Severity Of Diabetic Nephropathy Research Articles

Association between protein arginine N-methyltransferase 1 polymorphism and overt diabetic nephropathy: Role of asymmetric dimethylarginine in vascular tone

Backgroundω-NG,NG-asymmetric dimethylarginine (ADMA) regulates vascular tone and may participate in the pathogenesis of diabetic nephropathy (DN). ObjectiveTo investigate whether single-nucleotide polymorphisms (SNPs) around the protein arginine N-methyltransferase 1 gene (PRMT1) influence ADMA dynamics and DN incidence and severity. MethodsThis study utilized a hospital-based database containing 310 Japanese patients with type 2 diabetes mellitus (T2DM). The association of PRMT1-related tagged SNPs with DN stage distribution was examined using a dominant model of minor alleles. PRMT1 mRNA, serum ADMA, reactive hyperemia-peripheral arterial tonometry index (RHI), and brachial-ankle pulse wave velocity (baPWV) were compared between the genotype-based subgroups of causal SNP, and correlations between these variables were evaluated. ResultsThe composition of DN stages significantly differed between the GG and GA + AA subgroups of rs892151 (p = 0.026). In a propensity-matching cohort of rs892151, the GA + AA subgroup had an increased incidence of overt DN (odds ratio 2.92, 95 % confidence interval 1.12–7.62, p = 0.028), along with higher PRMT1 mRNA, serum ADMA levels, and baPWV than the GG subgroup (p < 0.001, p = 0.023 and 0.047, respectively). There were correlations between PRMT1 mRNA and serum ADMA levels, between serum ADMA levels and RHI, and between baPWV and urinary albumin excretion (r = 0.335, p < 0.001, r = -0.221, p = 0.029, and r = 0.254, p = 0.004, respectively). ConclusionsT2DM patients carrying the PRMT1-related variant rs892151 were susceptible to overt DN. ADMA-mediated endothelial dysfunction and arterial stiffness may be involved in the variant-related pathogenesis of overt DN.

Urine Exosomal MicroRNA Profiling in the Family Investigation of Nephropathy and Diabetes (FIND)

About 1 in 3 adults with either type 1 or type 2 diabetes (T2D) has some degree of renal injury or diabetic nephropathy (DN). There is a need to develop more sensitive and specific means of detecting and gauging DN progression so that therapies can be started as early as possible. We hypothesized that UE microRNAs (miRs), small, non-coding 21-25 nucleotide species, a relatively stable readout of renal metabolic health, could be utilized in this fashion. From the NIH, NIDDK Central Repository, we obtained 299 urine samples (300 ml) from African American subjects previously enrolled in the FIND study. The FIND study was initially designed to elucidate genetic determinants of DN in related patient populations using both T2D and non-diabetic control (CTRL), male (M) and female (F) subjects. Our samples included: 20 CTRL-M, 46 CTRL-F, 43 T2D-M, and 90 T2D-F). Other deidentified demographic and clinical data was obtained from the NIH. We measured urine albumin and creatinine in the samples and calculated ratios (mg albumin/g creatinine). Patients were categorized as normal (N, &lt; 30, 120 subjects), microalbuminuric (MIC, 30-300, 33 subjects), or macroalbuminuric (MAC, &gt;300, 46 subjects). Urine exosomes (UE) were isolated from each urine using the Total Exosome Isolation (from urine) kit (Thermofisher), which allows for precipitation of water-insoluble exosomes via centrifugation at medium speed (10,000g) for 1 hour. Small RNA was isolated followed by cDNA synthesis using commercially-available kits (Qiagen). Previously, we found miR-451a to be more highly expressed in UE from human subjects with chronic kidney disease, than in control subjects. We also found this miR to be a potential predictive biomarker for albuminuria in diabetic rats. Therefore, first we used conventional qRT-PCR to evaluate UE levels of miR-451a, as well as, the anti-sense product, miR-451b. MiR-127 was used as the internal standard, as it has been reported not to change with T2D. In MAC subjects, we found that the UE median miR-451a level increased with a fold change (FC) of 3.5 (relative to N). Similarly, miR-451b showed a 3.6-fold increase. FC in the MIC groups were 2.9 and 2.5 for miR-451a and b, respectively (relative to N). Next we conducted an unbiased screen of commonly excreted miRs in these subjects using a miR Array (miRCURY LNA miRNA Focus PCR panel, Qiagen) configured with 88 targets highly expressed in UE. We screened 19 subjects representing a range of conditions, i.e., albuminuric and normal, diabetic and non-diabetic, male and female. We found positive signals in 5 or more subjects for 16 miRs. Of those, 12, i.e., let-7b-5p, miR-16-5p, miR-23b-3p, miR-26a-5p, miR-27a-3p, miR-30a-5p, miR-30b-5p, miR-30c-5p, miR30e-5p, miR-141-3p, miR-203a, and miR-204-5p were expressed at mean levels 2-fold higher in MAC versus N subjects. Furthermore, 13 of these miRs were also over 2-fold higher when subjects were divided as T2D versus CTRL, i.e., the above list plus miR-200c-3p and miR-30d-5p, but not let-7b-5p in this case. When subjects were not divided by groups, miR-598-5p had the highest positive correlation with urinary albumin excretion, R = 0.53 and p = 0.035 (for slope ≠ 0). Using miRNet (McGill University), a freely available miR analysis software tool, we mined for common targets of miR-451(a &amp; b) and miR-598. One putative target of both miR-451b and miR-598 was vascular endothelial growth factor A (VEGFA), which has been shown to play a role in DN. In sum, these miRs represent candidate targets to undergo additional scrutiny. We conclude UE miRs may hold clinical value in the non-invasive assessment of DN severity and predicting progression. NIH/NINDS U01-DK103225 (Feldman, PI); Ecelbarger Pilot. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Indexes of ferroptosis and iron metabolism were associated with the severity of diabetic nephropathy in patients with type 2 diabetes mellitus: a cross-sectional study.

