Abstract
Background
Ectopic fat deposition in non-adipose organs is increasingly recognized as a driver of chronic metabolic disease, yet the relationship between intrapancreatic fat and impaired renal function remains poorly defined. We investigated whether pancreatic steatosis, quantified by computed-tomography (CT) attenuation, is independently associated with impaired renal function in a large Chinese health-screening cohort.
Methods
This cross-sectional study included adults (≥ 20 years) who underwent low-dose chest CT and same-day serum creatinine measurement at the Nanjing University of Chinese Medicine between 2018 and 2021. Pancreatic fat was assessed by mean CT attenuation (PanCT) and the pancreas-to-spleen attenuation ratio (P/S). Impaired renal function was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m².
Results
Among 9,432 participants (mean age 51.6 ± 15.4 years; 60.7% male), 232 (2.5%) had CKD. Both PanCT and P/S decreased monotonically with increasing impaired renal function prevalence across quartiles (p-trend < 0.001). The highest quartiles of PanCT (> 50.2 HU) and P/S (> 1.03) were associated with 48% (OR 0.52; 95% CI 0.27–0.99) and 54% (OR 0.46; 95% CI 0.23–0.90) lower odds of impaired renal function, respectively, compared with the lowest quartiles. Restricted cubic splines revealed a linear inverse relationship, and subgroup analyses confirmed consistency in non-diabetic, non-hypertensive, and high-liver-fat individuals.
Conclusions
Greater intrapancreatic fat deposition is independently associated with increased risk of impaired renal function in Chinese adults.
Keywords: Intrapancreatic fat deposition, Chronic kidney disease, Pancreatic CT attenuation
Introduction
Chronic kidney disease (CKD) is a key determinant of adverse health outcomes in major non-communicable diseases [1]. CKD is a global health issue, with a prevalence of approximately 13.4% [2]. In China, the adult CKD prevalence was reported to be 10.8% in 2012, and although it decreased to 8.2% in 2018, the disease burden remains high due to the large population [3]. CKD often lead to end-stage of renal disease (ESRD) and is one of the risk factor of cardiovascular disease [4, 5] and cardiovascular mortality [6, 7]. CKD and ESRD both cause a high economic burden [8]. Therefore, early and active intervention is crucial for delaying disease progression, improving patients’ physical and mental health, and reducing the economic burden on families and the healthcare system.
Growing evidence indicates that abnormal fat deposition, particularly in non-adipose tissues such as the liver, may be associated with the development and progression of various metabolic and chronic diseases [9, 10], such as diabetes and cardiovascular diseases. Recent studies also showed that intrapancreatic fat deposition was related to health issues [11, 12]. Although the link between abdominal fat burden and renal impairment has been established [13], especially as many studies have found a significantly increased risk of CKD in patients with metabolic dysfunction-associated fatty liver disease (MAFLD) [14–16], the potential impact of pancreatic fat deposition on CKD has attracted limited attention.
Given that both pancreatic diseases and renal impairment are associated with common risk factors such as metabolic syndrome, obesity, diabetes, and hypertension or cardiovascular disease [5, 17–19], it is reasonable to hypothesize that pancreatic fat deposition may play a role in the development of CKD. Understanding the potential association between pancreatic fat deposition and CKD is valuable for revealing the role of pancreatic fat in health issues. Impaired renal function (estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m²) is a key defining feature of CKD.20 Therefore, this study aimed to show the association between the intrapancreatic fat deposition and impaired renal function which is a marker reflecting CKD status in a general population.
Materials and methods
Study population
This retrospective, cross-sectional study used consecutive health-screening records of adults who underwent low-dose, non-contrast chest CT at the Health Management Center of Nanjing University of Chinese Medicine (Nanjing, Jiangsu Province, China) between January 2016 and December 2019. Chest CT was part of a standardized annual physical examination package offered to community-dwelling individuals. We included adults who (1) age ≥ 20 years; (2) CT scans covering the pancreas region, liver and spleen, and (3) had a same-day serum creatinine measurement. Participants were excluded if any of the following were documented in the electronic medical record or self-reported questionnaire: 1) Clinically significant cardiopulmonary disease (e.g., New York Heart Association class III/IV heart failure, 2) severe valvular disease, chronic obstructive pulmonary disease requiring home oxygen, interstitial lung disease with dyspnea at rest, and end stage of renal disease; 3) Active or prior malignancy of any organ system; 4) Use of systemic glucocorticoids for more than 30 consecutive days within the preceding 6 months; 5) Diagnosed autoimmune or inflammatory rheumatic disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis, vasculitis, systemic sclerosis). Application of these criteria yielded a final analytic cohort of 9,432 individuals. The study protocol was reviewed and approved by the Institutional Review Board (IRB) of the Affiliated Hospital of Nanjing University of Chinese Medicine (2019-NL158). Because the investigation involved analysis of pre-existing, de-identified data, the IRB granted a waiver of informed consent. All procedures were conducted in accordance with the ethical standards of the Declaration of Helsinki (revised 2013) and the relevant Chinese regulations for retrospective research.
