Clinical course and outcomes of acute pancreatitis in patients with chronic kidney disease: A retrospective case-control study

Authors

Abstract

Aim Acute pancreatitis (AP) ranges from mild inflammation to severe, life-threatening disease. Patients with chronic kidney disease (CKD) constitute a high- risk group, as metabolic disturbances, immune dysfunction, and dialysis-related factors may complicate diagnosis and worsen outcomes. However, the impact of CKD on AP prognosis remains unclear.
Materials and Methods This retrospective case-control study included adults with a first episode of AP hospitalized between January 2014 and December 2017. Group 1 comprised 63 patients with CKD (Stages 3–5), and Group 2 included 63 AP patients with normal renal function. Demographics, laboratory findings, and outcomes were compared, focusing on procalcitonin (PCT), alanine aminotransferase (ALT), C-reactive protein (CRP), white blood cell count (WBC), length of hospital stay, BISAP score (excluding the BUN criterion), ICU admission, and in-hospital mortality. Statistical significance was set at p < 0.05.
Results CKD patients were older (69.86 ± 13.25 vs. 57.14 ± 18.16 years; p = 0.01), had higher PCT (19.92 ± 41.33 vs. 1.63 ± 4.02 ng/mL; p = 0.001), but lower ALT (110.73 ± 164.67 vs. 208.97 ± 201.18 U/L; p = 0.04). BISAP scores (1.75 ± 1.07 vs. 1.35 ± 0.97; p = 0.032), ICU admission (17.5% vs. 3.2%; p = 0.008), mortality (17.5% vs. 3.2%; p = 0.008), and hospital stay (23.41 ± 77.91 vs. 9.33 ± 7.62 days; p = 0.03) were all higher in CKD patients.
Discussion CKD is associated with a more severe AP course and worse prognosis. Elevated PCT and BISAP scores may help identify high-risk patients. Early recognition and aggressive management are essential to improve outcomes.

Keywords

Introduction

Acute pancreatitis (AP) represents a spectrum of pancreatic inflammation, characterized by a variable clinical trajectory that ranges from mild, self-resolving episodes to severe necrotizing forms associated with a systemic inflammatory response and multiple-organ failure. It ranks among the most common gastrointestinal diagnoses that result in hospital admission globally and contributes significantly to the healthcare burden, in part because its evolution is often unpredictable, and the case- fatality rate rises markedly in the severe category. The disorder arises from the inappropriate intrapancreatic activation of digestive enzymes, which, in the context of concurrent systemic cytokine release, triggers inflammation that can compromise distant organ function [1]. Several triggers have been identified, including gallstones, ethanol excess, hypertriglyceridemia, and certain drugs. The past several years have seen increased scrutiny of AP in specific populations, with a particular focus on individuals with chronic kidney disease (CKD), in whom the clinical trajectory and prognosis may diverge from the general cohort [2, 3, 4].
CKD affects millions worldwide and induces profound disturbances in metabolism, immune responsiveness, and systemic inflammation. These disturbances may heighten vulnerability to AP or alter its clinical severity. Patients with CKD often exhibit elevated basal levels of pancreatic enzymes, including amylase and lipase, which complicate early clinical recognition of AP [1, 4]. In addition, uremia, oxidative stress, and dialysis-related complications—such as electrolyte derangements and recurrent infections—further threaten this population with adverse clinical evolution. Analyses by Li et al. and Hou et al. document an augmented risk of AP and an unfavorable prognosis in individuals with reduced renal function, manifesting as a greater incidence of multiorgan failure, increased admission to the intensive care unit, and heightened in-hospital mortality [4, 5, 6]. Yet, the literature on the influence of CKD on the trajectory and outcomes of AP remains limited and inconsistent, particularly concerning cohorts receiving routine hemodialysis [7].
The co-occurrence of AP and CKD constitutes a pressing clinical concern within both internal medicine and nephrology, yet the literature remains strikingly sparse. Prior reports have uniformly documented lengthened hospital stays and increased mortality among AP patients with CKD, yet counter- evidence suggests that disease severity, as gauged by clinical scoring systems and the radiological extent of pancreatic necrosis, remains comparable between cohorts with and without renal impairment. Compounding this heterogeneity, established prognostic indices such as the BISAP score may yield misleadingly favorable or austere assessments owing to the influence of baseline blood urea nitrogen elevations that are intrinsic to CKD. In light of these discordant findings, a concerted research effort is warranted to delineate the specific clinical signature and prognostic trajectory of AP in the context of CKD.
The present study endeavors to elucidate the interplay between kidney function and the AP disease process by systematically comparing clinical phenotypes, biochemical markers, severity indices, and outcomes among patients with CKD and those without. Through a retrospective, matched-cohort design, this investigation aspires to quantify the influence of renal dysfunction on the course of AP, thereby generating evidence that may refine risk stratification and clinical management for this exceptionally vulnerable patient subgroup.