To explore the correlations between diabetic nephropathy (DN) and serum levels of glutathione peroxidase 4 (GPX4), acyl-CoA synthetase long-chain family member 4 (ACSL4), iron, transferrin (Tf), and ferritin in patients with type 2 diabetes mellitus (T2DM). According to the urinary albumin excretion rate(UAER) or estimated glomerular filtration rate (eGFR) levels, a total of 123 patients with T2DM were separately divided into normoalbuminuria (NO), microalbuminuria (MI), macroalbuminuria (MA) groups, and G1 (eGFR ≥ 90 mL/min), G2 (eGFR ≤ 60 mL/min to < 90 mL/min), and G3 groups (eGFR< 60 mL/min), with 33 healthy participants as the control (HC). The differences in serum GPX4, ACSL4, iron, Tf, and ferritin levels between groups were compared, and the relationships between these levels were analysed. The independent correlations between UAER or DN severity and serum GPX4, ACSL4, iron, Tf, and ferritin levels were analysed by multiple linear and multinomial logistic regression, respectively. To the patients with T2DM, with the increase in UAER levels, GPX4, iron, and Tf levels gradually decreased, whereas ACSL4 levels increased, meanwhile with the decrease in eGFR levels, GPX4 and Tf levels gradually decreased, whereas ACSL4 levels increased. UAER were independently and positively correlated with ACSL4 [β = 17.53, 95% confidence interval (CI; 11.94, 23.13)] and negatively correlated with GPX4 [β = -1.633, 95% CI (-2.77, -0.496)] and Tf [β = -52.94, 95% CI (-95.78, -10.11)].The NO and MI groups were considered as reference groups, respectively. The severity of DN was negatively correlated with serum GPX4 [odds ratio (OR) = 0.925 and 0.902, p =0.015 and 0.001], and Tf (OR = 0.109 and 0.119, p =0.043 and 0.034), and positively correlated with ACSL4 (OR = 1.952 and 1.865, both p <0.001) in the MA group. DN severity was negatively correlated with serum GPX4 and Tf levels and positively correlated with serum ACSL4 levels in patients with T2DM.

L- Thyroxine ameliorates renal function in thyroidectomized diabetic nephropathy rats through downregulation of TGF- β1, Ang II and ET-1 expression

ABSTRACT Thyroidectomy is the gold standard in treating cancer thyroid patients. Thyroidectomy patients are more susceptible to type 2 diabetes mellitus (T2DM) development. T2DM is a major health problem worldwide, due to its chronic associated complications. Diabetic nephropathy (DN) is one of the most detrimental complications. Moreover, thyroidectomy could increase kidney injury incidence and hypothyroidism either clinical or subclinical frequently coincides with T2DM, significantly associated with DN occurrence and severity, however the exact mechanism still unclear and it is the aim of this study to explore the pathogenesis involved in Thyroidectomy mediated nephrotoxicity, besides assessing the therapeutic role of L-thyroxine on nephropathy. Using biochemical and histopathological techniques, glucose homeostasis, lipid profile, kidney architecture, function, transforming growth β1 (TGF- β1), angiotensin II (Ang II) and Endothelin (ET)-1 markers were investigated in type 2 diabetic rats with or without thyroidectomy and after L-thyroxine treatment. Data revealed that thyroidectomy impaired glucose tolerance, adversely affected the lipid profile, induced nephropathy and deteriorated kidney function significantly compared to the control and T2DM groups (proteinuria, 118.5 ± 16.2 versus 10.3 ± 1.6 and 118.5 ± 16.2 versus 102.2 ± 9.2). Moreover, L-thyroxine could ameliorate hyperglycemia, dyslipidemia, renal morphology and function compared to thyroidectomy group (proteinuria 51.1 ± 3.4 versus 118.5 ± 16.2), which was mediated by TGF-β1, Ang II and ET-1. This could be a guide to use L-thyroxine supplementation in thyroidectomy patients, especially if associated with T2DM to avoid or slow down nephropathy development.