Data collection
The following data were collected through the electronic medical system: demographic information (age, sex, body mass index (BMI)); laboratory test results (liver function: aspartate aminotransferase (AST); kidney function: serum creatinine and uric acid; blood glucose; blood lipids: high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), triglyceride (TG), total cholesterol (TC)). All laboratory tests and CT scans were performed on the same day. Diabetes was diagnosed if fasting plasma glucose was ≥ 7.0 mmol/L or if anti-diabetic therapy was self-reported. Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg, diastolic blood pressure (DBP) ≥ 90 mmHg, or a history of antihypertensive therapy. eGFR was calculated using CKD-EPI 2009 equation: estimated GFR = 175 × standardized Scr − 1.154 × age − 0.203 × 1.212 [if black] × 0.742 [if female] [20, 21]. This study used ‘impaired kidney function’ to refer to individuals with a baseline estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m².
Pancreatic and liver CT attenuation assessment
CT attenuation of the pancreas and liver was measured on chest CT images. The CT scan parameters were as follows: voltage 120 kV, tube current 100–120 mAs, section thickness 0.625 mm. Two 0.5 cm² regions of interest (ROIs) were placed at the body and tail of the pancreas at the level of the mid-T12 vertebra, and the average value was defined as the pancreatic CT attenuation. Similarly, liver CT attenuation, spleen CT attenuation, and the pancreas-to-spleen CT attenuation ratio (P/S ratio) were calculated.
Statistical analysis
All statistical analyses were conducted using R (version 4.3.0) and SPSS (version 26.0). The normality of data distribution was assessed using Kolmogorov–Smirnov test. Normally distributed data are presented as mean ± standard deviation (SD), non-normally distributed data as median (interquartile range), and categorical variables as number (percentage). Independent samples t-tests were used for normally distributed data, Mann-Whitney U tests for non-normally distributed data, and chi-square/Fisher’s exact tests for categorical variables. Pancreatic CT attenuation and P/S ratio were categorized into quartiles: pancreatic CT attenuation—Q1 < 43.2, Q2 43.2–46.9, Q3 46.9–50.2, Q4 > 50.2; P/S ratio—Q1 < 0.87, Q2 0.87–0.95, Q3 0.95–1.03, Q4 > 1.03. Multivariable logistic regression and restricted cubic splines were used to analyze the relationship between pancreatic CT attenuation (or P/S ratio) and impaired renal function risk. Two models were constructed: Model 1 adjusted for age, sex, and BMI; Model 2 further adjusted for liver function, diabetes, uric acid, blood pressure, high-density lipoprotein cholesterol, and liver CT attenuation (fully adjusted model). Multicollinearity was evaluated by the variance inflation factors (VIF) for all independent variables, and all values were below the commonly accepted threshold of 5, indicating no severe multicollinearity concerns. The linearity assumption for continuous variables was assessed by visually examining residual plots, which revealed no obvious deviations from linearity. Subgroup analyses were performed in non-diabetic, non-hypertensive, and high liver CT attenuation (> 45 HU) groups. Hosmer-Lemeshow tests were performed to check the goodness of fit. The predictive efficacy of pancreatic CT attenuation and P/S ratio for impaired renal function was assessed using ROC curves. A p-value < 0.05 was considered statistically significant.
Results
Baseline characteristics
Table 1 presents the demographic and clinical characteristics of the participants. The study included 232 individuals with impaired renal function and 9,200 non-impaired renal function controls. The mean age in the impaired renal function group was 68.72 ± 16.89 years, with 138 males (59.5%); the non-impaired renal function group had a mean age of 51.34 ± 15.23 years and included 5,593 males (60.8%). The impaired renal function group included 27 diabetic participants, compared with 563 in the control group.
