Marker Of Diabetic Nephropathy Research Articles

Complement 3a and Complement 5a as Biochemical Markers in Diabetic Nephropathy

Complement 3a and Complement 5a as Biochemical Markers in Diabetic Nephropathy

Podocalyxin in the onset of nephropathy among Indian type 2 diabetes mellitus patients.

The diabetic nephropathy is one of the most prevalent microvascular complications with type 2 diabetes mellitus. The most accurate and widely used marker for diabetic nephropathy is microalbuminuria and it is also regarded as conventional method. However, it is not a sensitive or specific nephropathy biomarker. Therefore, it is of interest to evaluate the role of podocalyxin to predict early onset of nephropathy in patients with type 2 diabetes mellitus. This cross - sectional study is conducted on 150 subjects. Among these 150 T2DM patients (Group 2: T2DM with normoalbuminuria and Group 3: T2DM with microalbuminuria) and 50 were age, gender and BMI matched healthy controls (Group 1). The biochemical and experimental parameters was analyzed. T2DM patients have higher levels of urine podocalyxin. This level was significantly elevated in patients with T2DM with microalbuminuria than normoalbuminuria. Urinary podocalyxin levels and HbA1c were found to be positively correlated. Thus, urinary podocalyxin is useful as early predictable marker for nephropathy in patients with type 2 diabetes mellitus.

Neutrophil to lymphocyte ratio as a marker of diabetic nephropathy

Aim of the study is to estimate and analyze neutrophil to lymphocyte ratio (NLR) in diabetes mellitus as a marker of diabetic nephropathy (DN). Forty individuals with DN and forty patients with diabetes mellitus without nephropathy were enrolled. Inclusion criteria included patients with diabetic nephropathy (albuminuria >30 mg/day and/or eGFR <60 mL/min/1.73 m2) in the absence of additional kidney damage symptoms. Complete blood count, glycated haemoglobin (HbA1c), 24-hour urine albumin and serum creatinine were evaluated and compared. The mean NLR of the patients with DN (Cases) was 3.09 ± 0.88 (1.34-4.91) and in patients with diabetes mellitus only (Controls) it was 2.17 ± 0.69 (0.89-3.98). The correlation between urinary albumin excretion (p value =0.0004) and estimated glomerular filtration rate (p value =0.0002) also came out positive and negative respectively. Based on unpaired t-test, the difference between NLR values among the group came out statistically highly significant (p < 0.05). Thus, the NLR in both groups was not comparable. NLR was substantially higher in diabetic nephropathy patients compared to diabetes mellitus patients. Thus, NLR provides us with a simple and low-cost assessment that may be employed as a predictive instrument to diagnose diabetic nephropathy at a preliminary phase.

Monocytes to High-Density lipoprotein Cholesterol Ratio as a New Marker for Diabetic Nephropathy and Retinopathy

Monocytes to High-Density lipoprotein Cholesterol Ratio as a New Marker for Diabetic Nephropathy and Retinopathy

Fatty Acid Binding Protein (1 & 2) as Markers of Diabetic Nephropathy in Elderly Patients with Type 2 Diabetes Mellitus

Fatty Acid Binding Protein (1 & 2) as Markers of Diabetic Nephropathy in Elderly Patients with Type 2 Diabetes Mellitus

Study of the reliability of serum vascular endothelial growth factor and its soluble receptor as markers of diabetic nephropathy in type 2 diabetes patients

The levels of circulating angiogenic and anti-angiogenic factors, namely vascular endothelial growth factor–A (VEGF-A) and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), have been linked to the development of renal dysfunction due to the proliferation of microvasculature within the kidneys of type 2 diabetic (T2DM) patients. The study aims to scrutinize serum levels of VEGF and sVEGFR-1 in a sample of Iraqi diabetic nephropathy patients to support their reliability as markers for the prediction of nephropathy in type 2 diabetes mellitus patients as well as to assess the ACE inhibitor’s effect on the levels of these two markers. Method: The ninety participants of this case-control study were split into three groups: thirty-five patients with T2DM and an equal number of patients with DN and the third group involve twenty apparently healthy individuals as the control group. The two diabetic groups have been further divided into four groups according to the ACE inhibitors use. Laboratory measurements involve the glycemic indices, renal function test with serum VEGF-A and sVEGFR-1. Results: the median serum levels of VEGF-A show valuable discrepancies between the three groups (p-value<0.05) but for sVEGFR-1 it doesn’t show a notable difference between the DM and the DN groups only(p-value> 0.05).

