Amylase and Isoamylase Activities in Renal Insufficiency J. EDWARD BERK, M.D.; LOUIS FRIDHANDLER, Ph.D.; and RUSSELL L. NESS, M.D. College of Medicine, University of California, Irvine; Orange, California I M P A I R E D R E N A L F U N C T I O N may be associated with rises in serum amylase activity (1-5) and the ratio of amyBrief Reports
Downloaded From: https://annals.org/ by a University of Texas User on 10/12/2018
351
The study group was composed of 36 patients with advanced renal insufficiency. Twenty-four were receiving hemodialysis, 19 for end-stage renal disease and five for acute renal failure. Another 13 patients with end-stage renal disease undergoing regular hemodialysis (made available by Manley Cohen, M.D., and Henry P. Shavell, M.D.) were additionally studied to ascertain whether dialysis affected amylase activity. Automated methods were used to measure both total amylase activity (7) and creatinine concentration. Serum and urine isoamylase patterns (7, 8) were ascertained in 20 normal subjects and in 34 of the 36 patients with renal insufficiency; isoamylase analysis was made only of the serum in one other patient in the latter group. Amylase clearance-to-creatinine clearance ratios for total amylase (Cam/Ccr) (6) were calculated in all 36 patients with renal disease. Similar clearance ratios for P-type and S-type isoamylase were computed in the 20 normal subjects and the 34 patients with renal disease in whom isoamylase analysis had been made in both the serum and urine. Total amylase activity before and after dialysis was measured in 32 paired serum samples obtained from the special group of 13 patients undergoing hemodialysis.
Figure 1 . Ratios of amylase clearance to creatinine clearance {Cam/Ccr) in control subjects and patients with marked renal insufficiency. The dots represent persons whose serum amylase levels were within normal limits and the open squares represent hyperamylasemic subjects. The broken horizontal line marks the accepted upper limit of normal for Cam/Ccr.
lase clearance to creatinine (Cam/Ccr) (3, 4, 6). These deviations cloud the interpretation of abdominal pain and hyperamylasemia in patients with chronic renal disease as indicators of complicating acute pancreatitis (5). This study is primarily concerned with the effect of marked renal impairment on the serum activities and relative urinary clearances of the pancreatic-type (P-type) and salivary-type (S-type) isoenzymes of amylase about which information is limited at present (3). 352
March 1979 • Annals of Internal Medicine • Volume 90 • Number 3
Downloaded From: https://annals.org/ by a University of Texas User on 10/12/2018
Total serum amylase activity at or above the upper limit of normal for the method used (glucose, 171 mg/dl) (7) was found in 18 of the 36 patients with renal insufficiency. In 14 of these 18, elevations were found in P-type isoamylase alone in five (glucose, > 96 mg/dl) (7), in Stype isoamylase alone in four (glucose, > 119 mg/dl) (7), and in both types in five. One patient, in whom total amylase activity was within normal limits, had an abnormal elevation of P-type isoamylase. The highest total serum amylase in the renal group was glucose, 521 mg/dl, a value less than three times the upper level of normal. Correspondingly, the highest value for serum P-type isoamylase was glucose, 281 mg/dl, a value just less than three times the upper level of normal. In 26 of the 36 patients with severe renal insufficiency, Cam/Ccr ratios in excess of our upper limit of normal (4%) were recorded. In 31 of the 34 patients with renal disease in whom isoamylase analysis was done in both the serum and urine, the clearance ratio for P-type was greater than the clearance ratio for S-type. The same relative situation obtained in the 20 normal subjects in whom these measurements were made. There was no uniform association between the serum amylase level and the Cam/Ccr (Figure 1). Similarly, the nature of the hyperamylasemia did not seem to bear any relation to that ratio. As noted by others (9), no significant difference was found between the pre- and postdialysis samples using a signed-rank test. Only some 24% of the circulating amylase in the baboon (10) and from 5% to 45% of the amylase removed from the circulation in man (9) is accounted for by excretion into the urine. Nevertheless, serum amylase activity has been noted to rise when the excretory capacity of the kidneys is diminished (1-5). This was attested to by the finding of hyperamylasemia in half of our 36 patients. The increase in total amylase activity that may occur in association with renal disease is generally of a low order (3). Indeed, our findings suggest that when the level of total serum amylase activity is affected by deficient renal function alone, the rise that may occur is likely to be less than three times the upper limit of normal. The Ptype isoamylase activity may likewise be affected by impaired renal function. Hence, even a rise in this isoenzyme form does not in itself specifically signify pancreatic disease in the face of renal insufficiency. It would appear from our data, however, that when serum P-type isoamy-