Table 1.
Characteristics of the subjects divided by renal function
| Overall | None-impaired renal function (n = 9200) | Impaired renal function (n = 232) | P | |
|---|---|---|---|---|
| Age (years) | 51.55 ± 15.37 | 51.34 ± 15.23 | 68.72 ± 16.89 | < 0.001 |
| Sex (men) | 5731 | 5593 | 138 | 0.69 |
| BMI (kg/m2) | 24.49 ± 1.94 | 25.54 ± 2.98 | 25.92 ± 3.11 | 0.04 |
| Pancreatic CT attenuation (HU) | 46.15 ± 6.44 | 46.20 ± 6.40 | 42.57 ± 8.10 | < 0.001 |
| P/S ratio | 0.94 ± 0.14 | 0.94 ± 0.19 | 0.87 ± 0.17 | < 0.001 |
| Liver CT attenuation (HU) | 54.97 ± 9.08 | 54.96 ± 9.08 | 54.81 ± 7.20 | 0.86 |
| L/S ratio | 54.97 ± 9.08 | 0.94 ± 0.19 | 0.87 ± 0.17 | < 0.001 |
| Creatinine (mmol/L) | 75.49 ± 16.60 | 74.68 ± 14.62 | 139.76 ± 31.54 | < 0.001 |
| Uric acid (mmol/L) | 334.78 ± 93.9 | 332.81 ± 92.85 | 441.10 ± 98.95 | < 0.001 |
| AST (U/L) | 24.31 ± 11.42 | 24.32 ± 13.75 | 23.90 ± 9.73 | 0.86 |
| Blood glucose (mmol/L) | 5.33 ± 1.31 | 5.32 ± 1.30 | 6.00 ± 2.11 | < 0.001 |
| HDL-c (mmol/L) | 1.51 ± 0.35 | 1.51 ± 0.0.35 | 1.39 ± 0.37 | < 0.001 |
| LDL-c (mmol/L) | 2.95 ± 0.81 | 2.96 ± 0.81 | 2.76 ± 0.91 | 0.01 |
| TC (mmol/L) | 4.67 ± 0.97 | 4.68 ± 0.97 | 4.48 ± 1.11 | 0.04 |
| TG (mmol/L) | 1.55 ± 1.31 | 1.55 ± 1.31 | 1.78 ± 1.43 | 0.07 |
| SBP (mmHg) | 129.5 ± 16.59 | 129.5 ± 16.56 | 138.0 ± 16.24 | < 0.001 |
| DBP (mmHg) | 76.5 ± 13.19 | 76.37 ± 13.16 | 89.08 ± 13.60 | < 0.001 |
| Diabetes | 590 | 563 | 27 | < 0.001 |
AST: aspartate aminotransferase; BMI: body mass index; CKD: chronic kidney disease; CT: computed tomography; DBP: diastolic blood pressure; HDL-c: high-density lipoprotein cholesterol; HU: Hounsfield unit; LDL-c: low-density lipoprotein cholesterol; P/S: pancreas/liver CT ratio; SBP: systolic blood pressure; TC: total cholesterol; TG: triglyceride
Statistically significant differences were observed between the impaired renal function and non-impaired renal function groups in BMI (25.92 ± 3.11 vs. 25.54 ± 2.98 kg/m², P = 0.04), pancreatic CT attenuation (42.57 ± 8.10 vs. 46.20 ± 6.40 HU, P < 0.001), P/S ratio (0.87 ± 0.17 vs. 0.94 ± 0.19, P < 0.001), L/S ratio (0.87 ± 0.17 vs. 0.94 ± 0.19, P < 0.001), serum creatinine (139.76 ± 31.54 vs. 74.68 ± 14.62 mmol/L, P < 0.001), uric acid (441.10 ± 98.95 vs. 332.81 ± 92.85 mmol/L, P < 0.001), blood glucose (6.00 ± 2.11 vs. 5.32 ± 1.30 mmol/L, P < 0.001), HDL-c (1.39 ± 0.37 vs. 1.51 ± 0.35 mmol/L, P < 0.001), LDL-c (2.76 ± 0.91 vs. 2.96 ± 0.81 mmol/L, P = 0.01), TC (4.48 ± 1.11 vs. 4.68 ± 0.97 mmol/L, P = 0.04), SBP (138.0 ± 16.24 vs. 129.5 ± 16.56 mmHg, P < 0.001), and DBP (89.08 ± 13.60 vs. 76.37 ± 13.16 mmHg, P < 0.001).