Determinants and Stratification of Microvascular Complications of Type 2 Diabetes Mellitus.

Background Diabetes mellitus (DM) is a prevalent metabolic disorder characterized by high blood sugar levels. It is classified into type 1 (T1DM) and type 2 (T2DM), which have different mechanisms and complications. The global prevalence of diabetes, particularly T2DM, has increased significantly in recent decades, leading to a need for standardized data collection of macrovascular and microvascular complications to track disease progression and guide treatment options. This study aims to assess and correlate the prevalence and severity of microvascular complications in patients with T2DM. Methodology This observational, cross-sectional study was conducted at Poonam Multispeciality Hospital in Ahmedabad, India. A total of 4,123 diabetic patients admitted to the hospital were included. Information on sociodemographics and medical history was collected using standardized forms. Fundus photography and fluorescein angiography were performed to assess diabetic retinopathy, and estimated glomerular filtration rate and albumin-to-creatinine ratio were measured to evaluate renal function. Neurological examinations were conducted to score diabetic neuropathy. Chi-square tests were used to determine associations between medical history with diabetic retinopathy and nephropathy, and t-tests were used to compare diabetic neuropathy scores. Kendall's Tau correlation was used to determine correlations between diabetic retinopathy and nephropathy. P-values <0.05 were considered statistically significant. Results The overall prevalence of diabetic retinopathy, nephropathy, and neuropathy was 37.5%. Of the patients included, 47.9% had diabetic nephropathy and 28.9% had diabetic neuropathy. A significant association was observed between the severity of diabetic retinopathy and age, body mass index, duration of diabetes, and hemoglobin A1c (HbA1C) levels. Similarly, significant associations were found between these factors and the severity of diabetic nephropathy. Unpaired t-tests revealed significant differences in diabetic neuropathy examination scores based on the duration of diabetes and Hba1C levels. Moreover, correlation analysis indicated a low, positive correlation between diabetic retinopathy and diabetic nephropathy. Conclusions This study provides insights into the prevalence, severity, and associations of microvascular complications in patients with T2DM, contributing to the understanding and management of these conditions. Additionally, the research revealed a direct association between diabetic retinopathy and different stages of chronic kidney disease determined by the Kidney Disease Improving Global Outcome guidelines.

The Relationship between Levels of Serum Vit. D and Kidney Function in Diabetic Nephropathy Iraqi Patient

Background: According to several animal and human studies, Vitamin D appears to play a substantial role in the development of diabetic nephropathy, However, the possibility of vitamin D's Reno protective impact and influence on the reversal of already-existing renal damage remains speculative. Vitamin D deficiency and insufficiency are ubiquitous worldwide and have been linked to a variety of pathophysiological conditions, including diabetes, allergies, autoimmune illnesses, pregnancy difficulties, and, more recently, worse COVID-19 clinical outcomes. From a translational perspective, the goal of this review is to look into the potential function of vitamin D in the development of diabetic kidney diseases Aim of the study: to evaluate the role of vit. D on renal function in patients with DMT1. Patient and Method: The total number of study participants was 120, divided into three groups: Group A: Included 40 patients have DM with NP (stage1, stage 2, stage 3a), Group B included 40 patients who had DM without NP, and group C included 40 healthy participants (control). Samples were taken from the Diabetic control clinic of Endocrinology and Diabetes Center/Al-Kindy Hospital, Baghdad Teaching Hospital/ Medical City, and Al-Shaheed Al-Sadder General Hospital during the period from October 2021 to March 2022. Result: Statistically significant weak positive correlations were detected between vitamin D and GFR (r= 0.321, P= 0.001); while a significant moderate negative correlation was seen between vitamin D and HbA1c (r= -0.494, P= 0.001) and weak negative correlation was seen with B. Urea (r= -0.2, P= 0.028). No statistically significant correlations were detected between vitamin D and all of age, DM duration, and s. creatinine. Conclusion: Our data suggest a correlation between reduced levels of vitamin D3 and diabetes nephropathy and it may be a potential predictor for both the occurrence and severity of diabetic nephropathy

Role of serum free fatty acids in determining severity of diabetic nephropathy: A case control study

