Early Stage Of Diabetic Nephropathy Research Articles

Systemic immune-inflammatory index and systemic inflammation response index in predicting renal impairment in children with type 1 diabetes mellitus

BackgroundThe aim of this study was to investigate the role of systemic immune-inflammatory index and systemic inflammation response index in predicting early renal impairment in children with type 1 diabetes mellitus (T1DM).MethodsThis is a retrospective cohort study which searched the electronic medical records of patients consecutively admitted to Pediatric Endocrinology Unit with the diagnosis of type 1 diabetes mellitus between August 2022 and July 2023.ResultsA total of 100 children with the diagnosis of T1DM were enrolled in the study. Early stage diabetic nephropathy (DN) was found in 34 patients. Patients with DN showed significantly higher HbA1C, microalbuminuria, cholesterol, TLC, platelet, neutrophil count, NLR, PLR, SII, and SIRI than the DM without DN. It was discovered that DN was independently correlated with NLR, PLR, SII, and SIRI.ConclusionsSIRI and SII are easily available and affordable inflammatory markers that may serve as independent early predictors of diabetic nephropathy in individuals with type 1 diabetes.

Fucoidan Improves Early Stage Diabetic Nephropathy via the Gut Microbiota-Mitochondria Axis in High-Fat Diet-Induced Diabetic Mice.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Fucoidan, a polysaccharide containing fucose and sulfate group, ameliorates DN. However, the underlying mechanism has not been fully understood. This study aimed to explore the effects and mechanism of fucoidan on DN in high-fat diet-induced diabetic mice. A total of 90 C57BL/6J mice were randomly assigned to six groups (n = 15) as follows: normal control (NC), diabetes mellitus (DM), metformin (MTF), low-dose fucoidan (LFC), medium-dose fucoidan (MFC), and high-dose fucoidan (HFC). A technique based on fluorescein isothiocyanate (FITC-sinistin) elimination kinetics measured percutaneously was applied to determine the glomerular filtration rate (GFR). After 24 weeks, the mice were sacrificed and an early stage DN model was confirmed by GFR hyperfiltration, elevated urinary creatinine, normal urinary albumin, tubulointerstitial fibrosis, and glomerular hypertrophy. Fucoidan significantly improved the GFR hyperfiltration and renal fibrosis. An enriched SCFAs-producing bacteria and increased acetic concentration in cecum contents were found in fucoidan groups, as well as increased renal ATP levels and improved mitochondrial dysfunction. The renal inflammation and fibrosis were ameliorated through inhibiting the MAPKs pathway. In conclusion, fucoidan improved early stage DN targeting the microbiota-mitochondria axis by ameliorating mitochondrial oxidative stress and inhibiting the MAPKs pathway.

Fibroblast Growth Factor 21 and 23 as Biomarkers for Early Stage Diabetic Nephropathy in Type 2 Diabetic Patients

Fibroblast Growth Factor 21 and 23 as Biomarkers for Early Stage Diabetic Nephropathy in Type 2 Diabetic Patients

Oleuropein Supplementation Ameliorates Long-Course Diabetic Nephropathy and Diabetic Cardiomyopathy Induced by Advanced Stage of Type 2 Diabetes in db/db Mice.

Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of diabetic nephropathy and diabetic cardiomyopathy. However, the efficacy of OP on the long-course of these diabetes complications has not been investigated. Therefore, in this study, to investigate the relieving effects of OP intake on these diseases, and to explore the underlying mechanisms, db/db mice (17-week-old) were orally administrated with OP (200 mg/kg bodyweight) for 15 weeks. We found that OP reduced expansion of the glomerular mesangial matrix, renal inflammation, renal fibrosis, and renal apoptosis. Meanwhile, OP treatment exerted cardiac anti-fibrotic, anti-inflammatory, and anti-apoptosis effects. Notably, transcriptomic and bioinformatic analyses indicated 290 and 267 differentially expressed genes in the kidney and heart replying to OP treatment, respectively. For long-course diabetic nephropathy, OP supplementation significantly upregulated the cyclic guanosine monophosphate-dependent protein kinase (cGMP-PKG) signaling pathway. For long-course diabetic cardiomyopathy, p53 and cellular senescence signaling pathways were significantly downregulated in response to OP supplementation. Furthermore, OP treatment could significantly upregulate the transcriptional expression of the ATPase Na+/K+ transporting subunit alpha 3, which was enriched in the cGMP-PKG signaling pathway. In contrast, OP treatment could significantly downregulate the transcriptional expressions of cyclin-dependent kinase 1, G two S phase expressed protein 1, and cyclin B2, which were enriched in p53 and cellular senescence signal pathways; these genes were confirmed by qPCR validation. Overall, our findings demonstrate that OP ameliorated long-course diabetic nephropathy and cardiomyopathy in db/db mice and highlight the potential benefits of OP as a functional dietary supplement in diabetes complications treatment.

Study of Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 in Patients with Type 2 Diabetes Mellitus Nephropathy.

There is a need for accurate and rapid biomarkers for the early diagnosis of diabetic nephropathy (DN). We aimed to study the accuracy of urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary kidney injury molecule-1 (uKIM-1), and blood NGAL (bNGAL) in type 2 diabetics as biomarkers for diagnosis of DN. The study was a retrospective case-control study that included 30 control subjects, 40 diabetics with normo-albuminuria < 30 mg/g and eGFR > 60 mL/minute/1.73 m2, and 30 diabetics with albuminuria > 30mg/g and eGFR < 60mL/minute/1.73 m2. Blood and urine samples were obtained to determine levels of bNGAL, uNAGAL, and uKIM1. There was a significant increase in bNGAL, uNGAL, uKIM 1, uNGAL/creatinine and uKIM 1/creatinine among diabetics with albuminuria compared to diabetics with normoalbuminuria and normal control (p < 0.001 for all markers). For diagnosis of early DN, both bNGAL and uKIM 1 had sensitivity and specificity of 100% for each at cutoff values of 322.5 pg/mL and 74.25 ng/mL, respectively. uNGAL had a sensitivity of 97.5% and a spec-ificity of 100% at a cutoff point of 565 ng/mL. uKIM1/creatinine at a cutoff of 51.2 had a sensitivity of 100% and specificity of 100%. The present study highlights the accuracy of urinary KIM1 and NGAL and blood NGAL as biomarkers for the diagnosis of nephropathy in the early stage of diabetic nephropathy. There were positive correlations with kidney function tests creatinine, blood urea nitrogen, and the presence of albuminuria.

&lt;i&gt;Siddha&lt;/i&gt; Therapeutic Approach to Diabetic Nephropathy – A Review

Diabetic Nephropathy (DN) is a severe kidney illness that presents with proteinuria, enlarged glomeruli, reduction in the process of glomerular filtration, and fibrosis of the kidneys. Approximately one-third of all instances of diabetes globally are brought to diabetic nephropathy, a common cause of end-stage kidney disease. In Siddha’s literature, the complications of Diabetes mellitus were expressed as ten Avathaigal in the Neerizhivu noi chapter. The feature of Avathaigal 1 to 7 depicts some of the clinical outcomes of Diabetic Nephropathy. The manifestation of clinical features in final stage Diabetic Nephropathy includes oliguria, fatigue, anorexia, nausea, vomiting, itching and dryness of skin, drowsiness, numbness and swelling in the limbs, muscle twitching or cramps, bone pain, breathlessness, increased thirst, sleep disturbance, and sexual problems. Oxidative stress is the standard mechanism involved in developing diabetic kidney disease. Most of the Siddha medicines used for managing diabetic Nephropathy are herbal formulations, and they protect against damage to the renal tubules due to their significant antioxidant property. This review summarizes the pathophysiology of Diabetic Nephropathy and the evidence for using Siddha herbal formulations to treat diabetic Nephropathy. For treating early-stage diabetic Nephropathy, Siddha practices primarily emphasize using herbal formulations; however, yoga therapy, diet, and other exercises are also included in Siddha treatment modalities.

