Specificity of increased amylase to creatinine clearance ratio in acute pancreatitis

The amylase to creatinine clearance ratio was found to be normal in 11 of 33 patients with acute pancreatitis. The ratio was elevated in 10 of 19 patients with renal insufficiency. Thus, it does not seem to be a specific index in the diagnosis of acute pancreatitis.     

Mechanism and specificity of increased amylase/creatinine clearance ratio in pancreatitis

The amylase/creatinine clearance ratio (Cam/Ccr ratio) was determined in 239 subjects. In 87 hospitalised patients without pancreatic disease (controls) the Cam/Ccr ratio was 3.02 +/- 0.69 (mean +/- ISD). The ratio was above the normal range in all patients with acute pancreatitis but was normal in those with chronic pancreatitis and carcinoma of the pancreas. In 18 patients with choledocholithiasis a raised ratio distinguished those with pancreatitis as assessed independently by the surgeon at laparotomy from those with a macroscopically normal pancreas. Raised Cam/Ccr ratios were also found in diabetics with ketoacidosis and in three patients with fulminant alcoholic liver disease. Though a positive correlation was found between the Cam/Ccr ratio and serum creatinine concentration, abnormally high ratios did not occur in 30 patients with chronic renal failure. A significant increase in Cam/Ccr ratios was produced in six healthy volunteers by intravenous injection of glucagon. However, it is unlikely that hyperglucagonaemia alone accounts for the increased Cam/Ccr ratio seen in acute pancreatitis, as no correlation was found between the clearance ratio and the plasma glucagon concentration in a series of patients. In two other patients in whom excess circulating pancreatic polypeptide was detected the Cam/Ccr ratio was normal. It is concluded that, in view of the sensitivity and relative specificity of finding an increased Cam/Ccr ratio in acute pancreatitis, its determination should be valuable clinically, especially in those cases of hyperamylasaemia where the cause is in doubt. The mechanism whereby the ratio is increased is unknown, and it is unlikely that either glucagon or pancreatic polypeptide is a major factor in its production.     

Serum amylase in patients with renal insufficiency and renal failure.

Results vary with regard to the upper limits of serum amylase seen in patients with renal failure, and very little has been reported with patients with renal insufficiency not yet requiring dialysis. To determine the level of serum amylase elevation in renal insufficiency and renal failure, we determined serum amylase values in 128 subjects with creatinine clearances less than 90 ml/min. Serum amylase remained in the normal range when creatinine clearance was greater than 50 ml/min, and did not become elevated until creatinine clearance was less than 50 ml/min. The highest serum amylase recorded in the absence of acute pancreatitis was 503 IU/L (normal, less than 128 IU/L). Serum lipase and trypsin values paralleled those for serum amylase; values remained normal when creatinine clearance was greater than 50 ml/min, and were normal or elevated when creatinine clearance was less than 50 ml/min. These results indicate that elevations of serum amylase (i.e., amylase greater than 128 but less than 500 IU/L) in asymptomatic patients with impaired renal function are not evident until creatinine clearances fall below 50 ml/min, and probably do not represent acute pancreatitis.     

Renal clearance of pancreatic and salivary amylase relative to creatinine in patients with chronic renal insufficiency.

Pancreatic and salivary amylase/creatinine clearance ratios in patients with various degrees of renal impairment were compared with those obtained for control subjects. In chronic renal insufficiency (mean GFR 30 ml/min +/- 15 SD; n = 13) the clearance ratios for pancreatic (mean 3.5 +/- 1.85 SD) and salivary (mean 2.3 +/- 1.3 SD) amylase were significantly higher (P less than 0.05) than those in controls. Corresponding control values (n = 26) were 2.64 +/- 0.86 (pancreatic) and 1.64 +/- 0.95 (salivary). Three patients showed values above the normal limit. In the diabetic group (mean GFR 41 ml/min +/- 22 SD; n = 10) salivary amylase/creatinine clearance ratios (mean 2.36 +/- 1.55 SD) were significantly higher than in controls (P less than 0.05). Three patients showed raised values. Pancreatic amylase clearance was raised in only one of these patients. Three patients with terminal disease (mean GFR 10 ml/min) showed markedly raised (two- to threefold) clearance ratios for both salivary and pancreatic amylase. Of a total of 26 patients, eight had increased total amylase/creatinine clearance ratios. Pancreatic amylase/creatinine clearance was increased in seven patients, while nine patients showed raised salivary amylase/creatinine ratios. Patients with raised clearance ratios did not have clinical evidence of pancreatitis. We suggest that, in the presence of impaired renal function, a high amylase/creatinine clearance ratio need not be indicative of pancreatic disease.     

