Cause Of Chronic Kidney Disease Research Articles

New insights into the role of immunity and inflammation in diabetic kidney disease in the omics era.

Diabetic kidney disease (DKD) is becoming the leading cause of chronic kidney disease, especially in the industrialized world. Despite mounting evidence has demonstrated that immunity and inflammation are highly involved in the pathogenesis and progression of DKD, the underlying mechanisms remain incompletely understood. Substantial molecules, signaling pathways, and cell types participate in DKD inflammation, by integrating into a complex regulatory network. Most of the studies have focused on individual components, without presenting their importance in the global or system-based processes, which largely hinders clinical translation. Besides, conventional technologies failed to monitor the different behaviors of resident renal cells and immune cells, making it difficult to understand their contributions to inflammation in DKD. Recently, the advancement of omics technologies including genomics, epigenomics, transcriptomics, proteomics, and metabolomics has revolutionized biomedical research, which allows an unbiased global analysis of changes in DNA, RNA, proteins, and metabolites in disease settings, even at single-cell and spatial resolutions. They help us to identify critical regulators of inflammation processes and provide an overview of cell heterogeneity in DKD. This review aims to summarize the application of multiple omics in the field of DKD and emphasize the latest evidence on the interplay of inflammation and DKD revealed by these technologies, which will provide new insights into the role of inflammation in the pathogenesis of DKD and lead to the development of novel therapeutic approaches and diagnostic biomarkers.

The Combination of Pakcoy Juice (Brassica Rapa L.) and Antihypertensive Medication in Reducing Blood Pressure in Pregnant Women with Hypertension

Hypertension in pregnant women ranks as the second highest cause of Chronic Kidney Disease (CKD). Hypertension is defined as a minimum diastolic blood pressure of 90 mmHg and a minimum systolic blood pressure of 140 mmHg, with an increase in diastolic and systolic pressure of at least 15 mmHg and 30 mmHg, respectively. This study aims to evaluate the impact of a combination of Pakcoy juice (Brassica rapa L) and antihypertensive medication on blood pressure in pregnant women with hypertension.Using a quasi-experimental design with a One Group Pre-Test – Post-Test without a control group, the study involved 14 pregnant women with hypertension at the Gunung Sugih Community Health Center from January to June 2023 as the population. The results of data analysis indicate a significant influence (p value 0.000 < α: 0.05) on the reduction of blood pressure after the administration of antihypertensive medication and Pakcoy juice.The discussion emphasizes that Pakcoy juice is effective as a supplement to antihypertensive medication due to its natural content of potassium, calcium, and magnesium, which can reduce blood pressure. Consuming 4,700 milligrams of potassium per day is known to lower blood pressure caused by high sodium intake. In conclusion, the combination of Pakcoy juice and antihypertensive medication has a positive effect of 19% on reducing blood pressure in pregnant women with hypertension at the Gunung Sugih Community Health Center, with a recommendation for health education outreach to prevent hypertension cases in pregnant women.

MicroRNA Expression Profile in Obesity-Induced Kidney Disease Driven by High-Fat Diet in Mice.

Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney injury and dysfunction in obesity-associated nephropathy remain unclear. The present study aimed to unveil the kidney microRNA (miRNA) expression profile in a model of obesity-induced kidney disease in C57BL/6J mice using next-generation sequencing (NGS) analysis. High-fat diet (HFD)-induced obesity led to notable structural alterations in tubular and glomerular regions of the kidney, increased renal expression of proinflammatory and profibrotic genes, as well as an elevated renal expression of genes involved in cellular lipid metabolism. The miRNA sequencing analysis identified a set of nine miRNAs differentially expressed in the kidney upon HFD feeding, with miR-5099, miR-551b-3p, miR-223-3p, miR-146a-3p and miR-21a-3p showing the most significant differential expression between standard diet (STD) and HFD mice. A validation analysis showed that the expression levels of miR-5099, miR-551b-3p and miR-146a-3p were consistent with NGS results, while Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that these three validated miRNAs modulated target genes involved in metabolic and adipocytokine pathways, fatty acid and lipid metabolism, and inflammatory, senescence and profibrotic pathways. Our results suggest that differentially expressed miRNAs play pivotal roles in the intricate pathophysiology of obesity-associated kidney disease and could potentially create novel treatment strategies to counteract the deleterious effects of obesity on kidney function.

