Clinical analysis of acute pancreatitis after kidney transplantation: a single-center retrospective observational study

Abstract

Object

The aim of this single-center study was to summarize the diagnosis and treatment experience of acute pancreatitis after kidney transplantation. To explore the etiology of acute pancreatitis in kidney transplant recipients and provide reference for the prevention and diagnosis.

Methods

We retrospectively collected the clinical data of patients who suffered acute pancreatitis after kidney transplant in our hospital from 2019 to 2023, clinical data of patients with the chronic kidney disease who suffered acute pancreatitis were also collected at the same time. We summarized the diagnosis and treatment process of acute pancreatitis after kidney transplantation; and the differences in the pathogenesis, clinical manifestations, complications and mortality of acute pancreatitis between the two types of patients were analyzed.

Results

A total of 10 cases of acute pancreatitis of kidney transplant recipients and 11 cases of acute pancreatitis in patients with chronic kidney disease were included in this study. The most common causes of acute pancreatitis in kidney transplant recipients was drug (50.0%), of which tigecycline accounted for 100.0%, one of these cases was considered acute pancreatitis caused by a combination of tacrolimus and tigecycline. The common causes of acute pancreatitis in patients with chronic kidney disease was idiopathic (50.0%). The complication rates of acute pancreatitis in two groups were 30.0% and 9.1%, and the mortality rate were 0% and 18.2%, respectively, and there was no significant difference in complications and mortality rate. There were 10 cases of kidney transplant recipients in our center, 6 cases had acute pancreatitis within 1 month after surgery, 4 cases had acute pancreatitis over 1 month after surgery, 8 cases combined with continuous blood purification treatment, and 1 case had exploratory laparotomy, all of those cases had good clinical outcomes.

Conclusion

Acute pancreatitis after kidney transplantation were mostly caused by drugs. For early identification of acute pancreatitis, attention should be paid to patient’s abdominal symptoms and physical examination especially when using tigecycline. Basic treatments including remove triggers, fasting and water, acid suppression, pancreatic enzymes suppression and nutritional support should be given. Continuous blood purification can remove inflammatory mediators, which has remarkable effects for acute pancreatitis after kidney transplantation.

Introduction

Acute pancreatitis (AP) is an inflammation of the glandular parenchyma of the retroperitoneal organs, leading to injury with or without destruction of pancreatic acines. This inflammatory process can lead to self-limiting disease, even life-threatening multi-organ complications. The incidence of AP ranges from 0.0049 to 0.04% per year. Peery and his colleagues reported in 2012 that AP is the most common admitting diagnosis occurred in the gastrointestinal department, with an estimated annual hospitalization cost of $2.6 billion. According to the report, the risk of death from AP is about 1%, however, some patients with AP may have other severe diseases, which mortality rate approaching 30% [1, 2].

Among kidney transplantation recipients (KTRs), AP is a rare postoperative complication, with an incidence of about 1.2-6.8%. Although medical staffs allways give them active treatments, the mortality rate of AP in KTRs is extremely high, like 53-60%, which is much higher than that of the general population [3,4,5].

In 1964, Starzl firstly described pancreatitis after kidney transplantation (KT) [6]. Acute pancreatitis remains a challenging disease both in KTRs and general population, it is characterized by high morbidity and mortality also a significant economic cost burden. At the same time, because the AP after KT is rare, most of case reports lack of systematic diagnosis, treatment plans and pathogenic factors, which have limited guiding significance for clinicians.

We retrospectively collected the data of patients with AP after KT in our department from January 1, 2019 to October 25, 2023, and also collected the clinical data of patients with the chronic kidney disease (CKD) who occurred AP during the same period. This paper summarizes the diagnosis and treatment process of AP after KT in our center, and provides a reference for the prevention, diagnosis and treatment of AP after KT.