Relationship between plasma leucine-rich α-2-glycoprotein 1 and urinary albumin excretion in patients with type 2 diabetes.

To explore the relationship between plasma leucine-rich α-2-glycoprotein 1 (LRG1) level and the degree of urinary albumin excretion in patients with type 2 diabetes. We evaluated 332 patients with type 2 diabetes in a cross-sectional study. The plasma LRG1 level differed significantly according to the quartiles of urinary albumin excretion (Q1 [<7.7 mg/g], 17.1 μg/mL; Q2 [7.7-15.0 mg/g], 17.5 μg/mL; Q3 [15.1-61.4 mg/g], 18.6 μg/mL; Q4 [≥61.5 mg/g], 22.3 μg/mL; p for trend = 0.003) under adjustment with other covariates. A positive correlation was found between plasma LRG1 level and urinary albumin excretion (ρ = 0.256, p <0.001). According to a multivariate model, the association between LRG1 and urinary albumin excretion remained significant, under adjustment for confounding factors (β = 0.285, p <0.001). Plasma LRG1 level was independently associated with urinary albumin excretion in patients with type 2 diabetes. This study suggests that LRG1 may be associated with increased excretion of urinary albumin in the early stages of diabetic nephropathy.

Omega-3 fatty acids supplementation improves early-stage diabetic nephropathy and subclinical atherosclerosis in pediatric patients with type 1 diabetes: A randomized controlled trial

Numerous studies have evaluated the beneficial effects of omega-3 fatty acids on inflammatory, autoimmune and renal diseases. However, data about the effects of omega-3 fatty acids on diabetic kidney disease in type 1 diabetes mellitus (T1DM) are lacking. This randomized-controlled trial assessed the effect of oral omega-3 supplementation on glycemic control, lipid profile, albuminuria level, kidney injury molecule-1 (KIM-1) and carotid intima media thickness (CIMT) in pediatric patients with T1DM and diabetic nephropathy. Seventy T1DM patients and diabetic nephropathy were enrolled with a mean age 15.2±1.96 years and median disease duration 7 years. Patients were randomly assigned into two groups; intervention group which received oral omega-3 fatty acids capsules (1g daily). The other group received a matching placebo and served as a control group. Both groups were followed-up for 6 months with assessment of fasting blood glucose (FBG), HbA1c, fasting lipids, urinary albumin creatinine ratio (UACR), KIM-1 and CIMT. After 6 months, omega-3 fatty acids adjuvant therapy for the intervention group resulted in a significant decrease in FBG, HbA1c, triglycerides, total cholesterol, LDL-cholesterol, UACR, KIM-1 and CIMT, whereas, HDL-cholesterol was significantly higher post-therapy compared with baseline levels and compared with the control group (p<0.05). Baseline KIM-1 levels were positively correlated to HbA1c, UACR and CIMT. Supplementation with omega-3 fatty acids was safe and well-tolerated. Omega-3 fatty acids as an adjuvant therapy in pediatric T1DM patients with diabetic nephropathy improved glycemic control, dyslipidemia and delayed disease progression and subclinical atherosclerosis among those patients. This trial was registered under ClinicalTrials.gov Identifier no. NCT05980026.

Renal ectopic lipid deposition in rats with early-stage diabetic nephropathy evaluated by the MR mDixon-Quant technique: association with the expression of SREBP-1 and PPARα in renal tissue.

