Serum elastase 1 in inflammatory pancreatic and gastrointestinal diseases and in renal insufficiency. A comparison with other serum pancreatic enzymes

Serum elastase 1 has been evaluated in 115 patients with pancreatic and nonpancreatic gastrointestinal diseases and in 36 healthy controls. Increased serum elastase 1 values were found in all 27 patients with acute pancreatitis. If the diagnostic cutoff was established as the 2-fold increase above the upper normal range, sensitivity of elastase 1 (100%) was superior to pancreatic lipase (90%), immunoreactive trypsin (87%) and pancreatic amylase (78%). Specificity was 96% for elastase 1 at this cutoff. No distinction was possible between edematous and necrotizing acute pancreatitis on the basis of peak serum elastase 1 concentrations. Among 32 patients with chronic pancreatitis increased serum elastase 1 values were found in 22% and decreased values in 16% of patients, showing a striking parallelism to serum values of pancreatic lipase and immunoreactive trypsin. Specificity, established in controls and 49 patients with different gastrointestinal diseases, was 77% for elastase 1, 76% for immunoreactive trypsin, 83% for pancreatic lipase and 91% for pancreatic amylase. In addition, we investigated 21 patients with severe chronic renal diseases. In patients with renal insufficiency elastase was increased in 33%, comparable to the frequency of increased amylase and pancreatic amylase serum levels, whereas immunoreactive trypsin was increased in 95%. Immunoreactive trypsin showed a significant correlation to creatinin serum concentration, whereas the other enzymes did not.     

Pancreatic exocrine insufficiency,diabetes mellitus and serum nutritional markers after acute pancreatitis

AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP).METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria.RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks.CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful.     

Elastase-1 vs trypsin, lipase and amylase serum levels in pancreatic diseases

Summary Serum levels of elastase-1 were measured in 174 patients with pancreatic diseases and in 131 controls and were compared with the circulating levels of trypsin, lipase and amylase and with clinical data. In 48 patients with chronic pancreatitis serum enzyme levels were also compared with the pancreatic exocrine capacity. About 50% of the patients with chronic pancreatic disease showed increased levels of serum elastase, sometimes even in the face of long lasting pain-free periods, and/or of severe pancreatic impairment. On the contrary, serum trypsin and lipase were almost always either normal or below the normal range in the absence of painful relapses and/or in the presence of an impairment of the exocrine pancreatic function. A strict correlation was found between elastase-1 and trypsin (r=0.778) and lipase (r=0.834). However, controls and patients with chronic pancreatic diseases behaved differently, an increase in trypsin and in lipase levels being associated in the patients with chronic pancreatitis with an increase in elastase-1 values significantly larger than that observed in controls. These findings raise the hypothesis, at present unproven, that trypsin and lipase serum assays are more reliable indices of pancreatic exocrine function, whereas serum elastase-1 levels may indicate the presence of acute pancreatic episodes, even if subclinical, the importance of which, in the natural history of the disease, remains unknown. *** DIRECT SUPPORT *** A00DX035 00007     

Peritoneal absorption of pancreatic enzymes in bile-induced acute pancreatitis in dogs

To clarify the contribution of peritoneal absorption of enzyme-rich exudate to the persistent elevation of serum amylase in bile-induced pancreatitis in dogs, serum amylase, lipase and immunoreactive trypsin (IRT) levels were measured during 24 h after induction of pancreatitis with and without peritoneal lavage. The basal level of serum amylase activity (m +/- s.e. = 1291 +/- 111 U/L) reached a plateau at 30 min (2688 +/- 185) after induction of pancreatitis and continued to rise until 24 h (7201 +/- 424). This persistent amylase elevation could be reduced significantly by peritoneal lavage. Serum IRT rose to a peak (378 +/- 103 ng/mL) at 30 min from the basal (20 +/- 5), then decreased until 3 h (211 +/- 34) and maintained a consistent level thereafter. Serum lipase elevation took an intermediate course between the levels of serum amylase and IRT. Intraperitoneal injection of 5 mL pancreatic juice could reproduce similar elevations to those of the respective enzymes, except lipase, seen in pancreatitis. These results suggest that transperitoneal absorption of pancreatic enzymes contributes to the elevation in serum enzymes levels and that rates of peritoneal absorption and serum disappearance differ from enzyme to enzyme.     

