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Role of Medical Prevention
0022-534 7/89/1413-0798$2.00/0 Vol. 141, March Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright© 1989 by The Williams & Wilkins Co.
ROLE OF MEDICAL PREVENTION CHARLES Y. C. PAK From the Center in Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
ABSTRACT
Despite dramatic advances in stone removal brought by extracorporeal shock wave lithotripsy, there is a continuing need for medical diagnosis and prevention. Justifications for the medical approach include prevention of recurrence (medical treatment could prevent further stone formation, unlike a surgical approach), efficacy of prophylactic program (recurrent stone formation may be inhibited in most patients using a variety of treatment programs), inhibition of spontaneous passage (by medical treatment, although not amenable to surgical treatment), potential avoidance of renal colic (occurring before stone removal avoided by preventing recurrence), reduced need for stone removal (achieved by successful medical treatment), correction of extrarenal manifestations (deleterious extrarenal manifestations of a stone-forming condition, such as bone disease in distal renal tubular acidosis, may be corrected by appropriate medical treatment) and cost-effectiveness. The cost of medical care is estimated to be half to a fourth that of surgical care. The need and type of medical treatment should be appraised continually to accommodate advances in techniques of stone removal. (J. Ural., part 2, 141: 798-801, 1989) The recent introduction of endoscopic stone removal' and extracorporeal shock wave lithotripsy (ESWL*) 2 has revolutionized the treatment of nephrolithiasis. Most stones currently can be removed with greater ease and less morbidity. While overshadowed by the aforementioned advances, there has been an equally notable progress in the medical arena. This progress has encompassed 3 closely linked, interdependent areas: 1) pathophysiological elucidation, 2) diagnostic separation and 3) medical prevention of recurrent nephrolithiasis. It now is known that the stone-forming urinary environment is characterized by an altered biochemical-physicochemical picture originating from metabolic or environmental disturbances. It currently is possible to identify the cause of stone formation in the majority of patients and to inhibit new stone formation in most patients. 3 Despite dramatic progress in surgical and medical areas, there has been an unfortunate tendency to promote one approach while disparaging or ignoring the other. Clearly, the continuing technological advances in the removal of stones have required a modification of the medical approach to nephrolithiasis. However, it should be apparent that the 2 approaches are complementary and that the ultimate control of nephrolithiasis mandates a conscious application of both approaches. Our objective is to engender arguments in support of continued application of the medical prophylactic program and to stress the need for an ongoing reappraisal of the need for medical treatment accommodating technological advances in the removal of stones. JUSTIFICATION FOR MEDICAL APPROACH
There are 7 broad justifications for the medical approach, including prevention of recurrence, efficacy of a prophylactic program, inhibition of spontaneous passage, potential avoidance of renal colic, reduced need for stone removal, correction of extrarenal manifestations and cost-effectiveness. Prevention of recurrence. There is a fundamental difference between the objective of a medical approach and that of a surgical approach. The former is the prevention of recurrent stone formation, while the latter is the removal of existing Supported by United States Public Health Service grants P01DK20543, R01-AR16061 and M01-RR00633. * Dornier Medical Systems, Inc., Marietta, Georgia.
