Non-Diabetic Nephropathies among Diabetic Patients of the Nephrology Department of Dakar

Introduction: Diabetic nephropathy is the most common cause of kidney disease in diabetics. However, in some cases the clinical symptoms is not typical and nephropathy may be different from diabetic and require the use of renal biopsy (RB) which is not usually indicated unless non-diabetic nephropathy (NND) is suspected. The objective of this study was to evaluate the prevalence of non-diabetic nephropathy (NDN) among the diabetic patients and to analyse the different predictive factors of its occurrence. Patients and methods: It was a retrospective, descriptive and analytical study which is carried out at the nephrology department of Aristide Le DANTEC hospital of Dakar over a period of 60 months. Diabetics with suspected NDN diagnosis based on renal anomalie that is associated with a recent diabetes, Acute renal failure with rapid progress, Diabetic retinopathy’s absence, and Extrarenal signs (cutaneous, digestive and articular) associated with an acute renal failure. Microscopic haematuria was included. The epidemiological, clinical, biological and histological parameters were collected and analysed using the SPSS, 3.5 version software. Results: Out of 34 biopsied diabetic patients, 12 had NDN that is a prevalence of 35, 3%. The average age was 49.88 ± 4.15 years, 0.78 for the sex-ratio and the mean duration of diabetes is 12.53 ± 4.7 years. Glomerular syndrome was found in 30 patients (88.23%), vascular nephropathy syndrome in 3 patients (8.82%) and tubule-interstitial nephropathy syndrome in only one patient (2.94%). Diabetic retinopathy (DR) and microscopic haematuria (HU) respectively existed in 10 patients (34%) and 15 patients (44. 12%). The Kidney biopsy (KB) indications were renal abnormalities associated with recent diabetes, acute renal failure with rapid progress, absence of DR, extrarenal signs associated with acute renal failure and microscopic haematuria. Twenty-two patients (64.7%) had diabetic nephropathy (DN) and 12 patients (38.2%) presented a NDN. Predictive factors of NDN diagnosis were a shorter diabetes duration (P = 0.0008), high blood pressure (P = 0.0015) and absence of DR (P = 0.005). Conclusion: Our data show that kidney injury in a diabetic is not always diabetic nephropathy. The Kidney biopsy (KB) is often needed in order to adopt an effective management.

Non-Diabetic Renal Disease in Patients with Type 2 Diabetes Mellitus with Proteinuria

Background: Diabetes mellitus (DM) is the leading cause of end stage renal disease (ESRD) worldwide. Although DM with proteinuria is the ultimate result of diabetic nephropathy (DN), a wide spectrum of non-diabetic renal diseases (NDRD) can occur in such patients. Objective: To observe the frequency and histological pattern of NDRD in diabetic patients with proteinuria and to explore their association with clinical and laboratory parameters. Methods: This cross-sectional study was conducted in the Department of Nephrology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh from April 2016 to September 2017. In this study a total of 38 cases of DM with proteinuria (>1 gm/24-hour) were selected purposively. Renal biopsy was done in all patients. Based on histological findings they were categorized into two groups;Group 1 with NDRD and Group II with DN. Their clinical and laboratory parameters were analyzed and compared. Results: Among the total study subjects, 21 (55.3%) were male and 17 (44.7%) were female, mean (±SD) age 43.45 ± 9.99 years in the NDRD group and 41.57 ± 9.50 years in the DN group. Thirty one cases (81.6%) out of thirty eight had NDRD and seven (18.4%) cases had isolated DN;therefore more than two third cases had NDRD. Duration of DM was found to be significantly shorter (p = 0.004) in the NDRD group. Diabetic retinopathy was present in 12.9% cases in NDRD group vs. 57.1% cases in DN group (p = 0.025). Frequency of microscopic hematuria was significantly higher (90.3%) in NDRD patients (p = 0.002). Conclusion: The frequency of NDRD in type 2 diabetic patients other than diabetic nephropathy is relatively high. Membrano proliferative glomeru-lonephritis and membranous nephropathy are more common in NDRD. Absence of diabetic retinopathy, presence of hematuria and shorter duration of DM are markers associated with NDRD in type 2 DM, which are important indicators for renal biopsy in diabetic patients with proteinuria.

