Cause Of Chronic Kidney Disease Research Articles

Protocol for a systematic review of the application of the kidney failure risk equation and Oxford classification in estimating prognosis in IgA nephropathy

BackgroundIgA nephropathy (IgAN) is a common cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). Outcomes are highly variable and predicting risk of disease progression at an individual level is challenging. Accurate risk stratification is important to identify individuals most likely to benefit from treatment. The Kidney Failure Risk Equation (KFRE) has been extensively validated in CKD populations and predicts the risk of ESRD at 2 and 5 years using non-invasive tests; however, its predictive performance in IgAN is unknown. The Oxford classification (OC) describes pathological features demonstrated on renal biopsy that are associated with adverse clinical outcomes that may also inform prognosis. The objective of this systematic review is to compare the KFRE with the OC in determining prognosis in IgAN.MethodsA systematic review will be conducted and reported in line with PRISMA guidelines (PRISMA-P checklist attached as Additional file 1). Inclusion criteria will be cohort studies that apply the KFRE or OC to determine the risk of CKD progression or ESRD in individuals with IgAN. Multiple databases will be searched in duplicate to identify relevant studies, which will be screened first by title, then by abstract and then by full-text analysis. Results will be collated for comparison. Risk of bias and confidence assessments will be conducted independently by two reviewers, with a third reviewer available if required.DiscussionIdentifying individuals at the highest risk of progression to ESRD is challenging in IgAN, due to the heterogeneity of clinical outcomes. Risk prediction tools have been developed to guide clinicians; however, it is imperative that these aids are accurate and reproducible. The OC is based on observations made by specialist renal pathologists and may be open to observer bias, therefore the utility of prediction models incorporating this classification may be diminished, particularly as in the future novel biomarkers may be incorporated into clinical practice.Systematic review registrationPROSPERO CRD42022364569

Benefits of using SLGT2 Inhibitors for Patients with CDK and DM2 to Reduce Mortality Risks

Type 2 diabetes mellitus (T2DM) is the most common cause of chronic kidney disease (CKD). CKD is characterized by progressive liver tissue damage and is an important risk factor for mortality due to renal and cardiovascular outcomes. Thus, randomized clinical trials have investigated the use of sodium-glucose cotransporter 2 (SLGT2) inhibitors as a promising therapy for patients with CKD and T2DM. This study aimed to analyze the benefits of using SGLT2 inhibitors in patients with CKD and T2DM to reduce mortality risks. To this end, a qualitative, descriptive methodological approach was adopted using a literature review in the PubMed, Embase, and VHL databases. The inclusion criteria were clinical trial articles, randomized or non-randomized, cohort studies, case-control studies, and open access, published in Portuguese and English, between 2018 and 2023 with topics associated with SGLT2 inhibitors, CDK, and T2DM patients. In this context, it was observed that the risk of death from CKD in patients treated with Canaglifozin was 30% lower than in those treated with a placebo and that Dapaglifozin prolonged survival. In this context, when assessing the progression of kidney disease or death from cardiovascular causes in patients taking Empagliflozin, only 13.1% achieved the outcome compared to 16.9% on placebo, so the drug safely reduces the risk of mortality. Consequently, SGLT2 inhibitors have shown excellent results in the treatment of CDK and T2DM, with a reduction in the risk of mortality, positive effects on reducing renal and cardiovascular outcomes, as well as prolonging survival.

Non-diabetic nephropathy in diabetic patients: incidence, HbA1c variability and other predictive factors, and implications.

Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) in the population. In patients with diabetes mellitus, the incidence of non-diabetic nephropathy (NDNP) has been estimated to range from 3% to 69.5%. Personal judgment is frequently employed while deciding whether or not to do a kidney biopsy(KB) on diabetic patients. NDNP alters the prognosis and course of treatment for people with DM. In our study, we examined the incidence of NDNP concurrent with the progression of diabetes mellitus, as well as the laboratory and clinical indicators that could be utilized to forecast it. A retrospective analysis of 76 diabetic patients who underwent KB was conducted. Based on the pathological diagnoses of these patients, they were categorized as DNP (diabetic nephropathy) or NDNP. The definition of HbA1c variability was determined by calculating the mean HbA1c and the average value of the HbA1c measurements, as well as the standard deviation (SD) for each participant. NDNP was detected in 50% of 76 patients. Among patients with NDNP, 36.8% had focal segmental glomerulosclerosis (FSGS), 23.6% had membranous glomerulonephritis, and 7.8% had IgA nephritis. The NDNP group exhibited significantly higher rates of female gender, absence of diabetic retinopathy, shorter time to diagnosis of diabetes mellitus, chronic kidney disease, and proteinuria, less intensive medication for diabetes mellitus, presence of hematuria and leukociduria, immunological serological marker positivity, and non-HbA1C variability. Risk factors for predicting non-diabetic nephropathy, as determined by multivariate analysis, included female gender, the absence of diabetic retinopathy, non-HbA1c variability and a positive immunological serological test. In this study, a significant number of diabetic patients with chronic kidney disease were diagnosed with NDNP. Identifying these patients allows for treatment of the specific underlying disease. Factors such as the absence of DR, non-HbA1c variability, female gender, and immunological serological test positivity can predict NDNP and guide the clinician's decision on kidney biopsy. Further prospective studies are warranted to validate the efficacy of potential predictive factors like HbA1c variability.

Roles of AhR/CYP1s signaling pathway mediated ROS production in uremic cardiomyopathy

PurposeUremic cardiomyopathy (UCM) is the leading cause of chronic kidney disease (CKD) related mortality. Uremic toxins including indoxyl sulfate (IS) play important role during the progression of UCM. This study was to explore the underlying mechanism of IS related myocardial injury. MethodsUCM rat model was established through five-sixths nephrectomy to evaluate its effects on blood pressure, cardiac impairment, and histological changes using echocardiography and histological analysis. Additionally, IS was administered to neonatal rat cardiomyocytes (NRCMs) and the human cardiomyocyte cell line AC16. DHE staining and peroxide-sensitive dye 2′,7′-dichlorofluorescein diacetate (H2DCFDA) was conducted to assess the reactive oxygen species (ROS) production. Cardiomyocyte hypertrophy was estimated using wheat germ agglutinin (WGA) staining and immunofluorescence. Aryl hydrocarbon receptor (AhR) translocation was observed by immunofluorescence. The activation of AhR was evaluated by immunoblotting of cytochrome P450 1 s (CYP1s) and quantitative real-time PCR (RT-PCR) analysis of AHRR and PTGS2. Additionally, the pro-oxidative and pro-hypertrophic effects were evaluated using the AhR inhibitor CH-223191, the CYP1s inhibitor Alizarin and the ROS scavenger N-Acetylcysteine (NAC). ResultsUCM rat model was successfully established, and cardiac hypertrophy, accompanied by increased blood pressure, and myocardial fibrosis. Further research confirmed the activation of the AhR pathway in UCM rats including AhR translocation and downstream protein CYP1s expression, accompanied with increasing ROS production detected by DHE staining. In vitro experiment demonstrated a translocation of AhR triggered by IS, leading to significant increase of downstream gene expression. Subsequently study indicated a close relationship between the production of ROS and the activation of AhR/CYP1s, which was effectively blocked by applying AhR inhibitor, CYP1s inhibitor and siRNA against AhR. Moreover, the inhibition of AhR/CYP1s/ROS pathway collectively blocked the pro-hypertrophic effect of IS-mediated cardiomyopathy. ConclusionThis study provides evidence that the AhR/CYP1s pathway is activated in UCM rats, and this activation is correlated with the uremic toxin IS. In vitro studies indicate that IS can stimulate the AhR translocation in cardiomyocyte, triggering to the production of intracellular ROS via CYP1s. This process leads to prolonged oxidative stress stimulation and thus contributes to the progression of uremic toxin-mediated cardiomyopathy.

Establishment and application of a database for hereditary kidney disease in Chinese children

Hereditary kidney diseases are common causes of chronic kidney disease (CKD) in children and adolescents, and also has an important role in the onset and progression of CKD in adulthood. Constructing a data sharing registration system for hereditary kidney disease and forming representative data with Chinese population specificity, is of great significance for achieving phenotype and genotype characterization, improving precision management level and mechanism research. The high heterogeneity of the disease and the scattered distribution of patients have led to a lack of understanding and unified management standards for hereditary kidney disease. Led by pediatric nephrology specialists and geneticists, integrating data sources from various centers can leverage clinical resource advantages. Focusing on different subtype disease cohorts, integrating and analyzing data such as genotype, multi-omics, and clinical outcomes, can achieve breakthroughs in the key points of disease diagnosis and treatment.

