Diabetic nephropathy (DKD) is a chronic disease that seriously affects the quality of life of patients. While the global prevalence of diabetes is increasing, the incidence of DKD is also increasing year by year [24]. And the rate is increasing. Age, poor blood sugar control, hypertension and hyperlipidemia are the main causes of DKD. Many diabetics with renal failure progress to uremia, which brings heavy burden to society and economy.Studies have shown that lead has an important effect on kidney damage, and long-term exposure to lead (Pb) can cause irreversible kidney damage [25]. The content of lead in kidney, pancreas and other tissues is significantly higher than that in other organs, which seriously affects the body's energy metabolism [26]. Lead (Pb) can induce hyperglycemia [27]. Lead can promote the release of pro-fibrotic factors such as TGF-β1 and VEGF by activating myofibroblasts [28], thus promoting fibroblast differentiation and the release of inflammatory factors. In addition, serum lead content was associated with conventional kidney injury such as ACR[29] and eGFR[30]. On the basis of previous work, this project intends to study the correlation between lead exposure and the development of DKD in Chinese population. Multivariate stepwise regression method was used to analyze the risk factors of diabetic nephropathy.
Our study showed from baseline data that many factors were associated with the progression of DKD.For example, age (13.30:12.89) (p-value < 0.001), marriage (549:275 for patients living with partner and 286:233 for patients living without partner) (p-value < 0.001), Education(576:290 for High school above and 259:218 for High school below) (p-value < 0.001),Urine.ALB (11.34:377.44) (p-value < 0.001), Serum.Crea (0.87:1.25) (p-value < 0.001), Hba1c (7.12:7.23) (p-value < 0.001), Glucose (7.92:8.90) (p-value < 0.001), Alkaline.phosphotase (73.10:80.06) (p-value < 0.001), HBP (295:121 for No and 540:387 for YES) (p-value < 0.001). blood.Lead(1.41:1.80) (p-value < 0.001), Both are risk factors for DKD progression.While other factors such as Gender(423:227 for female and 412:281 for male) (p-value = 0.039), ALT (27.01:23.94) (p-value = 0.004), AST(26.97:24.78) (p-value = 0.154) etc.were not correlated with the progression of DKD. To probe the relationship between serum lead and DKD, we formulated three multivariable glm regression models. Model 1(odds ratio (OR) = 1.35, 95% confidence iInterval (CI): 1.18–1.54, p-value < 0.0001;) adjusts for serum lead without any confounding factors. Model 2(OR = 1.18, 95% CI: 1.05–1.34, p-value = 0.0060) additionally adjusts for age, race, and gender based on Model 1. Finally, Model 3(OR = 1.39, 95% CI: 1.19–1.61, p-value < 0.0001) further adjusts for education, PIR, marital status, hypertension, BMI, urine lead, serum phosphate, serum calcium, serum iron, serum sodium, and serum potassium based on Model 2. Given that the p-values of all three models are less than 0.05, the correlation between serum lead and DKD remains uninfluenced by other factors. Our conclusions are consistent with previous studies, which have been reported Blood Pb (BPb) were positively associated with the risk of DKD among diabetic patients. Our conclusions are consistent with previous studies that reported a positive association between blood lead (BPb) and the risk of DKD in patients with diabetes. Our study found that elevated blood lead levels independently increased the risk of DKD progression. BPb and DKD have dose-effect and multiplier effect [31]. Previous studies have shown that blood lead can cause oxidative stress and inflammatory response of kidney cells, and is closely related to the occurrence and development of diabetic nephropathy [32].
It can also be seen from the forest map and the nomogram that bleeding lead, age, hypertension and blood potassium are all risk factors for DKD and promote the progression of DKD, while non-Hispanic, PIR and urinary lead are protective factors for DKD and can delay the progression of DKD. BPb has an important effect on renal function, and early low concentration BPb has an important effect on renal function, mainly affecting the progression of hypertension, nephropathy and renal failure [33], while lead can cause renal tubule injury [34]. Renal tubulointerstitial fibrosis, glomerular sclerosis, renal atherosclerosis, renal artery vitrification [35]. Age is a key factor in the development of diabetic nephropathy (DKD). A study on indicators of kidney injury, serum adiponectin and Leptin in elderly DKD patients showed that BPb could promote the occurrence and development of diabetic nephropathy [36]. Hypertension is related to the progression of DKD caused by BPb exposure. Pb can induce hypertension, increase oxidative stress, consume the antioxidant defense system, reduce the production of nitric oxide, and promote the progression of hypertension [37]. Pb-induced hypertension may be associated with decreased nitric oxide and consequent vasoconstriction, but not with decreased renal blood flow or decreased renal sodium [38]. Our results are consistent with the literature. Blood potassium level is a risk factor for the progression of DKD caused by BPb. Long-term lead exposure can lead to decreased kidney sodium potassium dependent phosphatase activity, decreased potassium excretion, and increased blood potassium mobilization [39]. Our study utilized stepwise multiple regression analysis to explore the correlation between exposure factors and DKD risk. Subsequently, three models were developed to sequentially adjust for other confounding risk factors. The results of these three multivariable glm regression models show that the level of serum PB was significantly correlated with DKD and it was a risk factor for DKD. Since the p-values of all three models were less than 0.05, the correlation between serum Pb and DKD was not affected by other factors The "rms" Receiver Operating Characteristic (ROC) curve was employed to assess the predictive capacity of the models, while decision curve analysis (DCA) was utilized to validate their net benefit and stability. Ultimately, our findings underscored the strong association between blood Pb levels and DKD risk, identifying them as independent risk factors for DKD.
This study investigated blood lead levels and their association with diabetic kidney disease (DKD). Analysis of data from the NHANES database revealed a significant correlation between blood lead levels and DKD, even after accounting for various covariates, indicating blood lead as a persistent risk factor for DKD. These findings, drawn from large-scale epidemiological data, shed light on the societal-level relationship between blood lead and DKD. Additionally, column-line charts were utilized to explore the potential clinical implications of these associations.Despite these valuable insights, the study has several limitations. Firstly, the data from the NHANES database rely on survey questionnaires, which may introduce recall bias, potentially affecting the accuracy and completeness of the data. Secondly, the representation of ethnic groups within the NHANES database is limited, thereby potentially constraining its ability to fully capture the characteristics and trends of the DKD population in our country.
This study determined that chronic elevated blood lead levels severely impair renal function in patients with DKD and are an independent risk factor for the development of DKD. These results provide an important contribution to understanding the relationship between blood lead levels and DKD. Future research and clinical practice should focus on assessing whether diabetic patients with elevated blood lead levels are at higher risk for DKD and implementing more effective treatment and intervention strategies accordingly.