Non-Diabetic Kidney Disease in Type 2 Diabetes Mellitus: A Study of 82 Patients and Review of the Literatures

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.

The role of innate immunity in diabetic nephropathy and their therapeutic consequences

Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.

Myricetin induces M2 macrophage polarization to alleviate renal tubulointerstitial fibrosis in diabetic nephropathy via PI3K/Akt pathway

BACKGROUND Development of end-stage renal disease is predominantly attributed to diabetic nephropathy(DN).Previous studies have indicated that myricetin possesses the potential to mitigate the pathological alterations observed in renal tissue.Never-theless,the precise molecular mechanism through which myricetin influences the progression of DN remains uncertain.AIM To investigate the effects of myricetin on DN and explore its potential therapeutic mechanism.METHODS Db/db mice were administered myricetin intragastrically on a daily basis at doses of 50 mg/kg or 100 mg/kg for a duration of 12 wk.Subsequently,blood and urine indexes were assessed,along with examination of renal tissue pathology.Kidney morphology and fibrosis were evaluated using various staining techniques including hematoxylin and eosin,periodic acid–Schiff,Masson’s trichrome,and Sirius-red.Additionally,high-glucose culturing was conducted on the RAW 264.7 cell line,treated with 25 mM myricetin or co-administered with the PI3K/Akt inhibitor LY294002 for a period of 24 h.In both in vivo and in vitro settings,quantification of inflammation factor levels was conducted using western blotting,real-time qPCR and ELISA.RESULTS In db/db mice,administration of myricetin led to a mitigating effect on DN-induced renal dysfunction and fibrosis.Notably,we observed a significant reduction in expressions of the kidney injury markers kidney injury molecule-1 and neutrophil gelatinase associated lipocalin,along with a decrease in expressions of inflammatory cytokine-related factors.Furthermore,myricetin treatment effectively inhibited the up-regulation of tumor necrosis factor-alpha,interleukin-6,and interluekin-1βinduced by high glucose in RAW 264.7 cells.Additionally,myricetin modulated the M1-type polarization of the RAW 264.7 cells.Molecular docking and bioinformatic analyses revealed Akt as the target of myricetin.The protective effect of myricetin was nullified upon blocking the polarization of RAW 264.7 via inhibition of PI3K/Akt activation using LY294002.CONCLUSION This study demonstrated that myricetin effectively mitigates kidney injury in DN mice through the regulation of macrophage polarization via the PI3K/Akt signaling pathway.

Hepcidin and Iron Metabolism in Non-diabetic Obese and Type 2 Diabetic Rats

Summary： The aim of this study was to investigate the changes of iron levels and hepatic regulatory molecules expression involved in iron metabolism in non-diabetic obese/type 2 diabetic rat models. Male Wistar rats were divided into 3 groups： control group, non-diabetic obese group and type 2 dia- betic group （n=20 each）. The rats were evaluated physiologically and biochemically. The hepatic histo- pathological changes were observed using haematoxylin and eosin （HE） staining. The mRNA expres- sion patterns of hepcidin, interleukin-6 （IL-6）, hypoxia-inducible factor （HIF） and ferroportin （Fpn） in the rat liver in control group, non-diabetic obese group and type 2 diabetic group were analyzed by real-time RT-PCR. The protein expression patterns of hepcidin in liver of each group were further ana- lyzed by immunohistochemistry and Western blotting. As compared with control group, the ferritin in non-diabetic obese group and type 2 diabetic group was increased significantly （P〈0.001）. However, there was no significant difference in soluble transferring receptor （sTfR）：ferritin ratio among the three groups （P〉0.05）. The real-time RT-PCR, immunohistochemistry and Western blotting results all re- vealed that the expression levels of hepcidin in non-diabetic obese group and type 2 diabetic group were elevated significantly as compared with those in control group （P〈0.001）. The expression levels of hep- cidin mRNA between non-diabetic obese group and type 2 diabetic group showed no significant differ- ence （P〉0.05）. However, the protein expression levels of hepcidin in type 2 diabetic group were sig- nificantly higher than those in non-diabetic obese group （P〈0.05）. Compared to control group, the ex- pression levels of IL-6 mRNA in non-diabetic obese group and type 2 diabetic group were increased significantly and the expression levels ofFpn mRNA decreased （P〈0.05）. However, the expression lev- els ofHIF mRNA had no significant difference among three groups. It is suggested that iron metabolism is substantially disturbed in non-diabetic obese and type 2 diabetic rats probably by the abnormal ex- pression of hepcidin in chronic inflammatory status. The increased hepcidin may restrain the iron re- lease from the cells by affecting the expression of Fpn, which probably associates with the development of diabetic complication.