Renal ectopic lipid deposition (ELD) plays a significant role in the development of diabetic nephropathy (DN). This study aimed to use the magnetic resonance (MR) mDixon-Quant technique to evaluate renal ELD and its association with the expression of sterol regulatory element binding protein 1 (SREBP-1) and peroxisome proliferator-activated receptor alpha (PPARα) in renal tissue. Seventy male Sprague-Dawley (SD) rats were randomly divided into experimental (n=50) and control groups (n=20). A high-fat diet combined with low-dose streptozotocin (STZ) was administered to the experimental group to establish a type 2 diabetes mellitus (T2DM) model. The rats received renal mDixon-Quant scans and blood lipid and histopathological examinations in batches after the T2DM model was established. According to the histopathological findings, the included rats were stratified into control and early DN groups. Renal fat fraction (FF), blood lipid level, the ratio of the integrated optical density of intracellular lipid droplets and the total area of all the cells (IOD/TAC), and the expression of SREBP-1 and PPARɑ in renal tissue were analyzed. Compared to the controls, renal FF, IOD/TAC, the expression of SREBP-1 in renal tissue, and serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) levels were higher in the early DN group, while the expression of PPARɑ in renal tissue and the high-density lipoprotein (HDL) level were lower (all P values <0.001). Renal FF gradually increased with the progression of disease [r=0.810 (95% CI: 0.675-0.928), P<0.001]. Positive correlations between renal FF and each of the following: TC, TG, LDL, IOD/TAC, and the expression of SREBP-1 [r=0.479 (95% CI: 0.353-0.640, P=0.012), 0.576 (95% CI: 0.283-0.842, P=0.002), 0.441 (95% CI: 0.305-0.606, P=0.021), 0.911 (95% CI: 0.809-0.964, P<0.001) and 0.800 (95% CI: 0.640-0.910, P<0.001), respectively] and negative correlations between renal FF and each of the following: HDL and the expression of PPARɑ [r=-0.611 (95% CI: -0.809 to -0.469, P=0.001) and -0.748 (95% CI: -0.886 to -0.585, P<0.001), respectively] were found. Renal lipid deposition evaluated by the MR mDixon-Quant technique is associated with the blood lipid level, histological fat quantification, and the expression of SREBP-1 and PPARɑ in renal tissue. The renal FF value might serve as a biomarker for better understanding of renal lipid metabolism in early-stage DN.

Reorganization and Suppression of Store-Operated Calcium Entry in Podocytes of Type 2 Diabetic Rats.

Type 2 diabetes mellitus (DM2) is a widespread metabolic disorder that results in podocyte damage and diabetic nephropathy. Previous studies demonstrated that TRPC6 channels play a pivotal role in podocyte function and their dysregulation is associated with development of different kidney diseases including nephropathy. Here, using single channel patch clamp technique, we demonstrated that non-selective cationic TRPC6 channels are sensitive to the Ca2+ store depletion in human podocyte cell line Ab8/13 and in freshly isolated rat glomerular podocytes. Ca2+ imaging indicated the involvement of ORAI and sodium-calcium exchanger in Ca2+ entry induced upon store depletion. In male rats fed a high-fat diet combined with a low-dose streptozotocin injection, which leads to DM2 development, we observed the reduction of a store-operated Ca2+ entry (SOCE) in rat glomerular podocytes. This was accompanied by a reorganization of store-operated Ca2+ influx such that TRPC6 channels lost their sensitivity to Ca2+ store depletion and ORAI-mediated Ca2+ entry was suppressed in TRPC6-independent manner. Altogether our data provide new insights into the mechanism of SOCE organization in podocytes in the norm and in pathology, which should be taken into account when developing pharmacological treatment of the early stages of diabetic nephropathy.

