Background: Ectopic fat deposition has been demonstrated to play a critical role in the onset and progression of renal dysfunction. However, research on renal parenchymal fat deposition and its association with renal dysfunction in type 2 diabetes mellitus (T2DM) remains limited, particularly regarding its association with early kidney injury. The present study aimed to further investigate the relationship between renal fat fraction (FF) and biomarkers of kidney injury, thereby providing new evidence for the potential link between intrarenal fat accumulation and early renal impairment in T2DM. Methods: This cross-sectional study enrolled 60 patients with T2DM. Renal FF was quantitatively assessed using magnetic resonance imaging (MRI). Clinical characteristics, body composition parameters, and biochemical indices were collected. Levels of kidney injury biomarkers, including tumor necrosis factor receptors 1 (TNF-R1), tumor necrosis factor receptors 2 (TNF-R2), chitinase-3-like protein 1 (YKL-40), and kidney injury molecule-1 (KIM-1), were measured using enzyme-linked immunosorbent assay (ELISA). To evaluate the correlations between fat distribution and inflammatory biomarkers, Pearson correlation analysis was performed. Furthermore, linear regression analysis was conducted to explore the associations between renal FF and kidney injury biomarkers with adjustments for potential confounders such as smoking status, diabetes duration, and visceral fat. Lasso regression was used to screen variables. Results: The results demonstrated that renal FF was significantly positively correlated with serum YKL-40 (r = 0.3, p = 0.021), TNF-R1 (r = 0.246, p = 0.042), and urinary KIM-1 (r = 0.396, p = 0.004), indicating a close association between renal fat accumulation and early kidney injury biomarkers. In regression analyses adjusted for age, sex, and duration of diabetes, the associations between renal FF and these biomarkers remained significant. After further adjustment for potential confounders, including smoking history, alcohol consumption, hypertension, renin-angiotensin-aldosterone system (RAAS) inhibitors, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, glucagon-Like Peptide-1 (GLP-1) receptor agonists, and lipid-lowering drugs, renal FF remained significantly associated with TNF-R1 (β = 0.327, p = 0.015), KIM-1 (β = 0.352, p = 0.021), and YKL-40 (β = 0.275, p = 0.025). Moreover, even after additional adjustment for visceral fat, the associations of renal FF with TNF-R1 and KIM-1 persisted. After using the Benjamini–Hochberg procedure for false discovery rate, the relationship between renal FF and KIM-1 had a significant difference. Variables of age and gender were excluded to build the parsimonious modeling using Lasso regression. It suggested that renal fat accumulation may contribute to kidney injury independently of visceral adiposity. Conclusions: The study systematically demonstrates a significant association between renal FF and early biomarkers of kidney injury in T2DM, which may suggest the potential role of renal fat accumulation in the pathogenesis of diabetic nephropathy. These findings provide clinical data support for the development of a fat-targeted intervention study. Future research should further elucidate the long-term mechanistic role of renal FF in diabetic nephropathy, as well as its potential value in early diagnosis and therapeutic applications.

Aims: This study aimed to examine the association between three-year changes in body mass index (BMI) and the risk of new-onset or progressive diabetic kidney disease (DKD) among people with type 2 diabetes and a normal BMI at baseline. Methods: A total of 416 people with type 2 diabetes (T2DM) and a normal BMI were enrolled from the Chongqing Diabetes Registry (CDR, NCT03692884) cohort and were followed for incident DKD until 2025. The change in BMI at the three-year follow-up was classified as follows: stable BMI (<5% change), decreased BMI (≥5% reduction), and increased BMI (≥5% gain). Cox proportional hazards models were used to analyze the association between BMI change categories and DKD risk. Results: During a mean follow-up of 3.4 years, people with an increased BMI exhibited a significantly higher risk of DKD onset or progression compared with people with a stable BMI [HR = 1.67, 95%CI: 1.15–2.43, p = 0.007]. Each 1% increase in BMI was significantly associated with an increased risk of DKD onset or progression [HR = 1.05, 95%CI: 1.02–1.07, p < 0.001]. This association remained significant after multivariable adjustment. Time-dependent receiver operating characteristic (ROC) curves showed that the area under the curve (AUC) of this indicator reached 0.683–0.729 for the prediction of new-onset or progressive DKD risk over 3–5 years. In subgroup analyses, decreased BMI was associated with a lower risk of DKD among people aged <60 years [HR = 0.21; 95% CI: 0.04–0.96; p = 0.044]. Conclusions: A ≥5% increase in BMI in three years may be a risk factor for new-onset or progressive DKD among people with T2DM and normal BMI. Conversely, a ≥5% decrease in BMI may be associated with renal protection in non-elderly individuals within the population.