Diabetic Nephropathy Patients Research Articles

Serum cell division cycle42 reflects the development and progression of diabetic nephropathy in patients with diabetes mellitus.

Cell division cycle 42 (CDC42) regulates podocyte apoptosis to take part in the development and progression of diabetic nephropathy (DN), but currently the clinical evidence is limited. The aim of the present study was to investigate the capability of serum CDC42 expression level to estimate the development and progression of DN in patients with diabetes mellitus (DM). Patients with type 2 DM (n=306) were enrolled and divided into normoalbuminuria (n=185), microalbuminuria (n=72) and macroalbuminuria (n=49) groups based on the urinary albumin-to-creatinine ratio. Serum CDC42 was measured in all subjects using enzyme-linked immunosorbent assay. The median (interquartile range) CDC42 in patients with DM was 0.461 (0.314-0.690) ng/ml (range, 0.087-1.728 ng/ml). CDC42 was positively associated with the estimated glomerular filtration rate (P<0.001), but negatively correlated with body mass index, systolic blood pressure, hemoglobin A1c, serum creatine, serum uric acid and C reactive protein (all P<0.050). CDC42 levels were lowest in the macroalbuminuria group, followed by the microalbuminuria group, and were highest in the normoalbuminuria group (P<0.001). CDC42 indicated that it was a favorable estimator for the presence of albuminuria [area under the curve (AUC), 0.792; 95% confidence interval (CI), 0.736-0.848] and macroalbuminuria (AUC, 0.845; 95% CI, 0.775-0.915). By analyses in four different multivariate logistic regression models, increased CDC42 was independently associated with the presence of microalbuminuria (all P<0.001), macroalbuminuria (most P<0.001) and microalbuminuria + macroalbuminuria (all P<0.001). Serum CDC42 level negatively correlated with microalbuminuria and macroalbuminuria in patients with DM, suggesting its ability for estimating the development and progression of DN.

Связь гена GSTP1 с функциональным состоянием почек у больных сахарным диабетом

Introduction of point genetic associations into clinical and laboratory diagnosis will allow the physician to determine the risk of severe diabetes mellitus and its complications with a focus on detection of the genetically determined disorder. The study was aimed to identify the molecular genetic markers of severe diabetic nephropathy in patients with type 1 and 2 diabetes mellitus (DM) based on the GSTP1 (I105V) gene assessment. Genotyping of the GSTP1 gene I105V locus was performed in patients with type 1 and 2 DM. Then we identified the features of oxidative status, free radical oxidation, and renal function in patients with various polymorphic variants of the studied gene. Patients with type 1 DM, who were carriers of the GSTP1 heterozygous polymorphic variant (Ile/Val), showed higher activity of the oxidative stress enzymes (glutathione-S-transferase, catalase) and malondialdehyde compared to homozygous carriers (р &lt; 0.001, р &lt; 0.001, р &lt; 0.05). They also showed a significant increase in the levels of triglycerides (1.6-fold) and the glycated hemoglobin levels (1.1-fold) (p &lt; 0.05). Patients with type 2 DM, who were carriers of the GSTP1 polymorphism homozygous for allele 2 (Val\Val), had a higher level of malondialdehyde (100.5 µmol/L, (р &lt; 0.001)), which was associated with the more severe diabetic nephropathy (average glomerular filtration rate — 48 mL/min/1.73 m2, 24-h urinary albumin excretion — 0.9 g/L; р &lt; 0.01). It has been proposed to assess the GSTP1 (I105V) gene in individuals with type 1 and 2 DM. This polymorphism that is heterozygous in individuals with type 1 DM and homozygous for allele 2 in individuals with type 2 DM is unfavorable in terms of the DM course and complications.

Evaluation of microalbuminuria in type-2 diabetes mellitus under oral hypoglycemic agents: Association with age, sex, BMI, and renal clearance.

