Urinary Albumin Excretion Rate Research Articles

Elucidating the effect of levothyroxine and triiodothyronine on methylglyoxal derived stress.

Methylglyoxal (MG) is the most potent precursor during the formation of the advanced glycation end products (AGEs). MG-dependent glycative stress contributes to pathogenesis of diabetes, age-related disorders, and cancer. There is a great need to study the reduction process of glycative stress for effective management of metabolic disorders. From natural compounds to synthetic drugs, each element contributes to the reduction of glycative stress. Previously, it was established that the lowering of uric acid, low-density lipoprotein cholesterol, and urine albumin excretion rate, as well as reducing total oxidative stress, were all achieved more effectively with a levothyroxine regimen. Still, there is no such study found that supports the MG-dependent glycative stress reduction with thyroid hormone compound. Our study aims to investigate the effects of T3 and T4 on MG-dependent glycative stress. The antiglycation effect was assayed through NBT assay, DNPH assay, ELISA, and fluorescence spectrophotometer. The intracellular reduction in reactive oxygen species (ROS) has been estimated through confocal microscopy. The results revealed an effective reduction in the formation of AGEs adducts and intracellular ROS formation. The investigation concludes AGEs formation was suppressed using these compounds, although in vivo and rigorous clinical trials are required in order to verify these findings.

Caloric and time restriction diets improve acute kidney injury in experimental menopausal rats: role of silent information regulator 2 homolog 1 and transforming growth factor beta 1.

Estrogen has a protective impact on acute kidney injury (AKI); moreover, reducing the daily intake of calories impedes developing diseases. The present study aimed to determine the effects of calorie restriction (CR) and time restriction (TR) diets on the expression of silent information regulator 2 homolog 1 (SIRT1), transforming growth factor beta 1 (TGF-β1), and other indicators in the presence and absence of ovaries in AKI female rats. The female rats were divided into two groups, ovariectomized (OVX) and sham, and were placed on CR and TR diets for eight weeks; afterward, AKI was induced by injecting glycerol, and kidney injury indicators and biochemical parameters were measured before and after AKI. After AKI, the levels of urine albumin excretion rate, urea, and creatinine in serum, and TGF-β1 increased, while creatinine clearance and SIRT1 decreased in kidney tissue. CR improved kidney indicators and caused a reduction in TGF-β1 and an increase in SIRT1 in ovary-intact rats. Moreover, CR prevented total antioxidant capacity (TAC) decrease and malondialdehyde (MDA) increase resulting from AKI. Before AKI, an increase in body weight, fasting blood sugar (FBS), low-density lipoprotein (LDL), triglyceride (TG), and total cholesterol (TC), and a decrease in high-density lipoprotein (HDL) were observed in OVX rats compared to sham rats, but CR prevented these changes. The effects of TR were similar to those of CR in all indicators except for TGF-β1, SIRT1, urea, creatinine, and albumin. The present study indicated that CR is more effective than TR in preventing AKI, probably by increasing SIRT1 and decreasing TGF-β1 in ovary-intact animals.

Comparison of Clinical Effects of Sacubitril Valsartan Sodium Tablets and Nifedipine Controlled-Release Tablets in the Treatment of Chronic Renal Insufficiency Complicated with Hypertension

Objective: To compare the clinical effects of using sacubitril valsartan sodium tablets with nifedipine controlled-release tablets in patients with chronic renal insufficiency combined with hypertension. Methods: 110 patients with chronic renal insufficiency combined with hypertension treated in our hospital from April 2023 to February 2024 were taken as the study subjects. They were divided into the test group (n = 55) and the comparison group (n = 55) by randomized numerical table method. The test group was provided with sacubitril valsartan sodium tablets and the comparison group was treated with nifedipine controlled-release tablets. The urine excretion rate of albumin and blood urea nitrogen levels as well as adverse effects were compared before and after treatment in both groups. Results: In the test group, the urinary albumin excretion rate was 101.77 ± 7.42 μg/min and the blood urea nitrogen level was 15.81 ± 1.76 mmol/L, which was much lower than that of the comparison group; the total rate of adverse reactions in the test group was 1.82%, which was significantly lower than that of the comparison group, the difference between the data of the test group and the comparison group after treatment is statistically significant (P < 0.05). Conclusion: By providing treatment with sacubitril valsartan sodium tablets for patients with chronic renal insufficiency combined with hypertension, their urinary albumin excretion rate and blood urea nitrogen level are significantly improved, and the total occurrence rate of adverse reactions is low.