Assessment of SH3YL1 protein as a marker for diabetic nephropathy in type 2 diabetes mellitus

Assessment of SH3YL1 protein as a marker for diabetic nephropathy in type 2 diabetes mellitus

Role of Diltiazem in Combination with Glimepiride in Diabetic Nephropathy in Experimental-induced NIDDM Model

Diabetic nephropathy (DN) is a major cause of end-stage renal disease in the general population. It is estimated that DN will eventually develop in about 40% of all patients with diabetes; therefore, the prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin (STZ) (90 mg/kg) in neonatal rats, and then, these rats were treated with diltiazem (15.0 mg/kg) in combination with glimepiride (0.5 mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5 mg/kg). DN markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of diltiazem with glimepiride is more effective in amelioration of DN than pioglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate, and augmented tumor necrosis factor-a signaling during the development of STZ-induced type 2 DN.

Potential Role of N-Cadherin in Diagnosis and Prognosis of Diabetic Nephropathy.

Diabetic nephropathy (DN) is a serious complication of diabetes affecting about half the people with diabetes and the leading cause of end stage renal disease (ESRD). Albuminuria and creatinine levels are currently the classic markers for the diagnosis of DN. However, many shortcomings are arising from the use of these markers mainly because they are not specific to DN and their levels are altered by multiple non-pathological factors. Therefore, the aim of this study is to identify better markers for the accurate and early diagnosis of DN. The study was performed on 159 subjects including 42 control subjects, 50 T2D without DN and 67 T2D subjects with DN. Our data show that circulating N-cadherin levels are significantly higher in the diabetic patients who are diagnosed with DN (842.6 ± 98.6 mg/l) compared to the diabetic patients who do not have DN (470.8 ± 111.5 mg/l) and the non-diabetic control group (412.6 ± 41.8 mg/l). We also report that this increase occurs early during the developmental stages of the disease since N-cadherin levels are significantly elevated in the microalbuminuric patients when compared to the healthy control group. In addition, we show a significant correlation between N-cadherin levels and renal markers including creatinine (in serum and urine), urea and eGFR in all the diabetic patients. In conclusion, our study presents N-cadherin as a novel marker for diabetic nephropathy that can be used as a valuable prognostic and diagnostic tool to slow down or even inhibit ESRD.

Urinary transferrin and proinflammatory markers predict the earliest diabetic nephropathy onset

Aim This study aimed to determine the earliest markers of diabetic nephropathy (DN) onset with discriminative potentials from controlled diabetes (CD). Methods Sixty male Wistar rats were allocated into three groups (20/group), the two diabetic groups CD and DN received 45 and 65 mg/kg STZ in 0.1 mole/L citrate buffer, respectively, while the control group received only the vehicle. Serum/urinary levels of glomerular, tubular, oxidative and proinflammatory markers were weekly monitored. Results Each diabetic group showed a different pattern of inflammatory, oxidative and signs of nephropathy along the study period, but none had a discriminative power until the fourth week. At this time point, levels of urinary transferrin, serum/urinary IL-6 and TNF-α as well as urinary IL-18 were significantly higher in DN group compared to CD (p = 0.0217, <0.0001, 0.0005, 0.0004, 0.0006, 0.0019, respectively). Predictive thresholds of these markers were calculated by receiver operating characteristic (ROC) curve that showed area under curve (AUC) of 0.9375 for transferrin with cut-off value of 35.2 mg/dL and 1.000 for serum/urinary IL-6 and TNF-α and urinary IL-18 with cut-of values 224.1, 82.11, 6.596, 125.9 and 21.86 pg/mL, respectively. Conclusion Urinary transferrin and the inflammatory endpoints proposed in this study might represent promising biomarkers for the early DN onset.