798
stones. Nephrolithiasis is a disease characterized by recurrent stone formation. 4 While an effective medical treatment could prevent further stone formation, successful facilitated removal of existing stones by ESWL is unlikely to affect the likelihood for new stone formation. Efficacy of a prophylactic program. Many reports indicate that recurrent renal stones may be inhibited in a majority of patients using a variety of treatment programs. 5- 3 This progress has coincided with the advances in pathophysiological elucidation and in diagnostic separation. It now is possible to discern metabolic or environmental disturbance(s) in virtually every patient with recurrent nephrolithiasis. 3 The beneficial response to a conservative program or the stone clinic effect on stone formation is well known. 9 However, the following lines of evidence support a positive effect of specific medical treatment. Coe reviewed 8 clinical trials of thiazide in patients with idiopathic calcium nephrolithiasis. 10 Stone recurrence rates during thiazide treatment were compared to either a parallel placebo control or a pre-treatment period. In most of the trials the remission rate and the reduction in group stone formation rate were lower in the thiazide group. Among patients with mild-tomoderate stone disease (1 or less stones per year) potassium citrate therapy reduced the stone formation rate from 0.52 to 0.02 per patient-year, and produced a remission rate of 96 per cent and a decrease in the group stone formation rate of 96 per cent. 11 In contrast, a review of 11 conservative or placebo trials disclosed a much less favorable response, with a reduction in stone formation rate from 0.54 to 0.25 stones per patient-year, a remission rate of 61 per cent and a decrease in group stone formation rate of 54 per cent. 11 This finding supported superior clinical response of medical therapy (potassium citrate) versus that of conservative or placebo trials among patients with comparable severity of stone disease. Moreover, in patients with hypercalciuric nephrolithiasis who continued to form stones on thiazide therapy the replacement of potassium chloride by potassium citrate produced an inhibition of stone formation in most patients. 12 However, it is not known that a rigorous selective treatment program is more effective than a less selective one. Ettinger and associates found chlorthalidone to be more effective than placebo in inhibiting new stone formation in patients with idiopathic calcium oxalate nephrolithiasis, noncategorized as to the cause of hypercalciuria and without separation into normal or excessive renal excretion of calcium or uric acid. 13
799
ROLE OF MEDICAL PREVENTION
However, our own studies indicated that a more selectively applied potassium citrate therapy in patients with hypocitraturia provided a better clinical response than in those with normocitraturic calcium nephrolithiasis. Thus, in the hypocitraturic group stone formation rate decreased from 4.14 to 0.4 stones per patient-year after potassium citrate treatment, 82.3 per cent of the patients achieved remission and the group stone formation rate decreased by 90.3 per cent. In contrast, the normocitraturic group showed a reduction in stone formation rate from 3.33 to 0. 75 stones per patient-year, a remission rate of 74 per cent and a decrease in group stone formation rate of 77.5 per cent. The less favorable response in the normocitraturic group probably reflected the presence of other metabolic abnormalities not corrected by potassium citrate therapy. Inhibition of spontaneous passage. Most stone episodes probably are resolved spontaneously without a need for surgical removal. Of 200 consecutive patients evaluated by us 2,485 stone episodes were experienced over a mean duration of 9.59 years per patient before referral and institution of specific treatment. These patients required 326 operations for removal of stones. Thus, only 13. l per cent of all stone episodes required surgical removal; the remaining episodes (86.9 per cent) were resolved spontaneously. The National Kidney Foundation po-
--•
•
•-+-----
sition paper on ESWL in 1985 indicated that 78 per cent of stone episodes do not require an operation. 11 It is expected that a wider application of improved methods for stone removal might reduce this percentage but would not eliminate stone episodes that are resolved spontaneously" It is apparent that medical treatment could prevent such stone episodes. It also may be argued that not all pre-existing stones require surgical intervention. Under proper medical treatment the morbidity of pre-existing stones may be surprisingly low.1.s Potential avoidance of renal colic. Stone episodes are often associated with severe renal colic. Even when amenable to correction by newer methods of stone removal there often is a lag time between the onset and removal when the patient may be exposed to severe suffering. By preventing recurrence effective medical therapy could reduce this morbidity. Reduced need for stone removal. A successful medical treatment program may greatly reduce the need for stone removal or fragmentation. Of our patients undergoing long-term treatment with potassium citrate 16 none has yet required an operation for the removal of newly formed stones (see figure). In our previous report involving patients undergoing various longterm selective treatment programs the stone surgery rate decreased from 0.21 per patient-year during the 3 years preceding
x-
-------• --<>---------!--------
x Surgery for Pre - existing Stones
-0-e>-$-----•--<------
.
