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Renacidin: A Urinary Calculi Solvent
THE JOURNAL OF UROLOGY
Vol. 87, No. 5 May 1962 Copyright © 1962 by The Williams & Wilkins Co. Printed in U.S.A.
RENACIDIN: A URINARY CALCULI SOLVENT S. WILLIAM RIES
AND
MAXWELL MALAMENT
From the Urological Section, Surgical Service, Veterans Administration Hospital, East Orange, N. J.
For many years a solvent has been sought for urinary calculi. A variety of substances, namely, citric acid compounds,1 proteolytic enzymes,2 salicylates, 3 chelating agents,4 as well as intramuscular hyaluronidase, 5 have been tried with rather limited success. In 1959, lVIu1vaney 6 reported on a new organic acid compound, renacidin, which appears promising. This substance is supplied commercially as a sterile powder soluble in water. It contains the lactones, anhydrides and acid salts of multivalent organic acids from the gluconic, citric, and malic group. Clinically a 10 per cent solution, with a pH of 3.9, is produced by adding 100 gm. renacidin to 1000 ml. distilled water. The solution is stable for long periods and may be boiled for sterilization without losing its potency. It is an excellent solvent for calcium phosphate, calcium carbonate and magnesium ammonium phosphate stones; however, calcium oxalate, cholesterol and uric acid calculi are relatively insoluble. Renacidin is non-toxic and in the concentration recommended is non-irritating to the mucosa of the urinary tract. It has been given in large doses to rabbits both intravenously and intraperitoneally without ill effects. INDICATIONS
Renacidin therapy is indicated whenever dissolution or reduction in size of certain renal, Accepted for publication October 13, 1961. 1 Suby, H. I., Suby, R. M. and Albright, F.: Properties of organic acid solutions which determine their irritability to the bladder mucous membrane, and the effect of its magnesium ions in overcoming this irritability. J. Urol., 48: 549559, 1942.
2 Keyser,, L. D., Scherer, P. C. and Claffey, L. W.: Studies in dissolution of urinary calculi: experimental and clinical aspects. J. Urol., 59:
826-841, 1948. 3 Prien, E. L. and Walker, B. S.: Salicylamide and acetylsalicylic acid in recurrent urolithiasis. J.A.M.A., 160: 355-360, 1956. 4 Abeshouse, B. S. and Weinberg, T.: Experimental study of solvent action of versene on urinary calculi. J. Urol., 65: 316-331, 1951. 5 Butt, A.: Clinical management of renal lithiasis with hyaluronidase. J. Urol., 72: 337-341,
1954. 6 Mulvaney, W. P.: A new solvent for certain urinary calculi. J. Urol., 82: 546-548, 1959.
657
ureteral or bladder calculi is desired. The poor risk patient or one who has submitted to multiple surgical procedures for calculi often falls into· this category. The compound is especially useful in prevention of calcification of catheters draining the urinary tract. This problem is frequently encountered where nephrostomy or urethral catheter drainage is required for prolonged periods. Inasmuch as the calcification that forms in these cases, calcium phosphate and magnesium ammonium phosphate, is soluble in renacidin solution, we have been successful in preventing encrustation for extended periods. Another indication for the use of renacidin occurs following litholapaxy. Evacuation of the tiny fragments of stone, which may become enmeshed in the bladder mucosa, may be impossible. These particles often act as nuclei for formation of new calculi. Renacidin has been useful in dissolving this calcareous material by way of urethral catheter irrigation. Following lithotomy for multiple small renal stones or a staghorn calculus, fragments or a calculus may be left behind. In these cases renacidin may be used postoperatively through a nephrostomy catheter. The method of kidney lavage at our hospital has been continuous irrigation with a 10 per cent solution of renacidin at the rate of 20 drops a minute, for a period of 7 days (fig. 1). A 5F polyethylene ureteral catheter is passed to a point above the calculus and a 6F' catheter to a point below the calculus. The irrigant is introduced through the smaller catheter and the larger acts as an out-flow tract. A Foley catheter is left indwelling to anchor the ureteral catheters. When necessarythishas been repeated onceafter a rest period of one week. COMPLICATIONS
The most frequent complication we have encountered with the use of renacidin has been obstruction of catheters, primarily ureteral, by fragments and debris caused by calculus dissolution. This is not a problem with the use of urethral or nephrostomy catheters. With the obstruction of
658
S. W. RIES AND M. MALAMENT
the outflow catheter there is distention of the renal pelvis with resultant pain and reflex ileus. This has presented no serious problem and responds to conservative management when the TECHNIQUE FOR LAVAGE OF RENAL CALCULI
Intake
Outlet
tf..