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。     

急性胰腺炎患者血淀粉酶变化和CT诊断的比较

目的探讨血淀粉酶的变化规律及其机制。方法本研究对确诊的172例急性胰腺炎(AP)患者随机分为3组,分别在发病≤12 h、12～24 h、48～72 h行CT和血淀粉酶检查。分析不同时间段CT和血淀粉酶检出率。结果 87.5%患者血淀粉酶在6～12 h升高;100%患者血淀粉酶在12 h以上升高。91.3%的患者在12～24 h之间CT检查发现胰腺炎症变化,但与发病大于48 h相比,无显著差异。12 h之内,血淀粉酶升高的阳性率高于CT诊断的阳性率(χ2=22.04,P<0.01)。48～72 h D级、E级检出率明显高于12 h之内和12～24 h之间的检出率。血淀粉酶随着轻症急性胰腺炎分级水平有上升趋势;随着重症急性胰腺炎分级水平有下降趋势。结论血淀粉酶升高的水平与胰腺炎的病情程度无明显相关性,推测其机制可能与胰腺微循环受损程度有关。     

Study of the gastrointestinal bioavailability of a pancreatic extract product (Zenpep) in chronic pancreatitis patients with exocrine pancreatic insufficiency

IntroductionThe Food and Drug Administration in 2006 required that all pancreatic enzyme products demonstrate bioavailability of lipase, amylase, and protease in the proximal small intestine.MethodsIn this phase I open-label, randomized, crossover trial, 17 adult chronic pancreatitis (CP) patients with severe exocrine pancreatic insufficiency (EPI) underwent two separate gastroduodenal perfusion procedures (Dreiling tube suctioning and [¹⁴C]-PEG instillation by an attached Dobhoff tube in the duodenal bulb). Patients received Ensure Plus® alone and Ensure Plus with Zenpep (75,000 USP lipase units) in random order. The bioavailability of Zenpep was estimated by comparing the recovery of lipase, amylase, chymotrypsin activity in two treatment conditions. ¹⁴C-PEG was used to correct duodenal aspirates volume. The primary efficacy endpoint was lipase delivery in the duodenum after Zenpep administration under fed conditions. Secondary efficacy endpoints included chymotrypsin and amylase delivery, serum CCK levels, and measuring duodenal and gastric pH.ResultsZenpep administration with a test meal was associated with significant increase in duodenal aspiration of lipase (p = 0.046), chymotrypsin (p = 0.008), and amylase (p = 0.001), compared to the test meal alone, indicating release of enzymes to the duodenum. Lipase delivery was higher in the pH subpopulation (the efficacy population with acid hypersecretors excluded) (p = 0.01). Recovery of [¹⁴C]-PEG was 61%. Zenpep was generally well tolerated. All adverse events were mild and transient.ConclusionsIn CP patients with severe EPI, lipase, chymotrypsin and amylase were released rapidly into the duodenum after ingestion of Zenpep plus meal compared to meals alone. Results also reflected the known pH threshold for enzyme release from enteric coated products.     

Fecal calprotectin and elastase 1 determinations in patients with pancreatic diseases: a possible link between pancreatic insufficiency and intestinal inflammation