WCN23-0899 Novel insights: differentially expressed tsRNAs modulate the advance of early stage Diabetic Nephropathy in mice

WCN23-0899 Novel insights: differentially expressed tsRNAs modulate the advance of early stage Diabetic Nephropathy in mice

Induction of experimental diabetes and diabetic nephropathy using anomer-equilibrated streptozotocin in male C57Bl/6J mice

Streptozotocin (STZ) is widely used to induce experimental diabetes in murine models. However, the ability to induce diabetic nephropathy (DN) is more challenging. It has been recommended to inject STZ at multiple low doses within 15 min after dissolution due to its alleged instability. However, some studies suggest that STZ is stable for days due to equilibration of its two anomers (α and β), 90 min after dissolution, and that this anomer-equilibrated STZ leads to higher survival rates and persistent hyperglycaemia with minimal weight loss. The aim of this study was to determine an optimal dose of anomer-equilibrated STZ to induce kidney tubular damage and compare it with the more commonly used freshly prepared STZ. We hypothesised that anomer-equilibrated STZ provides a better, reproducible experimental model of diabetes-induced kidney damage with improved animal welfare. Body measurements, fasting glycaemia, insulinemia and renal histology were assessed in male C57Bl/6J at two and six months of age treated with fresh (50 mg/kg) or anomer-equilibrated (dose ranging 35–50 mg/kg) STZ or vehicle control. We demonstrated a dose-dependent effect of anomer-equilibrated STZ on the induction of hypo-insulinaemia and hyperglycaemia, as well as body weight in two-month-old mice. Interestingly, in six-month-old mice STZ leads to body weight loss, independently of STZ preparation mode. Anomer-equilibrated STZ provoked moderate to severe kidney tubule structural damage, resulting in significant kidney hypertrophy, whereas freshly prepared STZ only caused mild alterations. In conclusion, our study proposes that anomer-equilibrated STZ provides a robust murine model of diabetes and early-stage diabetic nephropathy, which can be used to test therapeutic approaches to treat and/or prevent renal damage.

Assesment of serum taurine level as a potential biomarker for early diagnosis of diabetic nephropathy

Objective: Measuring of serum taurine as an early marker to detect and prevent complications of Diabetic nephropathy. Method: Ninty diabetic patients (male and female) were chosen from Ahmed Maher hospital after their approval, eighty patients classified into four groups (diabetic control group, early stage group, before dialysis group, after dialysis group) according to its Complete clinical examination, investigation and biochemical analysis, twenty diabetic controlled patients not suffered from kidney impairment considered as diabetic control group. ten frank healthy non diabetic persons enrolled as volunteers. Complete clinical examination, investigation and biochemical analysis (liver and kidney functions, lipid profile), add to measuring Blood sugar, HbA1c, and the recent biomarker taurine, was measured for all patient and volunteers. Results: The data showed non-significant change in lipid profile, creatinine in urine, and serum Albumine in all patients regarding to control group (P&gt;0.05). that Liver function in all groups demonstrated non significance between groups,but values recorded significant changes in all groups of patients related to frank control group (p&lt;0.05). Kidney function (urea – creatinine) values recorded very highly significant changes in all groups of patients related to frank control group (p&lt;0.00), except controlled diabetic group and Early stage of diabetic nephropathy. also, there is a highly significant changes in blood glucose and HbA1c (P&gt;0.001). On the other hand, the data showed extremely significant decrease in serum taurine in all diabetic patients according to the severity of diabetic nephropathy compared to that recorded in healthy control (P&lt;0.000). Conclusion: Serum taurine is reduced in diabetic patients with advanced conditions of diabetic nephropathy. Taurine Level is considered as an early marker (prognostic) to detect and prevent the diabetic nephropathy complications.