Diabetic Nephropathy – possibilities of early laboratory diagnostics and course prediction (review of literature)

The medical and social significance of diabetes mellitus is determined by a progressive increase in the incidence of the disease, as well as the development of disabling and reducing the quality of life of macro- and microvascular complications in patients of working age, in particular, with the development of diabetic nephropathy (DN), which develops in one third of patients with type 1 and 2 diabetes. DN is the third leading cause of death after diseases of the cardiovascular system and oncological pathologies. In this regard, the identification of DN at the early stages is an important task both from the standpoint of prevention and a more favorable prognosis of the course of diabetes. This review presents data on the possibilities of early diagnosis of DN using blood and urine biomarkers, as well as information on their diagnostic and prognostic value. The analysis of the interpretation of the indicator of microalbuminuria in type 1 and 2 diabetes was carried out. In addition, the literature data of recent years on the informative value of determining markers of podocyte damage, on the role of oxidative stress products, immune-inflammatory factors, and vascular endothelial growth factor in the process of the onset and development of DN are presented. The possibility of their practical use for the diagnosis of DN in clinical practice is discussed. The literature search for this review was carried out using the databases of the RSCI, CyberLeninka, Scopus, Web of Science, MedLine, PubMed for the period from 2011 to 2021. using the following keywords: diabetes mellitus, diabetic nephropathy, markers of diabetic nephropathy; kidney damage, early diagnosis of diabetic nephropathy.

Epigenetic Alterations in Podocytes in Diabetic Nephropathy.

Recently, epigenetic alterations have been shown to be involved in the pathogenesis of diabetes and its complications. Kidney podocytes, which are glomerular epithelial cells, are important cells that form a slit membrane—a barrier for proteinuria. Podocytes are terminally differentiated cells without cell division or replenishment abilities. Therefore, podocyte damage is suggested to be one of the key factors determining renal prognosis. Recent studies, including ours, suggest that epigenetic changes in podocytes are associated with chronic kidney disease, including diabetic nephropathy. Furthermore, the association between DNA damage repair and epigenetic changes in diabetic podocytes has been demonstrated. Detection of podocyte DNA damage and epigenetic changes using human samples, such as kidney biopsy and urine-derived cells, may be a promising strategy for estimating kidney damage and renal prognoses in patients with diabetes. Targeting epigenetic podocyte changes and associated DNA damage may become a novel therapeutic strategy for preventing progression to end-stage renal disease (ESRD) and provide a possible prognostic marker in diabetic nephropathy. This review summarizes recent advances regarding epigenetic changes, especially DNA methylation, in podocytes in diabetic nephropathy and addresses detection of these alterations in human samples. Additionally, we focused on DNA damage, which is increased under high-glucose conditions and associated with the generation of epigenetic changes in podocytes. Furthermore, epigenetic memory in diabetes is discussed. Understanding the role of epigenetic changes in podocytes in diabetic nephropathy may be of great importance considering the increasing diabetic nephropathy patient population in an aging society.

Value of Serum Copeptin Estimation for the Diagnosis of Diabetic Nephropathy in Type 2 Diabetes Mellitus Patients

Background: Serum copeptin, the terminal part of the arginine vasopressin (AVP), is stable in plasma. The AVP is increased in diabetic patients and may play a role in the development of diabetic kidney disease. Objective: To evaluate the role of serum copeptin in the diagnosis of diabetic nephropathy in type-2 diabetes mellitus. Patients and Methods: 40 type-2 diabetes mellitus (T2DM) patients; divided into two groups, (20 with poor glycemic control, and 20 with good glycemic control), in addition to 20 non-diabetic healthy control subjects. The following investigations had been made; HbA1C, FBS, blood urea, serum creatinine and sodium, creatinine clearance (Ccr), glomerular filtration rate (eGFR), urinary protein, and urinary sodium. Serum copeptin levels were measured using an enzyme-linked immunoassay (ELISA). Results: Serum copeptin levels were significantly higher in (T2DM) patients with poor glycemic control than in (T2DM) patients with good glycemic control compared to the healthy control group. There was a significant positive correlation between serum copeptin and FBS, HbA1C, blood urea, serum creatinine, urinary Na, and 24-hour urinary protein, and a significant negative correlation with serum Na, eGFR, and creatinine clearance. The receiver operating characteristic (ROC) curve for the validity of serum copeptin, as a marker for diabetic nephropathy, at cutoff point 3452 pg/ml, showed 90% sensitivity, and 95% specificity. Conclusion: Serum copeptin is independently related to markers of kidney injury in T2DM and may be used as a marker for diabetic nephropathy.

