Acute pancreatitis (AP) is a severe but insufficiently recognized adverse effect of tigecycline in kidney transplant (KT) recipients. This study aimed to identify the clinical characteristics and risk factors associated with tigecycline-induced AP in this population.

A single-center retrospective study was conducted in KT recipients treated with tigecycline. The clinical characteristics of patients who developed AP were analyzed, and risk factors for tigecycline-induced AP were assessed using univariate analysis and multivariate logistic regression.

80 KT recipients were enrolled, of whom nine developed AP (incidence: 11.25%), and four died. The mean time from tigecycline administration to AP onset was 7.00 days, to symptomatic relief after discontinuation was 4.87 days, and to normalisation of pancreatic enzymes after discontinuation was 8.75 days. The analysis revealed that tacrolimus trough concentration (C0 Tac) and post-transplant acute kidney injury (AKI) were independent risk factors for tigecycline-induced AP in KT recipients. Logistic regression analysis produced a combined predictive expression: Ycombined = AKI + 0.064C0 Tac-2.789. Receiver operating characteristic curve analysis determined that the C0  Tac cut-off was 13.9 ng/mL. The area under the curve for C0  Tac and combined predictor were 0.802 and 0.853, respectively.

The incidence of AP following tigecycline treatment was significantly higher in KT recipients than in non-transplant patients. Post-transplant AKI and elevated C0 Tac concentrations were identified as independent risk factors for the development of AP. Close monitoring of renal function and ensuring therapeutic monitoring of C0 Tac levels may help prevent AP.

Tacrolimus-induced acute pancreatitis (TAP) is rare and requires thorough evaluation, including genetic testing, to rule out other causes. While TAP has been documented in a few cases following kidney transplantation, we report the first case of TAP in an adult after liver transplantation, with a noteworthy feature of late-onset TAP occurring more than 12 months after initiating tacrolimus therapy. This case highlights the potential for delayed onset of TAP, and we suggest that tacrolimus may warrant reclassification from category III to Ic in the drug-induced pancreatitis classification. In addition, we introduce sirolimus as a viable alternative for immunosuppression following TAP.

Recent case report have highlighted the emergence of Fanconi syndrome as a potentially life-threatening complication linked to tacrolimus.

We undertook an observational retrospective pharmacovigilance study, leveraging data from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from its inception up to the third quarter of 2023. Our objective was to investigate the potential link between tacrolimus and Fanconi syndrome using statistical methods such as the Information Component (IC) and Reporting Odds Ratio (ROR). All statistical analyses were conducted using R version 3.2.5.

We identified 39 cases of Fanconi syndrome linked to tacrolimus. The frequency of fanconi syndrome associated with tacrolimus was significantly higher compared to all other drugs in the database (ROR 3.30 [2.40-4.53], IC 1.64[1.17-2.11], Table 2). When comparing to cyclosporine, the signal for tacrolimus-related fanconi syndrome also appears significant (ROR 15.21 [3.68, 62.94], IC 0.73 [0.09-1.37], Table 2). Further analysis revealed that, this signal was only present in the age group of 60 years and older.

Our study has identified a safety signal for tacrolimus in relation to Fanconi syndrome, particularly in individuals aged 60 and above. Additional research is needed to confirm and quantify the risk of tacrolimus-induced Fanconi syndrome.

Recent case reports have drawn attention to the emergence of acute pancreatitis, a potentially life-threatening complication associated with tacrolimus. This study uses the Food and Drug Administration Adverse Event Reporting System (FAERS) to investigate the risk signal of acute pancreatitis associated with calcineurin inhibitors (CNIs), with a focus on tacrolimus.

We conducted an observational retrospective pharmacovigilance study utilizing the FAERS database, encompassing data from its inception to the third quarter of 2023. The assessment of the association between CNIs and acute pancreatitis was carried out using the Information Component (IC) and Reporting Odds Ratio (ROR). Logistic regression analysis was employed to elucidate factors contributing to fatal outcomes. All analyses were performed using R version 3.2.5.