Predicting the Pharmacological Targets of Astragalus membranaceus against Hypertensive Nephropathy

Objective: Hypertension is one of the main causes of chronic kidney disease. Astragalus membranaceus (AM), an important traditional Chinese medicine for treating hypertensive nephropathy, has a complex composition that makes it challenging to explore its mechanism of action and limits its clinical application. This study aims to investigate the underlying mechanism of AM in treating hypertensive nephropathy. Methods: We retrieved all the compound data of AM from the Traditional Chinese Medicine Systems Pharmacology database and screened out the active compounds and their target proteins. Then, a network of candidate compounds and target compounds of AM was constructed using Cytoscape software. Furthermore, hypertensive nephropathy-related genes from the DisGeNET and GeneCards databases were intersected with AM target proteins and hypertensive nephropathy-related genes to determine the potential targets of AM in treating hypertensive nephropathy. Finally, after performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, we conducted molecular docking to verify the interaction between the main active ingredients of AM and the core targets. Results: A total of 87 effective components of AM were obtained from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. According to the network of active compounds and their target proteins, 18 of the 20 effective compounds in AM could act on 210 proteins. Taking the intersection of 274 hypertensive nephropathy-related genes and AM target proteins, 49 potential targets of AM in treating hypertensive nephropathy were identified. Using the median degree value, we determined 25 core targets of AM in treating hypertensive nephropathy. GO enrichment analysis showed that the biological processes of AM on hypertensive nephropathy mainly focused on the inflammatory response, hypoxia response, angiogenesis, cell proliferation, and cell migration. KEGG pathway enrichment analysis mainly involved cancer pathways, the AGE-RAGE signaling pathway in diabetic complications, blood flow shear stress, and atherosclerosis. Molecular docking results showed that quercetin, kaempferol, and 7-O-methylisomucronulatol had strong binding activity with several target proteins and may exert protective effects by stabilizing the interaction between molecules through the intermolecular forces of hydrogen bonds. Conclusion: This study reveals the targets of AM in treating hypertensive nephropathy using network pharmacology and molecular docking, providing new clues for developing novel drugs for hypertensive nephropathy and basic research development.

Current Status and Prospects of Viral Vector-Based Gene Therapy to Treat Kidney Diseases.

Inherited kidney diseases are among the leading causes of chronic kidney disease, reducing the quality of life and resulting in substantial socioeconomic impact. The advent of early genetic testing and the growing understanding of the molecular basis and pathophysiology of these disorders have opened avenues for novel treatment strategies. Viral vector-based gene therapies have evolved from experimental treatments for rare diseases to potent platforms that carry the intrinsic potential to provide a cure with a single application. Several gene therapy products have reached the market, and the numbers are only expected to increase. Still, none target inherited kidney diseases. Gene transfer to the kidney has lagged when compared to other tissue-directed therapies such as hepatic, neuromuscular, and ocular tissues. Systemic delivery of genetic information to tackle kidney disease is challenging. The pharma industry is taking steps to take on kidney disease and to translate the current research into the therapeutic arena. In this review, we provide an overview of the current viral vector-based approaches and their potential. We discuss advances in platforms and injection routes that have been explored to enhance gene delivery toward kidney cells in animal models, and how these can fuel the development of viable gene therapy products for humans.

A New Hope on the Horizon for Kidney and Cardiovascular Protection with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Mineralocorticoid Receptor Antagonists in Type 2 Diabetic and Chronic Kidney Disease Patients.

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). In addition, the cardiovascular prevalence in diabetic patients is around 32.2%, with a two-fold increased mortality risk compared to those without diabetes. Recent investigations have shed light on the promising cardioprotective and nephroprotective benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) for individuals with T2D. The evidence robustly indicates that SGLT2i and GLP-1RA significantly reduce the risk of CKD and cardiovascular disease (CVD), all while effectively managing blood glucose levels. Furthermore, combining SGLT2i with nsMRAs amplifies the benefits, potentially offering a more profound reduction in cardiovascular and renal outcomes. The data analysis strongly supports the integration of these pharmacological agents in the management strategies for CKD and CVD prevention among T2D patients, highlighting the importance of awareness among nephrologists, especially in regions with limited healthcare resources.

Identification and validation of immune and cuproptosis - related genes for diabetic nephropathy by WGCNA and machine learning.