=========-=-----=~--·==:::t=========================== ==============-•--+---------------=========-=--------~-•--+---:------------•-+--------
= __===============-·==========-=-: · ====_ri=-===================~-- - - - - - - ·-==t============================---__-_-_-_-_-_-_-_-_-_-_-,_·==t===-=---=----=---,-----=-=====------=========-__-_-_-- - = - - - - + - - - - - - - - - - - - - - - - • - - - - - - •- - { - - - - - - - - - - ~o
o-.;;--- x - - - - - - - - - - - - - - - -
--------•
.
==-=---=---=------_-_·-.-=-=----.--.=1-==============================--==========-=-----=---·-.==::t=======================------------•--+-------===================~==================--------,===================~==================-X-=·-=-=-=========--I------============-=------_-_-_---_--------·======---_-++-_-_-_-_-_-_-_-: . _-_-_-:_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_---=: --------•·--+--------------x--
-3
-2
0
Years Prior to Therapy
+1
+2
+3
+4
+5
+6
+7
+8
Years on K Citrate
Effect of potassium citrate therapy on requirement for stone surgery. Each line represents separate patient. Each circle represents separate operation, including ESWL, for removal of stones. Each x indicates operation required during potassium citrate therapy for stones that were already present when potassium citrate treatment was begun.
800
PAK
institution of medical treatment to 0.1 per patient-year during a mean treatment duration of 3. 7 years per patient. 15 Only 2 per cent of the patients required an operation for newly formed stones, whereas 58 per cent did so before institution of medical treatment. Correction of extrarenal manifestations. Medical treatment potentially could correct extrarenal manifestations of the stone disease, whereas a surgical approach concentrates on stone removal alone. Some forms of nephrolithiasis represent a multisystem disease in which stone formation is only 1 manifestation. In renal hypercalciuria with secondary hyperparathyroidism there may be skeletal involvement, as indicated by a reduced bone density. 17 Calcium balance may be relatively intact in young premenopausal women because of the compensatory intestinal hyperabsorption of calcium. However, in postmenopausal women with renal hypercalciuria, calcium balance may be negative due to inadequate response of 1,25-(0Hhvitamin D synthesis to the parathyroid stimulation and the consequent impairment in intestinal calcium absorption. 18 Thiazide therapy may restore normal parathyroid function and avert deleterious effects of renal hypercalciuria on the skeleton. 19 In the chronic diarrheal syndrome nephrolithiasis occurs secondarily from primary bowel disease. Bone disease also may be present from acquired metabolic acidosis and intestinal malabsorption, particularly of calcium. The treatment directed at the underlying bowel disease and acidosis may produce amelioration of extrarenal manifestations as well as nephrolithiasis. Hypokalemia and bone disease may complicate the course of distal renal tubular acidosis. In this condition there may be hypercalciuria, subnormal intestinal calcium absorption and negative calcium balance. Treatment with potassium citrate has been shown to reduce calcium excretion, augment intestinal calcium absorption and improve the state of calcium balance. 20 In patients with absorptive hypercalciuria presenting with hypophosphatemia an abnormal histomorphometric picture of bone may be encountered, characterized by high osteoclastic activity and impaired osteoblastic activity. 21 Orthophosphate treatment may correct these abnormalities. In contrast, it is not expected that removal of stones alone would affect favorably any of the extrarenal manifestations previously enumerated. Cost-effectiveness. A cogent argument may be made for the assertion that a medical prophylactic program may be costeffective relative to the surgical approach. The cost of surgical care was estimated from a slight modification of the report by Frangos and Rous. 22 The following assumptions were taken. Total number of hospitalizations for renal stones in the United States was considered to be 328,000 yearly. Of these hospitalizations 22 per cent were assumed to require surgical intervention, costing $3,500 for technical fees and $2,200 for physician services for each hospitalization. For 78 per cent of the hospitalizations that do not require an operation the physician fees were assumed to be $200 per hospitalization. The average duration of hospitalization was taken at 4.2 days, at $400 per day. Therefore, the total cost of surgical care in the United States for detection, hospital stay, technical fees and physician services was $1.08 billion per year. When the indirect cost (due to loss of work) 22 was added, total cost was $1.15 billion per year. Assuming that all operations are performed in an outpatient setting obviating hospitalization, total cost still was $528 million per year. The cost of medical care was calculated with the following assumptions. The cost for diagnosis and laboratory was considered to be an average of $300 per year for each patient, that of medication $200 per year and physician fees $200 per year. The cost of medical care for diagnosis and laboratory, medications and physician fees in the United States was, therefore, $229.6 million per year for all patients. Assuming that 5 per cent of all patients experience renal colic requiring surgical interven-
tion and that an operation is conducted in an inpatient setting, there would be an added cost of $57.5 million per year. Therefore, the total cost for medical care is $287 million per year. This estimate does not account for the reduced annual incidence of stones due to improved prophylaxis. The expected attrition in stone incidents due to medical therapy would further lower the cost of medical care. CONCLUSIONS
Despite potential advantages of a medical approach as enumerated, certain inherent problems of the medical treatment program should not be overlooked. To be effective the medical prevention program requires rigid compliance by the patient and constant surveillance by the physician. It demands commitment by the patient to adhere to the chosen program on a daily continuing basis for an extended period of many years. Regular followup evaluation by the physician is critical to assure that the response is appropriate. Moreover, all medical treatments have certain hazards, especially if they are misused. Finally, no cure for stone disease is obtainable by the current medical prophylactic program. It is expected that continued improvements will be made in the surgical removal techniques and in medical approaches regarding efficacy, facility, safety and cost. It is critical that the need for medical treatment be reappraised continually to accommodate these changing trends. REFERENCES
1. Segura, J. W., Patterson, D. E., LeRoy, A. J., May, G. R. and Smith, L. H.: Percutaneous lithotripsy. J. Urol., 130: 1051, 1983. 2. Chaussy, C., Brendel, W. and Schmiedt, E.: Extracorporeally induced destruction of kidney stones by shock waves. Lancet, 2: 1265, 1980. 3. Pak, C. Y. C.: Medical management of nephrolithiasis in Dallas: update 1987. J. Urol., 140: 461, 1988. 4. Coe, F. L., Keck, J. and Norton, E. R.: The natural history of calcium urolithiasis. J.A.M.A., 238: 1519, 1977. 5. Coe, F. L. and Kavalach, A.G.: Hypercalciuria and hyperuricosuria in patients with calcium nephrolithiasis. New Engl. J. Med., 291: 1344, 1974. 6. Yendt, E. R. and Cohanim, M.: Prevention of calcium stones with thiazides. Kidney Int., 13: 397, 1978. 7. Ettinger, B., Tang, A., Citron, J. T., Livermore, B. and Williams, T.: Randomized trial of allopurinol in the prevention of calcium oxalate calculi. New Engl. J. Med., 315: 1386, 1986. 8. Pak, C. Y. C.: Citrate and renal calculi. Min. Electrolyte Metab., 13: 257, 1987. 9. Hosking, D. H., Erickson, S. B., Van Den Berg, C. J., Wilson, D. M. and Smith, L. H.: The stone clinic effect in patients with idiopathic calcium urolithiasis. J. Urol., 130: 1115, 1983. 10. Coe, F. L.: Personal communication. 11. Preminger, G. M., Harvey, J. A. and Pak, C. Y. C.: Comparative efficacy of "specific" potassium citrate therapy versus conservative management in nephrolithiasis of mild to moderate severity. J. Urol., 134: 658, 1985. 12. Pak, C. Y. C., Peterson, R., Sakhaee, K., Fuller, C., Preminger, G. and Reisch, J.: Correction of hypocitraturia and prevention of stone formation by combined thiazide and potassium citrate therapy in thiazide-unresponsive hypercalciuric nephrolithiasis. Amer. J. Med., 79: 284, 1985. 13. Ettinger, B., Citron, J. T., Livermore, B. and Dolman, L. I.: Chlorthalidone reduces calcium oxalate calculous recurrence but magnesium hydroxide does not. J. Urol., 139: 679, 1988. 14. National Kidney Foundation Position Paper on Extracorporeal Shockwave Lithotripsy. Approved by the National Kidney Foundation Health and Scientific Affairs Committee, March 1, 1985. 15. Preminger, G. M., Peterson, R., Peters, P. C. and Pak, C. Y. C.: The current role of medical treatment of nephrolithiasis: the impact of improved techniques of stone removal. J. Urol., 134: 6, 1985. 16. Pak, C. Y. C., Fuller, C., Sakhaee, K., Preminger, G. M. and Britton, F.: Long-term treatment of calcium nephrolithiasis with potassium citrate. J. Urol., 134: 11, 1985.