Treatment of early stage diabetic nephropathy using Siddha drug Sirupeelai kudineer - Single Case Study

Background: Nephropathy is one of the major micro-vascular complications of DiabetesMellitus, which can be detected in the earlier stage by the investigation of urinarymicroalbumin excretion level, estimation of ACR and GFR. The Siddha drug SirupeelaiKudineer indicated for the complications of Diabetes Mellitus is selected for this Case study.The efficiency of the drug was reported by measuring the change in Renal function over theperiod of study and the KD QOL assessment. Case description: A male patient of 62 yearswith the history of DM and hypertension since 20 years came to the hospital with complaintsof bilateral pedal oedema, general weakness, frequent nocturnal micturition and weariness oflimbs since last two months. His renal profile and glycaemic index was deranged (SerumCreatinine -1.42 mg/dl; Blood Urea -54.3 mg/dl; Urine Micro albumin -99.45mg/L; UrineCreatinine -74.8 mg/dl; ACR -15.02 mg/mmol; eGFR - 64.5 ml/min; BSL (Fasting) -157mg/dl; BSL (Postprandial) -289 mg/dl). Patient was taking certain oral allopathic medicinesand injection huminsuline 30/ 70 in the dose of 35 units before lunch, and 30 units beforedinner subcutaneously. As per Siddha concept his three humours deranged and seen with theClinical features of Madhumega roga avathaigal and Neeradaippu. He was given Siddhamedicine Sirupeelai kudineer-120ml twice a day for the period of one month. Significantrelief in symptoms and improvement in certain renal parameters was noted in the subject.Conclusion: The clinical and laboratory parameters in this case study suggest that this drugmay be used along with other allopathic drugs in the treatment of Diabetic nephropathypatients.

Apoptosis-Controlling, Clinical, Laboratory, Anamnestic Factors in Prediction of the Early Stage of Diabetic Nephropathy in Children.

Background. The most prevalent microvascular consequence of type 1 diabetes (T1D) is diabetic nephropathy (DN). Aim of the Study. To find the clinical, anamnestic, and genetic markers that characterize and forecast early diabetic nephropathy in T1D children. Methods. One hundred four children with T1D and DN between the ages of 2 and 17 were surveyed. Stepwise logistic regression models and linear regression models were used. Results. BMI, systolic blood pressure, concurrent kidney pathology, anamnesis viral infections, ESR level, serum cholesterol, blood urea, number of DKA episodes/year, and GFR were determined to be predictors of early DN in children with T1D. Bcl-xL, caspase-3, and HIF-1alfa were discovered to predict DN among all previously identified variables influencing apoptosis. Conclusion. BMI, systolic blood pressure, concurrent kidney disease, anamnesis viral infections, ESR level, serum cholesterol, blood urea, number of DKA episodes/year, GFR, apoptotic and hypoxia markers were discovered as variables predicting early DN.

Moringa oleifera leaf extract ameliorates early stages of diabetic nephropathy in streptozotocin-induced diabetic rats

Moringa oleifera leaf extract ameliorates early stages of diabetic nephropathy in streptozotocin-induced diabetic rats

Randomized and comparative study analyzing efficacy and safety profile of sitagliptin in early diabetic nephropathy

Background: Diabetes mellitus is the most common cause of chronic kidney disease. Microalbuminuria is an early sign of diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibitors decrease albumin excretion and prevent its progression. Sitagliptin is a novel therapeutic agent for Type 2 diabetes mellitus. Hence, this study was carried out to investigate the effect of sitagliptin in albuminuria along with ACE inhibitors and its efficacy, and safety of glycemic profile in diabetic nephropathy. Aims and Objectives: This study evaluated the efficacy of sitagliptin in retarding the progression of albuminuria, and assessing its safety of glycemic profile in patients with Type 2 diabetes with early stage of nephropathy. Materials and Methods: In this randomized and open-label study, patients with diabetic nephropathy were randomized to two groups (n = 30 each). The control group received oral Anti Diabetic Drugs+ Tab. Enalapril 2.5 mg and the study group received antidiabetic drug + Tab. Enalapril 2.5 mg+ Tab. Sitagliptin 100 mg. The patients were evaluated at the end of 24 weeks. Results: Urinary albumin creatinine ratio decreased from 302.10 to 143.83 at 24 weeks in the sitagliptin-treated group (P = 0.001) and in the control group UCAR value reduced from 324.10 to 290.93 mg/g. Statistically significant reductions in hemoglobin, fasting blood sugar, post-prandial blood sugar, and systolic blood pressure were observed in the sitagliptin-treated group. Adverse effects reactions were less in the study group (10%) than in the control group (26%). Conclusion: Sitagliptin significantly reduced albuminuria and improved glycemic control and was well tolerated in patients with early-stage diabetic nephropathy.