Materials and methods

General data

We used our hospital’s medical record database, entered ICD-10 to diagnose AP, and selected nephrology department; After searching, a total of 21 cases of AP in our department were collected from January 1, 2019 to October 25, 2023, including 10 KTRs and 11 patients with CKD. In the KT group, there were 7 males and 3 females, the average age of these patients was 34.5 (29.5, 43.3) years and BMI 24.1 (20.3, 26.5), all of them had no history of alcoholism, gallstones or pancreatic disease, only 1of them had a history of diabetes. Among the patients who had CKD, there were 4 males and 7 females, age was 53 (36.5, 65) years, and their BMI was 25.2 (22.4, 28.0), all of them had no history of alcoholism or pancreatic disease, 2 of them had a history of cholestasis, and 4 of them had a history of diabetes.

The procedures followed in this study are in line with the requirements of the Helsinki Declaration of the World Medical Association, as revised in 2013. This study was reviewed by the Ethics Committee of the First Affiliated Hospital of PLA Army Medical University, No. (B)KY2022227.

Clinical data

We collected the causes of AP, AP onset, clinical manifestations, AP-related complications, serum amylase at onset, abdominal CT, treatment process, serum creatinine and serum amylase before discharge, prognosis and survival, and survival of transplanted kidneys from those 10 KTRs. In patients with the CKD group, the causes of AP, clinical manifestations, complications, diagnosis and treatment, serum amylase at onset, abdominal CT, serum amylase before discharge, prognosis and survival rate were also collected. The diagnostic criteria for AP are at least two of the following three features: (1) Abdominal pain due to AP, (2) Serum amylase or lipase is at least three times higher than the upper limit of normal, (3) The imaging manifestations of AP are presented on computerized tomography (CT)/ magnetic resonance imaging (MRI) [7]. To assess the effectiveness of treatment, we categorised patients according to the severity of AP, using the modified Marshall scoring system and the CT severity index (CTSI): Mild acute pancreatitis (MAP): no organ failure, no pancreatic or peripancreatic necrosis. Medium-severe acute pancreatitis (MSAP): transient organ failure (duration < 48 h) without pancreatic or peripancreatic necrosis. Severe acute pancreatitis (SAP): persistent organ failure (duration ≥ 48 h) or pancreatic/peripancreatic necrosis.

Statistical analysis

SPSS 26.0 statistical software was used for statistical analysis in this study. The measurement data of normal distribution was represented by $\bar x \pm s$, T-test was used for comparison between groups. Non-normally distributed measures are expressed as M(P25,P75) with nonparametric tests. Statistical data were measured by χ2 test. Nonparametric tests were used for comparison of grade data. P<0.05 was considered statistically significant.

Results

The causes of AP in these two groups are shown in Table 1; Figs. 1 and 2, and statistical differences were showed in these two groups. In the KT group, other etiologies were comprehensively screened and excluded in 5 patients diagnosed with drug-related AP. 5 patients underwent comprehensive screenin, including but not limited to testing for viral [e.g., cytomegalovirus (CMV), EBV, etc.], bacterial, and fungal infections. None of the patients had clear evidence of viral, tuberculosis, bacterial, or fungal infection, and no recent infections prior to the onset of acute pancreatitis were reported. In addition, we excluded other possible aetiologies such as biliary pancreatitis (none of the colour ultrasound examinations revealed the presence of gallbladder sediment-like stones or microstones), hypercalcemic pancreatitis (excluded by blood calcium testing), hyperlipidaemic pancreatitis (excluded by lipid testing). Idiopathic is AP for which no clear cause has been identified.

Table 1 Comparison of etiology between the two groups

Fig. 1

Pathogenesis of chronic kidney disease group

Fig. 2

Pathogenesis of chronic kidney disease group

Among the KTRs, 6 patients (60.0%) developed AP within 1 month and 4 patients (40.0%) developed AP 1 month after surgery. In the KT group, 2 patients had MAP, 5 MSAP, and 3 SAP; in the CKD group, 3 patients had MAP, 7 patients had MSAP, and 1 patients had SAP.