A study of the levels of urinary microalbumin in non-diabetic normotensive obese individuals

Diabetes mellitus, hypertension and obesity are associated with endothelial dysfunction. Microalbuminu-ria is an early sign of endothelial dysfunction. The occurrence of microalbuminuria in long standing diabetes mellitus and hypertension is well established. This study intends to find the occurrence of microal-buminuria in non-diabetic normotensive obese individuals. Objectives: To estimate urinary albumin creatinine ratio (UACR) in non-diabetic normotensive obese individuals. Design and Methods: 41 non- diabetic normotensive obese adults with Body Mass Index > 23 kg/m2 were taken as cases and 41 age and sex matched healthy non-obese adults with Body Mass Index < 23 kg/m2 were taken as controls. An-thropometric measurements (Body Mass Index and Waist circumference) and biochemical estimations (fasting blood glucose, lipid profile & spot urinary albumin creatinine ratio) were carried out. Results: urinary albumin creatinine ratio was lesser than the established microalbuminuric range of 30 - 300 mg/g, in both cases and controls irrespective of the values obtained for lipid profile and anthropometric indices. Conclusion: Microalbuminuria may not be present in obese patients without diabetes and/hypertension.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.

Biological Association and Expressions of NOS3 &SOD2 in Non-Diabetic Senile Cataractogenesis

Aim: To evaluate the functional relationship between the nitric oxide synthase (NOS) and superoxide dismutase (SOD) enzymes in the pathogenesis of human senile cataract lenses of non-diabetic patients. Methods: Total solubilized proteins from human cataract lens were compared with normal lens (control) by 2-Dimenstional gel electrophoresis (2-DE). Proteins with different abundances were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Western blot analysis was used to verify the changes in expression of NOS3 and SOD2. A further functional association of NOS3 with SOD2 and other proteins was seen by STRING 8.3 databases. Results: In the 2-DE maps, the cataract and normal lens proteins migrated in the region of pH 3 - 10 with a relative molecular weight of 20 - 130 kDa. Approximately two protein spots with differential intensity were detected as NOS3 and SOD2 using MALDI-TOF-MS. Western blot analysis showed high expression of NOS3 in cataract and SOD2 in normal lens samples. String interaction network revealed strong interactions between NOS3 and SOD2 at high confidence score, which is helpful in characterization of functional abnormalities that may be a causative factor in the pathogenesis of cataract. Conclusion: This study will offer new avenues for mechanistic evaluation and future prevention of cataractogensis. However, large scale studies will be required to evaluate the effect of this interaction on the clinical outcome in human cataract.