17. Lawoyin, S., Sismilich, S., Browne, R. and Pak, Y. C.: Bone mineral content in patients with calcium urolithiasis. Metabolism, 28: 1250, 1979. 18. Sakhaee, K., Nicar, M. J., Glass, K. and Pak, C. Y. C.: Postmenopausal osteoporosis presenting as a manifestation of renal hypercalciuria with secondary hyperparathyroidism. J. Clin. Endocr. Metab., 61: 368, 1985. 19. Zerwekh, J. E. and Pak, C. Y. C.: Selective effects of thiazide therapy on serum l",25-dihydroxyvitamin D and intestinal calcium absorption in renal and absorptive hypercalciurias. Metabolism, 29: 13, 1980.
20. Preminger, G. M., Sakhaee, K. and Pak, C. Y. C.: Hypercalciuria and altered intestinal calciun, absorption occurring independently of vitamin D in distal renal tubular acidosis. Metabolism, 36: 176, 1987. 21. Bordier, P., Ryckewart, A., Gueris, J. and Rasmussen, H.: On the pathogenesis of so-called idiopathic hypercalciuria. Amer. J. Med., 63: 398, 1977. 22. Frangos, D. N. and Rous, S. N.: Incidence and economic factors in urolithiasis. In: Stone Disease: Diagnosis and Management. Edited by S. N. Rous. Orlando: Grune & Stratton, Inc., chapt. 1, pp. 3-10, 1987.
THE JOURNAL OF UROLOGY
Copyright© 1989 by The Williams & Wilkins Co.
ROLE OF MEDICAL PREVENTION CHARLES Y. C. PAK From the Center in Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, Texas
ABSTRACT
Despite dramatic advances in stone removal brought by extracorporeal shock wave lithotripsy, there is a continuing need for medical diagnosis and prevention. Justifications for the medical approach include prevention of recurrence (medical treatment could prevent further stone formation, unlike a surgical approach), efficacy of prophylactic program (recurrent stone formation may be inhibited in most patients using a variety of treatment programs), inhibition of spontaneous passage (by medical treatment, although not amenable to surgical treatment), potential avoidance of renal colic (occurring before stone removal avoided by preventing recurrence), reduced need for stone removal (achieved by successful medical treatment), correction of extrarenal manifestations (deleterious extrarenal manifestations of a stone-forming condition, such as bone disease in distal renal tubular acidosis, may be corrected by appropriate medical treatment) and cost-effectiveness. The cost of medical care is estimated to be half to a fourth that of surgical care. The need and type of medical treatment should be appraised continually to accommodate advances in techniques of stone removal. (J. Ural., part 2, 141: 798-801, 1989) The recent introduction of endoscopic stone removal' and extracorporeal shock wave lithotripsy (ESWL*) 2 has revolutionized the treatment of nephrolithiasis. Most stones currently can be removed with greater ease and less morbidity. While overshadowed by the aforementioned advances, there has been an equally notable progress in the medical arena. This progress has encompassed 3 closely linked, interdependent areas: 1) pathophysiological elucidation, 2) diagnostic separation and 3) medical prevention of recurrent nephrolithiasis. It now is known that the stone-forming urinary environment is characterized by an altered biochemical-physicochemical picture originating from metabolic or environmental disturbances. It currently is possible to identify the cause of stone formation in the majority of patients and to inhibit new stone formation in most patients. 3 Despite dramatic progress in surgical and medical areas, there has been an unfortunate tendency to promote one approach while disparaging or ignoring the other. Clearly, the continuing technological advances in the removal of stones have required a modification of the medical approach to nephrolithiasis. However, it should be apparent that the 2 approaches are complementary and that the ultimate control of nephrolithiasis mandates a conscious application of both approaches. Our objective is to engender arguments in support of continued application of the medical prophylactic program and to stress the need for an ongoing reappraisal of the need for medical treatment accommodating technological advances in the removal of stones. JUSTIFICATION FOR MEDICAL APPROACH