Effect of glucagon infusion on the renal clearance of amylase relative to creatinine.

Recent data seem to support a tubular defect as the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon has been proposed by some to be an important factor in this phenomenon. To examine the role of glucagon as this "tubular dysfunction factor", we investigated the effect of intravenously infused glucagon on the fractional excretion of amylase and the tubular handling of a low molecular weight protein, beta2 microglobulin, in normal, healthy volunteers. At glucagon levels far in excess of those seen in pancreatitis, the clearance ratio of beta2 microglobulin relative to creatinine increased, whereas the clearance ratio of amylase relative to creatinine did not increase above the normal range. The dissociation between beta2 microglobulin clearance and amylase clearance allows one to question the theory that tubular dysfunction is the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon does not appear to be the sole factor responsible for the elevation of renal clearance of amylase relative to creatinine in acute pancreatitis.     

Specificity of serum amylase and amylase creatinine clearance ratio in the diagnosis of acute and chronic pancreatitis.

In 31 patients with pancreatitis, the amylase to creatinine clearance ratio (CACR) was significantly greater than for controls (10.7 +/- 1.7 vs. 2.6 +/- 0.3, P less than .001). Sixteen pancreatitis patients with serum amylase (SAm) within the normal range had a mean CACR significantly greater than that of 19 hospital control patients with normal SAm (9.2 +/- 1.5 vs. 3.0 +/- 0.4, P less than .001). For control patients a highly significant inverse correlation between SAm and CACR was observed. No relationship was detected between these parameters for pancreatitis patients. The results suggest that the CACR may be of aid in establishing the diagnosis of pancreatitis even in patients without hyperamylasemia.     

Clinical evaluation of amylase-creatinine clearance ratio and amylase isoenzyme clearance in chronic renal failure

Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function.     

Kidney ageing and renal excretion of amylase

In a cross-sectional study, the amylase to creatinine clearance ratio (ACCR) was determined in 180 patients, age range 18-93 years. An inverse correlation was found between ACCR and creatinine clearance (r = -0.40, p less than 0.001) in keeping with the known inverse relationship between the sieving fraction of macromolecules and the glomerular filtration rate. The fractional clearance of amylase was not significantly affected by amylasemia nor by age when the creatinine clearance was also considered in a multiple regression analysis. No increase in ACCR was observed in patients with low molecular weight proteinuria or with induced urine dilution. The authors assume that the tubular reabsorption of amylase is minimal and that the enhancement of ACCR in the elderly mainly reflects modifications in the glomerular filtration dynamics.     

Amylase creatinine clearance ratio after biliary surgery.

The amylase creatinine clearance ratio (ACCR) is considered to be a more sensitive index of acute pancreatitis than the serum amylase level. Serial ACCR estimations were undertaken in 25 patients undergoing an elective cholecystectomy. Using accepted criteria, 28% of these patients developed, in the postoperative period, biochemical evidence of pancreatic gland damage, although the serum amylase level remained normal. This raised ACCR was particularly noted in patients who had undergone an exploration of the common bile duct. The ACCR would appear to be a more sensitive index of pancreatic gland disruption secondary to biliary surgery than the serum amylase level.     

Amylase-creatinine clearance ratios and serum amylase isoenzymes in moderate renal insufficiency.

Both the amylase-creatinine clearance ratio (normal 1.55%) and proportion of pancreatic isoamylase in serum (normal 41.0%) increase in acute pancreatitis, and are therefore useful measurements to support that diagnosis. Whether renal insufficiency interferes with the accuracy and specificity of these tests has been debated. Our study indicates that even moderate renal insufficiency (creatinine clearance 30.5 ml/minute) raises the amylase-creatinine clearance ratio (3.23%) close enough to values characteristic of acute pancreatitis (4.41%) to cause potential diagnostic confusion. The fraction of pancreatic isoamylase in serum is also increased (69.9%), but not to the levels of acute pancreatitis (91.0%). We therefore caution against the use of the amylase-creatinine clearance ratio for the diagnosis of acute pancreatitis in patients with moderate renal insufficiency.     

Lipase/amylase ratio. A new index that distinguishes acute episodes of alcoholic from nonalcoholic acute pancreatitis.