The prevalence of impaired renal function across interquartile ranges (IQRs) of pancreatic CT attenuation (PanCT) and P/S ratio is shown in Fig. 1. Impaired renal function prevalence consistently declined from Q1 to Q4 for both indices (p for trend < 0.001) in the total population (Fig. 1A). A similar significant downward trend was observed in individuals older than 60 years (Fig. 1B, p for trend < 0.01), despite minor fluctuation in the P/S ratio at Q3, collectively supporting a positive correlation between pancreatic fat deposition and impaired renal function risk.
Fig. 1.
The prevalence of impaired renal function across IQRs of pancreatic CT attenuation (PanCT) and P/S ratio in total population (A) and participants aged over 60 years (B)
Association between the pancreatic CT attenuation or P/S ratio and the risk o f impaired renal function
We first investigated the association between pancreatic CT attenuation or P/S ratio and impaired renal function risk (Table 2). Higher pancreatic CT attenuation (third and fourth quartiles) was associated with a reduced risk of impaired renal function (Q3: OR = 0.53, 95% CI: 0.28–0.99; Q4: OR = 0.52, 95% CI: 0.27–0.99) compared with the lowest quartile, after adjusting for age, sex, BMI, liver function, diabetes, uric acid, blood pressure, high-density lipoprotein cholesterol, and liver CT attenuation. A similar trend was observed for the P/S ratio (Q4: OR = 0.46, 95% CI: 0.23–0.90). Restricted cubic splines further revealed that CKD risk decreased with increasing pancreatic CT attenuation (Fig. 2A) and P/S ratio (Fig. 2B) after adjustment for confounders. Hosmer-Lemeshow tests showed the models had excellent goodness of fit (P > 0.05).
Table 2.
Association between the pancreatic CT Attenuation or P/S ratio and the risk of impaired renal function
| Model 1 | p | Model 2 | p | |
|---|---|---|---|---|
| OR (95%CI) | OR (95%CI) | |||
| Pancreatic CT attenuation(continuous) | 0.97 (0.95-1.00) | 0.02 | 0.97 (0.95-1.00) | 0.03 |
| Q1 (< 43.2) | 1 | 1 | ||
| Q2 (43.2–46.9) | 0.77 (0.48–1.24) | 0.29 | 0.73 (0.44–1.20) | 0.22 |
| Q3 (46.9–50.2) | 0.51 (0.28–0.93) | 0.03 | 0.53 (0.28–0.99) | 0.047 |
| Q4 (> 50.2) | 0.52 (0.28–0.98) | 0.04 | 0.52 (0.27–0.99) | 0.047 |
| P/S ratio (continuous) | 0.31 (0.10–0.91) | 0.03 | 0.28 (0.09–0.89) | 0.03 |
| Q1 (< 0.87) | 1 | 1 | ||
| Q2 (0.87–0.95) | 0.94 (0.58–1.53) | 0.82 | 0.97(0.59–1.62) | 0.92 |
| Q3 (0.95–1.03) | 0.69 (0.40–1.18) | 0.18 | 0.72 (0.40–1.27) | 0.25 |
| Q4 (> 1.03) | 0.45 (0.24–0.86) | 0.02 | 0.46 (0.23–0.90) | 0.02 |
Model 1 was adjusted for age, sex and body mass index; Model 2 was further adjusted for liver function, diabetes, uric acid, blood pressure, high-density lipoprotein cholesterol and liver liver fat deposition
CI: confidence interval; HDL: high-density lipoprotein cholesterol; OR: odds ratio; P/S: pancreas/liver CT ratio
Fig. 2.