lase exceeds three times the upper limit of normal for this component, factors other than renal impairment deserve consideration. As noted by others (3, 4, 6), our findings indicate that the Cam/Ccr is without discriminatory value when renal function is severely deficient. Of particular note in this regard was the finding of an elevated Cam/Ccr in three of the four patients with renal disease in our group who had hyperamylasemia with normal P-type, but elevated S-type, isoamylase levels. Our study of the relative clearance ratios of the P- and S-type isoamylases also showed that the tendency toward a higher rate of renal excretion for P-type is essentially unaltered by impaired renal function (8, 10). This study was supported by a grant from the John A. Hartford Foundation, Inc., and in part by a grant from the Bockus International Society of Gastroenterology. REFERENCES 1. BAILEY GL, K A T Z AL, H A M P E R S CL, M E R R I L L JP: Alterations in
serum enzymes in chronic renal failure. JAMA 213:2263-2265, 1970 2. SCHONEBECK J, SODERBERG M: Serum amylase in renal failure. ScandJ Urol Nephrol 5:257-262, 1971 3. M O R T O N WJ, T E D E S C O FJ, H A R T E R HR, A L P E R S D H : Serum amylase
determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency. Gastroenterology 71:594-598, 1976 4. P E D E R S E N EB, BROCK A, K O R N E R U P H G : Serum amylase activity and
renal amylase activity clearance in patients with severely impaired renal function and in patients treated with renal allotransplantation. Scand J Clin Lab Invest 36:137-140, 1976 5. ROBINSON DO, A L P MH, G R A N T AK, L A W R E N C E JR: Pancreatitis
and renal disease. Scand J Gastroenterol
12:17-20, 1977
6. L E V I T T M D , R A P O P O R T M, C O O P E R B A N D SR: The renal clearance of
amylase in renal insufficiency, acute pancreatitis and macroamylasemia. Ann Intern Med 71:919-925, 1969 7. H E F F E R N O N JJ, F R I D H A N D L E R L, BERK JE, S H I M A M U R A J: Assay of
amylase and isoamylase activities in serum and urine. Am J Gastroenterol 61r:47'3-477, 1977 8. F R I D H A N D L E R L, B E R K JE, U E D A M: Isolation and measurement of
pancreatic amylase in human serum and urine. Clin Chem 18:14931497, 1972 9. N O R D HJ, W E I S HJ, C O L L E H: Untersuchungen zum Stoffwechsel der
Serumamylase. Verb Dtsch Ges Inn Med 79:868-970, 1973 10. D U A N E WC, F R E R I C H S R, L E V I T T M D : Distribution, turnover and
mechanism of renal excretion of amylase in the baboon. / Clin Invest 50:156-165, 1971 © 1 9 7 9 American College of Physicians
Brief Reports
Downloaded From: https://annals.org/ by a University of Texas User on 10/12/2018
353
Downloaded From: https://annals.org/ by a University of Texas User on 10/12/2018
351
The study group was composed of 36 patients with advanced renal insufficiency. Twenty-four were receiving hemodialysis, 19 for end-stage renal disease and five for acute renal failure. Another 13 patients with end-stage renal disease undergoing regular hemodialysis (made available by Manley Cohen, M.D., and Henry P. Shavell, M.D.) were additionally studied to ascertain whether dialysis affected amylase activity. Automated methods were used to measure both total amylase activity (7) and creatinine concentration. Serum and urine isoamylase patterns (7, 8) were ascertained in 20 normal subjects and in 34 of the 36 patients with renal insufficiency; isoamylase analysis was made only of the serum in one other patient in the latter group. Amylase clearance-to-creatinine clearance ratios for total amylase (Cam/Ccr) (6) were calculated in all 36 patients with renal disease. Similar clearance ratios for P-type and S-type isoamylase were computed in the 20 normal subjects and the 34 patients with renal disease in whom isoamylase analysis had been made in both the serum and urine. Total amylase activity before and after dialysis was measured in 32 paired serum samples obtained from the special group of 13 patients undergoing hemodialysis.
Figure 1 . Ratios of amylase clearance to creatinine clearance {Cam/Ccr) in control subjects and patients with marked renal insufficiency. The dots represent persons whose serum amylase levels were within normal limits and the open squares represent hyperamylasemic subjects. The broken horizontal line marks the accepted upper limit of normal for Cam/Ccr.