Because of observations that patients with acute episodes of alcoholic pancreatitis had high serum lipase levels whereas patients with gall stone pancreatitis had high serum amylase levels, a prospective study was undertaken to determine whether the ratio of serum lipase to serum amylase, a newly computed ratio, would discriminate between acute episodes of alcoholic and nonalcoholic pancreatitis. In phase one, 30 consecutive patients with acute pancreatitis were entered into the study and divided into groups A and B. Patients with renal failure were excluded from the study. Group A consisted of 20 patients in whom the etiology of pancreatitis was alcohol. Group B consisted of 10 patients whose pancreatitis was nonalcoholic in etiology (predominantly gallstones). Serum lipase values in group A ranged 492 to 25,706 U/L (median, 3433 U/L) and in group B from 711 to 31,153 U/L (median, 1260 U/L). These differences were not significant statistically. Serum amylase values in group A ranged from 104 to 2985 U/L (median, 331 U/L) and in group B from 423 to 13,000 (median, 1187 U/L). Although these figures were statistically different (P less than 0.005), there was a considerable degree of overlap in the values between the two groups. The lipase/amylase ratio calculated from the blood sample obtained at presentation appeared to be a promising discriminatory index. The lipase/amylase ratio was calculated by using the amylase and lipase levels expressed as multiples of the upper limit of normal in each case. The lipase/amylase ratios in the alcoholic group ranged from 2.2 to 14.8, whereas the lipase/amylase ratio in nonalcoholic pancreatitis ranged from 0.31 to 1.93. These differences were statistically significant (P less than 0.005). A lipase/amylase ratio of greater than 2 was indicative of an alcoholic etiology, and a ratio of less than 2 suggested that the pancreatitis was nonalcoholic in nature. In phase two, this lipase/amylase ratio of 2 was applied prospectively to an unselected population of 21 consecutive patients with acute pancreatitis. Thirteen patients had a lipase/amylase ratio of greater than 2; in 11 of them, the etiology of the pancreatitis was alcohol. Eight patients had a lipase/amylase ratio of less than 2; of them, only 1 patient had an alcoholic etiology for the pancreatitis. These differences were statistically significant (P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Lipase/amylase ratio in biliary acute pancreatitis and alcoholic acute/acutized chronic pancreatitis

BACKGROUND: Alcoholic or biliary acute pancreatitis may need different therapeutic approaches. AIM: Assessing the validity of lipase/amylase ratio in differentiating biliary from alcoholic acute pancreatitis/acutized chronic pancreatitis. METHODS: Nine male patients (mean age and standard deviation: 39.8 +/- 7.0 years) with alcoholic acute pancreatitis/acutized chronic pancreatitis (group I) and 29 patients, 8 male and 21 female (mean age: 43.6 +/-19.9 years), with biliary acute pancreatitis (group II) were evaluated. Serum lipase and amylase levels were measured in patients with symptoms for no more than 48 hours. The lipase/amylase ratio was calculated based on serum lipase and amylase levels and expressed as multiples of their respective superior reference values. RESULTS: Mean levels of serum lipase (4,814 +/- 3,670 U/L) and amylase (1,282 +/- 777 U/L) in patients of group I were comparable to group II (2,697 +/- 2,391 and 1,878 +/- 1,319 U/L, respectively), but the mean lipase/amylase ratio was significantly higher in group I (4.4 +/- 3.6) than in group II (2.2 +/- 2.2). Lipase/amylase ratio >3 occurred at significantly higher proportions in patients of group I (66.7%) than of group II (24.1%), differentiating the two groups with sensitivity of 67% and specificity of 76%. CONCLUSIONS: 1) Amylase and lipase serum levels did not differ in the two groups evaluated; 2) the lipase/amylase ratio >3 was more often seen in alcoholic acute pancreatitis/acutized chronic pancreatitis than biliary acute pancreatitis, and it may be useful in differentiating these two causes of pancreatitis.     

Pancreatic and salivary amylase/creatinine clearance ratios in normal subjects and in patients with chronic pancreatitis.

The clearance of pancreatic and salivary amylase relative to creatinine was measured in 26 control subjects and 22 patients with chronic pancreatitis. Control values for pancreatic amylase clearance (+/- SD) were 2.64 +/- 0.86% compared with 1.54 +/- 0.95% for salivary amylase. In chronic pancreatitis, pancreatic amylase clearance ratios were significantly higher than controls (P less than 0.0005, mean 4.09 +/- 1.63 SD). The difference in clearance rate of salivary amylase did not reach a level of significance when compared with the control group. Twelve of the 22 patients showed pancreatic amylase clearance values above the normal limit of 4.4, while only five were abnormal when the clearance of total amylase was measured. The patients also showed statistically higher (P less than 0.0005) levels of serum salivary amylase when compared with 69 control sera. No such difference was found for the pancreatic component of serum amylase. Comparison of beta2-microglobulin clearance values showed no statistical difference between patients and controls.     