Introduction and Aim: The Diabetic Nephropathy (DN) is a result of impaired renal function in Type 2 diabetes. At the onset of diabetes, microvascular complication increases due to accumulation of free fatty acids (FFA) causing renal damage. A study was conducted to estimate the concentration of serum FFA causing severity of diabetic nephropathy.&#x0D; &#x0D; Materials and Methods: 90 Type 2 diabetic subjects and 30 study controls (age group 35 to 65 years) were selected from the medicine OPD of S N Medical College and HSK Hospital, Bagalkot. Based on the presence of microalbuminuria, the 90 Type 2 diabetic patients were equally divided in to 3 groups, named as stage I to stage III. The serum FFA was estimated by ELISA method in these three groups and control subjects. The statistical analysis was done using SPSS software version 19 utilizing unpaired “t” test for quantitative data and Pearson’s correlation tests.&#x0D; &#x0D; Results: The estimated serum FFA levels in stage I to III was found to be higher and highly significant as compared to control (p=0.001). We find the best cut off value of serum FFA was 4.75 mmol/L, causing severity of diabetic nephropathy. The area under the curve (AUC) is 0.92 with the specificity of 86%, sensitivity 89% and the diagnostic accuracy was found to be of 87%.&#x0D; &#x0D; Conclusion: Serum free fatty acid levels were higher in diabetic nephropathy subjects, which could be used as diagnostic marker for the severity of renal damage with cut off value of 4.75 mmol/L.

Serum VEGF as a predictive marker of glycemic control and diabetic nephropathy in Chinese older adults with type 2 diabetes mellitus.

Recent researches have demonstrated good correlation between vascular endothelial growth factor (VEGF) and diabetic nephropathy (DN); however, this relationship seems less clear-cut when VEGF was measured in blood samples. We tended to explore the possible association between serum VEGF and glycemic control and diabetic nephropathy severity in Chinese older adults with type 2 diabetes mellitus (T2DM). This study retrospectively enrolled 595 older T2DM adults at random. Participants were clinically grouped across the urine albumin-to-creatinine ratio (UACR) and the HbA1c tertiles by genders. Linear regressions were performed for the correlation of VEGF with HbA1c and UACR and binary logistic regressions for the odds of DN after adjusting for confounders. The receiver operating characteristic (ROC) curves were conducted for the predictive value of VEGF for DN. Both males and females with DN exhibited higher VEGF levels than non-DN (P < 0.001). Furthermore, a positive correlation of VEGF with UACR and HbA1c was presented regardless of adjusting confounding factors (P < 0.001). Serum VEGF level and fasting plasma glucose (FPG) were independent risk factors of DN in older adults of both genders (P < 0.05), while the risk prediction of DN by HbA1c only reflected in female patients (P < 0.05). The ROC curve of VEGF for DN had the area under curve (AUC) of 0.819 for males and 0.793 for females, indicating the clinical value of serum VEGF as a predictive biomarker. Serum VEGF was strongly associated with UACR and HbA1c in both genders, and could be regarded as a predictive biomarker for glycemic control and diabetic nephropathy in older adults with T2DM.

MO624: The Relationship Between Renal Tubular Epithelial Cell Necroptosis and The Severity of Diabetic Nephropathy

Abstract BACKGROUND AND AIMS Diabetic nephropathy (DN), a common complication of diabetic patients, usually contributes to end-stage renal failure. Accidental cell death (ACD) and regulated cell death (RCD) cause renal cell loss and deteriorate renal function during the progression of DN. MLKL is the executor of necroptosis, a major form of RCD. The multimer of phosphorylated MLKL (p-MLKL) gather at the cell membrane and form the leaking pores, performing the last step of necroptosis. This study aims to study the relationship of p-MLKL expression and the disease severity in DN patients, providing promising treatment target. METHOD A total of 30 patients who diagnosed with DN clinical-pathologically in the Peking University First Hospital from January 1998 to August 2018 were enrolled (excluding DN with primary or secondary glomerular diseases, DN combined with thrombotic microangiopathies and small vasculitis). p-MLKL were stained on renal biopsy kidney sections by immunohistochemistry. Image-Pro Plus 6.0 software (IPP) was used to analyze the expression of p-MLKL on 10 randomly taken images for each patient. The relationship between p-MLKL expression and clinical-pathological parameters was explored. Clinical parameters of plasma creatinine, peak plasma creatinine during renal biopsy period, estimated glomerular filtration rate (eGFR) were used. DN pathological changes contained: (i) glomerular lesions, (ii) arteriole lesions (iii) tubular lesions and (iv) tubules chronic interstitial lesions. RESULTS Compared with normal control, the positive expression of p-MLKL could be detected in the renal tubular interstitium of patients with DN. However, no p-MLKL positive signal was seen in the glomeruli. Patients with p-MLKL positive signals accounted for 73.33% (22/30) of the enrolled patients. Among the 30 patients, the value of p-MLKL kidney tissue IOD (integrated optical density) was positively correlated with peak serum creatinine (r = 0.373, P = 0.042), the pathological score of spherical sclerosis (r = 0.364, P = 0.048) and tubular brush border (TBB) loss (r = 0.363, P = 0.049). CONCLUSION The expression of necroptosis marker p-MLKL was significantly correlated with the clinical-pathological changes of DN patients. Its role in the progression of DN deserves further exploration.

Salivary Glycopatterns as Potential Non-Invasive Biomarkers for Diagnosing and Reflecting Severity and Prognosis of Diabetic Nephropathy.