Background Fecal calprotectin determination has been demonstrated to be useful in diagnosing various inflammatory diseases of the gastrointestinal tract; however, data available for patients with pancreatic diseases are scarce. Our aim was to assess fecal calprotectin in order to evaluate the presence of intestinal inflammation in patients with pancreatic disease. Methods Eligible patients with suspected pancreatic illness were enrolled, and in all of them fecal calprotectin and elastase-1, as well as serum amylase and lipase activities, were assayed using commercially available kits. Results A total of 90 subjects (47 men, 43 women, mean age 58.6 ± 14.9 years) were enrolled: 20 (22.2%) had chronic pancreatitis; 15 (16.7%) had pancreatic cancer; six (6.7%) had chronic nonpathological pancreatic hyperenzymemia; 16 (17.8%) had nonpancreatic diseases; and 23 (25.6%) had no detectable diseases. Diarrhea was present in 19 patients (21.1%). In univariate analyses, the presence of diarrhea and low fecal elastase-1 concentrations were significantly associated (P = 0.019 and P = 0.002, respectively) with abnormally high fecal calprotectin concentration, and the multivariate analysis demonstrated that low fecal elastase-1 concentration was the only variable independently associated with a high fecal calprotectin concentration. Conclusions Pancreatic insufficiency may cause intestinal inflammation, probably because of a modification of the intestinal ecology.     

Contribution of pancreatic enzyme replacement therapy to survival and quality of life in patients with pancreatic exocrine insufficiency

The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.     

Association of faecal elastase 1 with non-fasting triglycerides in type 2 diabetes

AimsIntestinal absorption of esterified fatty acids depends on exocrine pancreatic function and influences plasma triglycerides levels. The aim was to investigate the association of reduced exocrine pancreatic function (low fecal elastase-1; FE1) with plasma triglycerides in type 2 diabetes and controls without diabetes.MethodsFE1 (μg/g stool) and non-fasting plasma triglyceride measurements were undertaken in 544 type 2 diabetes patients (age: 63 ± 8 years) randomly selected from diabetes registers in Cambridgeshire (UK), and 544 matched controls (age, sex, practice) without diabetes. Linear regression models were fitted using FE1 as dependent and log-triglycerides as independent variable adjusting for sex, age, body mass index, alcohol consumption, serum lipase, HbA1c, and smoking.ResultsFE1 concentrations were lower (mean ± SD: 337 ± 204 vs. 437 ± 216 μg/g, p < 0.05) and plasma triglycerides were higher (geometric mean */: standard deviation factor: 2.2*/:1.9 vs. 1.6*/:1.8 mmol/l, p < 0.05) in type 2 diabetes compared to controls, respectively. Within the category of type 2 diabetes and controls separately, a 10% increase in plasma triglycerides was associated with 4.5 μg/g higher FE1 concentrations (p < 0.01) after adjusting for confounders. In contrast, in diabetes patients and controls with pathological FE1 (<100 μg/g), low FE1 levels were associated with high plasma triglycerides (significant only in controls).ConclusionsNon-fasting triglycerides were positively related to FE1 in both type 2 diabetes and controls suggesting that impairment of exocrine pancreas function is influencing plasma triglycerides. Marked loss of exocrine pancreatic function had the opposite effect, resulting in higher levels of plasma triglycerides.     

Management of pain in chronic pancreatitis with emphasis on exogenous pancreatic enzymes

One of the most challenging issues arising in patients with chronic pancreatitis is the management of abdominal pain. Many competing theories exist to explain pancreatic pain including ductal hypertension from strictures and stones, increased interstitial pressure from glandular fibrosis, pancreatic neuritis, and ischemia. This clinical problem is superimposed on a background of reduced enzyme secretion and altered feedback mechanisms. Throughout history, investigators have used these theories to devise methods to combat chronic pancreatic pain including: Lifestyle measures, antioxidants, analgesics, administration of exogenous pancreatic enzymes, endo-scopic drainage procedures, and surgical drainage and resection procedures. While the value of each modality has been debated over the years, pancreatic enzyme therapy remains a viable option. Enzyme therapy restores active enzymes to the small bowel and targets the altered feedback mechanism that lead to increased pancreatic ductal and tissue pressures, ischemia, and pain. Here, we review the mechanisms and treatments for chronic pancreatic pain with a specific focus on pancreatic enzyme replacement therapy. We also discuss different approaches to overcoming a lack of clinical response update ideas for studies needed to improve the clinical use of pancreatic enzymes to ameliorate pancreatic pain.     