Jianpi Gushen Huayu decoction ameliorated diabetic nephropathy through modulating metabolites in kidney,and inhibiting TLR4/NF-κB/NLRP3 and JNK/P38 pathways

BACKGROUND Jianpi Gushen Huayu Decoction(JPGS)has been used to clinically treat diabetic nephropathy(DN)for many years.However,the protective mechanism of JPGS in treating DN remains unclear.AIM To evaluate the therapeutic effects and the possible mechanism of JPGS on DN.METHODS We first evaluated the therapeutic potential of JPGS on a DN mouse model.We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics.Furthermore,we examined the effects of JPGS on c-Jun N-terminal kinase(JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)/NOD-like receptor family pyrin domain containing 3(NLRP3).RESULTS The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress.Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice.A total of 51 differential metabolites were screened.Pathway analysis results indicated that nine pathways significantly changed between the control and model groups,while six pathways significantly altered between the model and JPGS groups.Pathways related to cysteine and methionine metabolism;alanine,tryptophan metabolism;aspartate and glutamate metabolism;and riboflavin metabolism were identified as the key pathways through which JPGS affects DN.Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors.CONCLUSION JPGS could markedly treat mice with streptozotocin(STZ)-induced DN,which is possibly related to the regulation of several metabolic pathways found in kidneys.Furthermore,JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathwaymediated apoptosis in DN mice.

New insight into the role of exosomes in idiopathic membrane nephropathy

Exosomes,nanoscale extracellular vesicles(EVs)derived from the invagination of the endosomal membrane,are secreted by a majority of cell types.As carriers of DNA,mRNA,proteins,and microRNAs,exosomes are implicated in regulating biological activities under physiological and pathological conditions.Kidney-derived exosomes,which vary in origin and function,may either contribute to the pathogenesis of disease or represent a potential therapeutic resource.Membranous nephropathy(MN),an autoimmune kidney disease characterized by glomerular damage,is a predominant cause of nephrotic syndrome.Notably,MN,especially idiopathic membranous nephropathy(IMN),often results in end-stage renal disease(ESRD),affecting approximately 30%of patients and posing a considerable economic challenge to healthcare systems.Despite substantial research,therapeutic options remain ineffective at halting IMN progression,underscoring the urgent need for innovative strategies.Emerging evidence has implicated exosomes in IMN’s pathophysiology;Providing a fresh perspective for the discovery of novel biomarkers and therapeutic strategies.This review aims to scrutinize recent developments in exosome-related mechanisms in IMN and evaluate their potential as promising therapeutic targets and diagnostic biomarkers,with the hope of catalyzing further investigations into the utility of exosomes in MN,particularly IMN,ultimately contributing to improved patient outcomes in these challenging disease settings.

Natural compounds improve diabetic nephropathy by regulating the TLR4 signaling pathway

Diabetic nephropathy(DN),a severe complication of diabetes,is widely recognized as a primary contributor to end-stage renal disease.Recent studies indicate that the inflammation triggered by Tolllike receptor 4(TLR4)is of paramount importance in the onset and progression of DN.TLR4 can bind to various ligands,including exogenous ligands such as proteins and polysaccharides from bacteria or viruses,as well as endogenous ligands such as biglycan,fibrinogen,and hyaluronan.In DN,the expression or release of TLR4-related ligands is significantly elevated,resulting in excessive TLR4 activation and increased production of proinflammatory cytokines through downstream signaling pathways.This process is closely associated with the progression of DN.Natural compounds are biologically active products derived from natural sources that have advantages in the treatment of certain diseases.Various types of natural compounds,including alkaloids,flavonoids,polyphenols,terpenoids,glycosides,and polysaccharides,have demonstrated their ability to improve DN by affecting the TLR4 signaling pathway.In this review,we summarize the mechanism of action of TLR4 in DN and the natural compounds that can ameliorate DN by modulating the TLR4 signaling pathway.We specifically highlight the potential of compounds such as curcumin,paclitaxel,berberine,and ursolic acid to inhibit the TLR4 signaling pathway,which provides an important direction of research for the treatment of DN.