RENACIOIN
1·1
'"
lumen of the obstructed catheter is cleared by aseptic manual irrigation. A more serious complication, again primarily with ureteral catheters, is infection due to the prolonged presence of the catheters. Because of this patients are routinely placed on a broad spectrum antibiotic and a chemotherapeutic drug during treatment. Recently antibiotics have been added to the solution to reduce incidence of infection. The inconvenience of prolonged bed rest may be considered a complication. This is necessary only in those cases in which indwelling ureteral catheters are used. If the patient is allowed to sit or stand, the catheters can very easily slip down the ureter into the bladder. CASE REPORTS
I, 11
I
Intake 5F cath. Outlet 6F cath.
Frn. 1. Diagrammatic sketch of renal lavage technique.
Case 1. R. C. (fig. 2), a 44-year-old white man, ,ms admitted to the hospital with left flank pain. The excretmy urogram revealed left hydronephrosis and left renal calculus. On April 13, 1959, a left pyelolithotomy and a pyeloplasty were performed. Postoperatively the patient's course was uneventful. He ,ms readmitted in November for follmYup observation. Pyelographic studies revealed a decrease in the hydronephrosis, but two small left ureteral calculi were noted. In view of his previous surgery it was decided to attempt dissolution of
Frn. 2. A, left renal calculi prior to lavage therauy. B, absence of calculi following irrigations
RENACIDIN: A URINARY CALCULI SOLVENT
659
Fm. 3. A, staghorn calculus of right kidney. B, branched portions dissolved after continuous irrigations.
FIG. 4. A, multiple calculi of right kidney. B, moderate reduction in size after therapy
the stones with renacidin. On November 24, continuous irrigation was begun, as described earlier. Irrigation was continued for 6 days, during which the patient took antibiotics. A mild degree of ileus presented no problem. A flat film of the abdomen at the end of the irrigation period revealed complete dissolution of the stones. Case 2. W. P. (fig. 3), a 25-year-old white man, was admitted to the orthopedic service because of non-union of a compound fracture of the left femur, sustained in an auto accident. He was first
seen by the urology service in April 1959, because of urinary frequency and urgency. Excretory urography revealed a calculus in the right kidney and bladder. The bladder calculus was removed transurethrally; no surgery ,vas undertaken for the kidney stone because of the complicating orthopedic problems. In November 1960, the patient began complaining of right flank pain. Excretory urography revealed a right staghorn calculus and moderate hydronephrosis. The branched portion of the stone appeared less
660
S. W. RIES AND M. MALAMENT
FIG. 5. 11, staghorn calculus, right kidney. B, fragmentation and decreased size following irrigations.
FIG. 6. Appearance of 3-month indwelling nephrostomy catheter subjected to renacidin irrigations. Note absence of encrustations.