Relationship between biochemical parameters and glomerular filtration rate by Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes

Annotation. The aim of research is to study correlations of biochemical parameters with glomerular filtration rate according to Cockcroft-Gault, CKD EPI and cystatin C in patients with type 1 diabetes (T1D). 78 men and 62 women aged 22-26 years with T1D were examined. The control group consisted of 8 almost healthy men and 13 almost healthy women of the same age. The level of microalbuminuria and cystatin C was determined in all patients by enzyme-linked immunosorbent assay. Biochemical evaluation of fasting blood glucose, glucose 2 h after exercise, mean value of glucose, creatinine, GFR according to Cockcroft-Gault, CKD EPI and GFR according to cystatin C. Correlation analysis between the series of indicators was calculated using Spearman statistics in the license package “Statistica 5.5”. In patients with T1D, there is no significant correlation in normoalbuminuria between urinary albumin levels and GFR by Cockcroft-Gault (in women), CKD EPI and cystatin C (in all study groups). No significant correlations were found between urinary albumin levels and GFR by Cockcroft-Gault, CKD EPI and cystatin C in the proteinuria group. The correlation analysis revealed in the general group and in women with proteinuria an association between the average value of blood glucose and low GFR levels by Cockcroft-Gault, CKD EPI (negative medium strength correlation r = from -0.31 to -0.46) and elevated creatinine (positive strong correlation r=0.62 and r=0.91), indicating an unfavorable role of hyperglycemia in the development of nephropathy in patients with T1D. Higher correlations of cystatin C with GFR by cystatin C (r= -1.0) than by creatinine with GFR by Cockcroft-Gault (r = from - 0.63 to 0.99) and by CKD EPI (r = from -0.73 to -0.99) were demonstrated. The strength of the correlations increases from GFR by Cockcroft-Gault to GFR by cystatin C. Correlations between creatinine and GFR by Cockcroft-Gault and CKD EPI were characterized by sex differences (greater in women) and an increase in their strength synchronously with an increase in urinary microalbumin. At the same time, there is a consistently high identical value (r= -1.0) of correlations of the level of cystatin C with GFR on cystatin C in all comparison groups. Neither the sex factor nor the degree of albuminuria affected the change in their strength. Only men with microalbuminuria had moderate feedback between creatinine and cystatin C (r= -0.46). In all groups of women, in the general group and in men with normoalbuminuria and proteinuria, the correlations are close to zero, which may indicate the absence of a linear relationship between these indicators. When dividing the sample according to the level of cystatin C between the level of creatinine and the level of cystatin C, the following were found: medium feedback (r= -0.37) in the general group with normoalbuminuria and cystatin C&gt;0.9; moderate feedback (r= -0.37) in the general group and in men with proteinuria and cystatin C&lt;0.9 strong feedback (r= -0.90 and r= -0.88). Thus, in the course of correlation analysis it was found: microalbuminuria is not an independent marker of diabetic nephropathy (DN), starting from preclinical and ending with a clinically manifested stage of this complication; for timely and adequate diagnosis of DN it is necessary to measure the level of albumin, creatinine and cystatin C, which are independent markers of renal dysfunction; cystatin C gives a more accurate approximation to the actual values of GFR than creatinine; cystatin C is more sensitive in the early stages, and creatinine is a marker of later stages of DN development; hyperglycemia is the main initiating metabolic factor in the development and progression of DN.