Discriminating between diabetic nephropathy (DN) and non-diabetic renal disease (NDRD) can help provide more specific treatments. However, there are no ideal biomarkers for their differentiation. Thus, the aim of this study was to identify biomarkers for diagnosing and predicting the progression of DN by investigating different salivary glycopatterns. Lectin microarrays were used to screen different glycopatterns in patients with DN or NDRD. The results were validated by lectin blotting. Logistic regression and artificial neural network analyses were used to construct diagnostic models and were validated in in another cohort. Pearson’s correlation analysis, Cox regression, and Kaplan–Meier survival curves were used to analyse the correlation between lectins, and disease severity and progression. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) and bioinformatics analyses were used to identify corresponding glycoproteins and predict their function. Both the logistic regression model and the artificial neural network model achieved high diagnostic accuracy. The levels of Aleuria aurantia lectin (AAL), Lycopersicon esculentum lectin (LEL), Lens culinaris lectin (LCA), Vicia villosa lectin (VVA), and Narcissus pseudonarcissus lectin (NPA) were significantly correlated with the clinical and pathological parameters related to DN severity. A high level of LCA and a low level of LEL were associated with a higher risk of progression to end-stage renal disease. Glycopatterns in the saliva could be a non-invasive tool for distinguishing between DN and NDRD. The AAL, LEL, LCA, VVA, and NPA levels could reflect the severity of DN, and the LEL and LCA levels could indicate the prognosis of DN.

Association between diabetic retinopathy and diabetic nephropathy: A clinical study

Diabetes mellitus is a leading cause of blindness worldwide. The disease affects the generalized micro and macro vasculature of various structures. Retina, kidney and peripheral nerves are the major sites of micro vasculature involvement. Our study aims to find the correlation between diabetic retinopathy (DR) and diabetic nephropathy. This non-randomized, prospective study was conducted at a tertiary care hospital in South India between November 2014 and May 2016. Study included 100 patients with diabetic nephropathy referred for fundoscopy from the nephrourology department, excluding those with hazy media enough to interfere with a detailed fundus examination and management. All subjects underwent complete ocular examination and systemic evaluation after obtaining informed consent. Visual acuity, fundoscopy by direct and indirect ophthalmoscope, fundus photography and optical coherence tomography were done as and when required. Blood investigations like fasting blood sugar, post prandial blood sugar, glycosylated haemoglobin, haemoglobin levels, serum creatinine and blood urea nitrogen, lipid profile, urine routine and 24-Hour urine albumin were recorded. DR was classified according to ETDRS classification and different grades were compared with grades of nephropathy and association was analysed statistically.: There was significant association between fundal changes and albumin excretion in urine. Among subjects with massive albuminuria, 64.7% of them had proliferative DR (PDR). Among subjects with moderate albuminuria, majority had Moderate NPDR and subjects with microalbuminuria majority had normal fundus. There was a positive correlation between DR and total cholesterol. The severity of DR correlates with severity of diabetic nephropathy.

Vitamin D in Different Stages of Type 2 Diabetic Nephropathy and its Correlation with Transforming Growth Factor Beta-1 (TGF-β1) –A Cross Sectional Study

Background: Diabetic nephropathy (DN) is a microvascular complication of Diabetes Mellitus (DM) and the prevalence of which is increasing in every year. Monitoring of Vitamin D status in diabetic nephropathy patients is important, as the deficiency of vitamin D appears as a risk factor for the development of diabetic nephropathy. Studies evaluating the role of vitamin D in DN are few. Conflicting data is available on the correlation between vitamin D and Diabetic Nephropathy. Studies revealed the sample population is Vitamin D deficient. Therefore, it is important to understand the correlation of Vitamin D with severity of Diabetic nephropathy and its role in fibrogenesis. The aim of this study is to analyse vitamin D status in different stages of type 2 diabetic nephropathy and its correlation with transforming growth factor beta-1.&#x0D; Methods: A 1.5-year cross-sectional study of 120 diabetic patients, 60 with nephropathy and 60 without nephropathy patients enrolled to MES Medical College. Patients with heart, liver, or thyroid disease, as well as those on dialysis, were excluded from the study. The VITROS 5600 integrated system were used to measure fasting blood sugar (FBS), HbA1c, creatinine and vitamin D. Transforming Growth Factor Beta-1 (TGF-β1) is measured using ELISA technique. According to HbA1c and estimated glomerular filtration rate (eGFR) values, the study population is divided into two groups. The statistical package for the social sciences (SPSS) software was used to conduct the analysis. The level of significance was calculated at 95%.&#x0D; Results: The level of vitamin D in diabetic patients with nephropathy is much lower than in diabetic patients without nephropathy. In diabetic nephropathy patients, serum creatinine, urea, HbA1c and TGF-β1 exhibited a highly significant negative correlation with vitamin D status, but eGFR showed a highly significant positive correlation.&#x0D; Conclusion: Vitamin D status has been found to be poor in all diabetic patients, with a greater drop in diabetic nephropathy patients. In diabetic nephropathy patients, serum creatinine, urea, HbA1c and TGF-β1 exhibited a highly significant negative association with vitamin D status, but eGFR showed a highly significant positive link. Deficiency of vitamin D have role in the development and severity of DN, and showed a highly significant correlation with the regulator of fibrosis, TGF-β1. This finding indicates that vitamin D couldbe an important factor for development and progression of Diabetic nephropathy. So supplementation of vitamin D may slow down progression of DN.

