Diabetic nephropathy

摘要： Background: Worldwide, diabetic nephropathy-DN is the leading cause of end-stage kidney disease-ESKD, DN is a common cause of renal failure with a reported frequency of 10% - 15% in type-2-diabetes-mellitus-T2DM patients, however there is a great discrepancy between countries. The aim of the pre-sent study is to evaluate the findings of kidney biopsies performed on diabetic patients. Materials and Methods: We studied native kidney histopathological findings in the period from January 2016 till end of December 2018 done for patients with T2DM with chronic kidney diseases-CKD. Results: A total of 82 DM-patients, 50 males (61%) and 32 females (39%) with age mean (95% CI) of 50.8 (47.1 - 55.2) years for all patients, ranged between 15 to 65 years. Histological findings showed that 57.3% of patients had DN. While focal-segmental-glomerulosclerosis-FSGS was present in 20.7%—primary in 8.6% and secondary in 12.1%. IgA represented 4.9%, while Lupus nephritis, Membranous and drug induced interstitial nephritis were each present in 3.7%. MCD was present in 2.4%. Lastly diffuse proliferative GN, ANCA associated glomerulonephritis, and hypertensive nephrosclerosis accounted for 1.2%. Conclusion: The prevalence of NDKD is remarkably frequent in DM patients who underwent kidney biopsy and FSGS was the most frequent diagnosis. To get a proper histopathological diagnosis, an adequate tissue biopsy is needed with an adequate number of glomeruli. There is a great need for more consideration to biopsy diabetic patients, as the finding of NDKD requires a different therapeutic approach. This, hopefully, will help to manage these patients better and therefore, ameliorate the progression to ESKD over time and therefore delay the need for RRT.

摘要： Background: Diabetic nephropathy (DN) is the dominant reason for end-stage kidney disease linked with a rise in cardiovascular mortality rate. However, besides DN, type 2 diabetic patients may also suffer from various non-diabetic renal diseases (NDRD). Aim: The objective of the current research was to assess the occurrence and type of NDRD diagnosed by kidney biopsy in type 2 diabetic subjects, evaluate the association of various clinical and laboratory characteristics with histopathology findings, and identify essential predictors of NDRD. Methods: Retrospective analysis has been performed through medical record revision of 101 patients with type 2 diabetes undergoing percutaneous renal biopsy at Qilu Hospital of Shandong University (Jinan, China) between January 2015 and December 2020. Results: Renal biopsy results showed that NDRD was found in 59 patients (58.42%), while DN existed in 32 patients (31.68%) and 10 patients (9.90%) showed DN complicated with NDRD. Membranous nephropathy was prevailing NDRD (42%), followed by focal segmental glomerulosclerosis (11.6%) and IgA nephropathy (10.1%). In univariate analysis, patients with NDRD had older age (p < 0.018), a short duration of diabetes (p < 0.000), lower proteinuria (p < 0.030), and had higher hemoglobin levels (p < 0.006) compared to non-NDRD patients. In multivariate logistic regression analysis, the short course of diabetes (OR 0.986;95% CI = 0.978 - 0.993;p = 0.000) and older age (OR 1.080;95% CI = 1.028 - 1.134;p = 0.002) were significant risk factors for NDRD occurrence. In ROC analysis for NDRD, the duration of diabetes ≤ 78 months (cut-off value (0.725, 0.313)) illustrated the highest AUC. Conclusions: Clinical parameters such as short duration of diabetes, older age, higher hemoglobin level, and lower proteinuria might be associated with NDRD in type 2 diabetic patients. An early diagnosis of NDRD poses a favorable renal prognosis because it requires a different approach than DN, further larger multicenter randomized prospective investigations focused on identifying possible risk markers of NDRD are still in priority.

摘要： (+)-Catechin(CE)is mainly found in green and black tea and has many biological effects,such as antiinflammatory,anti-cancer,anti-viral effects,protecting human organs,especially the kidney.This study aims to identify the circRNAs induced by CE in db/db mice and their roles in diabetic nephropathy progression.After the db/db mice were treated with CE,RNA-seq was performed to identify the differentially expressed circRNA and mRNAs.The ceRNA regulatory network was constructed and analyzed using bioinformatics software and public databases(Cytoscape,Clue GO,Mi RWalk,STRING,et al.).Our results revealed that 6 differentially expressed circRNAs are most associated with the cholinergic synapse,neurotrophin signaling pathway,and insulin signaling pathway.Among these,circRNA.5549 and circRNA.4712 might regulate Cd36,Cyp26 b1,C8 a,Cyp2 j13,Grem2 genes through ceRNA regulatory mechanism in the presence of CE treatment.The expanded network of proteins interacting with these 5 genes shows that the TGF-βsignaling pathway,signaling pathways regulating pluripotency of stem cell,fat digestion and absorption,and PPAR signaling pathway was highly enriched.Overall,circRNA.5549 and circRNA.4712 exhibit a promotive function in CE-treated db/db mice,especially in circRNA.5549/miR-29a-5P/Cd36 regulatory network,and this evidence suggest that their ceRNA regulatory network might be a therapeutic target for DN in humans.