The impact of chitooligosaccharides with a certain degree of polymerization on diabetic nephropathic mice and high glucose-damaged HK-2 cells.

Diabetic nephropathy (DN) is a primary diabetic complication ascribed to the pathological changes in renal microvessels. This study investigated the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch ECH associating protein (Keap1)/antioxidant response element (ARE) signaling pathway impact of chitooligosaccharides (COS) with a certain degree of polymerization (DP) on DN mouse models and high glucose-damaged human kidney 2 (HK-2) cells. The findings indicated that COS effectively reduced the renal function indexes (uric acid [UA], urinary albumin excretion rate [UAER], urine albumin-to-creatinine ratio [UACR], blood urea nitrogen [BUN], and creatinine [Cre]) of DN mice. It increased (p < .05) the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) antioxidant enzyme activity in the serum and kidneys, and decreased (p < .05) the malondialdehyde (MDA) content. The mechanistic investigation showed that COS significantly increased (p < .05) Nrf2 and downstream target gene (GCLM, GCLC, HO-1, and NQO-1) expression, and substantially decreased (p < .05) Keap1 expression. The protein level was consistent with the messenger RNA (mRNA) level in invitro and invivo models. The docking data indicated that COS and Keap1 protein binding included six hydrogen bond formation processes (Gly364, Arg415, Arg483, His436, Ser431, and Arg380). The COS intervention mechanism may be related to the Nrf2/Keap1/ARE antioxidant pathway. Therefore, it provides a scientific basis for COS application in developing special medical food for DN patients.

Associations of Kidney Tubular Biomarkers With Incident Macroalbuminuria and Sustained Low eGFR in DCCT/EDIC.

Tubulointerstitial injury contributes to diabetic kidney disease (DKD) progression. We tested tubular biomarker associations with DKD development in type 1 diabetes (T1D). We performed a case-cohort study examining associations of tubular biomarkers, measured across seven time points spanning ∼30 years, with incident macroalbuminuria ("severely elevated albuminuria," urinary albumin excretion rate (AER) ≥300 mg/day) and sustained low estimated glomerular filtration rate (eGFR) (persistent eGFR <60 mL/min/1.73 m2) in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study. Biomarkers included KIM-1 and sTNFR1 in serum/plasma, MCP-1 and EGF in urine, and a composite tubular secretion score reflecting secreted solute clearance. We assessed biomarkers using single values, as mean values from consecutive time points, and as change over consecutive time points, each as time-updated exposures. At baseline, mean diabetes duration was 5.9 years, with mean HbA1c 8.9%, eGFR 125 mL/min/1.73 m2, and AER 16 mg/day. There were 4.8 and 3.5 cases per 1,000 person-years of macroalbuminuria and low eGFR, respectively. Assessed according to single biomarker values, KIM-1 was associated with risk of subsequent macroalbuminuria and low eGFR (hazard ratio [HR] per 20% higher biomarker 1.11 [95% CI 1.06, 1.16] and 1.12 [1.04, 1.21], respectively) and sTNFR1 was associated with subsequent macroalbuminuria (1.14 [1.03, 1.25]). Mean KIM-1 and EGF-to-MCP-1 ratio were associated with subsequent low eGFR. In slope analyses, increases in KIM-1 and sTNFR1 were associated with subsequent macroalbuminuria (per 20% biomarker increase, HR 1.81 [1.40, 2.34] and 1.95 [1.18, 3.21]) and low eGFR (2.26 [1.65, 3.09] and 2.94 [1.39, 6.23]). Serial KIM-1 and sTNFR1 are associated with incident macroalbuminuria and sustained low eGFR in T1D.