Research on pediatric hereditary kidney disease: from now to the future

Hereditary kidney disease is an important cause of chronic kidney disease in children. With the progress of genome sequencing, single-cell technology, and organoid cultures, the research on hereditary kidney disease has entered a new era. How to integrate big data resources, discover new disease-causing genes, and develop effective treatment methods will be the focus of future research. This article discusses the classification, research progress, challenges and prospects of pediatric hereditary kidney disease, so as to provide valuable insights into the research of hereditary kidney disease in children.

Efficacy of Low-Dose Streptokinase Infusion in Late-Onset Permanent Tunnel Catheter Dysfunction: A Single-Center Interventional Study.

Introduction Hemodialysis is a vital modality for patients with renal dysfunction, with venous access being a significant factor in its success. While arteriovenous fistulas are preferred, tunneled catheters serve as important alternatives, especially in challenging cases. Late-onset tunneled catheter dysfunction, often due to fibrin sheath formation, impedes hemodialysis efficiency. Streptokinase, a low-cost thrombolytic agent, has shown promise in resolving such complications, yet its efficacy in the Indian context remains unexplored. Methods We conducted a single-center interventional study at Mahatma Gandhi Mission (MGM) Hospital, Aurangabad, India, from May 2023 to October 2023. Ethical approval was obtained, and 10 eligible patients experiencing late-onset permanent tunnel catheter dysfunction were enrolled. Patients were treated with low-dose streptokinase, and outcomes were monitored for 60 days. Results Ten patients, evenly distributed by gender, participated, with a mean age of 48.2 ± 11.96 years. Diabetes was the predominant cause of chronic kidney disease (CKD) at 33% (3/10). All patients achieved the primary endpoint of blood flow rate (BFR) >300 ml/min post-streptokinase treatment, with an overall success rate of 100%. Group A had the highest average gain in catheter days (80.6 ± 7.59), followed by Group B (64 ± 1), while Group C showed variations in catheter days between the first (26.2 ± 6.8) and second insertion (32.5 ± 1.76). Eight patients maintained catheter patency during the 60-day follow-up. Adverse effects, primarily minor, were observed. The dosage rationale involved an eight-hour infusion at 4,000 units per hour. Conclusion Streptokinase emerges as cost-effective and efficacious for maintaining the patency of late-onset tunnel catheter dysfunction in resource-limited settings, particularly in younger patients. Caution is advised for older individuals with prolonged CKD.

Evaluation of hepatosteatosis and gallstone disease in patients with chronic kidney disease.

The prevalence rates of hepatosteatosis and gallstones are increasing owing to the multifactorial causes of chronic kidney disease, and the prevalence may change with the availability of different forms of renal replacement therapy. We aimed to determine the incidence or prevalence rates of hepatosteatosis, cholelithiasis, and acute cholecystitis in patients with chronic kidney disease and compare them between renal replacement therapy modalities. A total of 270 patients (90 with chronic kidney disease stages III-V, 90 undergoing peritoneal dialysis, and 90 undergoing hemodialysis) were included and categorized into the pre-dialysis, hemodialysis, and peritoneal dialysis groups. The patients were questioned about previous gallbladder surgeries and chronic diseases. The results of abdominal ultrasonography, tomography, and magnetic resonance imaging were retrospectively evaluated with respect to the findings on the hepatobiliary system. Hepatosteatosis and cholelithiasis were diagnosed by expert radiologists on the basis of abdominal ultrasonography, tomography, and magnetic resonance imaging findings. The prevalence rates of hepatosteatosis, cholelithiasis, and other liver findings were compared between the groups. Hepatosteatosis and cholelithiasis were detected in 16.7% and 21.5% of the 270 cases, respectively. Hepatosteatosis was present in 17.8%, 25.6%, and 6.7% of patients in the pre-dialysis, hemodialysis, and peritoneal dialysis groups, respectively. The prevalence of hepatosteatosis was significantly higher in patients undergoing hemodialysis than in patients undergoing peritoneal dialysis (p = 0.002). However, no statistically significant difference was found between the peritoneal dialysis and pre-dialysis groups or between the hemodialysis and pre-dialysis groups (p >0.05). The prevalence rates of cholelithiasis were 15.6%, 28.9%, and 20.0%, in the pre-dialysis, hemodialysis, and peritoneal dialysis groups, respectively, and there were no statistically significant differences among the groups. The incidence of acute cholecystitis was significantly higher in the hemodialysis group than in the pre-dialysis group (p = 0.006). Our study showed that the hepatobiliary system is frequently affected in chronic kidney disease and that the findings may differ depending on the renal replacement therapy modality.

