OBJECTIVE: Podocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN).
METHODS: We collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed.
RESULTS: Mean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017).
CONCLUSIONS: Podocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

UNASSIGNED: To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN).
UNASSIGNED: We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye.
UNASSIGNED: The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients.
UNASSIGNED: Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.

BACKGROUND: The prevalence of type 2 diabetic nephropathy (T2DN) ranges from 20 % to 40 % among individuals with type 2 diabetes. Multiple immune pathways play a pivotal role in the pathogenesis of T2DN. This study aimed to investigate the immunomodulatory effects of active ingredients derived from 14 traditional Chinese medicines (TCMs) on T2DN.
METHODS: By removing batch effect on the GSE30528 and GSE96804 datasets, we employed a combination of weighted gene co-expression network analysis, least absolute shrinkage and selection operator analysis, protein-protein interaction network analysis, and the CIBERSORT algorithm to identify the active ingredients of TCMs as well as potential hub biomarkers associated with immune cells. Functional analysis was conducted using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and gene set variation analysis (GSVA). Additionally, molecular docking was employed to evaluate interactions between active ingredients and potential immunotherapy targets.
RESULTS: A total of 638 differentially expressed genes (DEGs) were identified in this study, comprising 5 hub genes along with 4 potential biomarkers. Notably, CXCR1, CXCR2, and FOS exhibit significant associations with immune cells while displaying robust or favorable affinities towards the active ingredients kaempferol, quercetin, and luteolin. Furthermore, functional analysis unveiled intricate involvement of DEGs, hub genes and potential biomarkers in pathways closely linked to immunity and diabetes.
CONCLUSIONS: The potential hub biomarkers and immunotherapy targets associated with immune cells of T2DN comprise CXCR1, CXCR2, and FOS. Furthermore, kaempferol, quercetin, and luteolin demonstrate potential immunomodulatory effects in modulating T2DN through the regulation of CXCR1, CXCR2, and FOS expression.

BACKGROUND: Herba epimedium brevicornu maxim is traditionally known as a sexual enhancement, and has the effect of tonifying kidney yang. Icariin is a flavonoid extracted from epimedium brevicornu maxim, and has been shown to improve nephropathy disease.
OBJECTIVE: This study investigated the possible role of icariin in regulating renal EndMT in type 2 diabetic nephropathy (T2DN).
METHODS: Male type 2 diabetic Sprague Dawley rats, Male D2.BKS(D)-Leprdb/J (db/db) mice, and mouse glomerular endothelial cells were utilized to evaluate the effect of icariin. Western blotting, Q-PCR, immunohistochemistry, H&E, Masson staining, immunofluorescence, and siRNA transfection, were performed in this study.
RESULTS: The inhibitory function of icariin in renal fibrosis and renal EndMT was verified in type 2 diabetic animals. Methyltestosterone suppressed renal fibrosis and EndMT in db/db mice. Androgen receptor (AR), the major receptor of testosterone, was upregulated by icariin. The AR antagonist MDV3100, blocked the inhibition by icariin in renal EndMT, revealing that icariin repressed renal EndMT by activating AR. In addition, icariin and methyltestosterone upregulated the Raf kinase inhibitor protein (RKIP) in db/db mice. Furthermore, siRNA-RKIP inhibited the effect of icariin on EndMT. The MEK/ERK pathway, as the downstream pathway of RKIP, was suppressed by icariin and methyltestosterone. Of note, the effect of icariin on the MEK/ERK pathway was abolished by MDV3100 or siRNA-RKIP.
CONCLUSIONS: These results supported that icariin targeted AR/RKIP/MEK/ERK pathway to suppress renal fibrosis and EndMT in T2DN.

UNASSIGNED: Dietary soy protein (SP) is a potential intervention for protecting the kidneys and improving glucose and lipid metabolism. However, whether this effect is related to the percentage of SP intake remains unclear.
UNASSIGNED: This study aims to review and analyze the results of randomized clinical trials (RCTs) in patients with type 2 diabetic nephropathy (T2DN) who received diets with different percentages of SP.
UNASSIGNED: The databases: PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), WanFang, Weipu (VIP), and ClinicalTrials.gov were searched until February 2023, for RCTs on T2DN and SP.
UNASSIGNED: A total of six studies comprising 116 participants were included. The interventions were classified as 0% SP, 35% SP, and 100% SP. To improve serum creatinine (Scr), blood urea nitrogen (BUN), 24-h urine total protein (24hUTP), and glomerular filtration rate (GFR), a 35% SP diet was the most effective, compared to a 0% SP diet, which showed a mean difference of -154.00 (95% confidence interval: -266.69, -41.31) for 24hUTP. Although it had significant benefits for 24hUTP, great heterogeneity was observed. To improve the glycolipid metabolism-related markers such as cholesterol (CHO), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FPG), and weight, the 35% SP diet demonstrated superior efficacy compared to the 0% SP diet. Specifically, the mean difference for CHO was -0.55 (95% confidence interval: -1.08, -0.03), and for LDL-C, it was -17.71 (95% confidence interval: -39.67, -4.24). The other indicators were not statistically significant. Most studies had concerns regarding the risk of bias.
UNASSIGNED: The findings of this study demonstrate that both 35% and 100% SP diets are more effective than a diet with no SP in improving renal function and glucolipid metabolism in patients with T2DN. As a result, a diet incorporating 35% SP may be the optimal choice for individuals with T2DN.
UNASSIGNED: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=352638, identifier CRD42022352638.