Longitudinal Trajectories of Biomarkers of Kidney Tubular Function in Type 1 Diabetes

Tubular biomarkers may shed insight into progression of kidney tubulointerstitial pathology complementary to traditional measures of glomerular function and damage. We examined trajectories of tubular biomarkers in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC Study) of type 1 diabetes (T1D). Biomarkers were measured in a subset of 220 participants across 7 time points over 26 years. Measurements included the following: kidney injury molecule 1 (KIM-1), soluble tumor necrosis factor 1 (sTNFR1) in serum or plasma, epidermal growth factor (EGF), monocyte chemoattractant protein-1 (MCP1) in timed urine, and a composite tubular secretion score. We described biomarker trajectories and examined how these were affected by intensive glucose-lowering therapy and glycemia. At baseline, participants had a mean age of 28 years, 45% were women, and 50% were assigned to intensive glucose-lowering therapy. The mean estimated glomerular filtration rate (eGFR) was 125 ml/min per 1.73 m2 and 90% of participants had a urinary albumin excretion rate (AER)<30 mg/24h. Mean changes in biomarkers over time (percent/decade) were: KIM-1: 27.3% (95% confidence interval [CI]: 21.4-33.5), sTNFR1: 16.9% (14.5-19.3), MCP1: 18.4% (8.9-28.8), EGF:-13.5% (-16.7 to-10.1), EGF-MCP1 ratio:-26.9% (-32.2 to-21.3), and tubular secretion score-0.9% (-1.8 to 0.0), versus-12.0% (CI:-12.9 to-11.1) for eGFR and 10.9% (2.5-20.1) for AER. Intensive versus conventional glucose-lowering therapy was associated with slower increase in sTNFR1 (relative difference in change: 0.94 [0.90-0.98]). Higher HbA1c was associated with faster increases in sTNFR1 (relative difference in change: 1.06 per 1% higher HbA1c [1.05-1.08]) and KIM-1 (1.09 [1.05-1.14]). Among participants with T1D and normal eGFR at baseline, kidney tubular biomarkers changed significantly over long-term follow-up. Hyperglycemia was associated with larger increases in serum or plasma sTNFR1 and KIM-1, when followed-up longitudinally.

The effect of periodic resistance training on obese patients with type 2 diabetic nephropathy

Resistance training is an exercise against resistance designed to train the endurance and strength of muscle. To observe the effect of intervention of periodic resistance training on obese patients with type 2 diabetic nephropathy. A total of 60 obese patients with type 2 diabetic nephropathy were randomized into resistance training group and aerobic exercise group (30 patients each group) for observing the changes of blood glucose, body weight, blood lipid, insulin resistance, serum creatinine (Scr), urinary microalbumin, urinary albumin excretion rate (UAER) calculated by urinary creatinine, and glomerular filtration rate (GFR) after 12 weeks of intervention, and relevant significance as well. The number of patients with hypoglycemia during the intervention was also recorded. After 12 weeks of intervention, the weight, Body mass index (BMI), Waist, Triglyceride (TG), Cholesterol (TC), Low-density lipoprotein cholesterol (LDL), Fasting glucose (FBG), Fasting insulin (FINS), Glycosylated hemoglobin (HbA1c) and urine Albumin–Creatinine Ratio (uACR) were decreased and GFR was increased in both groups (P < 0.05), but the effect was more significant in the resistance training group. GFR was increased from 92.21 ± 10.67 mL/(min·1.73 m2) to 100.13 ± 12.99 mL/(min·1.73 m2) in resistance training group (P < 0.05). In the aerobic exercise group, GFR was increased from 89.98 ± 9.48 mL/(min·1.73 m2) to 92.51 ± 11.35 mL/(min·1.73 m2) (P > 0.05). Periodic resistance training can not only control the weight, blood sugar and blood lipid of obese patients with type 2 diabetic nephropathy, but also improve the urinary albumin excretion rate and glomerular filtration rate of early obese patients with type 2 diabetic nephropathy, and delay the progression of diabetic nephropathy. It is an effective non-drug intervention.