Diabetes mellitus (DM) is increasing drastically and affecting the individuals globally, especially in the low- and middle-income countries like India. The poor glycaemic control results in micro-vascular and macro-vascular complications, leading to dysfunction of multiple organs. This study aimed to evaluate the association between the risk factors and microalbuminuria levels among patients with type 2 DM on oral hypoglycaemic agents. Hundred type 2 DM patients fulfilling the inclusion and exclusion criteria were selected by convenient random sampling. Demographic details, biochemical markers, and anti-diabetic medication details were collected. The findings were analyzed statistically using Chi-square test and one-way analysis of variance (ANOVA) with SPSS software 21.0. Among the different combination therapies, 59% were commonly using metformin and teneligliptin. There was a significant association noted between microalbuminuria and risk factors like age, duration of disease, body mass index (BMI) (25.5 ± 2.9), fasting blood sugar (151 ± 53.2 mg/dL), post prandial blood sugar (227.01 ± 70.9 mg/dL), blood urea (24.42 ± 9.3 mg/dL), and serum creatinine (1.5 ± 0.2 mg/dL) (P < 0.001). One-way ANOVA showed statistical significance between microalbuminuria and the different treatment groups (P < 0.0001). Microalbuminuria was associated with age, duration of diabetes, glycaemic control, and BMI. In contrast, there was no significant difference noted between the genders and microalbuminuria. Microalbuminuria is an early indication of nephropathy in diabetes patients. The early identification of the risk factors is important, and it is always recommended to screen for microalbuminuria in all the diabetic patients for early detection and prevention of diabetic nephropathy and their associated complications.

Synthesis of Mn2O3 Nanoparticles and Determination of Its Inhibition Effect On Sera of Iraqi Patients with Diabetes Mellitus Type-2 and Diabetes Nephropathy

Manganese is essential for the synthesis of antioxidant enzymes and metabolic issues in Diabetes type 2 (DMT2), which is a worldwide disease, Chronic metabolic disorders cause insulin resistance, hyperglycemia, and complications like diabetic nephropathy. Arginase converts arginine to ornithine and urea. Increased arginase activity in DMT2 and diabetes nephropathy (DN)which has been linked to kidney damage, and arginase inhibitors can increase NO which is essential to vascular function. However, the molecular mechanisms of arginased is regulationare in DMT2 and DN are still unclear. This study examined the effect of manganese oxide nanoparticles (Mn2O3NPs) on arginase activity inhibition inserum samples from DMT2 and DN patients. We hypothesized that Mn2O3NPs alter cell redox status and signaling pathways, affecting DMT2 and DN arginase activity. We used a colorimetric assay to measure arginase activity in 80 serum samples from DMT2 and DN patients treated with different MnO2 NP concentrations to test our hypothesis. The current study characterized nanoparticles using various techniques such as IR, SEM, AFM, XRD, and EDX, which found it within nanoscale nature. Our findings are that Mn2O3NPs modulate arginase activity specificity in DM2 samples. SuggestionsMn2O3NPs could be used to develop new treatments for these conditions.

SirT7-mediated transcription of fascin in hyperglycemic glomerular endothelial cells contributes to EndMT in diabetic nephropathy.

Diabetic nephropathy (DN) is the main cause of end-stage renal disease worldwide. It is reported that the endothelial-to-mesenchymal transition (EndMT) in glomerular endothelial cells plays an important role in DN. As a specific form of epithelial-to-mesenchymal transition, EndMT may involve common regulators of epithelial-to-mesenchymal transition. Fascin has been shown to mediate epithelial-to-mesenchymal transition. In addition, SirT7 has been confir med to contribute to inflammation in hyperglycemic endothelial cells via the modulation of gene transcription. In this study, we speculate that SirT7 modulates fascin transcription and is thus involved in EndMT in hyperglycemic glomerular endothelial cells. Our data indicate that α-smooth muscle actin (α-SMA) and fascin levels are increased, while CD31 levels are decreased in the kidneys of DN rats. Consistently, our cellular experiments reveal that high glucose treatment elevates fascin levels and induces EndMT in human glomerular endothelial cells (HGECs). Moreover, silencing of fascin inhibits EndMT in hyperglycaemic HGECs. In addition, SirT7 is found to be decreased in hyperglycemic cells and in the kidneys of DN mice. Moreover, the inhibition of SirT7 increases fascin level and mediates EndMT. An increase in SirtT7 expression decreases fascin expression, inhibits EndMT, and improves renal function in hyperglycemic cells and DN mice. SirT7 is found to bind to the promoter region of fascin. In summary, the present study indicates that SirT7 transcribes fascin to contribute to hyperglycemia-induced EndMT in DN patients.