Faecal elastase 1: not helpful in diagnosing chronic pancreatitis associated with mild to moderate exocrine pancreatic insufficiency

Background/Aim—The suggestion that estimation offaecal elastase 1 is a valuable new tubeless pancreatic function testwas evaluated by comparing it with faecal chymotrypsin estimation inpatients categorised according to grades of exocrine pancreatic insufficiency (EPI) based on the gold standard tests, thesecretin-pancreozymin test (SPT) and faecal fat analysis.
Methods—In 64 patients in whom EPI was suspected,the following tests were performed: SPT, faecal fat analysis, faecalchymotrypsin estimation, faecal elastase 1 estimation. EPI was gradedaccording to the results of the SPT and faecal fat analysis as absent,mild, moderate, or severe. The upper limit of normal for faecalelastase 1 was taken as 200 µg/g, and for faecal chymotrypsin 3 U/gstool. Levels between 3 and 6 U/g stool for faecal chymotrypsin areusually considered to be suspicious for EPI. In this study, both 3 and 6 U/g stool were evaluated as the upper limit of normal.
Results—Exocrine pancreatic function was normal in34 patients, of whom 94, 91, and 79% had normal faecal elastase 1 andfaecal chymotrypsin levels (<3 U/g and <6 U/g) respectively. Thirtypatients had EPI, of whom 53, 37, and 57% had abnormal faecal enzymelevels (differences not significant). When EPI was graded as mild,moderate, or severe, 63% of patients had mild to moderate EPI, and37% had severe EPI. In the latter group, between 73 and 91% ofpatients had abnormal faecal enzymes. In the group with mild tomoderate EPI, abnormal test results were obtained for both faecalenzymes in less than 50% of the patients (differences notsignificant). Some 40% of the patients had pancreatic calcifications.There were no significant differences for either faecal enzyme between the two groups with and without pancreatic calcifications. In 62% ofthe patients who underwent an endoscopic retrogradecholangiopancreatography (ERCP), abnormal duct changes were found.Again, there were no significant differences for either faecal enzymebetween the two groups with abnormal and normal ERCP.
Conclusion—Estimation of faecal elastase 1 is notdistinctly superior to the traditional faecal chymotrypsin estimation.The former is particularly helpful only in detecting severe EPI, but not the mild to moderate form, which poses the more frequent and difficult clinical problem and does not correlate significantly withthe severe morphological changes seen in chronic pancreatitis.

Keywords:faecal elastase 1; faecal chymotrypsin; secretin-pancreozymin test; faecal fat analysis; exocrine pancreaticinsufficiency; diagnosis

     

Serum cytokine profiles in patients with pancreatic cancer and chronic pancreatitis

BackgroundChronic pancreatitis (CP) may cause tumor-like lesions, creating a challenge in distinguishing between CP and pancreatic ductal adenocarcinoma (PDAC) in a patient. Given that invasive surgery is a standard cancer treatment, we aimed to examine whether a noninvasive diagnostic tool utilizing serum cytokines could safely differentiate between PDAC and CP.MethodsA pre-operative serum panel comprising 48 inflammatory cytokines, CA19-9, and C-reactive protein (CRP) was analyzed, consisting of 231 patients, 186 with stage I–III PDAC and 45 with CP. We excluded PDAC patients who underwent neoadjuvant therapy and those CP patients with other active malignancies. The laboratory variables most associated with PDAC diagnosis were assessed using logistic regression and selected using the lasso method.ResultsThe cytokines CTACK, GRO-α, and β-NGF were selected alongside CA19-9 and CRP for our differential diagnostic model. The area under the curve (AUC) for our differential diagnostic model was 0.809 (95% confidence interval [CI] 0.738–0.880), compared with 0.791 (95% CI 0.728–0.854) for CA19-9 alone (not significant).ConclusionsWe found that inflammatory cytokines CTACK, GRO-α, and β-NGF alongside CA19-9 and CRP may help distinguish PDAC from CP.     