radiopaque than the pelvic portion and probably phosphatic in character. Because of the intrarenal location of the pelvis in this kidney, fragmentation of the stone was considered inevitable at surgery. Therefore, it was decided to attempt dissolution of the branched portion and surgical removal of the remaining pelvic stone. On December 2, renacidin irrigation was initiated and continued for 7 clays. A flat film of the
abdomen at the encl of this period revealed complete dissolution of the branched portion. The more opaque pe!Yic portion was still present as was expected. On December 14, a right pyelolithotorny was carried out. The postoperative course was uneventful. Followup excretory urography revealed good function and no further evidence of calculi. Case 3. L. C. (fig. 4), a 37-year-old emaciated
RENACIDIN: A URINARY CALCULI SOLVENT
1
white man, with spastic paraplegia, secondary to multiple sclerosis, was first seen by the urology service because of gross hematuria and pyrexia. Excretory urography revealed a bladder calculus, a right staghorn calculus and moderate hydronephrosis. No function was seen on the left side. The bladder calculus was crushed transurethrally and evacuated. Since the patient was a poor surgical risk, renacidin irrigation of the kidney was recommended to reduce the size of the staghorn calculus and thereby relieve urinary obstruction. Continuous renacidin irrigation was instituted August 3, 1959 using the two-catheter technique. Acute pyelonephritis that developed responded to antibiotic and sulfa drugs. A flat film of the abdomen after 7 days of renacidin therapy revealed marked decrease in the size of the calculus. A second course of renacidin irrigation was started 1 week later, but after 4 days of irrigation the pyelonephritis recurred and the patient died. Case 4. C. E. (fig. 5), a 37-year-old paraplegic, secondary to an injury of his thoracic spine incurred in World War II, was admitted to the urology service for a routine followup study. He had bilateral, well functioning nephrostomies in place. An excretory urogram revealed good function bilaterally with several large calculi in the right pelvis. A 5F ureteral catheter was passed through the right nephrostomy into the kidney pelvis. A 10 per cent renacidin drip was started through the ureteral catheter with the nephrostomy tube acting as an outlet. A flat film of the abdomen after 7 days revealed a marked de-
661
crease in the size of the calculi. Treatment was not reinstituted since the patient desired to be discharged for personal reasons. He was sent home to continue manual renacidin irrigation of his nephrostomy catheters. Case 5. A. F., a 68-year-old Negro, was admitted to the urology service with advanced bilateral hydronephrosis and uremia, secondary to obstructive enlargement of his prostate. A left nephrostomy was performed on September 30, 1960. The nephrostomy tube was irrigated twice daily with 5 per cent renacidin for the next 3 months. The original nephrostomy tube was never changed and at the time of its removal, 3 months after surgery, there was little evidence of encrustation (fig. 6). SUMMARY
Renacidin, a compound of multivalent organic acids, has shown promise as a calculus solvent. Although its action is limited to the phosphate and carbonate elements, it has a definite place in the treatment of calculus disease. It will not replace surgical intervention, but is of value in the presence of calculi in a poor risk patient, as a postoperative irrigant and whenever prolonged catheter drainage is required. We believe that it is a valuable addition to urological armamentaria. The authors wish to thank the Department of Medical Illustration at the Veterans Administration Hospital, East Orange, N. J., for preparation of the photographs and medical illustration.
Vol. 87, No. 5 May 1962 Copyright © 1962 by The Williams & Wilkins Co. Printed in U.S.A.
RENACIDIN: A URINARY CALCULI SOLVENT S. WILLIAM RIES
AND
MAXWELL MALAMENT
From the Urological Section, Surgical Service, Veterans Administration Hospital, East Orange, N. J.
For many years a solvent has been sought for urinary calculi. A variety of substances, namely, citric acid compounds,1 proteolytic enzymes,2 salicylates, 3 chelating agents,4 as well as intramuscular hyaluronidase, 5 have been tried with rather limited success. In 1959, lVIu1vaney 6 reported on a new organic acid compound, renacidin, which appears promising. This substance is supplied commercially as a sterile powder soluble in water. It contains the lactones, anhydrides and acid salts of multivalent organic acids from the gluconic, citric, and malic group. Clinically a 10 per cent solution, with a pH of 3.9, is produced by adding 100 gm. renacidin to 1000 ml. distilled water. The solution is stable for long periods and may be boiled for sterilization without losing its potency. It is an excellent solvent for calcium phosphate, calcium carbonate and magnesium ammonium phosphate stones; however, calcium oxalate, cholesterol and uric acid calculi are relatively insoluble. Renacidin is non-toxic and in the concentration recommended is non-irritating to the mucosa of the urinary tract. It has been given in large doses to rabbits both intravenously and intraperitoneally without ill effects. INDICATIONS
Renacidin therapy is indicated whenever dissolution or reduction in size of certain renal, Accepted for publication October 13, 1961. 1 Suby, H. I., Suby, R. M. and Albright, F.: Properties of organic acid solutions which determine their irritability to the bladder mucous membrane, and the effect of its magnesium ions in overcoming this irritability. J. Urol., 48: 549559, 1942.