As the leading cause of chronic kidney disease, diabetic kidney disease (DKD) is an enormous burden for all healthcare systems around the world. However, its early diagnosis has no effective methods. First, gene expression data in GEO database were extracted, and the differential genes of diabetic tubulopathy were obtained. Immune-related genesets were generated by WGCNA and immune cell infiltration analyses. Then, differentially expressed immune-related cuproptosis genes (DEICGs) were derived by the intersection of differential genes and genes related to cuproptosis and immune. To investigate the functions of DEICGs, volcano plots and GO term enrichment analysis was performed. Machine learning and protein-protein interaction (PPI) network analysis helped to finally screen out hub genes. The diagnostic efficacy of them was evaluated by GSEA analysis, receiver operating characteristic (ROC) curve, single-cell RNA sequencing and the Nephroseq website. The expression of hub genes at the animal level by STZ -induced and db/db DKD mouse models was further verified. Finally, three hub genes, including FSTL1, CX3CR1 and AGR2 that were up-regulated in both the test set GSE30122 and the validation set GSE30529, were screened. The areas under the curve (AUCs) of ROC curves of hub genes were 0.911, 0.935 and 0.922, respectively, and 0.946 when taking as a whole. Correlation analysis showed that the expression level of three hub genes demonstrated their negative relationship with GFR, while those of FSTL1 displayed a positive correlation with the level of serum creatinine. GSEA was enriched in inflammatory and immune-related pathways. Single-nucleus RNA sequencing indicated the main distribution of FSTL1 in podocyte and mesangial cells, the high expression of CX3CR1 in leukocytes and the main localization of AGR2 in the loop of Henle. In mouse models, all three hub genes were increased in both STZ-induced and db/db DKD models. Machine learning was combined with WGCNA, immune cell infiltration and PPI analyses to identify three hub genes associated with cuproptosis, immunity and diabetic nephropathy, which all have great potential as diagnostic markers for DKD and even predict disease progression.

Aging and Diabetic Kidney Disease: Emerging Pathogenetic Mechanisms and Clinical Implications.

Diabetic kidney disease (DKD) is one of the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) worldwide. With the overpowering trend of aging, the prevalence of DKD in the elderly is progressively increasing. Genetic factors, abnormal glucose metabolism, inflammation, mitochondrial dysregulation, and oxidative stress all contribute to the development of DKD. Conceivably, during aging, these pathobiological processes are likely to be intensified, and this would further exacerbate the deterioration of renal functions in elderly patients, ultimately leading to ESRD. Currently, the pathogenesis of DKD in the elderly is not very well-understood. This study describes an appraisal of the relationship between diabetic nephropathy and aging while discussing the structural and functional changes in the aged kidney, the impact of related mechanisms on the outcome of DKD, and the latest advances in targeted therapies.

Risk factors associated with glomerular filtration rate in Mexican adults with type 2 diabetes mellitus

IntroductionType 2 diabetes mellitus (T2DM) is related to glomerular filtration rate (GFR) impairment, which is one of the main causes of chronic kidney disease. The objective of this study was to identify the risk factors related to GFR in Mexican adults with T2DM, using a validated multiple linear regression model (MLRM), with emphasis in body adiposity, glycemic control, duration of the diabetes and other relevant risk factors. Materials and methodsA cross-sectional, analytical, and observational study was carried out in 252 adults with a previous diagnosis of T2DM. Body mass index (BMI) and waist circumference (WC) were determined and a fasting blood sample was collected for glucose, creatinine and HbA1c determinations. GFR was calculated with the Cockcroft–Gault equation adjusted for body surface area. Four MLRM were performed to determine the factors related to the GFR; it was evaluated whether these models complied with the statistical assumptions of the linear regression model. ResultsThe average age of the participants was 60 ± 12 years, 62.3% of them were women. GFR correlated with BMI and WC; age and duration of the diabetes were associated inversely. Model 4 of the MLRM reported a coefficient of determination of 53.5% where the variables BMI (β = 1.31), male sex (β = −6.01), duration of T2DM (β = −0.57), arterial hypertension (β = −6.53) and age (β = −1.45) were simultaneously and significantly related to the GFR. ConclusionsOlder age, male sex, longer duration of T2DM and the presence of arterial hypertension were associated with a decrease in the GFR; BMI and WC were directly associated. No effect of glucose and HbA1c on GFR was observed.

Research progress on the treatment of diabetic nephropathy with leech and its active ingredients.