Diagnosis of pancreatitis masked by hyperlipemia.

It is often difficult to confirm a diagnosis of acute pancreatitis in the presence of hyperlipemic serum because the serum amylase and lipase and the urinary amylase are frequently normal. We were able to substantiate the diagnosis of pancreatitis in seven patients with hypertriglyceridemia (greater than 1200 mg/100 ml) by the use of the simple amylase/creatinine clearance ratio and by the serial dilution of hyperlipemic serum. The amylase/creatinine clearance ration in the hyperlipemic pancreatitis patients (10.0%) was significantly (P GREATER THAN 0.001) higher than in normal patients (3.1%) and essentially the same as in nonlipemic pancreatitis patients (9.2%). The calculated serum amylase activity after serial dilution of the serum showed up to a tenfold increase in hyperlipemic pancreatitis, with no significant increase in normal controls, hyperlipemic controls, and nonlipemic pancreatitis.     

血清淀粉酶和脂肪酶浓度及其比值对急性胰腺炎诊断价值的研究

目的探讨血清淀粉酶、脂肪酶浓度及脂肪酶／淀粉酶浓度比值在急性胰腺炎的病因分类和指导疾病的分级诊断中的作用。方法收集急性胰腺炎患者128例,按照病因分为胆源性、酒精性、其他病因三组,按照病情严重程度结合CT检查结果分为轻、中、重三组,比较各组间血清淀粉酶、脂肪酶浓度,脂肪酶／淀粉酶浓度比值的差异。结果酒精性急性胰腺炎患者的血清淀粉酶水平低于胆源性和其他病因患者（P=0．005、0．026）,胆源性和其他病因组间淀粉酶浓度差异无统计学意义。各病因分组之间,脂肪酶浓度和脂肪酶／淀粉酶浓度比值的差异均无统计学意义。按照疾病严重程度分组研究中,淀粉酶、脂肪酶浓度以及脂肪酶／淀粉酶浓度比值在各组间的差异无统计学意义。结论血清淀粉酶浓度在鉴别酒精性和非酒精性急性胰腺炎方面有指示作用,而脂肪酶浓度及脂肪酶／淀粉酶浓度比值不足以用来鉴别急性胰腺炎的病因,也不能单独作为指示疾病严重程度的指标。     

Sensitivity of the amylase-creatinine clearance ratio in acute pancreatitis

An elevated amylase-creatinine clearance ratio has been established as being highly specific for the diagnosis of acute pancreatitis. In the present study, the sensitivity of this test was compared to that of the serum amylase and the one-hour urinary amylase test in 29 patients with acute pancreatitis. Abnormal elevations of the amylase-creatinine clearance ratio were found less frequently than abnormal elevations of the serum and one-hour urinary amylases. Moreover, abnormal elevations of the amylase-creatinine clearance ratio showed less deviation from normal and values returned to normal sooner than those of the serum and one-hour urinary amylases. When compared to the serum amylase and the one-hour urinary amylase tests, the amylase-creatinine clearance ratio is a relatively insensitive test in patients with acute pancreatitis.     

Evaluation of a rapid urine amylase test using post-ERCP hyperamylasemia as a model

OBJECTIVE: The initial diagnosis of acute pancreatitis is often based on clinical criteria together with elevations of serum amylase and lipase. A reliable bedside urine test could facilitate the early diagnosis of pancreatitis. We evaluated a rapid urine amylase test (Rapignost) by using post-ERCP hyperamylasemia as a human model of acute development of hyperamylasemia suggestive of pancreatitis. METHODS: Seventy-five patients undergoing ERCP were prospectively evaluated. Patients with renal insufficiency, hyperlipidemia, or hyperglycemia were excluded. Before ERCP, patients had serum amylase and lipase measured, and urine amylase tested with the Rapignost test strip. At 4 and 16-24 h post-ERCP, a serum and urine (test strip) amylase were measured again; the adequacy of urine collection was verified by measuring a 2-h creatinine clearance. Patients were clinically assessed for the development of clinical pancreatitis. The concordance of the strip result with post-ERCP hyperamylasemia was assessed. RESULTS: The sensitivity of the test strip for the detection of hyperamylasemia was greatest at 16-24 h post-ERCP (78%). Specificity was uniformally high (100% specificity at 16-24 h post-procedure). The test strip was positive in all cases of clinical pancreatitis. Of three cases of clinically evident ERCP-induced pancreatitis, only one was urine test strip positive by 4 h post-procedure. CONCLUSIONS: Using post-ERCP hyperamylasemia as a model, the Rapignost rapid urine amylase test strip was only marginally sensitive but highly specific for hyperamylasemia. The urine test strip was positive in all cases of clinical pancreatitis and may be a useful bedside test for the diagnosis of acute pancreatitis.     