Exploring the Impact of Optimized Probiotic Supplementation Techniques on Diabetic Nephropathy: Mechanisms and Therapeutic Potential.

Worldwide, diabetic nephropathy (DN) is a significant contributor to end-stage renal failure and chronic kidney disease. Probiotic supplementation has recently gained popularity as a potential nutritional therapy in several clinical trials aimed at improving renal function, inflammation, oxidative stress, dyslipidemia, glycemic control, and inflammation. However, they still need to undergo a thorough assessment of DN. It is crucial that the optimal dosage, duration, and combination of probiotic strains administered for the purpose of slowing down the advancement of DN be assessed. Based on the available publications, including relevant randomized controlled trials, systematic reviews, and meta-analysisfrom 2013-2023 from search engines like MEDLINE (PubMed), Scopus, and Web of Science, a literature review was generated using the keywords "gut microbiota," "gut microbiome," "diabetic kidney disease," "diabetic nephropathy," "probiotic," and "prebiotic." Multiple clinical trials focusing on probiotic administration techniques revealed changes in renal, glucose, and lipid biomarkers. Probiotic supplementation using Bifidobacterium bifidum, Lactobacillus acidophilus, and Streptococcus thermophilus for 12 weeks indicated a reduction in glycosylated hemoglobin, fasting blood glucose, and the microalbuminuria/creatinine ratio. Multispecies as well as single-species probiotic administration containing Lactobacillus, Bifidobacterium, and Streptococcus thermophilus spp. greater than 4*109colony forming units (CFU)/day for 8-12 weeks in DN patients improves renal metabolic markers and reduces the progression of disease patterns. Optimal supplementation techniques of probiotics in conjunction with prebiotics and synbiotics in DN benefit glycaemic control, renal function, blood lipid profile, inflammation, and oxidative stress. Future randomized controlled trials supplementing specific probiotics coupled with prebiotics and synbiotics, with larger sample sizes and longer follow-up times, will generate more reliable findings for the impact of probiotic supplementation on DN.

Macrophage SHP2 Deficiency Alleviates Diabetic Nephropathy via Suppression of MAPK/NF-κB- Dependent Inflammation.

Increasing evidence implicates chronic inflammation as the main pathological cause of diabetic nephropathy (DN). Exploration of key targets in the inflammatory pathway may provide new treatment options for DN. Here, we aim to investigate the role of Src Homology 2 Containing Protein Tyrosine Phosphatase 2 (SHP2) in macrophages and its association with DN. The upregulated phosphorylation of SHP2 was detected in macrophages of both diabetic patients and mouse model. Using the macrophage-specific SHP2 knockout mice (SHP2-MKO) and SHP2fl/fl mice injected with streptozotocin (STZ), we showed that SHP2-MKO significantly attenuated renal dysfunction, collagen deposition, fibrosis, and inflammatory response in STZ-induced diabetic mice. RNA-sequencing analysis using primary mouse peritoneal macrophages (MPMs) showed that SHP2 deletion mainly affects mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B (NF-ĸB) signaling pathway and MAPKs/NF-ĸB-dependent inflammatory cytokine release in MPMs. Further study indicated that SHP2-deficient macrophages failed to release cytokines that induce phenotype transition and fibrosis in renal cells. Administration with a pharmacological SHP2 inhibitor, SHP099, remarkably protected kidneys in both type 1 and type 2 diabetic mice. In conclusion, these results identify macrophage SHP2 as a new accelerator of DN and suggest that SHP2 inhibition may be a therapeutic option for DN patients.

A retrospective cohort study of clinical characteristics and outcomes of type 2 diabetic patients with kidney disease.