Neutrophil–lymphocyte ratio as a diagnostic marker for predicting early-stage diabetic nephropathy in patients attending a tertiary health-care center

Background: Diabetes mellitus (DM) is a common metabolic disorder leading to microvascular and macrovascular complications. Chronic inflammation accelerates the development of complications associated with DM. Measurement of inflammatory mediators is not practically feasible. Neutrophil–lymphocyte ratio (NLR) serves as a cheap, reliable, and valid marker for assessing inflammatory activity. Aims and Objectives: (i) To evaluate the correlation of NLR and microalbuminuria in DM patients; (ii) to evaluate the correlation of NLR with HbA1c; and (iii) to evaluate the correlation of platelet count with microalbuminuria. Materials and Methods: One hundred patients of either sex with DM were evaluated for microalbuminuria, NLR, HbA1c, and platelet count after obtaining institutional human ethics committee clearance. NLR was evaluated for correlation with microalbuminuria and HbA1c. Platelet count was also evaluated for correlation with microalbuminuria. Results: Mean NLR of male patient was 2.1 and female was 2.33. The mean microalbuminuria level in male patient was 527.03 mcg/mg of creatinine and female was 215.36 mcg/mg of creatinine. There was a moderate degree of correlation of microalbuminuria with increased NLR. The study showed a strong correlation between NLR, microalbuminuria, HbA1c, and platelet count. Conclusion: NLR has a strong correlation with microalbuminuria and could be used to assess the onset and progression of diabetic nephropathy.

Receiver Operator Characteristic (ROC) Analysis of Lipids, Proteins, DNA Oxidative Damage, and Antioxidant Defense in Plasma and Erythrocytes of Young Reproductive-Age Men with Early Stages of Type 1 Diabetes Mellitus (T1DM) Nephropathy in the Irkutsk Region, Russia.