There are 7 broad justifications for the medical approach, including prevention of recurrence, efficacy of a prophylactic program, inhibition of spontaneous passage, potential avoidance of renal colic, reduced need for stone removal, correction of extrarenal manifestations and cost-effectiveness. Prevention of recurrence. There is a fundamental difference between the objective of a medical approach and that of a surgical approach. The former is the prevention of recurrent stone formation, while the latter is the removal of existing Supported by United States Public Health Service grants P01DK20543, R01-AR16061 and M01-RR00633. * Dornier Medical Systems, Inc., Marietta, Georgia.
798
stones. Nephrolithiasis is a disease characterized by recurrent stone formation. 4 While an effective medical treatment could prevent further stone formation, successful facilitated removal of existing stones by ESWL is unlikely to affect the likelihood for new stone formation. Efficacy of a prophylactic program. Many reports indicate that recurrent renal stones may be inhibited in a majority of patients using a variety of treatment programs. 5- 3 This progress has coincided with the advances in pathophysiological elucidation and in diagnostic separation. It now is possible to discern metabolic or environmental disturbance(s) in virtually every patient with recurrent nephrolithiasis. 3 The beneficial response to a conservative program or the stone clinic effect on stone formation is well known. 9 However, the following lines of evidence support a positive effect of specific medical treatment. Coe reviewed 8 clinical trials of thiazide in patients with idiopathic calcium nephrolithiasis. 10 Stone recurrence rates during thiazide treatment were compared to either a parallel placebo control or a pre-treatment period. In most of the trials the remission rate and the reduction in group stone formation rate were lower in the thiazide group. Among patients with mild-tomoderate stone disease (1 or less stones per year) potassium citrate therapy reduced the stone formation rate from 0.52 to 0.02 per patient-year, and produced a remission rate of 96 per cent and a decrease in the group stone formation rate of 96 per cent. 11 In contrast, a review of 11 conservative or placebo trials disclosed a much less favorable response, with a reduction in stone formation rate from 0.54 to 0.25 stones per patient-year, a remission rate of 61 per cent and a decrease in group stone formation rate of 54 per cent. 11 This finding supported superior clinical response of medical therapy (potassium citrate) versus that of conservative or placebo trials among patients with comparable severity of stone disease. Moreover, in patients with hypercalciuric nephrolithiasis who continued to form stones on thiazide therapy the replacement of potassium chloride by potassium citrate produced an inhibition of stone formation in most patients. 12 However, it is not known that a rigorous selective treatment program is more effective than a less selective one. Ettinger and associates found chlorthalidone to be more effective than placebo in inhibiting new stone formation in patients with idiopathic calcium oxalate nephrolithiasis, noncategorized as to the cause of hypercalciuria and without separation into normal or excessive renal excretion of calcium or uric acid. 13
799
ROLE OF MEDICAL PREVENTION