Serum Albumin Modifies the Effect of Peripheral Blood Monocytes on Severity of Diabetic Nephropathy in an Adult Population

BackgroundOur aim in this study was to characterize clinical associations between peripheral blood immune populations and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus. MethodsWe queried hospital records from an outpatient diabetes primary care clinic between 2018 and 2019 for clinical and laboratory data, including complete blood counts with differentials, serum albumin and globulin, glycated hemoglobin (A1C) and urine albumin-to-creatinine ratio. One hundred ninety-eight patients had complete cross-sectional data with temporally proximate complete blood counts and urine albumin-to-creatinine ratios. After univariable correlation assessment, we used a forward multivariable linear regression model to test the hypothesis that higher numbers of circulating innate immune populations would be associated with DKD, while accounting for known demographic, clinical and laboratory risk factors. We defined DKD as an albumin-to-creatinine ratio of >3 mg/mmol or an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 from the Chronic Kidney Disease Epidemiology Collaboration. ResultsAdjusted analyses demonstrated significant (p<0.01) associations between higher urine albumin-to-creatinine ratio and peripheral circulating monocytes, independent of other established significant risk factors, including blood pressure, A1C, age and sex. We also identified serum albumin as a potentially important modifying factor of albuminuric kidney disease, which interacts with monocytes in more advanced disease. In contrast, the variable most strongly predictive of eGFR was age. ConclusionsCirculating monocytes and serum albumin are significantly associated with albuminuria, but not eGFR in DKD. These results support the potential role of the innate immune system in diabetic microvascular end-organ damage and urinary protein loss, and may be readily translatable clinical markers to incorporate into risk-assessment models for prognostication in diabetes.

Clinical correlation of diabetic retinopathy with nephropathy and neuropathy.

Purpose:To evaluate the presence of nephropathy and neuropathy in patients with diabetic retinopathy (DR) and to correlate the severity of DR to that of diabetic nephropathy and diabetic neuropathy.Methods:This prospective noninterventional hospital-based study included 57 consecutive cases of DR of either sex, presenting to the eye OPD between January 2019 and November 2020 with minimum 5-year duration of Type 1 and 2 DM. Complete ophthalmic examination was done and DR was classified according to early treatment diabetic retinopathy study classification. Severity of diabetic nephropathy was based on urine albumin creatinine ratio and estimated glomerular filtration rate. Severity of diabetic neuropathy was based on nerve conduction velocity.Results:The study was conducted on 57 patients of whom patients 45 were males and 12 were females. Mild nonproliferative diabetic retinopathy was present in 22 patients, moderate in 14 patients, severe in 18 patients, and proliferative diabetic retinopathy in 3 patients. In our study, group 30 patients of DR presented without clinically significant macular edema (CSME) and 27 patients presented with CSME. The distribution of severity of DR according to CSME was observed to be statistically significant (P<<0.05). The association of severity of DR with severity of diabetic nephropathy was observed to be statistically significant (P<<0.05). The association of severity of DR with that of diabetic neuropathy was inconclusive.Conclusion:The association of severity of DR with severity of diabetic nephropathy and diabetic neuropathy can be used as a marker for future chronic kidney diseases progression and also to prognosticate neurological outcomes in diabetic patients.

Interstitial eosinophilic infiltration in diabetic nephropathy is indicative of poor prognosis, with no therapy benefit from steroid.

Studies suggested that eosinophils in diabetes might be associated with severity of diabetic nephropathy (DN). In a retrospective study of 102 Chinese patients with biopsy-proven DN, we aimed to evaluate relationships of both blood and renal eosinophils (Eos) to the severity of DN and check whether Eos can serve as an indicator of prognosis as well as the therapeutic effect of steroids. One hundred and two patients diagnosed with DN were enrolled. Demographical and clinical data and histopathological scores were associated. Interstitial eosinophilic aggregates (IEA) were defined as the presence of ≥10 Eos in at least one high-power field. End-stage renal disease was defined as the end point. We observed that log2 (blood eosinophil counts) correlated with neutrophil counts, proteinuria, and tubulointerstitial inflammatory cell infiltration. IEA was observed in 33.3% of the DN patients and was associated with decreased estimated glomerular filtration rate, higher proteinuria, hematuria, higher HbA1c, increased blood eosinophil counts, tubular injury, tubulointerstitial chronicity, and interstitial inflammation. IEA was associated with worse renal prognosis (hazard ratio [HR] 2.424, P = 0.008). Consistently, urine eosinophil cationic protein (ECP) (ng/mgCr) was associated with renal injury and poor renal prognosis (HR 1.173, P = 0.020). Patients with IEA were more likely to be treated with steroid/immunosuppressants (47.1% vs 14.7%, P = 0.001) but did not show renal benefit. It suggested that both blood and renal infiltrated eosinophils were prevalent in DN and associated with severity of DN. IEA in renal pathology showed better fit in correlation with renal prognosis. Treatment with steroid/immunosuppressants showed no significant improvement regarding renal prognosis.