Agmatine ameliorates diabetes type 2-induced nephropathy in rats

Objective:To assess the nephroprotective potential of agmatine in a rat model of streptozotocin-induced diabetic nephropathy.Methods:A single dose of streptozotocin(40 mg/kg)coupled with a fructose diet induced diabetes in Wistar rats.Agmatine(40 and 80 mg/kg)was administered to rats for 12 weeks.The body weight and fasting blood glucose were measured weekly.Insulin level,urine output,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C were also determined at the end of the experiment.Furthermore,superoxide dismutase,glutathione,interleukin-1β,interleukin-6,and tumor necrosis factor-alpha were evaluated in kidney tissue.Histopathological study was also performed using hematoxylin and eosin staining.Results:Agmatine at both doses significantly increased final body weight,and lowered fasting blood glucose,urine output,insulin,total protein,albumin,blood urea nitrogen,creatinine,and cystatin-C levels compared with the diabetic group(P<0.05).Inflammatory markers and antioxidant effect were significantly improved in agmatine-treated rats.Moreover,the histopathological changes in renal structure were ameliorated by agmatine treatment.Conclusions:Agmatine alleviates diabetic nephropathy by improving renal functions and reducing inflammation and oxidative stress.The molecular mechanisms of its nephroprotective actions need to be investigated in future study.

Regulatory role of the mTOR signaling pathway in autophagy and mesangial proliferation in IgA nephropathy

Objective:IgA nephropathy(IgAN)is the most common primary glomerular disease in China,but its pathogenesis remains unclear.This study aims to explore the regulatory role of the mammalian target of rapamycin(mTOR)signaling pathway in autophagy and mesangial proliferation during renal injury in IgA.Methods:The activity of mTOR and autophagy was evaluated in kidney samples from IgAN patients and in an IgAN mouse model induced by oral bovine serum albumin and carbon tetrachloride(CCl4)injection.mTOR inhibitors(rapamycin)and activators[bpV(phen)]were administered to the IgAN mouse model to observe the effects of mTOR on autophagy and renal lesions.In human mesangial cells treated with polymeric IgA1(p IgA1)and mTOR modulators,the expression and distribution of cell cycle proteins were assessed,along with the effects of mTOR on mesangial cell proliferation and autophagy.Results:Increased mTOR activity and decreased autophagy were observed in kidney tissues from IgAN patients and the mouse model,as evidenced by elevated phosphorylated mTOR(p-mTOR)levels and reduced LC3 expression.In the IgAN mouse model,rapamycin inhibited mTOR,restored autophagy,reduced mesangial IgA deposition,alleviated mesangial cell proliferation,and decreased proteinuria(all P<0.05).In contrast,bpV(phen)activated mTOR,further suppressed autophagy,exacerbated kidney damage,and increased proteinuria(all P<0.05).In vitro,p-IgA1 induced mesangial cell proliferation and inhibited autophagy,effects that were reversed by rapamycin and aggravated by bpV(phen)(all P<0.05).mTOR regulated mesangial cell proliferation by altering cell cycle distribution,with rapamycin inducing G1 phase arrest and bpV(phen)promoting cell cycle progression.Additionally,cyclinD1 expression in renal cortex was up-regulated in the IgAN mouse model,further increased by bpV(phen),and reduced by rapamycin(all P<0.05).Conclusion:Inhibition of the mTOR signaling pathway enhances renal autophagy,reduces mesangial cell proliferation,and improves renal injury in IgAN.

Ethanol extract of Abelmoschus manihot suppresses endoplasmic reticulum stress in contrast-induced nephropathy

Objective:To explore the efficacy and potential mechanisms of the ethanol extract of Abelmoschus manihot(L.)Medic in contrast-induced nephropathy(CIN).Methods:CIN rat models and human renal proximal tubular cells(HK-2)with iopromide-induced injury were employed to mimic CIN conditions.The effect of Abelmoschus manihot extract on the rat models and HK-2 cells was evaluated.In rat models,kidney function,histology,oxidative stress and apoptosis were determined.In HK-2 cells,cell viability,apoptosis,mitochondrial membrane potential,and endoplasmic reticulum stress were assessed.Results:Abelmoschus manihot extract significantly improved structural and functional impairments in the kidneys of CIN rats.Additionally,the extract effectively mitigated the decline in cellular viability and reduced iopromide-induced oxidative stress and lipid peroxidation.Mechanistic investigations revealed that Abelmoschus manihot extract prominently attenuated acute endoplasmic reticulum stress-mediated apoptosis by downregulating GRP78 and CHOP protein levels.Conclusions:Abelmoschus manihot extract can be used as a promising therapeutic and preventive agent in the treatment of CIN.