However, our own studies indicated that a more selectively applied potassium citrate therapy in patients with hypocitraturia provided a better clinical response than in those with normocitraturic calcium nephrolithiasis. Thus, in the hypocitraturic group stone formation rate decreased from 4.14 to 0.4 stones per patient-year after potassium citrate treatment, 82.3 per cent of the patients achieved remission and the group stone formation rate decreased by 90.3 per cent. In contrast, the normocitraturic group showed a reduction in stone formation rate from 3.33 to 0. 75 stones per patient-year, a remission rate of 74 per cent and a decrease in group stone formation rate of 77.5 per cent. The less favorable response in the normocitraturic group probably reflected the presence of other metabolic abnormalities not corrected by potassium citrate therapy. Inhibition of spontaneous passage. Most stone episodes probably are resolved spontaneously without a need for surgical removal. Of 200 consecutive patients evaluated by us 2,485 stone episodes were experienced over a mean duration of 9.59 years per patient before referral and institution of specific treatment. These patients required 326 operations for removal of stones. Thus, only 13. l per cent of all stone episodes required surgical removal; the remaining episodes (86.9 per cent) were resolved spontaneously. The National Kidney Foundation po-
--•
•
•-+-----
sition paper on ESWL in 1985 indicated that 78 per cent of stone episodes do not require an operation. 11 It is expected that a wider application of improved methods for stone removal might reduce this percentage but would not eliminate stone episodes that are resolved spontaneously" It is apparent that medical treatment could prevent such stone episodes. It also may be argued that not all pre-existing stones require surgical intervention. Under proper medical treatment the morbidity of pre-existing stones may be surprisingly low.1.s Potential avoidance of renal colic. Stone episodes are often associated with severe renal colic. Even when amenable to correction by newer methods of stone removal there often is a lag time between the onset and removal when the patient may be exposed to severe suffering. By preventing recurrence effective medical therapy could reduce this morbidity. Reduced need for stone removal. A successful medical treatment program may greatly reduce the need for stone removal or fragmentation. Of our patients undergoing long-term treatment with potassium citrate 16 none has yet required an operation for the removal of newly formed stones (see figure). In our previous report involving patients undergoing various longterm selective treatment programs the stone surgery rate decreased from 0.21 per patient-year during the 3 years preceding
x-
-------• --<>---------!--------
x Surgery for Pre - existing Stones
-0-e>-$-----•--<------
.
=========-=-----=~--·==:::t=========================== ==============-•--+---------------=========-=--------~-•--+---:------------•-+--------
= __===============-·==========-=-: · ====_ri=-===================~-- - - - - - - ·-==t============================---__-_-_-_-_-_-_-_-_-_-_-,_·==t===-=---=----=---,-----=-=====------=========-__-_-_-- - = - - - - + - - - - - - - - - - - - - - - - • - - - - - - •- - { - - - - - - - - - - ~o
o-.;;--- x - - - - - - - - - - - - - - - -
--------•
.
==-=---=---=------_-_·-.-=-=----.--.=1-==============================--==========-=-----=---·-.==::t=======================------------•--+-------===================~==================--------,===================~==================-X-=·-=-=-=========--I------============-=------_-_-_---_--------·======---_-++-_-_-_-_-_-_-_-: . _-_-_-:_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_-_---=: --------•·--+--------------x--
-3
-2
0
Years Prior to Therapy
+1
+2
+3
+4
+5
+6
+7
+8
Years on K Citrate
Effect of potassium citrate therapy on requirement for stone surgery. Each line represents separate patient. Each circle represents separate operation, including ESWL, for removal of stones. Each x indicates operation required during potassium citrate therapy for stones that were already present when potassium citrate treatment was begun.