lase clearance to creatinine (Cam/Ccr) (3, 4, 6). These deviations cloud the interpretation of abdominal pain and hyperamylasemia in patients with chronic renal disease as indicators of complicating acute pancreatitis (5). This study is primarily concerned with the effect of marked renal impairment on the serum activities and relative urinary clearances of the pancreatic-type (P-type) and salivary-type (S-type) isoenzymes of amylase about which information is limited at present (3). 352
March 1979 • Annals of Internal Medicine • Volume 90 • Number 3
Downloaded From: https://annals.org/ by a University of Texas User on 10/12/2018
Total serum amylase activity at or above the upper limit of normal for the method used (glucose, 171 mg/dl) (7) was found in 18 of the 36 patients with renal insufficiency. In 14 of these 18, elevations were found in P-type isoamylase alone in five (glucose, > 96 mg/dl) (7), in Stype isoamylase alone in four (glucose, > 119 mg/dl) (7), and in both types in five. One patient, in whom total amylase activity was within normal limits, had an abnormal elevation of P-type isoamylase. The highest total serum amylase in the renal group was glucose, 521 mg/dl, a value less than three times the upper level of normal. Correspondingly, the highest value for serum P-type isoamylase was glucose, 281 mg/dl, a value just less than three times the upper level of normal. In 26 of the 36 patients with severe renal insufficiency, Cam/Ccr ratios in excess of our upper limit of normal (4%) were recorded. In 31 of the 34 patients with renal disease in whom isoamylase analysis was done in both the serum and urine, the clearance ratio for P-type was greater than the clearance ratio for S-type. The same relative situation obtained in the 20 normal subjects in whom these measurements were made. There was no uniform association between the serum amylase level and the Cam/Ccr (Figure 1). Similarly, the nature of the hyperamylasemia did not seem to bear any relation to that ratio. As noted by others (9), no significant difference was found between the pre- and postdialysis samples using a signed-rank test. Only some 24% of the circulating amylase in the baboon (10) and from 5% to 45% of the amylase removed from the circulation in man (9) is accounted for by excretion into the urine. Nevertheless, serum amylase activity has been noted to rise when the excretory capacity of the kidneys is diminished (1-5). This was attested to by the finding of hyperamylasemia in half of our 36 patients. The increase in total amylase activity that may occur in association with renal disease is generally of a low order (3). Indeed, our findings suggest that when the level of total serum amylase activity is affected by deficient renal function alone, the rise that may occur is likely to be less than three times the upper limit of normal. The Ptype isoamylase activity may likewise be affected by impaired renal function. Hence, even a rise in this isoenzyme form does not in itself specifically signify pancreatic disease in the face of renal insufficiency. It would appear from our data, however, that when serum P-type isoamy-
lase exceeds three times the upper limit of normal for this component, factors other than renal impairment deserve consideration. As noted by others (3, 4, 6), our findings indicate that the Cam/Ccr is without discriminatory value when renal function is severely deficient. Of particular note in this regard was the finding of an elevated Cam/Ccr in three of the four patients with renal disease in our group who had hyperamylasemia with normal P-type, but elevated S-type, isoamylase levels. Our study of the relative clearance ratios of the P- and S-type isoamylases also showed that the tendency toward a higher rate of renal excretion for P-type is essentially unaltered by impaired renal function (8, 10). This study was supported by a grant from the John A. Hartford Foundation, Inc., and in part by a grant from the Bockus International Society of Gastroenterology. REFERENCES 1. BAILEY GL, K A T Z AL, H A M P E R S CL, M E R R I L L JP: Alterations in
serum enzymes in chronic renal failure. JAMA 213:2263-2265, 1970 2. SCHONEBECK J, SODERBERG M: Serum amylase in renal failure. ScandJ Urol Nephrol 5:257-262, 1971 3. M O R T O N WJ, T E D E S C O FJ, H A R T E R HR, A L P E R S D H : Serum amylase
determinations and amylase to creatinine clearance ratios in patients with chronic renal insufficiency. Gastroenterology 71:594-598, 1976 4. P E D E R S E N EB, BROCK A, K O R N E R U P H G : Serum amylase activity and
renal amylase activity clearance in patients with severely impaired renal function and in patients treated with renal allotransplantation. Scand J Clin Lab Invest 36:137-140, 1976 5. ROBINSON DO, A L P MH, G R A N T AK, L A W R E N C E JR: Pancreatitis
and renal disease. Scand J Gastroenterol
12:17-20, 1977
6. L E V I T T M D , R A P O P O R T M, C O O P E R B A N D SR: The renal clearance of
amylase in renal insufficiency, acute pancreatitis and macroamylasemia. Ann Intern Med 71:919-925, 1969 7. H E F F E R N O N JJ, F R I D H A N D L E R L, BERK JE, S H I M A M U R A J: Assay of
amylase and isoamylase activities in serum and urine. Am J Gastroenterol 61r:47'3-477, 1977 8. F R I D H A N D L E R L, B E R K JE, U E D A M: Isolation and measurement of
pancreatic amylase in human serum and urine. Clin Chem 18:14931497, 1972 9. N O R D HJ, W E I S HJ, C O L L E H: Untersuchungen zum Stoffwechsel der
Serumamylase. Verb Dtsch Ges Inn Med 79:868-970, 1973 10. D U A N E WC, F R E R I C H S R, L E V I T T M D : Distribution, turnover and
mechanism of renal excretion of amylase in the baboon. / Clin Invest 50:156-165, 1971 © 1 9 7 9 American College of Physicians
Brief Reports
Downloaded From: https://annals.org/ by a University of Texas User on 10/12/2018
353