Diagnosis and treatment of exocrine pancreatic insufficiency in chronic pancreatitis: An international expert survey and case vignette study

IntroductionDespite evidence-based guidelines, exocrine pancreatic insufficiency is frequently underdiagnosed and undertreated in patients with chronic pancreatitis. Therefore, the aim of this study is to provide insight into the current opinion and clinical decision-making of international pancreatologists regarding the management of exocrine pancreatic insufficiency.MethodsAn online survey and case vignette study was sent to experts in chronic pancreatitis and members of various pancreatic associations: EPC, E-AHPBA and DPSG. Experts were selected based on publication record from the past 5 years.ResultsOverall, 252 pancreatologists participated of whom 44% had ≥ 15 years of experience and 35% treated ≥ 50 patients with chronic pancreatitis per year. Screening for exocrine pancreatic insufficiency as part of the diagnostic work-up for chronic pancreatitis is performed by 69% and repeated annually by 21%. About 74% considers nutritional assessment to be part of the standard work-up. Patients are most frequently screened for deficiencies of calcium (47%), iron (42%), vitamin D (61%) and albumin (59%). In case of clinically steatorrhea, 71% prescribes enzyme supplementation. Of all pancreatologists, 40% refers more than half of their patients to a dietician. Despite existing guidelines, 97% supports the need for more specific and tailored instructions regarding the management of exocrine pancreatic insufficiency.ConclusionThis survey identified a lack of consensus and substantial practice variation among international pancreatologists regarding guidelines pertaining the management of exocrine pancreatic insufficiency. These results highlight the need for further adaptation of these guidelines according to current expert opinion and the level of available scientific evidence.     

Age- and sex-specific prevalence of diabetes associated with diseases of the exocrine pancreas: A population-based study

Background and aimsDiabetes associated with diseases of the exocrine pancreas (DP) is a recognized clinical condition but data on its prevalence are limited to a few single centre studies. Relative contribution of the three major diseases of the exocrine pancreas (acute pancreatitis, chronic pancreatitis, pancreatic cancer) to prevalence of DP as well as the effect of age and sex is largely unknown. The study aimed to determine age- and sex-specific prevalence of DP overall and after acute pancreatitis, chronic pancreatitis, and pancreatic cancer alone at the population level.MethodsNationwide population database covering nearly 3 million residents in New Zealand over a 10-year study period was used. DP was identified based on International Classification of Diseases-10 codes. Data were reported as prevalence per 1000 population and corresponding 95% confidence intervals.ResultsThe crude prevalence of DP was 1.13 [1.12, 1.14] per 1000, with 70–79 years age group having the highest prevalence at 3.94 [3.92, 3.97] per 1000. Men had an overall prevalence of 1.32 [1.31, 1.33] per 1000 and women—0.93 [0.92, 0.94] (p < 0.05). Acute pancreatitis contributed 61% to overall prevalence of DP.ConclusionsPrevalence of DP in the general population is close to that of type 1 diabetes. Three out of five DP cases develop after acute pancreatitis. There is a variation in age of onset of DP, with the working and ageing population most affected. Men have a 40% higher risk of developing DP than women.     

Pancreatin therapy in patients with insulin-treated diabetes mellitus and exocrine pancreatic insufficiency according to low fecal elastase 1 concentrations. Results of a prospective multi-centre trial

BACKGROUND: Recently, high prevalence of exocrine dysfunction in diabetic populations has been reported. Patients with fecal elastase 1 concentration (FEC) <100 microg/g have also been demonstrated to suffer from steatorrhea in about 60% of cases, indicating the need of pancreatic enzyme replacement therapy. Until now, there have only been a few reports on the use of enzyme replacement therapy in diabetic patients with exocrine pancreatic insufficiency. This investigation was designed to evaluate the impact of enzyme-replacement therapy on glucose metabolism and diabetes treatment in a prospective study of insulin-treated patients with diabetes mellitus. METHODS: A total of 546 patients with diabetes mellitus requiring insulin treatment were screened for exocrine dysfunction by FEC measurements. One hundred and fifteen patients (21.1%) had FEC <100 microg/g (normal >200 microg/g). Of these, 95 patients entered the study and 80 patients were randomized to receive either pancreatin (Creon) (39 patients) or placebo (41 patients) in a double-blind manner. Parameters of glucose metabolism, diabetes therapy and clinical symptoms were recorded in standardized protocols for 16 weeks. RESULTS: During the observation phase of 16 weeks, there were no significant differences between both groups concerning HbA(1c), fasting glucose levels, 2-h pp glucose levels, clinical parameters and safety parameters. A reduction in mild and moderate hypoglycemia was observed in the pancreatin group at the end of the study. CONCLUSIONS: Pancreatin therapy can be used safely in patients with diabetes mellitus and exocrine dysfunction. Parameters of glucose metabolism were not improved by enzyme replacement therapy.     