Restricted cubic splines show the association between the pancreatic CT attenuation or pancreas-to-spleen CT attenuation (P/S) ratio and the risk of impaired renal function
Subgroup analyses to show the association between the pancreatic CT attenuation or P/S ratio and the risk of impaired renal function
Stratified analyses of non-diabetic, non-hypertensive, and high liver CT attenuation (> 45 HU) subgroups further demonstrated the association between pancreatic CT attenuation (or P/S ratio) and impaired renal function risk (Table 3). Significant inverse associations were observed across all subgroups after adjusting for potential confounders. In the non-diabetic cohort, each 1-HU increase in pancreatic CT attenuation reduced impaired renal function risk by 3% (OR = 0.97, 95% CI: 0.94–0.99), with the fourth quartile showing a 52% lower risk (OR = 0.48, 95% CI: 0.24–0.98). Similarly, the fourth P/S ratio quartile reduced impaired renal function risk by 54% (OR = 0.46, 95% CI: 0.22–0.94). These trends persisted in non-hypertensive individuals (fourth CT quartile: OR = 0.42, 95% CI: 0.20–0.90; fourth P/S quartile: OR = 0.46, 95% CI: 0.21–0.99) and were strengthened in those with high liver CT attenuation (fourth CT quartile: OR = 0.42, 95% CI: 0.21–0.85; fourth P/S quartile: OR = 0.47, 95% CI: 0.24–0.95). Threshold effects emerged at > 46.9 HU (CT-Q3) and > 1.03 (P/S-Q4), with non-significant trends in lower quartiles (P > 0.05). Hosmer-Lemeshow tests showed the models had excellent goodness of fit (P > 0.05).
Table 3.
Subgroup analyses to show the association between the pancreatic CT Attenuation or P/S ratio and the risk of impaired renal function
| Model 1 | P | Model 2 | p | ||
|---|---|---|---|---|---|
| OR (95%CI) | OR (95%CI) | ||||
| None-diabetes | Pancreatic CT attenuation(continuous) | 0.97 (0.95–0.99) | 0.02 | 0.97 (0.94–0.99) | 0.01 |
| Q1 (< 43.2) | 1 | 1 | |||
| Q2 (43.2–46.9) | 0.83 (0.50–1.37) | 0.29 | 0.75 (0.44–1.28) | 0.30 | |
| Q3 (46.9–50.2) | 0.49 (0.26–0.95) | 0.03 | 0.48 (0.24–0.95) | 0.034 | |
| Q4 (> 50.2) | 0.51 (0.26-1.00) | 0.05 | 0.48 (0.24–0.98) | 0.044 | |
| P/S ratio (continuous) | 0.27 (0.08–0.86) | 0.03 | 0.26 (0.08–0.93) | 0.038 | |
| Q1 (< 0.87) | 1 | 1 | |||
| Q2 (0.87–0.95) | 0.96 (0.57–1.62) | 0.89 | 1.02 (0.60–1.75) | 0.92 | |
| Q3 (0.95–1.03) | 0.66 (0.37–1.18) | 0.16 | 0.70 (0.38–1.28) | 0.25 | |
| Q4 (> 1.03) | 0.42 (0.21–0.84) | 0.02 | 0.46 (0.22–0.94) | 0.03 | |
| None-hypertension | Pancreatic CT attenuation(continuous) | 0.97 (0.95–0.99) | 0.04 | 0.97 (0.94–0.99) | 0.04 |
| Q1 (< 43.2) | 1 | 1 | |||
| Q2 (43.2–46.9) | 0.79 (0.47–1.34) | 0.38 | 0.72 (0.41–1.26) | 0.25 | |
| Q3 (46.9–50.2) | 0.47 (0.24–0.94) | 0.03 | 0.49 (0.24-1.00) | 0.048 | |
| Q4 (> 50.2) | 0.48 (0.23–0.98) | 0.044 | 0.42 (0.20–0.90) | 0.026 | |
| P/S ratio (continuous) | 0.30 (0.08–1.04) | 0.052 | 0.26 (0.08–0.93) | 0.038 | |
| Q1 (< 0.87) | 1 | 1 | |||
| Q2 (0.87–0.95) | 0.88 (0.51–1.53) | 0.66 | 0.98 (0.55–1.74) | 0.95 | |
| Q3 (0.95–1.03) | 0.69 (0.38–1.25) | 0.22 | 0.70 (0.37–1.32) | 0.27 | |
| Q4 (> 1.03) | 0.41 (0.20–0.87) | 0.02 | 0.46 (0.21–0.99) | 0.047 | |
| Liver CT attenuation > 45HU | Pancreatic CT attenuation(continuous) | 0.97 (0.95–0.99) | < 0.01 | 0.96 (0.94–0.99) | < 0.01 |
| Q1 (< 43.2) | 1 | 1 | |||
| Q2 (43.2–46.9) | 0.66 (0.40–1.09) | 0.10 | 0.62 (0.36–1.06) | 0.08 | |
| Q3 (46.9–50.2) | 0.48 (0.25–0.90) | 0.02 | 0.49 (0.25–0.95) | 0.034 | |
| Q4 (> 50.2) | 0.45 (0.23–0.88) | 0.02 | 0.42 (0.21–0.85) | 0.016 | |
| P/S ratio (continuous) | 0.27 (0.08–0.86) | 0.03 | 0.24 (0.07–0.82) | 0.023 | |
| Q1 (< 0.87) | 1 | 1 | |||
| Q2 (0.87–0.95) | 0.88 (0.53–1.46) | 0.62 | 0.91 (0.53–1.55) | 0.72 | |
| Q3 (0.95–1.03) | 0.64 (0.36–1.13) | 0.12 | 0.70 (0.38–1.27) | 0.24 | |
| Q4 (> 1.03) | 0.42 (0.21–0.82) | 0.01 | 0.47 (0.24–0.95) | 0.04 |