Type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD) poses a serious health threat and becomes a new challenge. T2DM patients with CKD fall into three categories, diabetic nephropathy (DN), non-diabetic kidney disease (NDKD), and diabetic nephropathy plus non-diabetic kidney disease (DN + NDKD), according to kidney biopsy. The purpose of our study was to compare the clinical characteristics and kidney outcomes of DN, NDKD, and DN + NDKD patients. Data on clinical characteristics, pathological findings, and prognosis were collected from June 2016 to July 2022 in patients with previously diagnosed T2DM and confirmed DN and or NDKD by kidney biopsy at Tongji Hospital in Wuhan, China. The endpoint was defined as kidney transplantation, dialysis, or a twofold increase in serum creatinine. In our 6-year retrospective cohort research, a total of 268 diabetic patients were admitted and categorized into three groups by kidney biopsy. The 268 patients were assigned to DN (n=74), NDKD (n=109), and DN + NDKD (n=85) groups. The most frequent NDKD was membranous nephropathy (MN) (n=45,41.28%). Hypertensive nephropathy was the most common subtype in the DN+NDKD group (n=34,40%). A total of 34 patients (12.7%) reached the endpoint. The difference between the Kaplan-Meier survival curves of the DN, NDKD, and DN + NDKD groups was significant (p<0.05). Multifactorial analysis showed that increased SBP [HR (95% CI): 1.018(1.002-1.035), p=0.025], lower Hb [HR(95% CI): 0.979(0.961-0.997), p=0.023], higher glycosylated hemoglobin [HR(95% CI): 1.338(1.080-1.658), p=0.008] and reduced serum ALB [HR(95% CI): 0.952(0.910-0.996), p=0.032] were risk factors for outcomes in the T2DM patients with CKD. This research based on a Chinese cohort demonstrated that the risk of endpoint events differed among DN, NDKD, and DN+NDKD patients. In T2DM patients with CKD, DN patients displayed worse kidney prognosis than those with NDKD or DN + NDKD. Increased SBP, higher glycosylated hemoglobin, lower Hb, and decreased serum ALB may be correlated with adverse kidney outcomes in T2DM patients.

Investigation of MHR-nephropathy relationship and the effect of SGLT2is on MHR in patients with type 2 diabetes.

The aim of this study was to evaluate the relationship between monocyte/high-density lipoprotein (HDL) ratio (MHR), an inflammatory marker, and diabetic nephropathy (DN), a microvascular complication of diabetes in diabetic patients and to investigate the effect of sodium-glucose co-transporter 2 inhibitors (SGLT2i) on MHR. The study included 119 diabetic patients. Hemogram, glucose, HbA1c, urea, creatinine, albumin, HDL cholesterol, LDL cholesterol, triglycerides, total cholesterol, MHR, NLR (neutrophil-lymphocyte ratio), and CRP parameters were evaluated in blood parameters taken after 8-10 h of fasting before and 6 months after SGLT2 inhibitor use, and albumin, creatinine, and albumin/creatinine parameters were evaluated in urine samples. Parameters were compared according to nephropathy status and SGLT2i type used. The MHR in diabetic nephropathy (DN (+)) patients was significantly higher than in DN (-) patients (p = 0.005). There was no significant difference in NLR value in both groups. The MHR value decreased significantly after the use of SGLT2i in all patients participating in the study (p = 0.01). NLR value decreased in DN (-) patients after SGLT2i use. No difference was observed in DN (+) patients. In this study, results supporting the relationship between DN and MHR and the effect of SGLT2i drugs on MHR were found. The use of MHR value as a marker in clinical course monitoring and shaping the treatment according to these markers may be useful in terms of prediction and treatment of complications.

SGLT2i relieve proteinuria in diabetic nephropathy patients potentially by inhibiting renal oxidative stress rather than through AGEs pathway

