed by the patient, while the number and size of calculi seen radiologically diminished markedly. The patient was discharged from the hospital 2 months after commencing irrigations. Lavage was continued on an ambulatory basis with 3.5 L D-penicillamine solution being infused during 4 to 6 hours twice a week in the evening. Only a single, small dense stone remained in the right kidney 2 months later (fig. 5). Since we thought that this calculus consisted of calcium salts or phosphates we changed the irrigating solution to 1.5 1. hemiacidrin1• 2 twice weekly. After 2 months of this therapy the solitary stone in the right kidney also disappeared. The injection of contrast material via the nephrostomy tube showed no filling defects suggestive of radiotranslucent calculi. At this stage the nephrostomy tube was removed. Throughout the 6-month period of penicillamine irrigation the patient remained free of symptoms, while blood counts, serum chemistry, urine bacteriology and urinalyses remained normal. During the 2½ years since removal of the nephrostomy tube she has remained asymptomatic. Treatment has been continued with 1.8 gm. D-penicillamine orally daily, alkalization to maintain urine pH around 7.0 and a high fluid intake. The patient has been cooperative and adhering well to the therapeutic regimen. No renal calculi have been evident radiologically, while repeated urinalyses have shown no cystine crystals or erythrocytes. Kidney function is normal.
severe side effects, precluding its systemic administration, 2) markedly reduced renal function, limiting excretion into the collecting system by the affected kidney and 3) lack of patient compliance in regular ingestion of the tablets. It was the last factor that was responsible for the therapeutic failure in our patient. Although intrarenal irrigation of cystine calculi does not appear to have been attempted we believe that this should be an efficient way of dissolving cystine calculi. Much higher concentrations could be used than those attainable with systemic therapy. The irrigating solution could be maintained more easily at high pH values. A high flow rate could be maintained readily. Patient cooperation would not be required for drug ingestion or the maintenance of a high fluid intake. A 0.5 per cent solution of D-penicillamine was chosen as representing a concentration approximating 2 to 3 times that expected in the urine of a patient receiving 2 gm. per day systemically, assuming that the drug is entirely excreted unchanged in the urine. The solution was brought to pH 8.0 with the aim of maximizing the rate of solution of cystine at the stone surface5 and the efficacy of penicillamine (which has a pKsH of 7.9), 6 while remaining in a presumably safe pH range. The dissolved cystine is then presumed either to undergo a direct exchange reaction with penicillamine to form the more soluble penicillamine-cysteine disulfide or to undergo first reduction to cysteine, which in turn combines with the penicillamine to form the same mixed disulfide. The rapid removal of free cystine would then favor further solution of cystine from the stone surface. The frequent passage during therapy of numerous small calculi compared to the large size of the stones seen radiographically before treatment suggests that these stones first underwent partial dissolution until small enough to be washed out of
DISCUSSION
Since 19653• 4 it has been shown repeatedly that D-penicillamine therapy is useful not only in the prevention of cystine stone formation but can, when administered orally, actually dissolve existing cystine calculi in the urinary tract. However, the effectiveness of this drug may be limited by 3 factors: 1)
Fm. 2. Plain radiogram of abdomen after systemic penicillamine therapy. Arrow points to single calculus in right kidney.
897
DISSOLUTION OF CYSTINE CALCULI
.___.__..,__,..,._____.,..
0. 75 , - - , - - - - - - - - - ~ - - - - - . - - - - - , - - ,
0.70
--
&
E
pH 8.0
0
Lu
z 0 I-
0.9 % NaCl
e
0.65.
0.5 % D-PENICILLAMINE pH 8.0
C/)
IL.
0
~
0.60
<.!)
Lu
3
0.55
0.50 ..._..___ _ __,__ _ ___._ _ _ _.___ _ __,__, 0
4
8
12
16
DAYS Fm. 4. Experimental in vitro dissolution of calculus removed from patient. Two halves of calculus were irrigated with alkaline D-penicillamine or saline solutions, respectively. Fm. 3. Plain radiogram of abdomen after attempted surgical removal of calculi. Arrows point to groups of calculi in right kidney.
the calices by the irrigating solution. The successful in vitro dissolution of the patient's own calculus using the same penicillamine solution strongly supports this concept. The concomitant supervised oral administration of D-penicillamine may have contributed to the effectiveness of this therapy. However, the relative rapidity of stone dissolution suggests that this factor had only a minor role in the success of the therapeutic regimen. In a study of the physicochemical basis for the use of mixed disulfides in the treatment of cystinuria Eldjarn and Hambraeus attempted to dissolve cystine calculi in vitro using diethylcysteamine.6 They unaccountably concluded that this was not effective, although their reported dissolution rate of 1 mg. of cystine in a 10-minute incubation period would appear to be definitely significant and useful and, in fact, comparable to the magnitude in our study. The dissolution of a ureteral cystine stone by irrigation with tromethamine has been reported recently. 7 The effect is presumably solely the result of the high pH (10.2) of this organic amine buffer and an attempt to dissolve a staghom renal calculus in the same patient was unsuccessful. The removal of cystine calculi in our patient by means of local irrigation with an alkaline D-penicillamine solution suggests that this may be a useful mode of therapy for those rare but unfortunate cystinuric patients in whom systemic therapy is ineffective or contraindicated and total surgical removal of calculi is not feasible or is hazardous. As in all such forms of therapy, irrigation should only be performed in the absence of renal infection and at low pressures. Taking these precautions the irrigating solution we used would not be expected to cause local or systemic reactions. However, changes in the composition of the solution and, in particular, increasing pH and concentration of penicillamine may improve further its effectiveness.
Fm. 5. Plain radiogram of abdomen after 4 months of irrigation with alkaline D-penicillamine. Remaining, dense shadow (arrow) was believed to be that of calcium or phosphate stone.
898
STARK AND SA VIR
REFERENCES 1. Lazebnik, Y., Bechar, L. and Savir, A.: Dissolution of stones in the
urinary tract by renacidin. Harefuah, 63: 457, 1962. 2. Dretler, S. P., Pfister, R. C. and Newhouse, J. H.: Renal-stone dissolution via percutaneous nephrostomy. New Engl. J. Med., 300: 341, 1979. 3. Lotz, M. and Bartter, F. C.: Stone dissolution with D-penicillamine in cystinuria. Brit. Med. J., 2: 1408, 1965. 4. McDonald, J. E: and Henneman, P.H.: Stone dissolution in vivo and control of cystinuria with D-penicillamine. New Engl. J. Med., 273: 578, 1965. 5. Dent, C. E. and Senior, B.: Studies on the treatment of cystinuria. Brit. J. Urol., 27: 317, 1955. 6. Eldjarn, L. and Hambraeus, L.: The rationale of mixed disulphides
in the treatment of cystinuria. Scand. J. Clin. Lab. Invest., 16: 153, 1964. 7. Crissey, M. M. and Gittes, R. F.: Dissolution of cystine ureteral calculus by irrigation with tromethamine. J. Urol., 121: 811, 1979. EDITORIAL COMMENT This is a case report of the successful application of vigorous therapeutic measures to rid a young girl of renal calculi. This also represents another instance of what has become a frequently recognized occurrence, that is the formation of calcareous calculi in a patient with cystinuria.
William C. Thomas, Jr. Department of Medicine Veterans Administration Hospital Gainesville, Florida