OBJECTIVE: The influencing factors of quality of life (QOL) in patients with type 2 diabetic nephropathy (T2DN) were explored, a practical risk prediction model was constructed and independent verification was conducted.
METHODS: The clinical data of 273 patients with T2DN in Tai\'an Maternal and Child Health Care Center from February 2021 to February 2023 were used for retrospective analysis, and the patients were divided into modelling group (n = 173) and validation group (n = 100). According to 36-item short form health survey (SF-36) scores, the research subjects in the modelling group were divided further into poor group (n = 78) and good group (n = 95). Multivariate logistic regression was used in analysing the influencing factors of QOL and establishing a clinical prediction model based on the results. Then, a receiver operating characteristic (ROC) curve was used in evaluating the model\'s prediction efficiency.
RESULTS: Remarkable differences in age, duration of diabetes, presence or absence of hypertension, education level, exercise frequency and family monthly income were found among the patients (p < 0.001). Multivariate logistic regression analysis suggested age ≥60 (odds ratio (OR) = 3.395, 95% CI = 1.269-9.083), duration of diabetes ≥3 years (OR = 4.574, 95% CI = 1.623-12.885), presence of hypertension (OR = 4.011, 95% CI = 1.490-10.796), education level of junior high school and below (OR = 7.318, 95% CI = 3.648-14.678), no or little exercise (OR = 3.948, 95% CI = 1.989-7.839) and family monthly income <3500 yuan (OR = 2.871, 95% CI = 1.089-7.573) are risk factors for poor QOL (p < 0.05). The regression model was logit (p) = -5.412 + 1.222X1 + 1.520X2 + 1.389X3 + 1.990X4 + 1.373X5 + 1.055X6 (X1 as age ≥60, X2 as duration of diabetes ≥3 years, X3 as presence of hypertension, X4 as education level of below junior high school, X5 as no or little exercise and X6 as family monthly income <3500 yuan). Based on this model, the ROC curve showed that the AUC value, standard error and 95% CI were 0.842, 0.043 and 0.758-0.926, respectively. An analysis was made on the re-included 100 patients, and the predictive sensitivity, specificity and Kappa coefficient of the constructed model were 82.10%, 86.90% and 0.703.
CONCLUSIONS: Age ≥60, duration of diabetes ≥3 years, presence of hypertension, education level of junior high school and below, no or little exercise and family monthly income <3500 yuan were independent influencing factors for poor QOL in patients with T2DN. The use of this model has certain clinical application value.

BACKGROUND: The objective was to observe the expression of miR-23a-3p in the serum of patients with type 2 diabetic nephropathy (T2DN) and to explore its clinical significance.
METHODS: 112 patients with type 2 diabetes were divided into a simple diabetes mellitus (NON) group, T2DN microalbuminuria (MIC) group, and T2DN macroalbuminuria (MAC) group, according to the urinary protein-creatinine ratio (uACR). Clinical data were collected, miR-23a-3p levels in serum were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR), and clinical parameters were measured by an automatic biochemical analyser; the influencing factors of diabetic kidney disease (DKD) and the correlation between miR-23a-3p expression and clinical parameters were analysed.
RESULTS: The expression of miR-23a-3p in the serum of the DKD group was lower than that of the normal control (CON) and NON groups. Correlation analysis showed that miR-23a-3p was positively correlated with urinary albumin (Albu), glycosylated haemoglobin (HbA1c), total cholesterol (CHOL), glycated albumin (GA-L), serum creatinine (Scr), fasting blood glucose (GLU), and uric acid (UA), negatively correlated with uACR and high-density lipoprotein cholesterol (HDL-C), but not correlated with urinary creatinine (CREA). The area under the receiver operating characteristic (ROC) curve (AUC) of miR-23a-3p for the diagnosis of DKD was 0.686 [95% confidence interval (CI): 0.599-0.773], with a sensitivity of 64.5% and a specificity of 71.2%; the AUC for differentiating NON from DKD was 0.700 (95% CI: 0.598-0.802), with a sensitivity of 61.8% and a specificity of 77.8%. Multivariate logistic regression analysis showed that serum miR-23a-3p levels were not associated with the development of DKD after adjusting for other levels of influence and were not significant for the differentiation of NON and DKD.
CONCLUSIONS: Serum miR-23a-3p levels are decreased in T2DN patients, and this change becomes more significant with the severity of the disease, which may be a marker for the early diagnosis and progression of T2DN.