Diabetic nephropathy (DN) is a major microvascular complication of diabetes and a common cause of chronic kidney disease. There is currently a lack of effective treatments for DN, and the prognosis for patients remains poor. Hirudin, one of the primary active components derived from leeches, demonstrates anti-coagulant, anti-fibrotic, anti-thrombotic, and anti-inflammatory properties, exhibiting significant protective effects on the kidneys. In recent years, there has been a surge of interest in studying the potential benefits of hirudin, especially in its role in the management of DN. This article delves into the mechanisms by which hirudin contributes to the treatment of DN and its clinical efficacy.

Association between ELMO1 gene polymorphisms and diabetic kidney disease: A systematic review and meta-analysis.

Previous research has suggested that the ELMO1 gene may play a role in the development of diabetic kidney disease. Diabetic kidney disease (DKD) is a serious complication of diabetes and the leading cause of chronic kidney disease and end-stage renal disease (ESRD). This study aim was to systematically review and explore the association between ELMO1 gene polymorphisms and diabetic kidney disease. A comprehensive systematic review provides a clear conclusion and high-level evidence for the association between ELMO1 gene and DKD for future application in personalized medicine. A comprehensive search of electronic databases, per PRISMA instructions, was conducted in Scopus, EMBASE, Web of Science, and PubMed databases from 1980 to January 2023. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using appropriate models. Subgroup and sensitivity analyses were performed to explore potential sources of heterogeneity and assess the robustness of the findings. A total of 5794 diabetes patients with DKD, 4886 diabetes patients without DKD, and 2023 healthy controls were included in the 17 studies that made up this systematic review. In the investigation of DM (Diabetes Mellitus) with DKD vs. DM without DKD, the susceptibility for DKD for the EMLO1 rs741301 polymorphism indicated a significant difference under the dominant, homozygote, and recessive genetic models. The susceptibility for DKD for the EMLO1 rs1345365, rs10255208, and rs7782979 polymorphisms demonstrated a significant difference under the allele genetic models in the analysis of DM with DKD vs. DM without DKD groups. There was a considerable increase in DKD risk in the Middle East when the population was stratified by the region. The findings of the meta-analysis show that there are a significant connection between the EMLO1 rs741301 polymorphism and DKD susceptibility in overall analyses; as well as rs1345365, rs10255208, and rs7782979 polymorphisms; especially in the Middle East region.

Critical role of FGF21 in diabetic kidney disease: from energy metabolism to innate immunity.

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

A synthetic agent ameliorates polycystic kidney disease by promoting apoptosis of cystic cells through increased oxidative stress

Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic cause of chronic kidney disease and the fourth leading cause of end-stage kidney disease, accounting for over 50% of prevalent cases requiring renal replacement therapy. There is a pressing need for improved therapy for ADPKD. Recent insights into the pathophysiology of ADPKD revealed that cyst cells undergo metabolic changes that up-regulate aerobic glycolysis in lieu of mitochondrial respiration for energy production, a process that ostensibly fuels their increased proliferation. The present work leverages this metabolic disruption as a way to selectively target cyst cells for apoptosis. This small-molecule therapeutic strategy utilizes 11beta-dichloro, a repurposed DNA-damaging anti-tumor agent that induces apoptosis by exacerbating mitochondrial oxidative stress. Here, we demonstrate that 11beta-dichloro is effective in delaying cyst growth and its associated inflammatory and fibrotic events, thus preserving kidney function in perinatal and adult mouse models of ADPKD. In both models, the cyst cells with homozygous inactivation of Pkd1 show enhanced oxidative stress following treatment with 11beta-dichloro and undergo apoptosis. Co-administration of the antioxidant vitamin E negated the therapeutic benefit of 11beta-dichloro in vivo, supporting the conclusion that oxidative stress is a key component of the mechanism of action. As a preclinical development primer, we also synthesized and tested an 11beta-dichloro derivative that cannot directly alkylate DNA, while retaining pro-oxidant features. This derivative nonetheless maintains excellent anti-cystic properties in vivo and emerges as the lead candidate for development.