We identified 221 cases of acute pancreatitis linked to CNIs. The median age of individuals experiencing acute pancreatitis induced by tacrolimus was 43, with a predominant occurrence among male patients. Our study showed a significant association between CNIs and acute pancreatitis (ROR 1.82 [1.60-2.08], IC 0.85 [3.66-3.92]). Comparing tacrolimus and cyclosporine, the signal for tacrolimus seemed to be higher. Further analysis revealed that, with the exception of patients aged 60 and above, the signal for tacrolimus remained stable. Contrastingly, the signal for cyclosporine was unstable and limited to the male group and individuals aged less than 20 years. In cases of CNIs-related acute pancreatitis, the mortality rate was 31.67% (70/221 cases). Logistic regression analysis indicated that a younger age acts as a protective factor for death due to CNIs-related acute pancreatitis (OR 0.943, 95% CI 0.915-0.972, P = 0.000).

Our study has identified a safety signal for tacrolimus in relation to acute pancreatitis. Additionally, we observed advanced age as a significant risk factor for tacrolimus-related acute pancreatitis, leading to mortality. Given the widespread use of tacrolimus, it is crucial for healthcare providers to be vigilant and informed about the potential association with acute pancreatitis.

The number of solid organ transplantations performed annually is increasing and are increasing in the following order: Kidney, liver, heart, lung, pancreas, small bowel, and uterine transplants. However, the outcomes of transplants are improving (organ survival > 90% after the 1st year). Therefore, there is a high probability that a general surgeon will be faced with the management of a transplant patient with acute abdomen. Surgical problems in immunocompromised patients may not only include graft-related problems but also nongraft-related problems. The perioperative regulation of immunosuppression, the treatment of accompanying problems of immunosuppression, the administration of cortisol and, above all, the realization of a rapidly deteriorating situation and the accurate evaluation and interpretation of clinical manifestations are particularly important in these patients. The perioperative assessment and preparation includes evaluation of the patient's cardiovascular system and determining if the patient has hypertension or suppression of the hypothalamic-pituitary-adrenal axis, or if the patient has had any coagulation mechanism abnormalities or thromboembolic episodes. Immunosuppression in transplant patients is associated with the use of calcineurin inhibitors, corticosteroids, and antiproliferation agents. Many times, the clinical picture is atypical, resulting in delays in diagnosis and treatment and leading to increased morbidity and mortality. Multidetector computed tomography is of utmost importance for early diagnosis and management. Transplant recipients are prone to infections, especially specific infections caused by cytomegalovirus and Clostridium difficile, and they are predisposed to intraoperative or postoperative complications that require great care and vigilance. It is necessary to follow evidence-based therapeutic protocols. Thus, it is required that the clinician choose the correct therapeutic plan for the patient (conservative, emergency open surgery or minimally invasive surgery, including laparoscopic or even robotic surgery).

Background: The aim of this multicentre retrospective study is to determine the incidence, etiology, clinical characteristics, and outcomes of kidney transplant recipients diagnosed and treated for acute pancreatitis. Methods: We analyzed data from kidney transplant recipients who received kidney allografts between October 1973 and December 2023 and were diagnosed and treated for acute pancreatitis. Results: Of 2482 patients who received kidney allografts, 10 (0.4%) (5 male) were diagnosed with acute pancreatitis, with a mean age of 48.6 years. Patients were diagnosed with acute pancreatitis between 3 weeks and 24 years after the transplantation. Possible etiologies included cholecystolithiasis, COVID-19, hypercalcemia, postprocedural, use of cannabis, trimetoprim-sulphometoxasole, statins, sirolimus, tacrolimus and obesity. There was no suspected etiology in two patients. Patients were treated with aggressive hydration, pain alleviation and antibiotics if indicated. Four patients developed complications. Local complications included peripancreatic collections, pseudocyst, and abscesses formation, while systemic complications occurred in the form of Cytomegalovirus (CMV) reactivation and urinary tract infection. All patients survived with preserved kidney allograft function. Conclusions: Acute pancreatitis in kidney transplant recipients is rare. However, it may be linked to significant morbidity and mortality. While symptoms may be nonspecific and brought on by a variety of viral and non-infectious illnesses, as well as adverse effects from immunosuppressive medications, a high degree of awareness is required.

Carbapenem-resistant gram-negative bacterial (CRGNB) infections are increasing among kidney transplant recipients, and effective therapeutic options are limited. This study aimed to investigate the efficacy and adverse events associated with combination therapy tigecycline in renal transplant patients with CRGNB infections.

This study retrospectively analyzed 40 Chinese patients with confirmed or suspected CRGNB infections who received tigecycline therapy. The patients' case features and clinical and microbiological data were analyzed.