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

Use of Transcriptome Sequencing to Analyze the Effects of Different Doses of an Astragalus-Rhubarb-Saffron Mixture in Mice with Diabetic Kidney Disease.

To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p<0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin.

Role of CKD273 in Diabetic Nephropathy: A Systematic Review

Introduction: Diabetic Nephropathy (DN) is a major cause of increased morbidity and mortality in patients with Diabetes Mellitus (DM). The development of novel biomarkers for kidney disease, especially DN, is becoming a focus of medical research. Serum creatinine and urine albumin measurements had been the gold standards for the diagnosis of DN until the advent of newer markers like Cystatin C, Kidney Injury Molecule-1, etc. Currently, there is no non invasive investigation for the prediction of DN. Nevertheless, the field of proteomics is advancing at a rapid pace, such that urinary proteomic biomarkers have found a spot in the diagnosis of DN. The role of the urinary proteomic Chronic Kidney Disease 273 (CKD273) classifier, in particular, has been demonstrated in early prediction. Aim: To highlight the performance of the CKD273 classifier in the early prediction of DN. Materials and Methods: Pubmed and Scopus databases were extensively searched using the keywords diabetes, DM, renal disease or kidney disease, proteomics or peptide, urinary markers or biomarkers. Full-text original articles conducted on humans and written in English, published between 2014 and 2022, specifically prospective and retrospective observational studies, crosssectional studies, Randomised Controlled Trials (RCT), and casecontrol studies investigating the efficacy of the urinary biomarker CKD273 in the prediction of DN were included in the review. The literature search, strictly based on Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, led to the identification of eight relevant studies, which were included in the present review. The quality and Risk of Bias (RoB) of the selected articles were assessed using the Newcastle Ottowa scale (NOS) and Risk Of Bias 2 (ROB2) tool. Results: The selected studies proved the efficacy of the urinary proteomic classifier CKD273 as a cost-effective biomarker in predicting the decline in renal function in both normoalbuminuric diabetics and DN patients. Conclusion: Based on the articles included in the present systematic review, it has been found that CKD273 plays a vital role in the early prediction of renal dysfunction in normoalbuminuric diabetics as well as in the detection of progressing renal disease in DN patients. It has also been found to be cost-effective compared to established markers such as estimated Glomerular Filtration Rate (eGFR), Urine Albumin Excretion Rate (UAER), etc.

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.

Planting a path to kidney health: The vegetarian diet and diabetic nephropathy

Abstract About 40% of people with diabetes experience diabetic nephropathy (DN), which is the main cause of renal problems. The aberrant urine albumin excretion rate, diabetic glomerular lesions, and a reduction in glomerular filtration rate are its defining characteristics. Numerous studies have found a strong link between eating animal protein and conditions like glucagon activation, insulin resistance, proteinuria, microalbuminuria, and the worsening of kidney problems in diabetic individuals. A vegan diet, which forgoes all animal products including leather and other non-edibles like fish, shellfish, and insects as well as dairy, eggs, and honey, has demonstrated significant benefits. It has been connected to enhanced insulin sensitivity, less glucagon activation, a decreased risk of developing chronic kidney disease (CKD), and a slowed rate of DN progression. According to several studies, avoiding animal products and switching to plant-based protein sources can be a better nutritional plan than simply limiting dietary protein. This change may prove very helpful in reducing the risk of kidney and cardiovascular illnesses, especially for those who have diabetes and severe insulin resistance in addition to CKD. A vegan diet contains considerable benefits for those with diabetes and CKD, acting as a brake on the advancement of DN and renal failure, according to the literature evaluation done for this study. Nevertheless, more interventional studies involving humans are needed to elucidate the processes underlying the increased insulin sensitivity brought on by vegan diets. It is also advised to conduct more research to fully explore the effectiveness and security of vegan diets in people with diabetes and DN.