Factores de riesgo asociados con la tasa de filtración glomerular en adultos mexicanos con diabetes mellitus tipo 2

IntroductionType 2 diabetes mellitus (T2DM) is related to glomerular filtration rate (GFR) impairment, which is one of the main causes of chronic kidney disease. The objective of this study was to identify the risk factors related to GFR in Mexican adults with T2DM, using a validated multiple linear regression model (MLRM), with emphasis in body adiposity, glycemic control, duration of the diabetes and other relevant risk factors. Materials and methodsA cross-sectional, analytical, and observational study was carried out in 252 adults with a previous diagnosis of T2DM. Body mass index (BMI) and waist circumference (WC) were determined and a fasting blood sample was collected for glucose, creatinine and HbA1c determinations. GFR was calculated with the Cockcroft-Gault equation adjusted for body surface area. Four MLRM were performed to determine the factors related to the GFR; it was evaluated whether these models complied with the statistical assumptionsof the linear regression model. ResultsThe average age of the participants was 60±12 years, 62.3% of them were women. GFR correlated with BMI and WC; age and duration of the diabetes were associated inversely. Model 4 of the MLRM reported a coefficient of determination of 53.5% where the variables BMI (β=1.31), male sex (β=-6.01), duration of T2DM (β=-0.57), arterial hypertension (β=-6.53) and age (β=-1.45) were simultaneously and significantly related to the GFR. ConclusionsOlder age, male sex, longer duration of T2DM and the presence of arterial hypertension were associated with a decrease in the GFR; BMI and WC were directly associated. No effect of glucose and HbA1c on GFR was observed.

Development and validation of a diagnostic nomogram to evaluate tubular atrophy/interstitial fibrosis of IgA nephropathy.

Background: IgA nephropathy (IgAN) is a cause of chronic kidney disease (CKD). Tubular atrophy/interstitial fibrosis is associated with IgAN prognosis. However, simple tools for predicting pathological lesions of IgAN remain limited. Our objective was to develop a tool for evaluating tubular atrophy/interstitial fibrosis in patients with IgAN. Methods: In this cross-sectional study, 410 biopsy-verified IgAN patients were included. The factors associated with the incident interstitial fibrosis or tubular atrophy in IgAN were confirmed by using logistic regression analysis. A nomogram was developed using logistic regression coefficients to evaluate tubular atrophy or interstitial fibrosis. Receiver operating characteristic curves (ROC) and calibration curves were used to determine the discriminative ability and predictive accuracy of the nomogram. Results: In this study, the IgAN patients with tubular atrophy or interstitial fibrosis were older and had a higher percentage of males, hypertension and urinary protein excretion (UPE), with high levels of serum cystatin C, serum creatinine, high-sensitivity C-reactive protein and serum C4. The eGFRcr-cys equation calculated using serum creatinine, cystatin C and UPE were considered independent influencing factors of tubular atrophy or interstitial fibrosis in patients with IgAN. Furthermore, the nomogram demonstrated good discrimination (AUC: 0.87, 95% CI 0.81 to 0.93) and calibration in the validation cohort. Conclusion: The eGFRcr-cys and UPE are associated with tubular atrophy or interstitial fibrosis in patients with IgAN. Diagnostic nomogram can predict tubular atrophy or interstitial fibrosis in IgAN.

Chronic kidney disease associated with hypertension

Background: Globally, chronic kidney disease (CKD) is acknowledged as a major public health issue. Both the incidence and prevalence of chronic kidney disease (CKD) are rising with immense pace worldwide. Hypertension and diabetes mellitus is the main risk factor of chronic kidney disease. Objective: To determine chronic Kidney disease associated with hypertension Methods: A cross-sectional study was conducted at district headquarter hospital, Mianwali, Pakistan, which was performed between June 2020 and February 2022, the total number of patients in our study were 120. The number of Male patients were 49 and female were 71. In 120 consecutive patients who underwent for blood tests and Blood pressure monitoring. We also took stages of chronic kidney disease (CKD stage 1,2,3A,3B,4 and 5). We did renal function test for all patients (serum creatinine and serum urea). Data was tabulated and analyzed by SPSS. Results: In a current study total 120 patients were enrolled. The minimum age of patients were30 and the maximum age of the patients were 84. The mean age were 50.60±10.9 years. The minimum systolic blood pressure were 130 and maximum systolic blood pressure were 200. The mean systolic blood pressure were 149.55±13.5. The minimum diastolic blood pressure were 80 and the maximum diastolic blood pressure were 100. The mean diastolic blood pressure were 89.57±3.76 The frequency of male patients were 49 and its percentage were 40.8. The frequency of female patients were 71 and its percentage were 59.2. The frequency of age group 30-50 years were 61 and its percentage were 50.8. The frequency of age group 51-70 years were 52 and its percentage were 43.3. The frequency of age group >70 years were 7 and its percentage were 5.8. The mean of renal functional test Serum creatinine were 7.82 mg/dl and its SD value were 3.59 mg/dl. The mean of renal functional test Serum urea were 109.90 mg/dl and its SD value were 24.30 mg/dl. · The mean glomerular filtration rate were 20.36 ml/min and its SD value were 13.2 ml/min. · The mean weight of patients were 56.61 kg and its SD value were 10.19 kg. · The P-value of stages of Chronic kidney disease (CKD) were 0.133. The P-value of hypertension were 0.074. Conclusion: Hypertension and diabetes mellitus is the main cause of Chronic kidney disease (CKD). Stage 5 Chronic kidney disease (CKD) patients were more in our study as compare to other stages of CKD. We concluded in our study that after age of 30, patients have higher risk of Chronic kidney disease (CKD).