2 Keyser,, L. D., Scherer, P. C. and Claffey, L. W.: Studies in dissolution of urinary calculi: experimental and clinical aspects. J. Urol., 59:
826-841, 1948. 3 Prien, E. L. and Walker, B. S.: Salicylamide and acetylsalicylic acid in recurrent urolithiasis. J.A.M.A., 160: 355-360, 1956. 4 Abeshouse, B. S. and Weinberg, T.: Experimental study of solvent action of versene on urinary calculi. J. Urol., 65: 316-331, 1951. 5 Butt, A.: Clinical management of renal lithiasis with hyaluronidase. J. Urol., 72: 337-341,
1954. 6 Mulvaney, W. P.: A new solvent for certain urinary calculi. J. Urol., 82: 546-548, 1959.
657
ureteral or bladder calculi is desired. The poor risk patient or one who has submitted to multiple surgical procedures for calculi often falls into· this category. The compound is especially useful in prevention of calcification of catheters draining the urinary tract. This problem is frequently encountered where nephrostomy or urethral catheter drainage is required for prolonged periods. Inasmuch as the calcification that forms in these cases, calcium phosphate and magnesium ammonium phosphate, is soluble in renacidin solution, we have been successful in preventing encrustation for extended periods. Another indication for the use of renacidin occurs following litholapaxy. Evacuation of the tiny fragments of stone, which may become enmeshed in the bladder mucosa, may be impossible. These particles often act as nuclei for formation of new calculi. Renacidin has been useful in dissolving this calcareous material by way of urethral catheter irrigation. Following lithotomy for multiple small renal stones or a staghorn calculus, fragments or a calculus may be left behind. In these cases renacidin may be used postoperatively through a nephrostomy catheter. The method of kidney lavage at our hospital has been continuous irrigation with a 10 per cent solution of renacidin at the rate of 20 drops a minute, for a period of 7 days (fig. 1). A 5F polyethylene ureteral catheter is passed to a point above the calculus and a 6F' catheter to a point below the calculus. The irrigant is introduced through the smaller catheter and the larger acts as an out-flow tract. A Foley catheter is left indwelling to anchor the ureteral catheters. When necessarythishas been repeated onceafter a rest period of one week. COMPLICATIONS
The most frequent complication we have encountered with the use of renacidin has been obstruction of catheters, primarily ureteral, by fragments and debris caused by calculus dissolution. This is not a problem with the use of urethral or nephrostomy catheters. With the obstruction of
658
S. W. RIES AND M. MALAMENT
the outflow catheter there is distention of the renal pelvis with resultant pain and reflex ileus. This has presented no serious problem and responds to conservative management when the TECHNIQUE FOR LAVAGE OF RENAL CALCULI
Intake
Outlet
tf..
RENACIOIN
1·1
'"
lumen of the obstructed catheter is cleared by aseptic manual irrigation. A more serious complication, again primarily with ureteral catheters, is infection due to the prolonged presence of the catheters. Because of this patients are routinely placed on a broad spectrum antibiotic and a chemotherapeutic drug during treatment. Recently antibiotics have been added to the solution to reduce incidence of infection. The inconvenience of prolonged bed rest may be considered a complication. This is necessary only in those cases in which indwelling ureteral catheters are used. If the patient is allowed to sit or stand, the catheters can very easily slip down the ureter into the bladder. CASE REPORTS
I, 11
I
Intake 5F cath. Outlet 6F cath.
Frn. 1. Diagrammatic sketch of renal lavage technique.
Case 1. R. C. (fig. 2), a 44-year-old white man, ,ms admitted to the hospital with left flank pain. The excretmy urogram revealed left hydronephrosis and left renal calculus. On April 13, 1959, a left pyelolithotomy and a pyeloplasty were performed. Postoperatively the patient's course was uneventful. He ,ms readmitted in November for follmYup observation. Pyelographic studies revealed a decrease in the hydronephrosis, but two small left ureteral calculi were noted. In view of his previous surgery it was decided to attempt dissolution of
Frn. 2. A, left renal calculi prior to lavage therauy. B, absence of calculi following irrigations
RENACIDIN: A URINARY CALCULI SOLVENT
659
Fm. 3. A, staghorn calculus of right kidney. B, branched portions dissolved after continuous irrigations.