AimsTo estimate the effects of the sodium-glucose cotransporter 2 inhibitor (SGLT2i) on proteinuria and oxidative stress expression in type 2 diabetes patients.Materials and methods68 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according urinary albumin-to-creatinine ratio (UACR), including T2DM with non-albuminuria group (UACR < 30 mg/g), T2DM with microalbuminuria group (30 ≤ UACR ≤ 300 mg/g), T2DM with macroalbuminuria group (UACR>300 mg/g). They all received SGLT2 inhibitors (SGLT2i) treatment for 12 weeks. The expression of advanced glycation end products (AGEs) in plasma and 8-hydroxy-2-deoxyguanosine (8-OHdG) in urine were measured as indications of oxidative stress. The 24-hour urine samples were collected to measure the concentration of proteinuria and 8-OHdG before and after 12 weeks SGLT2i treatment. Plasma renin activity (PRA), angiotensin II (Ang II) and Aldosterone (ALD) were measured to evaluate renin angiotensin aldosterone system (RASS) levels.ResultsAfter 12 weeks SGLT2 inhibitors treatment, the median values of 24-hour proteinuria decreased in macroalbuminuria compared to baseline (970 vs. 821 mg/d, P = 0.006). The median values of AGEs and 8-OHdG decreased in microalbuminuria and macroalbuminuria groups when compared to baseline, AGEs (777 vs. 136 ug/ml, P = 0.003) and (755 vs. 210 ug/ml, P = 0.001), 8-OHdG (8.00 vs. 1.88 ng/ml, P = 0.001) and (11.18 vs. 1.90 ng/ml, P < 0.001), respectively. Partial correlations showed that 8-OHdG were relevant to the baseline 24-h proteinuria (r = 0.389, p = 0.001), the reduction of OHdG (Δ8-OHdG) were positively correlated with the decrease of 24-h proteinuria (Δ24-h proteinuria) after 12 weeks of SGLT2i treatment (r = 0.283, P = 0.031). There was no significant correlation between 24-h proteinuria and AGEs in baseline (r = −0.059, p = 0.640) as well as between ΔAGEs and Δ24-h proteinuria (r = 0.022, p = 0.872) after12 weeks of SGLT2i treatment in T2DM patients.ConclusionsSGLT2i may reduce proteinuria in diabetic nephropathy patients, potentially by inhibiting renal oxidative stress, but not through the AGEs pathway and does not induce RAAS activation.Trial registrationThis clinical trial was registered on 15/10/2019, in ClinicalTrials.gov, and the registry number is NCT04127084.

Analisis Interaksi Obat Secara Farmakokinetik dan Farmakodinamik Terhadap Pasien Nefropati Diabetik di Rumah Sakit X Kota Jambi Tahun 2022

Diabetic nephropathy (ND) is a complication of diabetes in the kidney. Nephropathy, or kidney disease, is the leading cause of death and disability in diabetes. The first clinical manifestation of diabetic nephropathy is microalbuminuria. If a patient is diagnosed with microalbuminuria, the development of end-stage renal and cardiovascular disease can be prevented by controlling blood pressure, glucose, and lipids. This study aimed to determine pharmacokinetic and pharmacodynamic drug interactions, determine drug interactions and severity in patients, determine the relationship between age and drug severity and gender relationship with drug severity in patients with diabetic nephropathy at X Hospital Jambi City in 2022. The method used in this research is descriptive method. The data collected in this study came from the medical records of diabetic nephropathy patients at X Hospital Jambi City in 2022. The total population in this study was 67 patients with a total sample of 46 patients. The results showed that the highest prevalence in the sample was female (56.52%), elderly patients aged 46-55 years (47.83%), drugs that interact with lantus ˃˂ novorapid (8.43%), patients experiencing drug interactions (71.74%), pharmacodynamic interactions (92.77%), pharmacokinetic interactions (4.82%), minor (10.84%), moderate (78.31%), and major severity (10.84%). The conclusions drawn from this study were based on the interaction mechanism, namely there were 6 cases (7.23%) of pharmacokinetic interactions and 77 cases of pharmacodynamic interactions (92.77%). Based on interactions with 9 cases of minor severity (10.84%), 65 cases of moderate severity (78.31%), and 9 cases of major severity (10.84%). And there is no relationship between the severity of the drug and age and gender.

Exosomes as nanostructures deliver miR-204 in alleviation of mitochondrial dysfunction in diabetic nephropathy through suppressing methyltransferase-like 7A-mediated CIDEC N6-methyladenosine methylation.