Further understanding and paying attention to normoalbuminuric diabetic kidney disease

Diabetes mellitus (DM) has grown up to be an important issue of global public health because of its high incidence rate. Diabetic kidney disease (DKD) is the main cause of end-stage kidney disease (ESKD). Therefore, early diagnosis and timely prevention and treatment of DKD are essential for the progress of DM. The clinical diagnosis and staging of DKD are mostly based on the urinary albumin excretion rate (UAER) and estimated glomerular filtration rate (eGFR). However, clinically, DKD patients show normoalbuminuric diabetic kidney disease (NADKD) instead of clinical proteinuria. The old NADKD concept is no longer suitable and should be updated accordingly with the redefinition of normal proteinuria by NKF/FDA (National Kidney Foundation/Food and Drug Administration). Based on the relevant guidelines of DM and chronic kidney disease (CKD) and combined with the current situation of clinical research, the review described NADKD from the aspects of epidemiology, pathological mechanism, disease diagnosis, clinical characteristics and biomarkers, to arouse the new understanding of NADKD in the medical profession and pay attention to it.

Efficacy of "Dihuang pill prescriptions" combined with conventional treatment for diabetic kidney disease: A network meta-analysis and systematic review.

With the increasing incidence of diabetic nephropathy, there is currently no means to completely cure the disease. However, a large number of clinical data proved that traditional Chinese medicine combined with modern medical conventional treatment of diabetic kidney disease has achieved better efficacy than simple Western medicine conventional treatment. Based on the mesh meta-analysis method, the objective evaluation of clinical efficacy of conventional treatment of diabetic kidney disease and comparison provided more evidence-based basis for the treatment of diabetic kidney disease and further select effective intervention measures to delay the process of diabetic kidney disease. 41 randomized controlled trials were included, involving 4 kinds of "Dihuang pill prescriptions," with a total sample size of 3562 cases, including 1793 patients in the experimental group and 1769 patients in the control group. Network meta-analysis suggested that the best SUCRA-ranked 2 interventions were Jingui Shenqi pills/decoction + Western medicine routine" and Jisheng Shenqi pills/decoction + Western medicine routine in terms of reducing 24-hour urinary protein. In terms of reducing urinary albumin excretion rate, the top 2 SUCRA-ranked interventions were Zhibai Dihuang pills/decoction + Western medicine routine and Liuwei Dihuang Pills/decoction + Western medicine routine. In terms of reducing serum creatinine, the top 2 SUCRA ranked interventions were Jisheng Shenqi pills/decoction + Western medicine routine, Zhibai Dihuang Pills/decoction + Western medicine routine. In terms of lowering fasting blood glucose, the top 2 SUCRA-ranked interventions were Zhibai Dihuang pills/ decoction + Western medicine routine and Jisheng Shenqi pills/decoction + Western medicine routine. The results showed that the treatment plan of conventional Western medicine combined with Chinese patent medicine could reduce serum creatinine, 24-hour urinary protein, fasting blood glucose urine protein excretion rate and improve the total clinical effective rate. The combination of medicine was obviously better than conventional Western medicine alone.

Optimizing diabetic kidney disease animal models: Insights from a meta-analytic approach.

Diabetic kidney disease (DKD) is a prevalent complication of diabetes, often leading to end-stage renal disease. Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies. However, current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD. Additionally, modeling DKD is often a time-consuming, costly, and labor-intensive process. The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research. A total of 1215 articles were retrieved with the keywords of "diabetic kidney disease" and "animal experiment" in the past 10 years. Following screening, 84 articles were selected for inclusion in the meta-analysis. Review manager 5.4.1 was employed to analyze the changes in blood glucose, glycosylated hemoglobin, total cholesterol, triglyceride, serum creatinine, blood urea nitrogen, and urinary albumin excretion rate in each model. Renal lesions shown in different models that were not suitable to be included in the meta-analysis were also extensively discussed. The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations. In conclusion, our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.

Hedysarum polybotrys polysaccharide attenuates renal inflammatory infiltration and fibrosis in diabetic mice by inhibiting the HMGB1/RAGE/TLR4 pathway.