Epidemiology of Diabetic Kidney Disease among US Veterans.

With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown. We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population. We performed a retrospective observational research using electronic health-care records and administrative databases. The DKD patient cohort was abstracted from the Veterans Health Administration health-record data from January 2016 to March 2022. We defined DKD patients using the laboratory test data based on Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines. Summary statistics include the five-year cumulative incidence of progression to an advanced stage from the DKD stage at the cohort entry date and prevalence at a series of single time points. A total of 685,288 patients (male [96%], mean age 62 years, Caucasian [64%], non-Hispanic [87%]) met our eligibility criteria. The 5-year cumulative incidence of progression to an advanced DKD stage or all-cause death from DKD stages G1 A2/A3, G2 A2/A3, G3a, and G3b were 52.0%, 47.4%, 50.5%, and 60.9%, respectively. In sum, 594,082 patients were classified as moderate or high risk as per KDIGO guidelines in 2021, and stages G3a and G3b accounted for 51.2% and 25.3%, respectively, of cases. More than half of DKD patients underwent a stage progression or death within 5 years. A substantial number of DKD patients at an earlier stage might be left undetermined. The study findings warrant a revision of DKD patient identification and management in US veterans.

Clinical Profile of Pediatric Patients with Steroid-resistant Nephrotic Syndrome Treated by Cyclophosphamide, Cyclosporin A, Mycophenolate Mofetile and Tacrolimus in Hasan Sadikin General Hospital

BackgroundSteroid-resistant nephrotic syndrome is a major cause of chronic kidney disease in children and adolescents. These diseases require appropriate management, while in some developing countries, the availability of agents recommended by international guidelines is very limited.Research objectivesTo determine and describe the patient profiles of pediatric Steroid Resistant Nephrotic Syndrome (SRNS) that use Cyclophosphamide(CPA), Cyclosporine(CyA), Tacrolimus, and Mycofenolat Mofetil (MMF) in Dr. Hasan Sadikin Hospital (RSHS), Bandung as a tertiary hospital in West Java, Indonesia.Methods and materialsThis research used a retrospective study with cross-sectional study design, total sampling method and medical record of pediatric (1-18 years old) patients from January 1st 2017–September 31st 2019 who were diagnosed as SRNS .Results : From 99 subjects that belonged to inclusion criteria, 35.4% pediatric SRNS patients were in the age group 6-10 years and 60.6% were males. Laboratorium profiles showed among all population, ureum <100 mg/dL were found as high as 97%, creatinine 0.3-1.0 mg/dL (71.7%) albumin >2,5 gr/dL (51.5%), negative hematuria (68.7%) , protein dipstick < 3 (50.5%), and LFG > 90 mL/min/1.73 m2 (79.8%).. The patients generally had use CPA (87.9%) and remission <6 month (51.5%).Conclusion: Profiles of pediatric patients are important to diagnose and prognose SRNS. By using these approaches, it is feasible to access and detect the most effective treatment for SRNS.

DIABETES MANAGEMENT IN CHRONIC KIDNEY DISEASE: A COMPREHENSIVE SYSTEMATIC REVIEW

Background: The increase in type 2 diabetes has positioned it as the leading cause of chronic kidney disease (CKD) and is responsible for approximately half of all cases of end-stage kidney disease (ESKD) worldwide. Managing CKD in diabetic patients entails addressing its complications and minimizing the risk of other associated conditions, such as cardiovascular disease. This study aims to serve a comprehensive systematic review on diabetes management in CKD patients in literatures of the last 10 years. Methods: The systematic review followed PRISMA 2020 standards and examined full-text English literature published between 2014 and 2024. This review excluded editorials, review papers from the same journal, and submissions without a DOI. Literature was sourced from online platforms such as PubMed, SagePub, SpringerLink, and Google Scholar. Result: A total of 43,740 articles were retrieved from online databases (PubMed, SagePub, SpringerLink and Google Scholar). After three rounds of screening, four articles directly relevant to the systematic review were selected for full-text reading and analysis. Conclusion: Chronic kidney disease (CKD) is a common and serious complication in individuals with diabetes. Management involves controlling hypertension and hyperglycemia, along with using ACE inhibitors like finerenone and SGLT2 inhibitors such as dapagliflozin, sotagliflozin, and bexagliflozin.