Model 1 was adjusted for age, sex and body mass index; Model 2 was further adjusted for liver function, blood pressure, diabetes, uric acid, high-density lipoprotein cholesterol and liver fat deposition
CI: confidence interval; HDL: high-density lipoprotein cholesterol; OR: odds ratio; P/S: pancreas/liver CT ratio
ROC analyses
ROC analysis evaluated the performance of pancreatic CT attenuation and P/S ratio in predicting impaired renal function (Fig. 3). The areas under the curves were 0.620 for pancreatic CT attenuation and 0.597 for P/S ratio.
Fig. 3.
Receiver operating characteristic (ROC) curve showing the performance of the pancreatic CT attenuation (PanCT) and pancreas-to-spleen CT attenuation (P/S) ratio in predicting impaired renal function
Discussion
Intrapancreatic fat deposition has gained great attention in recent years. Some studies have shown its role in diabetes, pancreatic cancer and cardiovascular disease [19, 22–24]. This study explored the association between intrapancreatic fat deposition and the risk of impaired renal function in a large Chinese population. The key findings revealed that higher pancreatic CT attenuation (indicating less intrapancreatic fat) was independently associated with a lower risk of impaired renal function—after adjusting for confounding factors. A similar inverse association was observed for the P/S ratio, with Q4 showing an OR of 0.46 (95% CI: 0.23–0.90) for impaired renal function. Moreover, subgroup analyses further confirmed these trends in non-diabetic, non-hypertensive, and participants with high liver CT attenuation). ROC analysis also supported the potential of these two indices for impaired renal function risk stratification. These results provide novel insights into the role of intrapancreatic fat in impaired renal function pathogenesis and risk assessment.
To date, most studies on fat deposition and CKD have focused on visceral adipose tissue or MAFLD. For example, Gao et al. [25] demonstrated that MAFLD severity correlates with CKD incidence and Wei et al. [26] reported that MAFLD significantly increases CKD risk in adults with type 2 diabetes which was consistent with the well-established “liver-kidney crosstalk” involving insulin resistance, inflammation, and lipid disorders [14, 27]. However, the role of intrapancreatic fat deposition in impaired renal function has remained understudied, despite growing evidence showed that pancreatic fat is a key mediator of metabolic dysfunction.
Petrov and Taylor [11] emphasized that intra-pancreatic fat (pancreatic steatosis) is strongly associated with insulin resistance, β-cell dysfunction, and type 2 diabetes mellitus, which are known risk factors for CKD [28, 29]. Our findings extend this work by establishing a direct association between intrapancreatic fat and impaired renal function risk, independently of conventional confounding factors. Notably, previous research has primarily focused on pancreatic fat and diabetes [18], but our subgroup analysis in non-diabetic participants (OR = 0.97 per 1-HU increase in pancreatic CT attenuation, 95% CI: 0.94–0.99) suggests that intrapancreatic fat may affect impaired renal function through pathways beyond hyperglycemia. This result is consistent with previous studies, which emphasized that inflammation, rather than just glycemia, drives CKD progression [30] and body fat percentage correlates with systemic inflammation and renal dysfunction [31]. ROC analysis also showed some value of pancreatic CT attenuation and P/S ratio in identifying impaired renal function. However, predictive performance is limited. Our research encompasses opportunistic screening via routine CT scans, metabolic risk stratification in health-check cohorts, and the comprehensive assessment of ectopic fat in individuals with diabetes, obesity, or hypertension.