The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI)

Background

Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls.

肾功能不全对急性心肌梗死患者治疗方案及预后的影响

目的观察肾功能不全对急性心肌梗死(AMI)患者治疗方案及预后的影响。方法入选2011年6月~2012年5月因AMI住院治疗患者523例,根据改良的MDRD方程计算估测的肾小球滤过率(eGFR),根据eGFR水平将患者分为肾功能正常及轻度肾功能不全组(A组,eGFR≥60ml/min.1.73m2),中重度肾功能不全组(B组,eGFR60ml/min.1.73m2)。比较两组患者临床特点、治疗方案和预后的差异。结果 A组患者占71.7%(375/523),B组患者占28.3%(148/523)。与A组患者相比,B组患者年龄偏大、女性较多(P0.01),合并高血压、糖尿病、脑卒中及贫血比例较高(P0.05)。B组患者接受抗凝、β受体阻滞剂、他汀类、ACEI/ARB类药物以及PCI治疗的比例显著低于A组患者(P0.01)。B组患者院内死亡率显著高于A组(P0.01)。影响院内死亡的多因素回归分析显示:除年龄、女性、合并高血压、糖尿病、PCI治疗外,eGFR下降与院内死亡率增加独立相关(OR=6.362,95%CI:2.154~16.892,P0.01)。结论急性心肌梗死合并中重度肾功能不全患者住院期间接受急性心肌梗死指南推荐治疗的比例低于肾功能正常及轻度异常组;急性心肌梗死合并中重度肾功能不全患者院内死亡率增高;中重度肾功能不全是急性心肌梗死患者院内死亡的独立危险因素。     

不同剂量替格瑞洛对老年急性冠状动脉综合征合并中度肾功能不全患者疗效及肾功能的影响

目的探讨不同剂量替格瑞洛对老年(70岁)急性冠状动脉综合征(ACS)合并中度肾功能不全(CRI)患者疗效及肾功能的影响。方法将72例老年ACS合并中度CRI患者按照数字表法随机分为全量组(36例)和半量组(36例),在原有冠心病、肾功能不全常规治疗的基础上,全量组采用替格瑞洛全量治疗(180 mg负荷量后,再以90 mg/次,2次/天);半量组采用替格瑞洛半量治疗(90 mg负荷量后,再以45 mg/次,2次/天)。于分组治疗前及治疗后1个月、3个月、6个月、12个月分别检测血小板抑制率(PIR)、血清肌酐(Scr)及丙氨酸氨基转移酶(ALT),计算估算的肾小球滤过率(e GFR),观察两组治疗12个月内的缺血事件、出血事件及药物的不良反应。结果治疗1个月、3个月、6个月、12个月后,两组患者PIR、Scr较治疗前呈升高趋势,e GFR较治疗前呈下降趋势。两组患者PIR比较差异无统计学意义(F=3.679,P=0.059);半量组患者Scr和ALT低于全量组(F=234.288、19.451,P=0.000、0.000),e GFR高于于全量组(F=54.521,P=0.000)。用药12个月内随访:两组缺血事件发生率比较差异无统计学意义(χ2=0.050,P=0.824),半量组出血事件发生率和呼吸困难发生率低于全量组(χ2=5.188、5.030,P=0.023、0.025)。结论对于老年急性冠状动脉综合征合并中度肾功能不全患者,应用半量与全量替格瑞洛时其PIR无显著差异,疗效相当,但半量替格瑞洛对肾功能及肝功能的影响较小,出血率较低,安全性更好。