FC 086GLOMERULI PROTEOME ANALYSIS REVEALS EARLY DIFFERENCES BETWEEN PRE-EXISTING AND DE-NOVO TYPE 2 DIABETES IN HUMAN RENAL ALLOGRAFTS

Abstract Background and Aims Diabetes mellitus, either preexisting or developing after kidney transplantation remains a crucial clinical problem. The aim of this study is to compare the proteome of histologically normal glomeruli from normoglycemic (NG), T2DM, and PTDM patients one year after kidney transplantation to identify novel early biomarkers detectable prior to the development of histologically visible diabetic nephropathy. Method We comparatively analyzed the proteome of histologically normal glomeruli from normoglycemic (NG) recipients, and recipients with pre-existing type 2 diabetes mellitus (T2DM), or post-transplant diabetes mellitus (PTDM), in protocol biopsies obtained one year after kidney transplantation. Glomerular cross-sections were microdissected in core biopsies from 8 NG, 8 PTDM and 8 T2DM kidney transplant recipients. Proteome was determined by liquid chromatography-tandem mass spectrometry. Relative differences in protein abundance and significantly dysregulated pathways were analyzed. Results Proteins related to immune response and inflammation, transport regulation and cell organization and communication, including the nephrin family, were more abundant in NG, as compared to the combined groups of diabetic patients. Proteins involved in cell morphogenesis and adhesion were less abundant in PTDM, as compared to T2DM. In contrast, CCT3, CCT4 and CNDP2 diabetic nephropathy markers, LDHB and tacrolimus binding protein FKBP1A were significantly overrepresented in glomeruli from PTDM, as compared to T2DM patients. Conclusion These data suggest that glomerular proteome profile differentiates PTDM from NG and T2DM, and disruption of cell-cell interactions at molecular level represents an early event in PTDM development.

Microalbuminuria and its associations with clinical profile and complications of type 2 Diabetes Mellitus

Background and Aims: Microalbuminuria is an early marker of diabetic nephropathy, which accounts for a significant reduction in life expectancy of diabetic patients. Timely detection of microalbuminuria facilitates appropriate preventive and therapeutic approaches to minimize risks. The aim of this study is to determine the prevalence and association of microalbuminuria with clinical profile and complications of type 2 diabetes mellitus.&#x0D; Methods: This study was a descriptive, cross sectional study involving 100 diabetic subjects between July 2018 to January 2019 at Bir Hospital. Microalbuminuria (mg/dl) was defined as spot urine albumin to creatinine ratio of 30-300 mg/g (Kidney Disease Improving Global Outcomes guidelines) in a single spot urine sample. Statistical analysis was done using Statistical package for the social sciences version 20.&#x0D; Results: Microalbuminuria was found in 35% of the sample and the rate was significantly higher among males (P =0.027). Microalbuminuria was significantly related to Body mass index (P = 0.018), duration of diabetes (P =0.000), retinopathy (P = 0.000) and stroke (P = 0.043). No statistically significant relation was found between microalbuminuria and age (P = 0.366), hypertension (P = 0.208), HbA1c (P = 0.098), dyslipidemia (P = 0.171) and ischemic heart disease (P = 0.651).&#x0D; Conclusions: This study shows high prevalence of microalbuminuria in Nepalese Type 2 diabetes mellitus. Screening for microalbuminuria should be done for all the type 2 diabetes mellitus patients for early detection and management of complications of diabetes mellitus.