Study of clinical correlation of diabetic retinopathy with diabetic nephropathy and diabetic neuropathy in patients with type 2 diabetes mellitus

To study the relationship of various stages of Diabetic Retinopathy with severity of Diabetic Nephropathy and Diabetic Neuropathy. 120 patients of type 2 diabetic patients were screened for Retinopathy, nephropathy and neuropathy. Investigations like Fundus examination with Indirect Ophthalmoscopy, CBC, RBS, RFT – S. Creatinine, S. Urea; Urine Samples – Microalbuminuria; HbA1c; Lipid Profile and Creatinine clearance, Vitamin B12, Nerve conduction Velocity Test and Clinical Reflex Test were performed on the patients with. In present study we have found significant correlation between Retinopathy, Diabetic Nephropathy and Neuropathy. Severity of neuropathy and nephropathy increased with increase in the grade of retinopathy. In our study the incidence of neuropathy and nephropathy also increases as severity of diabetic retinopathy increases. Thus, all diabetic patients must be screened for retinopathy as it can help determine the presence of other organ involvement.

Serum uric acid is independently associated with diabetic nephropathy but not diabetic retinopathy in patients with type 2 diabetes mellitus.

This study aims to investigate the relationship between serum uric acid (SUA) and the severity of diabetic nephropathy (DN) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). A total of 2961 patients were enrolled in the present cross-sectional study. The severity of DN was determined by 24-hour urinary albumin excretion (UAE), which was classified as normal (UAE <30 mg/24 h), microalbuminuria (UAE: 30-299 mg/24 h), and macroalbuminuria (≥300 mg/24 h). The severity of DR was determined by non-mydriatic retinal photography and was classified as non-diabetic retinopathy (NDR), non-proliferative diabetic retinopathy (NPDR), and proliferative DR (PDR). Patients with high SUA levels (≥420 μmol/L for males and ≥360 μmol/L for females) had a significantly higher prevalence of DN (UAE ≥30 mg/24 h, 39.3% vs 26.3%; p < 0.001), higher UAE levels (140 ± 297 vs 63 ± 175 mg/24 h; p < 0.001), and lower estimated glomerular filtration rate (eGFR; 79.3 ± 26.8 vs 96.8 ± 19.6 mL/min/1.73 m; p < 0.001), when compared with patients with normal SUA levels. However, the prevalence of DR, NPDR, or PDR did not differ. Furthermore, the concentration of SUA was higher in patients with higher severity of DN (all, p < 0.001) and patients with PDR (compared with NDR or NPDR, p < 0.05). SUA levels were positively associated with male gender, body mass index, the use of diuretics, triglyceride, low-density lipoprotein, and UAE levels, whereas they were negatively correlated with high-density lipoprotein, fasting blood glucose, glycosylated hemoglobin, and eGFR. After adjustment, SUA remained significantly associated with UAE (r = 0.069, p < 0.001). For patients with T2DM, higher SUA levels are associated with higher UAE, lower eGFR, and higher prevalence of DN, but not DR.

Glycogen synthase kinase 3β hyperactivity in urinary exfoliated cells predicts progression of diabetic kidney disease

Burgeoning evidence points to glycogen synthase kinase (GSK)3β as a key player in diverse kidney diseases. However, as a pivotal transducer of the insulin signaling pathway, the role of GSK3β in diabetic kidney disease remains uncertain. In db/db mice, renal expression of total and activated GSK3β was increasingly elevated. This preceded the development of diabetic kidney disease, and correlated with the progression of signs of diabetic kidney injury, including albuminuria and extracellular matrix accumulation in glomeruli and tubulointerstitia. Invitro, exposure of glomerular podocytes, mesangial cells, and renal tubular cells to a diabetic milieu induced GSK3β overexpression and hyperactivity, which seem essential and sufficient for eliciting diabetic cellular damages in kidney cells, because the cytopathic effect of the diabetic milieu was mitigated by GSK3β knockdown, but was mimicked by ectopic expression of constitutively active GSK3β even in the normal milieu. In consistency, kidney biopsy specimens procured from patients with varying stages of diabetic nephropathy revealed an amplified expression of total and activated GSK3β in glomeruli and renal tubules, associated with the severity of diabetic nephropathy. Moreover, in retrospective cohorts of type 2 diabetic patients that were followed for over five years, the relative activity of GSK3β in banked urinary exfoliated cells represented an independent risk factor for development or progression of renal impairment. Furthermore, receiver operating characteristic curve analysis demonstrated that GSK3β activity in urinary exfoliated cells provided much better power than albuminuria in discriminating diabetic patients with progressive renal impairment from those with stable kidney function. Thus, renal expression and activity of GSK3β are amplified in experimental and clinical diabetic nephropathy. Hence, GSK3β in urinary exfoliated cells may serve as a novel biomarker for predicting diabetic kidney disease progression.