800
PAK
institution of medical treatment to 0.1 per patient-year during a mean treatment duration of 3. 7 years per patient. 15 Only 2 per cent of the patients required an operation for newly formed stones, whereas 58 per cent did so before institution of medical treatment. Correction of extrarenal manifestations. Medical treatment potentially could correct extrarenal manifestations of the stone disease, whereas a surgical approach concentrates on stone removal alone. Some forms of nephrolithiasis represent a multisystem disease in which stone formation is only 1 manifestation. In renal hypercalciuria with secondary hyperparathyroidism there may be skeletal involvement, as indicated by a reduced bone density. 17 Calcium balance may be relatively intact in young premenopausal women because of the compensatory intestinal hyperabsorption of calcium. However, in postmenopausal women with renal hypercalciuria, calcium balance may be negative due to inadequate response of 1,25-(0Hhvitamin D synthesis to the parathyroid stimulation and the consequent impairment in intestinal calcium absorption. 18 Thiazide therapy may restore normal parathyroid function and avert deleterious effects of renal hypercalciuria on the skeleton. 19 In the chronic diarrheal syndrome nephrolithiasis occurs secondarily from primary bowel disease. Bone disease also may be present from acquired metabolic acidosis and intestinal malabsorption, particularly of calcium. The treatment directed at the underlying bowel disease and acidosis may produce amelioration of extrarenal manifestations as well as nephrolithiasis. Hypokalemia and bone disease may complicate the course of distal renal tubular acidosis. In this condition there may be hypercalciuria, subnormal intestinal calcium absorption and negative calcium balance. Treatment with potassium citrate has been shown to reduce calcium excretion, augment intestinal calcium absorption and improve the state of calcium balance. 20 In patients with absorptive hypercalciuria presenting with hypophosphatemia an abnormal histomorphometric picture of bone may be encountered, characterized by high osteoclastic activity and impaired osteoblastic activity. 21 Orthophosphate treatment may correct these abnormalities. In contrast, it is not expected that removal of stones alone would affect favorably any of the extrarenal manifestations previously enumerated. Cost-effectiveness. A cogent argument may be made for the assertion that a medical prophylactic program may be costeffective relative to the surgical approach. The cost of surgical care was estimated from a slight modification of the report by Frangos and Rous. 22 The following assumptions were taken. Total number of hospitalizations for renal stones in the United States was considered to be 328,000 yearly. Of these hospitalizations 22 per cent were assumed to require surgical intervention, costing $3,500 for technical fees and $2,200 for physician services for each hospitalization. For 78 per cent of the hospitalizations that do not require an operation the physician fees were assumed to be $200 per hospitalization. The average duration of hospitalization was taken at 4.2 days, at $400 per day. Therefore, the total cost of surgical care in the United States for detection, hospital stay, technical fees and physician services was $1.08 billion per year. When the indirect cost (due to loss of work) 22 was added, total cost was $1.15 billion per year. Assuming that all operations are performed in an outpatient setting obviating hospitalization, total cost still was $528 million per year. The cost of medical care was calculated with the following assumptions. The cost for diagnosis and laboratory was considered to be an average of $300 per year for each patient, that of medication $200 per year and physician fees $200 per year. The cost of medical care for diagnosis and laboratory, medications and physician fees in the United States was, therefore, $229.6 million per year for all patients. Assuming that 5 per cent of all patients experience renal colic requiring surgical interven-
tion and that an operation is conducted in an inpatient setting, there would be an added cost of $57.5 million per year. Therefore, the total cost for medical care is $287 million per year. This estimate does not account for the reduced annual incidence of stones due to improved prophylaxis. The expected attrition in stone incidents due to medical therapy would further lower the cost of medical care. CONCLUSIONS
Despite potential advantages of a medical approach as enumerated, certain inherent problems of the medical treatment program should not be overlooked. To be effective the medical prevention program requires rigid compliance by the patient and constant surveillance by the physician. It demands commitment by the patient to adhere to the chosen program on a daily continuing basis for an extended period of many years. Regular followup evaluation by the physician is critical to assure that the response is appropriate. Moreover, all medical treatments have certain hazards, especially if they are misused. Finally, no cure for stone disease is obtainable by the current medical prophylactic program. It is expected that continued improvements will be made in the surgical removal techniques and in medical approaches regarding efficacy, facility, safety and cost. It is critical that the need for medical treatment be reappraised continually to accommodate these changing trends. REFERENCES
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