Assessment of plasma fibrinogen as a marker of diabetic nephropathy

Diabetes is one of the most common chronic hyperglycemic syndrome. Diabetic Nephropathy is one of the major complications of DM characterized by persistent albuminuria, increased arterial blood pressure, a relentless decline in glomerular filtration rate (GFR) &amp; a high risk of cardiovascular morbidity &amp; mortality. The biological marker of DN is fibrinogen. Fibrinogen, is increased in diabetic patients. An increase in plasma fibrinogen levels is also considered an independent risk factor for diabetic nephropathy. Fibrinogen is the major coagulation protein in blood.To find out whether the levels of Plasma Fibrinogen levels can be used as markers for the early diagnosis of DN.A case control study. The study includes total of 150 patients, of which 50 were diabetic without any complications, 50 were diabetic nephropathy patients and remaining 50 were age matched healthy controls. The mean plasma fibrinogen level in control group was 190.34 ± 72.83 mg/dl. The mean plasma fibrinogen levels in DM &amp; DN groups were 522.76 ± 115.79 mg/dl &amp; 657.64 ± 124.61 mg/dl respectively. In our study, fibrinogen levels were increased significantly in DM group compared to controls which was further increased in DN group. Hence above studies interpret that fibrinogen increases in diabetes with complications.Fibrinogen correlated positively with FBS, HbA, TC, triglyceride, LDL, Blood Urea, serum creatinine, TC/HDL, LDL/HDL &amp; urine A/C ratio in both DM &amp; DN group, whereas there was negative correlation of fibrinogen with HDL &amp; eGFR. Thus fibrinogen could be used as early biomarkers for the diagnosis of DN.

The effect of probiotics on lipid profile & anthropometric indices in diabetic nephropathy; a systematic review and meta-analysis of clinical trials.

Recent trials have demonstrated the possible improvements in lipid profile & anthropometric indices after probiotics supplementation. We aimed to reanalyze the related literature to explore the efficacy of probiotics in Diabetic Nephropathy (DN) patients. PubMed, Embase, Web of science, google scholar, Scopus, and Cochrane Library databases were systematically searched to find the related data on diabetic nephropathy population. All Randomized controlled trials (RCTs) that investigated the effect of probiotics on serum lipid markers (High-Density Lipoprotein [HDL], Triglyceride, Total Cholesterol, TC-to-HDL ratio, Low-Density Lipoprotein, Very Low-Density Lipoprotein) and anthropometric indices (Body Weight, Body Mass Index, waist-to-hip ratio) were included (PROSPERO No.CRD42020186189). Meta-analysis was performed using the random-effect model. Of 156 studies, seven were eligible for inclusion. Lipid biomarkers had a marginal reduction (except for HDL; WMD = 2.59mg/dl; 95% CI = -0.28, 5.47; P = 0.077); whereas anthropometric indices increased in a non-significant manner. There is limited evidence to support the efficacy of probiotics for the modulation of lipid profile and anthropometric indices in DN patients. Probiotics did not beneficial effect on lipid profile & anthropometric markers in Diabetic Nephropathy; anyway, more trials should be conducted. The online version contains supplementary material available at 10.1007/s40200-021-00765-8.

Matrix metalloproteinase-9 gene polymorphism (-1562 C/T) and its correlation with diabetic nephropathy

BackgroundMatrix metalloproteinase 9 (MMP-9) is an important inflammatory marker in diabetic nephropathy. Many studies assessed the association between MMP-9 gene polymorphism and different microvascular complications of type 2 diabetes mellitus, though the results were inconclusive and need further exploration. Our study aimed to assess the association between MMP-9 -1562C/T gene polymorphism and diabetic nephropathy in patients with type 2 diabetes mellitus.ResultsTaking CC genotype of rs3918242 (MMP-9-1562C/T SNP) as the reference genotype and C as the reference allele, TT genotype, T allele showed significantly lower frequency in diabetic nephropathy group than without nephropathy (2.9% versus 20%, 20% versus 35.7% respectively), with the possible significant protective effect against diabetic nephropathy development (OR = 0.269, 0.450 respectively); it was considered as an independent predictor for diabetic nephropathy occurrence.ConclusionsThis study suggested that T allele of MMP-9 -1562C/T single nucleotide polymorphism had a protective role against diabetic nephropathy development and also had a role for early prediction of patients susceptible to this complication, so it helps in prevention and management of those patients.

Tryptophan Level as a Potential Prognostic Marker of Diabetic Nephropathy

Tryptophan Level as a Potential Prognostic Marker of Diabetic Nephropathy