Intravitreal injection of conbercept for diabetic macular edema complicated with diabetic nephropathy

AIM:To observe the therapeutic effect of conbercept on diabetic macular edema(DME)complicated with diabetic nephropathy(DN).METHODS:In this retrospective study,54 patients(54 eyes)that diagnosed as DME from January 2017 to October 2021 were collected.The patients were divided into two groups:DME patients with DN(25 eyes),and DME patients without DN(29 eyes).General conditions were collected before treatment,laboratory tests include fasting blood glucose,HbA1c,microalbumin/creatinine,serum creatinine.Optical coherence tomography(OCT)was used to check the ellipsoidal zone(EZ)and external limiting membrane(ELM)integrity.Central macular thickness(CMT),best corrected visual acuity(BCVA),and retinal hyperreflective foci(HF)as well as numbers of injections were recorded.RESULTS:There were significant differences between fasting blood glucose,HbA1c,serum creatinine,urinary microalbumin/creatinine,and estimated glomerular filtration rate(eGFR)between the two groups(all P<0.05).EZ and ELM continuity in the DME+DN group was worse than that in the DME group(P<0.05).BCVA(logMAR)in the DME group was significantly better than that in the DME+DN group at the same time points during treatment(all P<0.05).CMT and HF values were significantly higher in the DME+DN group than that in the DME group at the all time points(all P<0.05)and significantly decreased in both groups with time during treatment.At 6mo after treatment,the mean number of injections in the DME+DN and DME group was 4.84±0.94 and 3.79±0.86,respectively.CONCLUSION:Conbercept has a significant effect in short-term treatment of DME patients with or without DN,and can significantly ameliorate BCVA,CMT and the number of HF,treatment efficacy of DME patients without DN is better than that of DME patients with DN.

Combination treatment with telitacicept,mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy:A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A(IgA)antibody production by inhibiting the activity of B lymphocyte stimulator(BLyS)and a proliferation-inducing ligand(APRIL),thereby decreasing IgA deposition in the glomeruli and local inflammatory response.This ultimately protects the kidneys from damage.This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy.CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment.Pathologically,she exhibited focal proliferative glomerulonephritis.Treatment with angiotensin II receptor blocker,hormones,and mycophenolate mofetil did not lead to a significant improvement in her condition.However,upon the addition of telitacicept,the patient’s renal function recovered and her proteinuria rapidly reduced.Hormones were swiftly tapered and discontinued,with no occurrence of severe infections or related complications.CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

BACKGROUND Diabetic nephropathy(DN)is a severe microvascular complication of diabetes characterized by inflammation,oxidative stress,and renal fibrosis.Asiaticoside(AC)exhibits anti-inflammatory,antioxidant,and anti-fibrotic properties,suggesting potential therapeutic benefits for DN.This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2(NRF2)/heme oxygenase-1(HO-1)antioxidant pathway.METHODS The effects of AC on high glucose(HG)-induced proliferation,inflammation,oxidative stress,and fibrosis were evaluated in rat glomerular mesangial cells(HBZY-1)in vitro.A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury,inflammation,oxidative stress,and fibrosis.The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model.RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats,including reduced body weight,and elevated blood glucose,serum creatinine,blood urea nitrogen,and 24-h urine protein.Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin(IL)-6,IL-8,tumor necrosis factor-alpha,reactive oxygen species,and malondialdehyde levels while increasing superoxide dismutase activity.Additionally,AC suppressed the expression of fibrogenic markers such as collagen I,collagen IV,and fibronectin.AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase(Quinone)1 protein expression in renal tissues and HG-induced HBZY-1 cells.CONCLUSION AC improves DN by reducing inflammation,oxidative stress,and fibrosis through the activation of the NRF2/HO-1 signaling pathway.These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Tiliroside protects against diabetic nephropathy in streptozotocininduced diabetes rats by attenuating oxidative stress and inflammation