The exosomal cargo mainly comprises proteins, lipids, and microRNAs (miRNAs). Among these, miRNAs undertake multiple biological effects of exosomes (Exos). Some stem cell-derived exosomal miRNAs have shown the potential to treat diabetic nephropathy (DN). However, there is little research into the therapeutic effects of adipose-derived stem cell (ADSC)-derived exosomal miRNAs on DN. We aimed to explore the potential of miR-204-modified ADSC-derived Exos to mitigate DN. Exos were extracted and identified from ADSCs. Histopathological injury, oxidative stress (OS), mitochondrial function, cell viability, and apoptosis were assessed to explore the effects of ADSC-derived Exos on DN. For mechanism exploration, quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure miR-204, methyltransferase (METTL3, METTL14, and METTL7A), and CIDEC. Also, CIDEC m6A methylation and miR-204-METTL7A, and METTL7A-CIDEC interactions were determined. Initially, OS-induced mitochondrial dysfunction was observed in DN rats. ADSC-derived Exos inhibited histopathological injury, cell apoptosis, OS, and mitochondrial dysfunction in DN rats. The similar therapeutic effects of ADSC-derived Exos were detected in the in vitro model. Intriguingly, miR-204 was released by ADSC-derived Exos and its upregulation enhanced the anti-DN effects of Exos. Mechanically, miR-204 reduced METTL7A expression to CIDEC m6A methylation, thus suppressing OS and mitochondrial dysfunction. ADSC-derived exosomal miR-204 rescued OS-induced mitochondrial dysfunction by inhibiting METTL7A-mediated CIDEC m6A methylation. This study first revealed the significant role of ADSC-derived exosomal miR-204 in DN, paving the way for the development of novel therapeutic strategies to improve the clinical outcomes of DN patients.

MiR-205-5p-Mediated MAGI1 Inhibition Attenuates the Injury Induced by Diabetic Nephropathy

Introduction: Membrane-associated guanylate kinase with an inverted domain structure-1 (MAGI1) is dysregulated in diabetes; however, its role in diabetic nephropathy (DN) remains unclear. In this study, we determined the function and associated mechanisms of MAGI1 in DN. Methods: Serum samples from 28 patients with DN and 28 normal volunteers were collected. High-glucose (HG)-treated human renal mesangial cells (HRMCs) and streptozotocin-treated rats were used as cell and animal models of DN, respectively. MAGI1 mRNA expression was measured by quantitative reverse transcription polymerase chain reaction. An 5-Ethynyl-2′-deoxyuridine assay was used to assess cell proliferation, whereas Western blot analysis was performed to quantitate the levels of markers associated with proliferation, the extracellular matrix (ECM), and inflammation. These included collagens I, collagen IV, cyclin D1, AKT, phosphorylated-AKT (p-AKT), PI3K, and phosphorylated-PI3K (p-PI3K). The predicted binding of miR-205-5p with the MAGI1 3′UTR was verified using a luciferase assay. Results: MAGI1 expression was increased in serum samples from DN patients and in HRMCs treated with HG. MAGI1 knockdown attenuated excessive proliferation, ECM accumulation, and inflammation in HG-induced HRMCs as well as injury to DN rats. MiR-205-5p potentially interacted with the 3′UTR of MAGI1 and binding was verified using a dual-luciferase reporter assay. Moreover, miR-205-5p repression offset the inhibitory influence of MAGI1 knockdown on proliferation, collagen deposition, and inflammation in HG-treated HRMCs. Conclusion: MAGI1 contributes to injury caused by DN. Furthermore, miR-205-5p binds to MAGI1 and suppresses MAGI1 function. These findings suggest that miR-205-5p-mediates MAGI1 inhibition, which represents a potential treatment for DN.

Determination of Glyoxalase-1 levels and Identification of Genetic Variants in GLO1 Gene in Patients of Diabetic Nephropathy.