The main clinical manifestations in both two groups were acute mid-abdominal pain, and their amylase was more than 3 times higher than the upper limit of normal at the time of onset. In the KT group, abdominal CT findings were consistent with AP in 5 patients (50%), and the CT manifestations of AP were shown in Fig. 3. In the CKD group, 8 patients (72.7%) abdominal CT findings met the AP.

Fig. 3

CT findings of acute pancreatitis

As indicated by the red arrow, the pancreas was swollen with blurred edges, the surrounding fat space was blurred, and exudation was visible

In terms of treatment, in the KT group, 6 cases of MSAP and 2 patients of SAP were treated with bedside continuous blood purification + basic supportive therapy (including fasted water, proton pump inhibitors, parenteral nutrition, somatostatin), and 2 patients of MAP were treated with basic supportive treatment. 1 patient of SAP complicated by pancreatic leakage, leading to intraperitoneal hemorrhage, necessitated an emergency laparotomy. In the CKD group, 6 patients of MSAP and 1 patient of SAP were treated with bedside continuous blood purification + basic supportive therapy, and 4 patients of MAP were treated with basic supportive care. There were 3 patients (30.0%) in the KT group developed complications related to AP, one of whom was intraperitoneal hemorrhage due to pancreatic leakage, and other 2 patients were localized effusion; 1 patient (9.1%) in the CKD group had pancreatic pseudocyst. The mortality rate in the KT group was 0, 2 patients (18.2%) in the CKD group died, and the causes of death were cardiac arrest and hyperthyroid crisis due to sinus node dysfunction, respectively.

In the KT group, serum amylase and lipase were 1261.79 (1030.57, 1605.31) IU/L and 600.20 (450.33, 1100.35) IU/L before treatment and 200.07 (189.87, 266.43) IU/L and 200.56 (173.11, 311.00) IU/L before discharge. In the CKD group, serum amylase and lipase were 1209.45 (1024.91, 1319.34) IU/L and 688.39 (583.64, 786.48) IU/L before treatment and 268.89 (223.69, 380.5) IU/L and 189.57 (106.03, 264.43) IU/L before discharge. Serum amylase and lipase changed significantly in both groups after treatment (p < 0.01). See Table 2.

Table 2 Pre-treatment and pre-discharge/pre-death serum amylase, lipase in both groups

The creatinine of patients in the KT group were 126.3 (110.7, 157.1) umol/L at discharge, and the transplanted kidney function was acceptable.

Discussion

AP is a rare complication for KTRs, and there are few reports of AP in this special population, but we have reported those who have AP after KT in a single center for four years. According to the results, the prognosis for these patients was good, no patients died, and there were only 3 patients developed complications relevant to AP. Therefore, we summarized the experience of our center in diagnosing and treating AP after KT, hoping to help the phisicians in the future work.

From January 1, 2019 to October 25, 2023, a total of 344 cases of KT were completed in our center. Among these KTRs, the incidence rate of AP was 2.9%, consistent with the 1.2-6.8% reported abroad [4, 5] and 1-5% previously reported in China [8]. Our results further confirmed that AP is rare in KTRs.

In previous reports, biliary calculus and alcoholism (40-70% and 25-35% respectively) are the main causes of AP in the general population, and hypercalcemia, hypertriglyceridemia, endoscopic retrograde cholangiopancreatography, drugs and infection are rare causes [1]. In patients with CKD, there may be an increase in the proportion of AP caused by hypercalcemia, diabetes, hyperlipidemia, and immunosuppressants secondary to hyperparathyroidism, but in our results, most of patients have unexplained acute pancreatitis, which may be related to pancreatic vascular disease. As previous reported, pancreatic ischemia caused by vasculitis, atherosclerotic embolism, low blood pressure and hemorrhagic shock may lead to AP [9,10,11,12,13,14]. In this study, we considered drugs as the main etiological factor for AP after KT, with tigecycline accounting for 50.0% and tacrolimus 10.0%, which is similar to previous reports [8, 15,16,17,18,19,20]. The causes of AP were different in patients with the KT, CKD and general population. Therefore, in KTRs, special attention should be paid to the patient’s abdominal symptoms when tacrolimus concentrations are too high or when tigecycline is used for anti-infective therapy, especially in the early post-transplant period. This facilitates early recognition of AP, promote discontinuation of suspected drugs timely, and earlier treatment of AP, which help patients achieve better clinical outcomes.