Materials and Methods

This study was conducted through a retrospective analysis of adult patients diagnosed with AP who presented to the departments of gastroenterology, internal medicine, general surgery, and emergency at our hospital between January 1, 2014, and December 31, 2017.
Two groups of patients were evaluated. The diagnosis of AP was established based on the presence of at least two of the following criteria: (1) acute abdominal pain radiating to the back, primarily in the epigastric region, (2) serum amylase and/ or lipase levels ≥ 3 times the upper limit of normal, and (3) radiological evidence of pancreatitis via imaging studies.
Group 1 consisted of 63 AP patients with CKD, and Group 2 (control group) included 63 AP patients without CKD. CKD stages were classified according to KDIGO criteria (Stages 3–5), and glomerular filtration rate (GFR) values were calculated using the Modification of Diet in Renal Disease (MDRD) formula. Patients with Stage 1 or 2 CKD and those under 18 years of age were excluded from the study group. In the control group, patients with acute kidney injury (AKI) or under 18 years old were excluded.
Data were obtained through a retrospective review of hospital electronic records (PROBEL system). Demographic characteristics (age, sex), laboratory values (amylase, lipase, procalcitonin (PCT), alanine aminotransferase (ALT), white blood cell (WBC) count, calcium, C-reactive protein (CRP)), clinical indicators (hospital length of stay, intensive care unit (ICU) admission, BISAP 48 scores), and disease outcomes (discharge or death) were recorded. WBC values and CRP were also assessed on day 3 and day 5, respectively.
The BISAP (Bedside Index for Severity in Acute Pancreatitis) score was calculated for each patient based on the presence of systemic inflammatory response syndrome (SIRS), altered mental status, pleural effusion, and age. The BUN > 25 mg/ dL criterion was excluded from the scoring system due to chronically elevated levels in CKD patients, and the maximum BISAP score for both groups was therefore 4.
Contrast-enhanced abdominal CT scans, when available, were evaluated using the Modified Balthazar Severity Index to assess pancreatic inflammation, necrosis, and extrapancreatic complications. However, these data were used for subgroup comparison only and were not included in primary analyses, as no statistically significant differences were observed between groups. Similarly, data regarding CKD etiologies (e.g., hypertension, diabetes, glomerulonephritis, etc.) and hemodialysis (HD) duration in a subset of patients were recorded for descriptive purposes only and were not subjected to comparative statistical testing.
Laboratory Measurements
PCT was measured using the Siemens Advia Centaur XPT immunoassay system (Siemens Healthcare GmbH, Erlangen, Germany; reference range: 0–0.1 ng/mL). CRP, ALT, amylase, lipase, and calcium were analyzed using the Abbott Architect c16000 spectrophotometer (Abbott Park, Illinois, USA). Reference ranges were as follows: CRP (0–0.5 mg/dL), ALT (0– 55 U/L), amylase (25–125 U/L), lipase (8–78 U/L), and calcium (8.5–10.5 mg/dL). WBC count was measured with a Sysmex XN- 1000 hematology analyzer (Sysmex Corp., Kobe, Japan) with a reference range of 4–10 × 10⁹/L.
Statistical Analysis
Statistical analyses were performed using the SPSS version 22.0 software package (IBM Corp., Armonk, NY, USA). The distribution of continuous variables was tested using the Shapiro–Wilk test. Data were presented as mean ± standard deviation for normally distributed variables and median (interquartile range) for non-normally distributed variables. Between-group comparisons were conducted using Student’s t-test or Mann–Whitney U test, as appropriate. Categorical variables were analyzed using the Chi-square test or Fisher’s exact test. Correlations between continuous variables were evaluated using Spearman’s rank correlation coefficient. All statistical comparisons were conducted as described above, and significance was accepted at p < 0.05.
Ethical Approval This study was approved by the Ethics Committee of İzmir Katip Çelebi University (Date: 2018-04-25, No: 181).