To determine the association of diabetic nephropathy with glyoxalase-1 enzyme levels and a genetic missense variation (SNP rs4746) in its gene (GLO-1). This cross-sectional comparative study was conducted at the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi from November 2020 to December 2022. One hundred patients and one hundred and thirteen healthy controls were enrolled using the nonprobability convenience sampling method. Medical history and 10ml blood were obtained from each individual after written informed consent. Blood samples were subjected to biochemical tests and DNA extraction which was later used for single nucleotide polymorphism (SNP) analysis (C332C variant of rs4741 GLO-1 gene) using Tetra primer ARMS PCR and gel electrophoresis. Glyoxalase-1 enzyme activity in serum was measured using ELISA. There was a significant difference in serum glyoxalase-1 levels in the two groups (p-value< 0.001). The patient group had lower levels (16.24 ± 22.51mg/dl) of glyoxalase-1 as compared to the control group (48.70 ± 42.54mg/dl). In genotypic analysis, 98 out of 100 control individuals had AA genotype-while only one had CC and another AC genotype. In the patient group, 94 out of 100 patients showed AA genotype, three AC, and three CC genotypes. As the statistical significance (p-value) was 0.37, there was no significant association found between AC or CC genotype and diabetic nephropathy. Glyoxalase-1 levels are linked to the development of diabetic nephropathy in our patients while a known missense variant rs4746 in the GLO-1 gene is not associated with increased risk.

Pericyte activation accompanied by peritubular capillaries dysfunction and pericyte-to-myofibroblast transition is associated with renal fibrosis in diabetic nephropathy.

Tubulointerstitial renal fibrosis is an essential feature of diabetic nephropathy (DN). Pericytes play a critical role in microvascular diseases and renal fibrogenesis. However, the role of pericytes in DN remains unclear. Herein, we aimed to explore the properties and possible mechanisms of pericytes in renal fibrosis in DN. We used multiplex immunofluorescence staining to evaluate the location and expression of activated pericytes and to assess capillary dilation and interstitial fibrosis in the kidneys of db/db mice. Pericytes were co-stained for alpha-smooth muscle actin (α-SMA) to determine which ones differentiate into myofibroblasts in db/db mice. Expression of CD34 and platelet-derived growth factor receptor beta (PDGFR-β) was assessed in kidney tissue from patients with DN by immunohistochemical staining. We found that cell staining for nerve/glial antigen 2 (NG2)+ and PDGFR-β+ was greater in the kidneys of db/db mice than in those of db/m mice. There was impaired pericyte coverage of blood vessels and capillary dilation in the renal interstitium. These changes were accompanied by increased collagen I staining and an increase in the number of pericytes with profibrotic phenotypes, as identified by increased NG2+/PDGFR-β+/α-SMA+ and decreased NG2+/PDGFR-β+/α-SMA- staining. In DN patients, expression of PDGFR-β was stronger and there was loss of CD34 compared with the findings in control patients with minor glomerular lesions. In this study, we demonstrated that pericyte activation accompanied by peritubular capillary dysfunction and pericytemyofibroblast transition is associated with renal fibrosis in DN.

Serum Cystatin C Level as an Early Biomarker for Detecting Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta - Analysis Study

Serum Cystatin C Level as an Early Biomarker for Detecting Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A Meta - Analysis Study

Investigation the Relationship Between Myonectin Levels and Both Lipid Profiles and Liver Function Tests in Diabetic Nephropathy Patients

Myonectin, or CTRP12, is a relatively recent adipokine—a protein released by adipose tissue that has gained interest in the context of metabolic health, including its possible implications in diabetic complications. Volunteers were divided into three groups, healthy subjects as controls (group A), they don't suffer from any disease, patients with T2D without nephropathy (group B) and T2D with nephropathy (group C), the age ranges between (35-70) years and the average duration disease of T2D (5-25) years, attending to the AL-Kindi teaching hospital, Baghdad Iraq. There was a highly significant increase P ≤ 0.01 of FBS, Insulin level, HOMA-IR, HbA1c, TC, TG, HDL and TSB among different groups (T2D with nephropathy, T2D without nephropathy, and control), a highly significant increase P ≤ 0.01 of myonectin levels among different groups. There was no significant difference present in AST U/L, and ALP U/L. A statistically significant increase in ALT U/L when compared with the control group. Conclusion: Levels of serum myonectin were significantly higher in patients with (T2D without nephropathy) as compared with ( T2D with nephropathy) and the control group.

The relationship between diabetic retinopathy and diabetic nephropathy in type 2 diabetes.