Diabetic kidney disease (DKD) is a leading cause of kidney failure. Previous studies demonstrated the therapeutic potential of Astragalus polysaccharide in treating diabetic nephropathy. Astragalus and Hongqi both come from the leguminous plant Astragalus, but their species and genera are different, belonging to the same family and different genera of traditional Chinese medicinal plants. However, the effects of Hedysarum polybotrys polysaccharide (HPS), a polysaccharide compound from Hongqi, on DKD, including its components and efficacy, have remained elusive. The present study utilized db/db mice as a DKD animal model administered with low (30 mg/kg) and high doses (60 mg/kg) of HPS, in addition to glyburide (7.2 mg/kg). Blood and urine samples were collected from mice and blood glucose, serum creatinine, urinary albumin excretion and urinary β2-microglobulin were measured. In addition, apoptosis and histological changes in kidney tissue were observed using TUNEL and HE staining, respectively, and the secretion and expression of inflammatory factors in kidney tissue were detected using EILSA and reverse transcription-quantitative PCR. Furthermore, we the expression of fibrosis-related proteins and NF-κB signaling pathway proteins was determined using western blot analysis. HPS was found to reduce the blood glucose concentration, serum creatinine levels, urinary albumin excretion rates and urinary β2-microglobulin in a dose-dependent manner. In addition, HPS treatment mitigated apoptosis and pathological damage in the kidney tissues of DKD mice. The expression levels of fibrosis-related proteins fibronectin, α-smooth muscle actin and TGF-β1 were observed to be decreased in kidney tissues of DKD mice following HPS treatment. The secretion levels of inflammatory factors (IL-6, TNF-α and IL-1β) were also reduced in kidney tissues, with high-dose HPS treatment found to be more effective, similar to the effects mediated by the glyburide. Further mechanistic analysis revealed that the therapeutic effects of HPS on DKD mice may be mediated by inhibiting the high mobility group box 1/receptor for advanced glycation end-products/toll-like receptor 4 pathway. In conclusion, the present findings could provide insight for the treatment of DKD.

Systematic Review to Gauge the Effect of Levothyroxine Substitution on Progression of Diabetic Nephropathy in Patients With Hypothyroidism and Type 2 Diabetes Mellitus.

Diabetes mellitus (DM) and thyroid dysfunction are two disorders that are closely related. This systematic review aimed to investigate the effect of levothyroxine supplementation on diabetic nephropathy in type 2 diabetic patients with co-existing thyroid dysfunction. We explored medical databases such as PubMed, Medline, Multidisciplinary Digital Publishing Institute (MDPI), and Cochrane Library for relevant medical literature. The papers were screened, and 12 research papers involving 10,371 patients were identified after applying eligibility criteria and quality assessment using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The included papers analyzed the effect of aberrant thyroid profile on kidney disease in diabetic individuals and the role that achieving euthyroid status with levothyroxine supplementation could play in diabetic nephropathy. Reduced free triiodothyronine (FT3) was the most common independent factor associated with diabetic microvascular and macrovascular complications. Levothyroxine (LT4) regimen was more effective than the placebo in lowering urinary albumin excretion rate (UAER), low-density lipoprotein cholesterol, and uric acid and decreasing oxidative stress overall. However, replacement therapy's effect may differ in the short and long terms. Thyroid hormone replacement therapy (THRT) may reduce the risk of diabetic nephropathy and cardiovascular disease (CVD) development in hypothyroid patients, but more randomized trials are needed to confirm the effect of THRT.

Novel Diabetic Nephropathy-Based Hypertension Treatment for Type-2 Diabetes Mellitus and CKD Patients: A Mini Review