Finerenone: From the Mechanism of Action to Clinical Use in Kidney Disease.

Diabetic kidney disease is a frequent microvascular complication of diabetes and is currently the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Although the prevalence of other complications of diabetes is falling, the number of diabetic patients with end-stage kidney disease in need of kidney replacement therapy is rising. In addition, these patients have extremely high cardiovascular risk. It is more than evident that there is a high unmet treatment need in patients with diabetic kidney disease. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist used for treating diabetic kidney disease. It has predominant anti-fibrotic and anti-inflammatory effects and exhibits several renal and cardiac protective effects. This review article summarizes the current knowledge and future prospects of finerenone in treating patients with kidney disease.

Exploring kidney biopsy findings in congenital heart diseases: Insights beyond cyanotic nephropathy.

The association between congenital heart disease and chronic kidney disease is well known. Various mechanisms of kidney damage associated with congenital heart disease have been established. The etiology of kidneydisease has commonly been considered to be secondary to focal segmental glomerulosclerosis (FSGS), however, this has only been demonstrated in case reports and not in observational or clinical trials. To identify baseline and clinical characteristics, as well as the findings in kidney biopsies of patients with congenital heart disease in our hospital. This is a retrospective observational study conducted at the Nephrology Department of the National Institute of Cardiology "Ignacio Chávez". All patients over 16 years old who underwent percutaneous kidney biopsy from January 2000 to January 2023 with congenital heart disease were included in the study. Ten patients with congenital heart disease and kidney biopsy were found. The average age was 29.00 years ± 15.87 years with pre-biopsy proteinuria of 6193 mg/24 h ± 6165 mg/24 h. The most common congenital heart disease was Fallot's tetralogy with 2 cases (20%) and ventricular septal defect with 2 (20%) cases. Among the 10 cases, one case of IgA nephropathy and one case of membranoproliferative glomerulonephritis associated with immune complexes were found, receiving specific treatment after histopathological diagnosis, delaying the initiation of kidney replacement therapy. Among remaining 8 cases (80%), one case of FSGS with perihilar variety was found, while the other 7 cases were non-specific FSGS. Determining the cause of chronic kidney disease can help in delaying the need for kidney replacement therapy. In 2 out of 10 patients in our study, interventions were performed, and initiation of kidney replacement therapy was delayed. Prospective studies are needed to determine the usefulness of kidney biopsy in patients with congenital heart disease.

Pattern of Glomerulonephritis in Nigeria and Challenges Faced in Treating It

Glomerulonephritis is one of the leading causes of chronic kidney disease in Nigeria. The pattern of glomerulonephritisis said to be different from other parts of the world which can be attributed to the prevalence of APOL1 gene in the blackpopulation and prevalence of tropical diseases. Treating glomerulonephritis in Nigeria can be challenging due to poorawareness and understanding of the disease, limited access to health care facility and lack of trained nephrologist. Possiblesolutions to this problems include creating awareness and education of the populace, partnering with NGOs to subsidizetreatment and training of Nephrologist.

Clinical effect of roxadustat vs. erythropoietin in non-dialysis CKD with diabetes: a single center propensity score matching analysis.