Diabetic Nephropathy: Pathogenesis and Drug Delivery System

Diabetic nephropathy is the leading cause of chronic kidney disease. The pathogenesis of diabetic nephropathy consists of four main pathways that indicate intracellular metabolic abnormalities identified in diabetic nephropathy, namely the activation of polyol and protein kinase C pathways, formation of advanced glycation end products, increased oxidative stress, and intraglomerular hypertension. Conventional treatment approaches for diabetic nephropathy that have been through clinical trials are, among others, the use of glucose-lowering agents, reduction of blood pressure, reduction of capillary permeability, and antioxidants. Although such treatments have been proven to slow the severity of diabetic nephropathy which leads to chronic kidney failure, their effectiveness does not cure diabetic nephropathy in patients. Thus, the modification of drug delivery systems and the widely-performed gene therapy need to be reviewed for their effectiveness with the previous treatments of diabetic nephropathy. This review article discusses the perspective of implementing the most effective diabetic nephropathy treatment system in order to achieve the therapeutic goals of diabetic nephropathy. The modification of drug delivery system and the gene therapies are expected to be able to increase the effectiveness of the drugs and guarantee their safety. The characteristics of the therapeutic targets in each kidney cell need to be understood more deeply so that the therapeutic goals can be achieved. It is hoped that the testing in the clinical phase of diabetic nephropathy by modifications of the drug delivery system and gene-based therapies will be widely carried out in the future.

State-of-the-art trends in the treatment of immune-mediated inflammatory kidney diseases: Translation of the fundamental science into clinical practice. A review

Immune-mediated kidney diseases like glomerulonephritis and tubulointerstitial nephritis are not the most common cause of chronic kidney disease in the population, however the difficulties in their management, as well as a more rapid deterioration of kidney function, compared to diabetes mellitus and hypertension, justify the importance of this problem for internal medicine. Due to the fundamental discoveries in pathology and to the introduction of various methods of laboratory and instrumental investigation in the second half of the XX century substantial progress was made in the diagnostic approaches and treatment of these conditions. State-of-the-art diagnostic approach requires complex evaluation of the clinical, laboratory and morphological data to identify the nosological form of the disease. The accumulation of knowledge in the field of diseases' pathogenesis led to the revision of the current classification of glomerulonephritis that should be based on the immunopathogenesis of these conditions. The following phenotypes were suggested: autoimmunity-related, autoinflammation-related, alloimmunity-related, infections-related, and monoclonal gammopathy-related. The assessment of disease activity and chronicity in the kidney tissue should be mandatory. Personalized selection of the optimal treatment modality on the basis of the diagnosis, severity, and individual features of the patient is currently possible. The leading trends include rational prescription of glucocorticoids (steroid-sparing regimens) and cytotoxic agents, e.g. cyclophosphamide, as well as the introduction of multitarget regimens that include biologic agents or small molecules selectively suppressing B-cells or various complement pathways. Another mandatory component of treatment on par with immune suppression is nephroprotective therapy, which currently comprises not only traditional renin-angiotensin-aldosterone antagonists, but also endothelin receptor antagonists and sodium-glucose cotransporter-2 inhibitors. Current guidelines emphasize the importance of the non-pharmacological interventions for the implementation of the nephroprotective strategy. Rational combination of the aforementioned approaches allows for the optimization of the management of patients with immune-mediated kidney diseases, although it requires high competencies and strict adherence to the principles of the evidence-based medicine from the healthcare providers.