The prognosis of KTRs in our center is very good, with a 100% cure rate, and no deaths. This result is different from previous reports, in the study performed by Ren Huijun, Shang Wenjun and other scholars, there was 1 death from multiple organ failure in 12 patients, with a mortality rate of 8.3% [8]. Asztalos L; Kincses Z et al. reported that 3 of the 9 patients died due to multi-organ failure, with a mortality rate of 33.3% [3]. In summary, we believe that the more advanced testing methods have helped us to identify AP and take more proactive measures, which has greatly reduced the mortality rate of patients. For patients presenting with SAP or MSAP in the early postoperative period, we used bedside continuous blood purification combined with basic supportive care based on fasting water, proton pump inhibitors, somatostatin, and parenteral nutrition. Continuous blood purification, also known as continuous renal replacement therapy. Its application value lies in: (1) In the early stage of severe acute pancreatitis, pancreatic cells are destroyed and a large amount of inflammatory mediators are released, which may induce systemic inflammatory response syndrome and lead to multi-organ failure; (2) The systemic inflammatory response caused by acute pancreatitis increases capillary permeability, resulting in fluid leakage to the third space, however, the blood purification can slowly remove water from the blood vessels, form a negative fluid balance, and improve heart failure pulmonary edema; (3) Blood purification can re-stabilize the immune system by regulating neutrophil function, improving monocyte function, and restoring leukocyte reactivity; (4) Blood purification can replace kidney function, remove water, metabolites and liver toxins, replenish coagulation factors [21]. As far as we know, this is the first manuscript that report the treatment of AP after KT with continuous blood purification technology. We summarized the treatment methods of 8 KTRs who used continuous blood purification therapy, all of these 8 patients underwent at least 72 h of continuous blood purification, combined with basic supportive therapy, to remove the pathogenic factors, and then decided whether to get off the machine according to the patient’s amylase level, whether their symptoms are relieved and transplanted kidney function. In KTRs, such patients are more likely to have co-infection, meanwhile, the transplanted kidney function is often not as good as that of the general population, their ability to remove metabolites, water and regulate the internal environment is slightly poor, especially in the early postoperative period, the risk of infection in KTRs is higher, and the recovery of transplanted kidney function in some patients is delayed, which puts the KTRs with AP at a higher risk of death. Therefore, for patients with MSAP or SAP after KT, we recommend the continuous blood purification therapy can be used at early stage after surgery to help patients control volume, remove inflammatory mediators, regulate immune function, and control infection. In KTRs with MAP, the same treatment regimen as in the general population can be used initially, but early use of continuous blood purification is also recommended if the patient has delayed recovery of grafted renal function and acute kidney injury.

Inevitably, there are some flaws in our research: (1) there is no higher level of evidence such as prospective randomized controlled trials to verify the clnical application value of continuous blood purification, (2) the benefits and cost-effectiveness of this treatment can be better evaluated if a opposite group of KTRs with continuous blood purification can be established, and (3) The number of cases in this study is small although this is the largest number of cases reported so far.

In summary, most of patients developed AP after KT are caused by drugs, especially tigecycline and tacrolimus. When patients using these drugs, we can actively pay attention to the patient’s abdominal symptoms and abdominal examination, so as to identify AP at an early stage; For patients with SAP or MSAP after KT, we suggest basic supportive care in combination with at least 72 h of continuous blood purification to help patients achieve good clinical outcomes.