Diabetic retinopathy (DR) and diabetic nephropathy (DN), are major microvascular complications of diabetes. DR is an important predictor of DN, but the relationship between the severity of DR and the pathological severity of diabetic glomerulopathy remains unclear. To investigate the relationship between severity of diabetic retinopathy (DR) and histological changes and clinical indicators of diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM (n=272) who underwent a renal biopsy were eligible. Severity of DR was classified as non-diabetic retinopathy, non-proliferative retinopathy, and proliferative retinopathy (PDR). Relationship between DN and DR and the diagnostic efficacy of DR for DN were explored. DN had a higher prevalence of DR (86.4%) and DR was more severe. The sensitivity and specificity of DR in DN were 86.4% and 78.8%, while PDR was 26.4% and 98.5%, respectively. In DN patients, the severity of glomerular lesions (p=0.001) and prevalence of KW nodules (p<0.001) significantly increased with increasing severity of DR. The presence of KW nodules, lower hemoglobin levels, and younger age were independent risk factors associated with more severe DR in patients with DN. DR was a good predictor of DN. In DN patients, the severity of DR was associated with glomerular injury, and presence of KW nodules, lower hemoglobin levels and younger age were independent risk factors associated with more severe DR. ClinicalTrails.gov, NCT03865914.

Risk Factors of the Progression of Renal Function Deterioration Among Patients with Diabetic Nephropathy

Objective: To explore the risk factors for the progression of renal function deterioration in patients with diabetic nephropathy (DN). Methods: The clinical data and biochemical indexes of 100 diabetic patients admitted to our hospital from October 2021 to October 2022 were retrospectively analyzed. The patients were divided into a DN group, which consisted of 55 cases, and a nondiabetic nephropathy group (NDN), which consisted of 45 cases. The urinary microalbumin to creatinine ratio, the clinical data (gender, age, duration of the disease, and BMI), and the biochemical indexes (triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], glycated hemoglobin A1c [HbA1c], systolic blood pressure [SBP], diastolic blood pressure [DBP]) of the two groups were compared. Subsequently, the risk factors related to the progression of renal function deterioration in DN were analyzed through multifactorial logistic regression analysis. Results: No statistically significant difference was observed in the comparison of gender, age, BMI, LDL-C, and DBP between the two groups (P &gt; 0.05). The DN group demonstrated a longer disease duration and higher SBP, TC, HDL-C, HbA1c, and TG compared to the NDN group (P &lt; 0.05). Through multifactorial logistic regression analysis, it was found that the duration of the disease, the TC, the HDL-C, the HbA1c, the TG, and the SBP were independent risk factors of the deterioration of renal function in DN patients. Conclusion: Other than conventional indicators, TC, HDL-C, HbA1c, TG, and SBP are also crucial indicators in determining the progression of renal function deterioration in DN patients.

Association between Lipoprotein(a) and diabetic nephropathy in patients with type 2 diabetes.

Diabetic nephropathy (DN) is one of the most prevalent and severe microvascular complications of type 2 diabetes (T2DM). However, little is currently known about the pathogenesis and its associated risk factors in DN. The present study aims to investigate the potential risk factors of DN in patients with T2DM. A total of 6,993 T2DM patients, including 5,089 participants with DN and 1,904 without DN, were included in this cross-sectional study. Comparisons between the two groups (DN vs. non-DN) were carried out using Student's t-test, Mann-Whitney U-test, or Pearson's Chi-squared test. Spearman's correlation analyses were performed to assess the correlations of serum lipids and indicators of renal impairment. Logistic regression models were applied to assess the relationship between blood lipid indices and the presence of DN. T2DM patients with DN were older, and had a longer duration of diagnosed diabetes compared to those without DN. Of note, the DN patients also more likely develop metabolic disorders. Among all serum lipids, Lipoprotein(a) [Lp(a)] was the most significantly correlated indicators of renal impairment. Moreover, univariate logistic regression showed that elevated Lp(a) level was associated with an increased risk of DN. After adjusted for confounding factors, including age, gender, duration of T2DM, BMI, SBP, DBP and lipid-lowering drugs usage, Lp(a) level was independently positively associated with the risk of DN [odds ratio (OR):1.115, 95% confidence interval (CI): 1.079-1.151, P=6.06×10-11]. Overall, we demonstrated that serum Lp(a) level was significantly positively associated with an increased risk of DN, indicating that Lp(a) may have the potential as a promising target for the diagnosis and treatment of diabetic nephropathy.