A total of 40 renal transplant recipients received tigecycline therapy for a median duration of 9 (range, 3-25) days. CRGNB isolates were obtained from the organ preservation solution of the donor kidney in 28 patients, with confirmed transmission in 4 patients. Infections were detected in the bloodstream, urinary tract, sputum, and wound. The most prevalent isolates were Klebsiella pneumoniae (75%, 30/40), Acinetobacter baumannii (15%, 6/40), and Escherichia coli (10%, 4/40). A clinical response was observed in 32 (80%) patients. The 28-day all-cause mortality rate was 7.5% (3/40), while the one-year all-cause mortality rate was 2.5% (1/40). While one patient died owing to severe pancreatitis, no serious adverse events related to tigecycline therapy were reported. However, multiple indices of liver function and pancreatitis precursors increased after treatment with tigecycline compared to before treatment.

Tigecycline therapy appears to be well tolerated in renal transplant recipients with multidrug-resistant bacterial infections. Nevertheless, attention should be paid to adverse reactions related to tigecycline therapy, especially gastrointestinal reactions, and the related laboratory tests should be closely monitored.

Tacrolimus (FK506) is an immunosuppressant that is experiencing a continuous rise in usage worldwide. The related side effects are known to be globally dose-dependent. Despite numerous studies on FK506, the mechanisms underlying FK506 toxicity are still not well understood. It is therefore essential to explore the toxicity mediated by FK506. To accomplish this, we conducted a targeted metabolomic analysis using LC-MS on the plasma samples of patients undergoing FK506 treatment. The aim was to identify any associated altered metabolic pathway. Another anti-calcineurin immunosuppressive therapy, ciclosporin (CSA), was also studied. Increased plasma concentrations of pipecolic acid (PA) and sarcosine, along with a decrease in the glycine/sarcosine ratio and a tendency of increased plasma lysine was observed in patients under FK506 compared to control samples. Patients under CSA do not show an increase in plasma PA compared to the control samples, which does not support a metabolic link between the calcineurin and PA. The metabolomics changes observed in patients under FK506 highlight a possible link between FK506 and the action of an enzyme involved in both PA and sarcosine catabolism and oxidative pathway, the Peroxisomal sarcosine oxidase (PIPOX). Moreover, PA could be investigated as a potential biomarker of early nephrotoxicity in the follow-up of patients under FK506.

Pancreatic diseases, such as pancreatitis and pancreatic cancer, remain the most threatening gastrointestinal diseases with a high mortality due to atypical symptoms. MicroRNA plays crucial roles in regulating metastasis and cell proliferation of pancreatic cancer, constituting important biomarkers for the early diagnosis of pancreatic cancers. Herein, we develop a sensitive and simple exosomal miRNA detection method with only a dual-hairpin-probe. In detail, the dual-hairpin-probe is constructed through combination of two functional sections for both target miRNA identification and signal amplification. With only one probe, the method possesses the capability to avoid interferences from concentration changes of other probes, and exhibits a higher stability which is demonstrated through the obtained low coefficients of variation (CV) of 6.73%. With let-7a as detection target, the LOD of the established method is determined to be 243 aM, while maintaining a high discriminating capability towards let-7a homogenous miRNAs.

Calcineurin inhibitors (CNIs) are often associated with abnormalities in glucose and lipid metabolism. Tacrolimus is the most potent CNI which is nowadays used almost universally as a part of triple-drug immunosuppression after kidney transplantation. Tacrolimus can cause islet cell damage and decrease in insulin secretion which can lead to post-transplant diabetes mellitus and rarely diabetic ketoacidosis. Although rare, acute pancreatitis has also been implicated by a few case reports to be associated with tacrolimus. However, tacrolimus-induced acute pancreatitis has not been reported in pediatric kidney transplant recipient till date.

We report the first case of tacrolimus-induced acute pancreatitis in association with hypertriglyceridemia and DKA in a child early after kidney transplant. The patient was managed with supportive treatment, and tacrolimus was stopped for three days and then switched to cyclosporine-based regimen. The patient became euglycemic within 8 weeks of switching to cyclosporine and did not have any recurrence of pancreatitis.

Tacrolimus-induced pancreatitis is rare in the setting of kidney transplants and prompt diagnosis and management can lead to a successful outcome.