Pancreatitis and alcoholism disorder the renal tubule and impair reclamation of some low molecular weight proteins

We sought to determine whether the clinical setting in which pancreatitis occurs affects the incidence and distribution of increased values of renal clearance of amylase relative to creatinine, CAm/CCr, and whether the increased values reflect a tubular disorder that impairs renal reclamation of certain low molecular weight proteins. We measured the renal clearance of three low molecular weight proteins (amylase, beta 2-microglobulin, and lysozyme) and urinary excretion of three lysosomal enzymes that originate from the renal tubule in three groups of patients (alcoholic pancreatitis, pancreatitis without alcoholism, and alcoholism without pancreatitis). When compared to normal controls, the mean CAm/CCr was significantly elevated in alcoholic pancreatitis (p less than 0.05) but not in equally severe pancreatitis without alcoholism nor in alcoholism without pancreatitis. The clearance ratio of beta 2-microglobulin was significantly increased in each of the three patient groups; mean clearance ratio of lysozyme was not significantly increased in any of the patient groups. Excretion of each of the three lysosomal enzymes was significantly increased in each of the patient groups. We conclude that the etiology of pancreatitis affects the distribution of values for CAm/CCr, impaired tubular reclamation of amylase is the mechanism of the increase in CAm/CCr, and a factor or factors associated with both pancreatitis and with alcoholism per se appear to disorder the renal tubule and to impair tubular reclamation of some but not all low molecular weight proteins-a novel finding of considerable potential significance.     

尿胰蛋白酶原-2的测定对急性胰腺炎的诊断价值

目的探讨尿胰蛋白酶原2(Trypsinogen2Try2)的测定对急性胰腺炎(AcutepancreatitisAP)的诊断价值。方法对280例急腹症患者同时测定尿Try2及血、尿淀粉酶,其中尿Try2测定采用免疫层析法,血、尿淀粉酶采用酶学方法检测。结果55例急性胰腺炎患者中有53例尿Try2阳性,敏感性为96.4%,225例非AP的急腹症患者尿Try2有12例假阳性,特异性为94.7%;而血淀粉酶的敏感性和特异性分别为81.8%(45/55)和88.9%(25/225),尿淀粉酶的敏感性和特异性分别为80.0%(44/55)和88.4%(26/225),差异有显著性(P<0.05);7例重症急性胰腺炎患者尿Try2均为阳性。结论尿Try2是急腹症患者筛选AP快速而简便的方法,具有较高的特异性和敏感性。     

Serum amylase and lipase concentrations and lipase/amylase ratio in assessment of etiology and severity of acute pancreatitis

We studied the behavior of serum amylase and lipase in 66 consecutive patients with acute pancreatitis in order to assess the ability of these tests and of the serum lipase-amylase ratio to establish the etiology and predict the severity of acute pancreatitis. Forty-two patients had biliary acute pancreatitis, 14 had alcoholic acute pancreatitis, and the remaining 10 nonbiliary, nonalcoholic (NBNA) acute pancreatitis. Serum amylase and lipase were abnormally high in all patients. The elevations of both serum amylase and lipase were significantly lower in patients with alcoholic pancreatitis than in those with biliary pancreatitis, although a considerable overlap was observed between the two groups. No statistically significant differences were found between NBNA patients and those with either biliary or alcoholic forms of the disease. The serum lipase-amylase ratios in patients with alcoholic pancreatitis ranged from 0.2 to 5.6, in those with biliary pancreatitis from 0.1 to 7.9, and in those with NBNA pancreatitis from 0.1 to 4.4. These differences were not statistically significant. No differences in serum enzyme levels were observed among patients without apparent imaging signs of acute pancreatitis (N=20), those with signs of Pancreatic edema (N=36), and those with necrotizing pancreatitis (N=10). The results indicate that serum amylase and lipase concentrations are not able to establish either the etiology or to predict the severity of acute pancreatitis as assessed by imaging techniques. Furthermore, the serum lipase-amylase ratio is not useful in distinguishing acute episodes of alcoholic from nonalcoholic acute pancreatitis.