Results

The research cohort comprised 63 individuals diagnosed with AP and concurrent CKD and 63 matched control individuals with AP alone. No statistically significant disparity in sex ratio was detected between the cohorts (p = 0.373), affirming comparability in sex distribution (see Table 1). However, the mean age of the CKD cohort (69.86 ± 13.25 years) exceeded that of the control cohort (57.14 ± 18.16 years) with statistical significance (p = 0.01), as summarized in Table 1.
Table 1. Demographic and laboratory characteristics of the study groups Marked distinctions were recorded in both laboratory and clinical parameters. Serum procalcitonin concentrations in the CKD group were appreciably elevated (19.92 ± 41.33 ng/mL) relative to the control group (1.63 ± 4.02 ng/mL), with a significant p value of 0.001. Alanine aminotransferase concentrations on the day of admission were, conversely, notably lower in the CKD group (110.73 ± 164.67 U/L) than in the control group (208.97 ± 201.18 U/L) (p = 0.04). Among clinical outcomes, the mean duration of hospitalization was substantially prolonged in the CKD group (23.41 ± 77.91 days) in comparison to the control group (9.33 ± 7.62 days) (p = 0.03). These results are graphically represented in Figure 1 and elaborated in Table 1.
The mean BISAP score, derived by omitting the blood urea nitrogen criterion because of pre-existing CKD, was statistically significantly elevated in the CKD cohort (1.75 ± 1.07) when compared to the control of patients without renal impairment (1.35 ± 0.97) (p = 0.032), as detailed in Table 2. Additionally, 11 patients in the CKD group were subsequently admitted to the intensive care unit, compared to 2 patients in the control cohort. This disparity in ICU admission rates was significant (p = 0.008) (Table 2).
Concerning in-hospital mortality, 11 individuals (17.5%) in the CKD cohort died during hospitalization, with all patients having necessitated intensive care unit management. In the control cohort, 2 patients (3.2%) died, also after ICU admission. The disparity in mortality rates between the CKD group and the control group attained statistical significance (p = 0.008) (Table 2).
All parameters that achieved statistical significance between the CKD cohort and the control, specifically age, procalcitonin, alanine aminotransferase, duration of hospital stay, BISAP score, ICU admission, and mortality, are comprehensively collated in Table 3.