The association between pancreatic fat and renal function is complex and likely involves multiple mechanisms. In addition to systemic inflammation and insulin resistance, ectopic fat in the pancreas may contribute to lipotoxicity, oxidative stress, and altered adipokine profiles, all of which can impair renal function. Experimental studies have shown that pancreatic steatosis is associated with increased production of pro-inflammatory cytokines such as IL-6 and TNF-α [22, 32], which are known to promote renal fibrosis and dysfunction. Moreover, pancreatic steatosis has been linked to dysregulated autophagy and mitochondrial dysfunction, which are also implicated in CKD pathogenesis [33, 34]. Future studies should explore these mechanistic pathways in more detail, possibly using longitudinal designs and incorporating measures of pancreatic fat dynamics over time.
There may be several reason for the relatively low prevalence of impaired renal function (2.5%) in our population. First, those patients with end stage of renal disease were excluded. Second, our study was performed in a health-screening population which may cause selection bias. Third, we only defined impaired renal function based on eGFR, not including CKD defined by albuminuria (urine albumin-to-creatinine ratio of ≥ 30 mg/g). A recent study in China showed the prevalence of eGFR based CKD was 2.2%20 which was consistent with our results. Moreover, it is possible that our defined cohort with “impaired renal function” may include some individuals who were actually in a state of acute kidney injury (AKI). AKI may have clinical symptoms, such as acute oliguria or anuria, azotemia and water and electrolyte imbalances. Such symptoms were not reported in our subjects. Although we cannot totally rule out AKI, its prevalence in our cohort may be very low.
This study has several limitations. First, it was conducted at a single center using a clinical database, which may limit generalizability to other Chinese populations or global cohorts. Due to the retrospective cross-sectional study design, we could not establish a causal relationship or determine the temporal sequence between pancreatic fat and impaired renal function onset. Second, pancreatic CT attenuation is a surrogate for fat content but is less precise than magnetic resonance imaging proton density fat fraction. Third, several unmeasured variables may have influence on the results, such as dietary fructose intake, physical activity levels, and the use of specific medications including statins or SGLT2 inhibitors. For example, fructose intake is known to exacerbate both pancreatic fat accumulation and chronic kidney disease [27], yet it was not quantified in this study. Fourth, without follow-up data, we only showed the impaired kidney function which may include individuals with transient reductions in kidney function. This may lead to misclassification (typically an overestimation) of the true CKD prevalence. We also cannot confirm whether intrapancreatic fat predicts incident impaired renal function or merely correlates with pre-existing renal damage. Moreover, the absence of impaired renal function staging also restricts the interpretation of underlying mechanisms. Finally, our analyses did not include any internal or external validations which may raises the risk of overfitting and limit generalizability.
In conclusion, this study demonstrated that intrapancreatic fat deposition is independently associated with an increased risk of impaired renal function. A low pancreatic CT attenuation or high intrapancreatic fat deposition should be considered an important associated factor for impaired renal function. In clinical practice, the evaluation and management of this indicator may be valuable for impaired renal function management and may be emphasized to prevent adverse outcomes.
Acknowledgements
None.
Author contributions
XC participated in the design of the study. YP, DZ, XC, HZ and XC wrote the manuscript. YP, DZ, XC, HZ, RY and JW collected and analyzed the data. YP, DZ, XC, HZ, RY, JW and XC contributed to the interpretation of the data and the preparation of the manuscript. All the authors have read and approved the final manuscript.
Funding
The Medical Development and Medical Assistance Foundation of Jiangsu Province Hospital of Chinese Medicine (Y22030).
Data availability
Data available on request from authors.
Declarations
Ethics approval and consent to participate
Ethics approval was obtained from the Affiliated Hospital of Nanjing University of Chinese Medicine. The study was performed in accordance with the Declaration of Helsinki. The need for informed consent was waived by the Ethics Committee of the Affiliated Hospital of Nanjing University of Chinese Medicine because of the retrospective nature of the study.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Dingzhe Zhang and Yiping Zhang contributed equally to this work.
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Data Availability Statement
Data available on request from authors.