摘要： Diabetic nephropathy(DN)is a major cause of end-stage renal disease,and therapeutic options for preventing its progression are insufficient.The number of patients with DN has been increasing in Asian countries because of westernization of dietary lifestyle,which may be associated with the following changes in gut microbiota.Alterations in the gut microbiota composition can lead to an imbalanced gastrointestinal environment that promotes abnormal production of metabolites and/or inflammatory status.Functional microenvironments of the gut could be changed in the different stages of DN.In particular,altered levels of short chain fatty acids,D-amino acids,and reactive oxygen species biosynthesis in the gut have been shown to be relevant to the pathogenesis of the DN.So far,evidence suggests that the gut microbiota may play a key role in determining networks in the development of DN.Interventions directing the gut microbiota deserve further investigation as a new protective therapy in DN.In this review,we discuss the potential roles of the gut microbiota and future perspectives in the protection and/or treatment of kidneys.

摘要： Objective:Previous studies have found that Qidi Tangshen granules(QDTS),a combination therapy of supplementing essence(Tianjing,TJ)and unblocking the collaterals(Tongluo,TL),can reduce kidney damage in db/db mice.This study aimed to explore the effect of QDTS and their separate prescriptions on podocytes in mice with diabetic nephropathy.Methods:The db/db mice were used in this experiment as an animal model,while wild-type C57BL/6J mice were used as normal controls.At the age of 12 weeks,the db/db mice were randomly divided into 5 groups(db/db,db/dbþvalsartan,db/dbþQDTS,db/dbþTJ and db/dbþTL).The urine albumin excretion ratio(UAE)was measured by enzyme-linked immunosorbent assay before and after the intervention.The ultrastructure of the kidney podocytes was observed by transmission electron microscopy.The protein expression levels of nephrin and desmin were detected by immunohistochemistry.Results:QDTS and their separate prescriptions significantly decreased the UAE and attenuated the renal pathological injury.QDTS and their separate prescriptions also reduced the fusion rate of the foot processes and increased the expression of nephrin protein.In contrast,QDTS and their separate prescriptions(TJ and TL)reduced the expression level of desmin protein.Conclusion:QDTS and their separate prescriptions might reduce diabetes-induced renal injury by reducing podocyte damage.The therapeutic effect of QDTS was more pronounced than TJ and TL.

摘要： BACKGROUND NLRP3-mediated pyroptosis is recognized as an essential modulator of renal disease pathology.Long noncoding RNAs(lncRNAs)are active participators of diabetic nephropathy(DN).X inactive specific transcript(XIST)expression has been reported to be elevated in the serum of DN patients.AIM To evaluate the mechanism of lncRNA XIST in renal tubular epithelial cell(RTEC)pyroptosis in DN.METHODS A DN rat model was established through streptozotocin injection,and XIST was knocked down by tail vein injection of the lentivirus LV sh-XIST.Renal metabolic and biochemical indices were detected,and pathological changes in the renal tissue were assessed.The expression of indicators related to inflammation and pyroptosis was also detected.High glucose(HG)was used to treat HK2 cells,and cell viability and lactate dehydrogenase(LDH)activity were detected after silencing XIST.The subcellular localization and downstream mechanism of XIST were investigated.Finally,a rescue experiment was carried out to verify that XIST regulates NLR family pyrin domain containing 3(NLRP3)/caspase-1-mediated RTEC pyroptosis through the microRNA-15-5p(miR-15b-5p)/Toll-like receptor 4(TLR4)axis.RESULTS XIST was highly expressed in the DN models.XIST silencing improved renal metabolism and biochemical indices and mitigated renal injury.The expression of inflammation and pyroptosis indicators was significantly increased in DN rats and HG-treated HK2 cells;cell viability was decreased and LDH activity was increased after HGtreatment. Silencing XIST inhibited RTEC pyroptosis by inhibiting NLRP3/caspase-1. Mechanistically,XIST sponged miR-15b-5p to regulate TLR4. Silencing XIST inhibited TLR4 by promotingmiR-15b-5p. miR-15b-5p inhibition or TLR4 overexpression averted the inhibitory effect ofsilencing XIST on HG-induced RTEC pyroptosis.CONCLUSIONSilencing XIST inhibits TLR4 by upregulating miR-15b-5p and ultimately inhibits renal injury inDN by inhibiting NLRP3/caspase-1-mediated RTEC pyroptosis.