A review on the classification and current treatment of Chronic Kidney Disease

Introduction:
 Chronic Kidney Disease (CKD) is a chronic condition which is characterized by the gradual loss of kidney function over time leading to End-Stage Renal Disease (ESRD). Role of kidneys is very vital to maintain homeostasis of the system. CKD is classified into five stages based on the estimated Glomerular Filtration Rate (eGFR). CKD is a long-term condition which cannot be completely cured. Treatment focuses on managing underlying conditions , slowing disease progression and addressing complications. 
 Aim of the study: 
 Purpose of this study is to encapsulate available knowledge about classification and therapeutic options for patients with Chronic Kidney Disease and End-Stage Kidney Disease. Both old and new treatment methods have been summarized in the following publication.
 Material and methods: 
 Literature available in the PubMed database was reviewed using the following keywords:
 “Chronic kidney disease”, “ACE inhibitors” , “Angiotensin II Type 1 Receptor Blockers", “Diabetic Kidney Disease” ,”End-Stage Kidney Disease”, “Dapagliflozin”, 
 Conclusions:
 Chronic Kidney Disease is a condition which is progressive and affects more than 10% of the general population worldwide totaling over 800 million people. There are many causes of chronic kidney disease; therefore, it is important to focus on slowing the progression of the disease, minimizing complications and modifying risk factors.

The Terminalia chebula retz extract treats hyperuricemic nephropathy by inhibiting TLR4/myd88/NF-κb axis

Ethnopharmacological relevanceHyperuricemic nephropathy (HN) is a renal injury caused by hyperuricemia and is the main cause of chronic kidney disease and end-stage renal disease. ShiWeiHeZiSan, which is composed mainly of components of Terminalia chebula Retz. And is recorded in the Four Medical Tantras, is a typical traditional Tibetan medicinal formula for renal diseases. Although T. chebula has been reported to improve renal dysfunction and reduce renal cell apoptosis, the specific mechanism of the nephroprotective effects of T. chebula on HN is still unclear. Aim of the studyThis study was conducted to evaluate the effects and specific mechanism of T. chebula extract on HN through network pharmacology and in vivo and in vitro experiments. Materials and methodsPotassium oxalate (1.5 g/kg) and adenine (50 mg/kg) were combined for oral administration to establish the HN rat model, and the effects of T. chebula extract on rats in the HN model were evaluated by renal function indices and histopathological examinations. UPLC-Q-Exactive Orbitrap/MS analysis was also conducted to investigate the chemical components of T. chebula extract, and the potential therapeutic targets of T. chebula in HN were predicted by network pharmacology analysis. Moreover, the activation of potential pathways and the expression of related mRNAs and proteins were further observed in HN model rats and uric acid-treated HK-2 cells. ResultsT. chebula treatment significantly decreased the serum uric acid (SUA), blood urea nitrogen (BUN) and serum creatinine (SCr) levels in HN rats and ameliorated renal pathological injury and fibrosis. A total of 25 chemical components in T. chebula extract were identified by UPLC-Q-Exactive Orbitrap/MS analysis, and network pharmacology analysis indicated that the NF-κB pathway was the potential pathway associated with the therapeutic effects of T. chebula extract on HN. RT‒PCR analysis, immunofluorescence staining and ELISA demonstrated that the mRNA and protein levels of TLR4 and MyD88 were significantly decreased in the renal tissue of HN rats after treatment with T. chebula extract at different concentrations, while the phosphorylation of P65 and the secretion of TNF-α and IL-6 were significantly inhibited. The results of in vitro experiments showed that T. chebula extract significantly decreased the protein levels of TLR4, MyD88, p-IκBα and p-P65 in uric acid-treated HK-2 cells and inhibited the nuclear translocation of p65 in these cells. In addition, the expression of inflammatory factors (IL-1β, IL-6 and TNF-α) and fibrotic genes (α-SMA and fibronectin) was significantly downregulated by T. chebula extract treatment, while E-cadherin expression was significantly upregulated. ConclusionT. chebula extract exerts nephroprotective effects on HN, such as anti-inflammatory effects and fibrosis improvement, by regulating the TLR4/MyD88/NF-κB axis, which supports the general use of T. chebula in the management of HN and other chronic kidney diseases.