FIG. 4. A, multiple calculi of right kidney. B, moderate reduction in size after therapy
the stones with renacidin. On November 24, continuous irrigation was begun, as described earlier. Irrigation was continued for 6 days, during which the patient took antibiotics. A mild degree of ileus presented no problem. A flat film of the abdomen at the end of the irrigation period revealed complete dissolution of the stones. Case 2. W. P. (fig. 3), a 25-year-old white man, was admitted to the orthopedic service because of non-union of a compound fracture of the left femur, sustained in an auto accident. He was first
seen by the urology service in April 1959, because of urinary frequency and urgency. Excretory urography revealed a calculus in the right kidney and bladder. The bladder calculus was removed transurethrally; no surgery ,vas undertaken for the kidney stone because of the complicating orthopedic problems. In November 1960, the patient began complaining of right flank pain. Excretory urography revealed a right staghorn calculus and moderate hydronephrosis. The branched portion of the stone appeared less
660
S. W. RIES AND M. MALAMENT
FIG. 5. 11, staghorn calculus, right kidney. B, fragmentation and decreased size following irrigations.
FIG. 6. Appearance of 3-month indwelling nephrostomy catheter subjected to renacidin irrigations. Note absence of encrustations.
radiopaque than the pelvic portion and probably phosphatic in character. Because of the intrarenal location of the pelvis in this kidney, fragmentation of the stone was considered inevitable at surgery. Therefore, it was decided to attempt dissolution of the branched portion and surgical removal of the remaining pelvic stone. On December 2, renacidin irrigation was initiated and continued for 7 clays. A flat film of the
abdomen at the encl of this period revealed complete dissolution of the branched portion. The more opaque pe!Yic portion was still present as was expected. On December 14, a right pyelolithotorny was carried out. The postoperative course was uneventful. Followup excretory urography revealed good function and no further evidence of calculi. Case 3. L. C. (fig. 4), a 37-year-old emaciated
RENACIDIN: A URINARY CALCULI SOLVENT
1
white man, with spastic paraplegia, secondary to multiple sclerosis, was first seen by the urology service because of gross hematuria and pyrexia. Excretory urography revealed a bladder calculus, a right staghorn calculus and moderate hydronephrosis. No function was seen on the left side. The bladder calculus was crushed transurethrally and evacuated. Since the patient was a poor surgical risk, renacidin irrigation of the kidney was recommended to reduce the size of the staghorn calculus and thereby relieve urinary obstruction. Continuous renacidin irrigation was instituted August 3, 1959 using the two-catheter technique. Acute pyelonephritis that developed responded to antibiotic and sulfa drugs. A flat film of the abdomen after 7 days of renacidin therapy revealed marked decrease in the size of the calculus. A second course of renacidin irrigation was started 1 week later, but after 4 days of irrigation the pyelonephritis recurred and the patient died. Case 4. C. E. (fig. 5), a 37-year-old paraplegic, secondary to an injury of his thoracic spine incurred in World War II, was admitted to the urology service for a routine followup study. He had bilateral, well functioning nephrostomies in place. An excretory urogram revealed good function bilaterally with several large calculi in the right pelvis. A 5F ureteral catheter was passed through the right nephrostomy into the kidney pelvis. A 10 per cent renacidin drip was started through the ureteral catheter with the nephrostomy tube acting as an outlet. A flat film of the abdomen after 7 days revealed a marked de-
661
crease in the size of the calculi. Treatment was not reinstituted since the patient desired to be discharged for personal reasons. He was sent home to continue manual renacidin irrigation of his nephrostomy catheters. Case 5. A. F., a 68-year-old Negro, was admitted to the urology service with advanced bilateral hydronephrosis and uremia, secondary to obstructive enlargement of his prostate. A left nephrostomy was performed on September 30, 1960. The nephrostomy tube was irrigated twice daily with 5 per cent renacidin for the next 3 months. The original nephrostomy tube was never changed and at the time of its removal, 3 months after surgery, there was little evidence of encrustation (fig. 6). SUMMARY
Renacidin, a compound of multivalent organic acids, has shown promise as a calculus solvent. Although its action is limited to the phosphate and carbonate elements, it has a definite place in the treatment of calculus disease. It will not replace surgical intervention, but is of value in the presence of calculi in a poor risk patient, as a postoperative irrigant and whenever prolonged catheter drainage is required. We believe that it is a valuable addition to urological armamentaria. The authors wish to thank the Department of Medical Illustration at the Veterans Administration Hospital, East Orange, N. J., for preparation of the photographs and medical illustration.