Oxidative stress plays a leading role in the pathogenesis of diabetic nephropathy. However, many aspects of oxidative stress reactions in the initial stages of this disease are not fully understood. The men cohort is of particular interest because of the severe effects of diabetes on their urogenital system. The aim of this study is to assess the intensity of lipids, proteins, DNA oxidative damage, blood antioxidant defense enzymatic, and activity of non-enzymatic components in men with type 1 diabetes mellitus (T1DM) in the early stages of diabetic nephropathy using receiver operator characteristic (ROC) analysis. This study included eighty-nine reproductive-age men in the initial stages of diabetic nephropathy (DN) and thirty-nine age- and sex-matched individuals not suffering from glycemic disorders. The DN patients were divided into two subgroups: stage 1 patients (urinary albumin < 30 mg/day and albumin/creatinine ratio < 3 mg/mmol (n = 45)) and stage 2 patients (urinary albumin 30−300 mg/day and albumin/creatinine ratio 3−30 mg/mmol (n = 44)). Levels of oxidative damage products (conjugated dienes (CDs), thiobarbituric acid reactants (TBARs), methylglyoxal (MGO), and 8-hydroxy-2’-deoxyguanosine (8-OHdG)) and antioxidants (glutathione peroxidase (GPx), glutathione S-transferases π (GSTp), glutathione reductase (GR), copper and zinc-containing superoxide dismutase 1 (SOD-1), total antioxidant status (TAS), α-tocopherol, retinol, reduced glutathione (GSH), and oxidative glutathione (GSSG)) were estimated in plasma and erythrocytes. Oxidative damage to cellular structures (higher values of median CDs (1.68 µmol/L; p = 0.003), MGO (3.38 mg/L; p < 0.001) in the stage 1 group and CDs (2.28 µmol/L; p < 0.0001), MGO (3.52 mg/L; p < 0.001), 8-OHdG (19.44 ng/mL; p = 0.010) in the stage 2 group) and changes in the antioxidant defense system (lower values of TAS (1.14 units; p = 0.011), α-tocopherol (12.17 µmol/L; p = 0.009), GPx (1099 units; p = 0.0003) and elevated levels of retinol (1.35 µmol/L; p < 0.001) in the group with stage 1; lower values of α-tocopherol (12.65 µmol/L; p = 0.033), GPx (1029.7 units; p = 0.0001) and increased levels of GR (292.75 units; p < 0.001), GSH (2.54 mmol/L; p = 0.010), GSSG (2.31 mmol/L; p < 0.0001), and retinol (0.81 µmol/L; p = 0.005) in the stage 2 group) were identified. The ROC analysis established that the following indicators have the highest diagnostic significance for stage 1 diabetic nephropathy: CDs (AUC 0.755; p < 0.0001), TBARs (AUC 0.748; p = 0.0001), MGO (AUC 0.720; p = 0.0033), retinol (AUC 0.932; p < 0.0001), GPx (AUC 0.741; p = 0.0004), α-tocopherol (AUC 0.683; p = 0.0071), and TAS (AUC 0.686; p = 0.0052) and the following for stage 2 diabetic nephropathy: CDs (AUC 0.714; p = 0.001), TBARs (AUC 0.708; p = 0.001), 8-OHdG (AUC 0.658; p = 0.0232), GSSG (AUC 0.714; p = 0.001), and GSH (AUC 0.667; p = 0.0108). We conclude that changes in indicators of damage to lipids, proteins, DNA, and the insufficiency of antioxidant defense factors already manifest in the first stage of diabetic nephropathy in men with T1DM. The ROC established which parameters have the greatest diagnostic significance for stages 1 and 2 of diabetic nephropathy, which may be utilized as additional criteria for defining men with T1DM as being in the risk group for the development of initial manifestations of the disease and thus allow for substantiating appropriate approaches to optimize preventive measures.

Assessment of urinary podocalyxin as an alternative marker for urinary albumin creatinine ratio in early stage of diabetic kidney disease in older patients

This study's objective is to evaluate the correlation relationship between Podocalyxin (PCX), an urinary marker of podocytes, urinary albumin-creatinine ratio (ACR) and the predictive value of PCX in the routine screen of early diabetic kidney disease (DKD) among older people. We also aimed to explore its prediction value despite of other metabolic factor and how PCX alters in the predictive power for early stage of diabetic nephropathy. In retrospective, 320 cases of older patients diagnosed with type 2 diabetes mellitus who met both inclusion and exclusion criteria were collected and divided with levels of urinary albumin, that is, normal albuminuria group, microalbuminuria group and healthy group. The correlation coefficient between PCX and ACR, and the odds ratio of PCX were gauged in the study. Area under the receiver operating characteristic (ROC) curve was also calculated. There were 188 patients in the normal group with urine ACR<30mg/g, and 132 patients in the microproteinuria group with urine ACR 30–300mg/g. 132 cases of DKD diagnosed with ACR, among them, 104 cases of DKD were predicted by PCX. The percentage correction value was 78.8%. The following parameters such as gender, age, course of disease, glycated hemoglobin, triglyceride, total cholesterol, BMI, blood pressure, uric acid, and eGFR were used as variables for adjustment to establish the prediction model of urine PCX and ACR. Multiple logistic regression test was carried out to evaluate against the predictive ability of the model. The area under the ROC curve corresponding to the regression model after adjustment is 0.952. Although factors such as the course of disease, HbA1C, UA, and eGFR could influence on the predictive ability of PCX, PCX still has a good ability to predict early DKD in older patients. Therefore, it could be used as a diagnostic indicator for early-stage DKD in older patients.