BACKGROUND Diabetic nephropathy(DN),affecting half of diabetic patients and contributing significantly to end-stage kidney disease,poses a substantial medical challenge requiring dialysis or transplantation.The nuanced onset and clinical progression of kidney disease in diabetes involve consistent renal function decline and persistent albuminuria.AIM To investigate Tiliroside's(Til)protective effect against diabetic nephropathy(DN)in rats under diabetic conditions.METHODS Five groups of six rats each were included in this study:Rats treated with DMSO by intraperitoneal injection as controls,those treated with STZ by intraperitoneal injection,those treated with STZ+Til(25 mg/kg body weight[bwt])or Til(50 mg/kg bwt),and those treated with anti-diabetic medication glibenclamide(600μg/kg bwt).Biochemical markers,fasting blood glucose,food intake,kidney weight,antioxidant enzymes,inflammatory and fibrotic markers,and renal injury were monitored in different groups.Molecular docking analysis was performed to identify the interactions between Til and its targeted biomarkers.RESULTS Til significantly reduced biochemical markers,fasting blood glucose,food intake,and kidney weight and elevated antioxidant enzymes in diabetic rats.It also mitigated inflammatory and fibrotic markers,lessened renal injury,and displayed inhibitory potential against crucial markers associated with DN as demonstrated by molecular docking analysis.CONCLUSION These findings suggest Til's potential as a therapeutic agent for DN treatment,highlighting its promise for future drug development.

Corilagin alleviates podocyte injury in diabetic nephropathy by regulating autophagy via the SIRT1-AMPK pathway

BACKGROUND Diabetic nephropathy(DN)is the most frequent chronic microvascular consequence of diabetes,and podocyte injury and malfunction are closely related to the development of DN.Studies have shown that corilagin(Cor)has hepatoprotective,anti-inflammatory,antibacterial,antioxidant,anti-hypertensive,antidiabetic,and anti-tumor activities.AIM To explore the protective effect of Cor against podocyte injury in DN mice and the underlying mechanisms.METHODS Streptozotocin and a high-fat diet were combined to generate DN mice models,which were then divided into either a Cor group or a DN group(n=8 in each group).Mice in the Cor group were intraperitoneally injected with Cor(30 mg/kg/d)for 12 wk,and mice in the DN group were treated with saline.Biochemical analysis was used to measure the blood lipid profiles.Hematoxylin and eosin staining was used to detect pathological changes in kidney tissue.Immunohistochemistry and Western blotting were used to assess the protein expression of nephrin and podocin.Mouse podocyte cells(MPC5)were cultured and treated with glucose(5 mmol/L),Cor(50μM),high glucose(HG)(30 mmol/L),and HG(30 mmol/L)plus Cor(50μM).Real-time quantitative PCR and Western blotting RESULTS Compared with the control group,the DN mice models had increased fasting blood glucose,glycosylated hemoglobin,triglycerides,and total cholesterol,decreased nephrin and podocin expression,increased apoptosis rate,elevated inflammatory cytokines,and enhanced oxidative stress.All of the conditions mentioned above were alleviated after intervention with Cor.In addition,Cor therapy improved SIRT1 and AMPK expression(P<0.001),inhibited reactive oxygen species and oxidative stress,and elevated autophagy in HG-induced podocytes(P<0.01).CONCLUSION Cor alleviates podocyte injury by regulating autophagy via the SIRT1-AMPK pathway,thereby exerting its protective impact on renal function in DN mice.