The prognostic value of lymphocyte-to-monocyte ratio in nephropathy of type 2 diabetes mellitus

Background Inflammatory markers like interleukin-1, 6, and 8, transforming growth factor-β (TGF-β)1, and tumor necrosis factor-α have been found to be associated with diabetic nephropathy (DN), indicating that its pathogenesis may be inflammatory. These inflammatory markers are not routinely used, so, creating the need for easily and routinely done markers aim to enhance the prognostic process of diabetic microvascular complications. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) can be routinely assessed, in addition to being considered as predictors for the survival of patients in renal diseases and malignancies. Aim The aim was to evaluate the prognostic value of LMR in DN of type 2 diabetes mellitus, and to compare it with other ratios: NLR and PLR. Patients and methods A case–control study including 100 type 2 diabetes mellitus patients and 25 apparently healthy controls. It was carried out at the inpatient and outpatient clinics, Internal Medicine Department, Al-Azhar University Hospital, New Damietta. Three groups were formed according to urinary albumin-to-creatinine ratio; group I, type 2 diabetics with normoalbuminuria, group II, type 2 diabetics with increased albuminuria, with further division into group IIA: with microalbuminuria/group IIB: macroalbuminuria or overt DN, and group III: controls. Full history, clinical examination, and laboratory tests: urinary albumin-to-creatinine ratio and complete urine analysis, complete blood count with assessment of LMR, NLR, and PLR, beside, blood sugar, HbA1c, renal function with assessment of estimated glomerular filtration rate, liver function, abdominal ultrasonography, fundus examination, and ECG were done for all the participants. Results The LMR mean was 2.4/2.8/3.2/2.1 in group I/IIA/IIB/III, respectively, showing the increasing ratios in parallel with the progression of DN severity and albuminuria through the groups, with the highest ratios in group IIB of overt DN. The NLR mean was 1.8/2.9/3.7/1.2 and the PLR mean was 175, 8/249, 2/277, 3/108, 3 in the corresponding group. Receiver operating characteristic curve analysis for ratios between groups I and IIA demonstrated that with a best cutoff point of 2.66 for the LMR, the sensitivity was 44%, the specificity: 92% (the ability of the LMR to predict DN risk); 2.2 for the NLR, the sensitivity: 84%, the specificity: 98%; 207 for the PLR, the sensitivity: 72%, and the specificity: 80%. So, in predicting the DN risk, NLR came first as regards the specificity followed by LMR and then PLR, but followed by PLR and then LMR as regards the sensitivity. Conclusion LMR may be considered as a surrogate inflammatory marker for DN in early stages and in between stages, but it is not better than NLR as a screening tool for DN diagnosis.

The association between the red cell distribution width and diabetic nephropathy in patients with type-2 diabetes mellitus

Background: Red cell distribution width (RDW) has been reported to be involved in metabolic syndrome and cardiovascular events. Patients with diabetic nephropathy (DN) are often found to be with high level of RDW. The aim of this study was to explore whether RDW was associated with DN severity and progression in patients with type-2 diabetes mellitus (T2DM).Methods: A total of 175 T2DM patients with biopsy-proven DN were enrolled. The baseline clinical and pathologic data of these patients was extracted from the medical records. The patients then were divided into two groups based on the median (13.6%) of RDW level; group 1: <13.6% and group 2: ≥13.6%. The effect of RDW level on the renal outcomes was evaluated by using cox regression analysis.Results: Compared with the patients with lower RDW level, the patients with higher level of RDW had higher proportions of female, longer DM duration, lower levels of eGFR, albumin and hemoglobin, and more serious glomerular damage. Moreover, the RDW levels were negatively corrected with eGFR (r = −0.283, p < 0.001), but positively related with proteinuria (r = 0.227, p = 0.003). In the follow-up period, 81(46.3%) patients had reached ESRD from baseline. Importantly, the Cox regression analyses showed that the levels of RDM had a significant effect on the risk of progression to ESRD (HR = 1.92, p < 0.01), albeit not emerged as an independent predictor.Conclusions: These data indicated that the levels of RDW were significantly associated with increased risk of progression to ESRD in patients with DN, despite did not an independent predictor.