摘要： Conventional medicine-based Chinese herbal prescriptions,have fascinated much attention due to their extensive and unique diversity of biological effects without toxicity and/or adverse effects.Treatment with Hachimi-jio-gan(Ba-Wei-Di-Huang-Wan in Chinese)improved the dysregulated levels of hyperglycemic condition-related oxidative stress generation,advanced glycation endproduct generation,and renal function parameters.These results indicate that Hachimi-jio-gan is a prospective therapeutic agent against the pathogenesis of diabetic nephropathy.Cornel iridoid glycosides and polyphenol are the active compounds of Corni Fructus,the active component of Hachimi-jio-gan,against kidney damage caused by diabetes.Additionally,major components of the Corni Fructus,morroniside and 7-O-Galloyl-D-sedoheptulose(GS)are considered to be important contributors to prevent and/or delay the onset of kidney damage caused by diabetes.Chief of all,GS is expected to be developed as a novel therapeutic drug for the diabetes-accelerated kidney damage.

摘要： There are about over 100 trillion microbial cells in human gut,which affect the nutritional,metabolic,physiological and immune functions of the host.This paper reviews the differences in gut microbiota between patients with diabetic nephropathy(DN)and healthy people.These differences lead to the disorder of symbiotic relationship,which may have induced the progression of DN,as well as targeted interventions to reconstruct the symbiotic relationship.Recent studies have found that endotoxin from intestinal bacteria and a large number of toxic metabolites were produced by fermentation of gut microbiota,such as trimethylamine-N-oxide,indoxyl sulfate and p-cresol sulfate,leading to the disruption of intestinal barrier function.Endotoxin and bacterial metabolites,entering the systemic circulation,were involved in DN progression by mediating inflammatory responses,renin-angiotensin-system and vascular injury.The reduction of some beneficial bacterial metabolites in DN patients,such as short-chain fatty acids,would weak body energy metabolism and destroy glucose homeostasis.In addition,gut microbiota is essential for the conversion of bile acids,and plays an important role in the development of DN by synthesizing secondary bile acids and regulating glucose and metabolic balance through foresaid X receptor(FXR)and G protein-coupled bile acid receptor(TGR5).Animal and clinical studies have revealed that probiotics,prebiotics,fecal microbiota transplantation,and Chinese medicine intervention may have potential therapeutic effects in maintaining a metabolically balanced gut microbiota to reduce the progression of DN,end-stage renal disease and cardiovascular complications.

摘要： By searching TCM disease names"Xiao Shen","Shen Xiao"and"Xin Xiao",which are considered higher degree of coincidence with diabetic nephropathy according to study.And combined with the theory of collateral disorders,sort out the classic literature of traditional Chinese medicine and modern experts'works in chronological order.To make a preliminary exploration of the origin of diabetic nephropathy based on the theory of collateral disorders.Hope to provide reference for TCM theory and clinical research on treating diabetic nephropathy from the theory of collateral disorders in the future.

摘要： Objective:To investigate the effect of Moringa oleifera leaf extract on angiogenesis and inflammatory process in a rat model of streptozotocin-induced diabetic nephropathy.Methods:Four weeks after a single injection of 50 mg/kg streptozotocin,rats were treated with 100 or 200 mg/kg/day Moringa oleifera leaf extract,1 mg/kg/day dapagliflozin,or a combination of Moringa oleifera leaf extract and dapagliflozin for further eight weeks.Renal function,kidney histology,and gene expression were evaluated at the end of the experiment.Results:Renal function of diabetic rats was significantly impaired as evidenced by increased blood urea nitrogen,albuminuria,24-h proteinuria,and high creatinine clearance which indicated glomerular hyperfiltration.In addition,diabetic rats showed an increase in gene expressions of vascular endothelial growth factor-A(VEGF-A),angiopoietin-2(Ang2),the Ang2/Ang1 ratio,tumor necrosis factor-α,interleukin-1βand monocyte chemoattractant protein-1.Immunohistochemical staining demonstrated a significant increase in the density of glycoprotein CD34.Moringa oleifera leaf extract markedly improved all renal dysfunction markers and modulated the upregulated expression of angiogenic factors and inflammatory genes.Conclusions:Moringa oleifera leaf extract could suppress abnormal angiogenesis and inflammatory processes possibly by downregulating gene expression of angiogenesis factors and proinflammatory cytokines.