BACKGROUND: Type 2 diabetic nephropathy is a common diabetic complication and the main cause of death in patients with diabetes. Research has aimed to find an ideal drug with minimal side effects for treating this disease. Banana peel has been shown to be anti-diabetic, with lupenone isolated from banana peel exhibiting antidiabetic and anti-inflammatory activities; However, the effects of lupenone on type 2 diabetic nephropathy are largely unknown.
OBJECTIVE: This study aimed to investigate the ameliorative effect of lupenone on type 2 diabetic nephropathy, and its mechanism from both anti-inflammatory and anti-fibrotic perspectives.
METHODS: Spontaneous type 2 diabetic nephropathy db/db mouse models were given three levels of lupenone (24 or 12 or 6 mg/kg/d) via intragastric administration for six weeks, and irbesartan treatment was used for the positive control group. We explored the effects and mechanism of lupenone action using enzyme-linked immunosorbent assay, automatic biochemical analyzer, hematoxylin-eosin and Masson staining, real time-PCR, and western blotting. Concurrently, a high-sugar and high-fat diet combined with a low-dose streptozotocin-induced type 2 diabetic nephropathy rat model was used for confirmatory research.
RESULTS: Lupenone administration maintained the fasting blood glucose; reduced glycosylated hemoglobin, insulin, and 24 h proteinuria levels; and markedly regulated changes in biochemical indicators associated with kidney injury in serum and urine (including 24 h proteinuria, micro-albumin, N-acetyl-β-d-glucosaminidase, α1-micro-globulin, creatinine, urea nitrogen, uric acid, total protein, and albumin) of type 2 diabetic nephropathy mice and rats. Hematoxylin-eosin and Masson staining as well as molecular biology tests revealed that inflammation and fibrosis are the two key processes affected by lupenone treatment. Lupenone protected type 2 diabetic nephropathy kidneys by regulating the NF-κB-mediated inflammatory response and TGF-β1/Smad/CTGF pathway-associated fibrosis.
CONCLUSIONS: Lupenone has potential as an innovative drug for preventing and treating diabetic nephropathy. Additionally, it has great value for the utilization of banana peel resources.

OBJECTIVE: Type 2 diabetic Mellitus (T2DM) is the most common systemic and endocrine disease in humans, and diabetic nephropathy is one of the most serious complications of this disorder. The polymorphisms in the apolipoprotein A5 (ApoA5) gene are strongly related to hypertriglyceridemia and are considered a predisposing factor for diabetic nephropathy. The current study proposed to examine the association of APOA5-S19W polymorphism with serum lipids levels in patients with type 2 diabetic nephropathy in Mazandaran province.
METHODS: This case-control study was designed to determine the association of APOA5-S19W polymorphism with plasma lipid profile in 161 T2DM patients with nephropathy (DN+), without nephropathy (DN-), and in 58 healthy individuals. Lipid profile values were measured using Pars Azmoun commercial kits. S19W variant, one of the polymorphisms of the APOA5 gene, was determined by PCR-restriction fragment length polymorphism (PCR-RFLP) and Taq1 restriction enzyme.
RESULTS: In comparison between the three groups, DN+ had a higher mean TG than DN- and the control group (p<0.001). The incidence of the G allele in DN+ was not significant compared to groups of DN-. Comparing the relationship between the mean of biochemical variables with CC and CG genotypes showed that the mean level of TG in people with CC genotype was increased compared to people with CG genotype in diabetic patients. However, this increase was not significant (p=0.19).
CONCLUSIONS: There was no association between SNP APOA5 S19W and serum lipids in diabetic patients with and without nephropathy.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of type 1 and type 2 diabetes that can lead to kidney damage and high blood pressure. Increasing evidence support the important roles of microproteins and cytokines, such as β2-microglobulin (β2-MG), glycosylated hemoglobin (HbA1c), and vascular endothelial growth factor (VEGF), in the pathogenesis of this disease. In this study, we identified novel therapeutic options for this disease.
OBJECTIVE: To analyze the guiding significance of β2-MG, HbA1c, and VEGF levels in patients with DN.
METHODS: A total of 107 patients with type 2 diabetes mellitus complicated with nephropathy and treated in our hospital from May 2018 to February 2021 were included in the study. Additionally, 107 healthy individuals and 107 patients with simple diabetes mellitus were selected as the control groups. Changes in β2-MG, HbA1c, and VEGF levels in the three groups as well as the different proteinuria exhibited by the three groups were examined.
RESULTS: Changes in β2-MG, HbA1c, and VEGF levels in the disease, healthy, and simple diabetes groups were significantly different (P < 0.05). The expression of these factors from high to low were evaluated in different groups by pairwise comparison. In the disease group, high to low changes in β2-MG, HbA1c, and VEGF levels were noted in the massive proteinuria, microproteinuria, and normal urinary protein groups, respectively. Changes in these factors were positively correlated with disease progression.
CONCLUSIONS: The expression of serum β2-MG, HbA1c, and VEGF was closely correlated with DN progression, and disease progression could be evaluated by these factors.