Diabetes mellitus is known to result in persistent renal impairment among individuals with the condition and is presently the primary aetiology of terminal-stage renal disease, with more than fifty percent of dialysis patients being affected. The prevalence of diabetes continues to rise, resulting in a decline in individuals' health status and imposing significant financial burdens on healthcare systems. Accurately distinguishing between the various types of diabetes is crucial in order to provide appropriate treatment that mitigates the severity of associated complications and their significant consequences. The co-occurrence of diabetes and renal disease has been found to be linked with a significant fourfold rise in both the frequency and fatality of cardiovascular disease. Pharmacological interventions aimed at reducing blood pressure have been a crucial component in the management of diabetic nephropathy for several decades. The past decade has witnessed a decline in the occurrence of end-stage renal disease, owing to enhanced care measures such as the administration of hypertension medication. It is assumed in clinical practice recommendations that angiotensin-converting enzyme inhibitors and angiotensin-receptor antagonists hold an equivalent status. The efficacy of low doses of ACEI and ARB in reducing proteinuria was found to be superior to that of high doses. The co-administration of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) has been observed to elicit a more pronounced reduction in 24-hour proteinuria and urinary albumin excretion rate (UAER) in comparison to the singular administration of either ACEI or ARB.

Assessment of Renal Function of Bodybuilders Using Anabolic Androgenic Steroids and Diet Supplements.

Introduction Anabolic androgenic steroids (AAS) and diet supplements (DS) are frequently used by bodybuilders. In this specific group, increased muscle mass, the acute effects of exercise, and the use of creatine may affect the creatinine-based estimated glomerular filtration rate (eGFRcr), potentially leading to an underestimation of the GFR. Cystatin C equations offer a more accurate prediction of GFR that is independent of muscle mass. We aimed to assess the renal functions of bodybuilders who use both AAS+DS, as well as those who only use DS, by calculating the GFR based on cystatin C (eGFRcys) and also using a combination of cystatin C and creatinine (eGFRcys/cr). Methods The study included 12 bodybuilders using AAS+DS and 12 bodybuilders using DS. In both groups, serum cystatin C levels, eGFRcys, eGFRcys/cr, urine albumin excretion rates, urine protein excretion rates, and routine tests were examined. Results In AAS+DS users, the average duration of AAS use was 3.08±2.02 years, while for DS users, the duration of supplement use was 3.67±2.49 years. The spot urine albumin/creatinine and protein/creatinine ratios were higher in AAS+DS users (p<0.001 and p=0.006, respectively). Although eGFRcr was found to be similar in the AAS+DS and DS groups (119.67 ± 24.12 ml/min and 122.08 ± 18.03 ml/min, respectively; p=0.426), eGFRcys and the eGFRcys/cr ratio were significantly lower in the AAS+DS group compared to the DS group (eGFRcys: 120.67 ± 19.48 ml/min vs. 122.08 ± 18.03 ml/min, p=0.039; eGFRcys/cr: 121.83 ± 20.62 ml/min vs. 126.33 ± 21.163 ml/min, p= 0.036, respectively). Conclusion Cystatin-based GFR values were found to be significantly lower in AAS+DS users, and urinary albumin and protein excretion were considerably higher compared to DS users. Although these findings suggest a potential link between early kidney damage and the direct use of AAS, the topic requires further investigation.

Therapeutic improvements of nifedipine controlled-release tablets combined with sacubitril valsartan on patients with diabetic nephropathy complicated with hypertension

This study aimed to evaluate the efficacy of nifedipine controlled-release tablets combined with sacubitril valsartan in diabetic nephropathy (DN) patients with hypertension. One hundred and twelve DN patients with hypertension were enrolled. They were randomly divided into the control group (treated with nifedipine controlled-release tablets combined with valsartan) and the observation group (treated with nifedipine controlled-release tablets combined with sacubitril valsartan). Renal function, endothelial function and inflammatory response were examined. After three-months treatment, the levels of clinical indexes (glycosylated hemoglobin, fasting blood glucose, systolic and diastolic blood pressure), renal function indicators (urinary albumin excretion rate, blood urea nitrogen, serum creatinine and cystatin C), endothelial function indicators (microalbumin, angiotensin II, thrombomodulin and cartilage oligomeric matrix protein) and inflammatory response factors (interleukin-6 and tumor necrosis factor-α) in the observation group were significantly lower than those in the control group. Nifedipine controlled-release tablets combined with sacubitril valsartan could effectively alleviate the progression of DN combined with hypertension.