Discussion

AP is a systemic condition ranging from mild inflammation to life-threatening multiorgan failure, resulting from enzymatic reactions leading to pancreatic necrosis [1]. While it may present as a localized, self-limiting inflammation, it can also cause severe complications such as multiorgan dysfunction and death [1]. Several studies have identified various etiological factors associated with AP, including medications used for metabolic disorders, uremia, hypercalcemia, and secondary hyperparathyroidism—all of which are commonly observed in patients with CKD [2]. In severe cases of AP, the prevalence of acute kidney injury (AKI) alone ranges between 5% and 20%, increasing to 14–28% when accompanied by complications like respiratory failure, sepsis, or pleural effusion [3, 4]. Li et al. also emphasized that AKI significantly increases mortality in patients with severe AP [5].
In our study, 63 CKD patients (stages 3–5) and 63 controls were evaluated. The majority of CKD patients were in advanced stages, and their mean age was significantly higher than that of the control group. This suggests that advanced age may be a risk factor for AP in CKD patients. Hou et al. found a direct association between increasing age and AP prevalence among CKD patients [6]. Similarly, an increased risk of AP with aging was reported. As the elderly population continues to grow, a proportional rise in AP cases is anticipated. Some studies, however, have reported contradictory findings, stating that age is not a significant risk factor for AP in CKD patients [13, 14].
These discrepancies may stem from variations in disease severity, patient selection, and comorbidities.
Amylase and lipase are central biochemical markers in diagnosing AP, though their interpretation in CKD patients can be challenging due to baseline elevations. In our study, ALT values on day 1 were significantly higher in the control group. ALT, AST, and CRP levels are generally elevated in patients with comorbidities such as chronic kidney disease, diabetes mellitus, or liver failure, which may indicate increased disease severity. [9]. In our cohort, only ALT showed a significant difference. This could be attributed to pre-existing liver dysfunction, variable etiologies of AP, and retrospective data limitations.
One of our key findings was the prolonged hospitalization of CKD patients with AP. This was likely influenced by uncontrolled diabetes, cardiovascular comorbidities, catheter infections, and disruptions in dialysis schedules. Basic-Jukic et al. similarly reported increased hospitalization and intensive care requirements among kidney transplant recipients with AP [10]. Nasir and Ahmad also demonstrated high hospitalization rates in CKD patients with AP, particularly those undergoing dialysis [11].
Biliary causes predominated in the CKD group (76.2%), with only a minority of cases linked to alcohol. Although alcohol is cited as the leading cause of AP in the literature, its contribution was lower in our population, possibly due to cultural factors [14]. In contrast, Lankisch et al. reported biliary and alcoholic etiologies as the most common AP triggers in non-CKD patients [12].
Pancreatic necrosis (PN) is a known predictor of poor prognosis in AP [14]. In our study, no significant difference in PN prevalence was observed between groups, likely due to the limited use of contrast-enhanced CT in CKD patients. Guo et al. emphasized the prognostic value of vascular complications and necrosis in AP, linking them with higher morbidity and mortality [15].
Regarding the Modified Balthazar Severity Index (MBSI), most CKD patients exhibited mild AP. However, due to limited imaging, MB scores could only be calculated in 15 CKD patients, restricting robust comparisons. Han et al. validated a severity prediction model based on CT findings and supported the prognostic utility of imaging-based indices in AP [16].
Serum procalcitonin (PCT) levels were significantly elevated in CKD patients (mean 19.92 ± 41.33 vs. 1.63 ± 4.02; p = 0.001). Wang & Liu reported that PCT levels are often elevated in CKD due to reduced clearance and increased inflammation, suggesting that elevated PCT may signal infectious complications and warrant early antibiotic therapy [17]. Conflicting reports exist regarding whether PCT is influenced by renal function, but evidence supports its diagnostic relevance in this context [18]. BISAP scores were significantly higher in CKD patients, indicating increased risk for organ failure. Wang et al. showed that patients with persistent organ failure had higher BISAP scores compared to those with transient dysfunction [19]. Likewise, other studies have confirmed the association between BISAP scores and AP severity [20].
ICU admissions were significantly more frequent in the CKD group, with 100% mortality among those requiring ICU care. Similar findings have been reported, indicating worse outcomes in AP patients with renal dysfunction. [21] In our study, the overall mortality rate for CKD patients with AP was approximately 17%, which is notably higher than the general AP population, where mortality typically ranges between 2–5%, and up to 30% in severe cases [22].
Another noteworthy finding was the lack of significant differences in metabolic risk factors (e.g., diabetes, hyperlipidemia, calcium levels) and AP attack frequency between groups. This may be due to our limited sample size and inability to evaluate all metabolic contributors.
Finally, BISAP scores were recalculated, excluding the BUN > 25 criterion to avoid bias in CKD patients, where BUN levels are naturally elevated. Even after adjustment, BISAP scores remained significantly higher in the CKD group. When analyzing CKD etiology, the most common causes were hypertension (42.9%) and diabetes (19.0%). These findings differ from larger cohorts, possibly due to sample size and the exclusion of peritoneal dialysis patients in our study.

Limitations

This single-center retrospective study with a relatively small sample size may limit the generalizability of the results. Lack of complete imaging and dialysis-related data, as well as potential confounding from CKD-related baseline laboratory abnormalities, may have influenced severity assessment and outcomes.

Conclusion

Determining the clinical course and prognosis of AP is essential for timely and appropriate intervention. In our study, AP in CKD patients was associated with higher mortality (~17%), prolonged hospitalization, and greater ICU needs. Elevated PCT levels and BISAP scores suggest more severe disease. These findings underline the importance of early and aggressive management in this population. Multicenter prospective studies including peritoneal dialysis patients are needed to further clarify the pathophysiological mechanisms and improve survival outcomes in CKD patients with AP.

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