Renal anemia is a common complication of chronic kidney disease. Currently, recombinant human erythropoietin and roxadustat are the main treatments. In China, diabetic kidney disease is the primary cause of chronic kidney disease. However, high-quality evidence on the efficacy of roxadustat in patients with non-dialysis-dependent chronic kidney disease and diabetes mellitus is scarce. This study aimed to assess the clinical effect of roxadustat in such patients. Patients with non-dialysis-dependent anemia and diabetes mellitus who received roxadustat or recombinant human erythropoietin for ≥ 4weeks were enrolled. We compared baseline characteristics, including age, gender, hypertension, and hemoglobin level, and then employed a 1:3 ratio propensity score matching. The primary efficacy outcomes were changes in hemoglobin levels. After propensity score matching, 212 patients were analyzed, including the roxadustat (n = 53) and recombinant human erythropoietin (n = 159) groups. Baseline characteristics were comparable, including hemoglobin level, estimated glomerular filtration rate, and glycated hemoglobin A1c (p > 0.05). After 4, 12, and 24weeks of treatment, the median hemoglobin levels in the roxadustat group were 97.5g/L, 104g/L, and 106.5g/L, respectively, significantly surpassing the corresponding levels in the recombinant human erythropoietin group at 91g/L, 94.5g/L, and 94.5g/L (p = 0.002, p = 0.025, p = 0.006, respectively). Additionally, subgroup analysis demonstrated better treatment efficacy of roxadustat patients with elevated high-sensitivity C-reactive protein and low albumin levels. In Chinese patients with anemia and diabetes not on dialysis, roxadustat efficiently and rapidly improved and maintained hemoglobin levels unaffected by elevated high-sensitivity C-reactive protein and low albumin levels.

Quantitative phenotyping of Nphs1 knockout mice as a prerequisite for gene replacement studies.

Steroid-resistant nephrotic syndrome (SRNS) is the second most frequent cause of chronic kidney disease before the age of 25 yr. Nephrin, encoded by NPHS1, localizes to the slit diaphragm of glomerular podocytes and is the predominant structural component of the glomerular filtration barrier. Biallelic variants in NPHS1 can cause congenital nephrotic syndrome of the Finnish type, for which, to date, no causative therapy is available. Recently, adeno-associated virus (AAV) vectors targeting the glomerular podocyte have been assessed as a means for gene replacement therapy. Here, we established quantitative and reproducible phenotyping of a published, conditional Nphs1 knockout mouse model (Nphs1tm1.1Pgarg/J and Nphs2-Cre+) in preparation for a gene replacement study using AAV vectors. Nphs1 knockout mice (Nphs1fl/fl Nphs2-Cre+) exhibited 1) a median survival rate of 18 days (range: from 9 to 43 days; males: 16.5 days and females: 20 days); 2) an average foot process (FP) density of 1.0 FP/µm compared with 2.0 FP/µm in controls and a mean filtration slit density of 2.64 µm/µm2 compared with 4.36 µm/µm2 in controls; 3) a high number of proximal tubular microcysts; 4) the development of proteinuria within the first week of life as evidenced by urine albumin-to-creatinine ratios; and 5) significantly reduced levels of serum albumin and elevated blood urea nitrogen and creatinine levels. For none of these phenotypes, significant differences between sexes in Nphs1 knockout mice were observed. We quantitatively characterized five different phenotypic features of congenital nephrotic syndrome in Nphs1fl/fl Nphs2-Cre+ mice. Our results will facilitate future gene replacement therapy projects by allowing for sensitive detection of even subtle molecular effects.NEW & NOTEWORTHY To evaluate potential, even subtle molecular, therapeutic effects of gene replacement therapy (GRT) in a mouse model, prior rigorous quantifiable and reproducible disease phenotyping is necessary. Here, we, therefore, describe such a phenotyping effort in nephrin (Nphs1) knockout mice to establish the basis for GRT for congenital nephrotic syndrome. We believe that our findings set an important basis for upcoming/ongoing gene therapy approaches in the field of nephrology, especially for monogenic nephrotic syndrome.

Recent Advances in the Management of Diabetic Kidney Disease: Slowing Progression.

Diabetic kidney disease (DKD) is a major cause of chronic kidney disease (CKD), and it heightens the risk of cardiovascular incidents. The pathogenesis of DKD is thought to involve hemodynamic, inflammatory, and metabolic factors that converge on the fibrotic pathway. Genetic predisposition and unhealthy lifestyle practices both play a significant role in the development and progression of DKD. In spite of the recent emergence of angiotensin receptors blockers (ARBs)/angiotensin converting enzyme inhibitor (ACEI), sodium-glucose cotransporter 2 (SGLT2) inhibitors, and nonsteroidal mineralocorticoid receptors antagonists (NS-MRAs), current therapies still fail to effectively arrest the progression of DKD. Glucagon-like peptide 1 receptor agonists (GLP-1RAs), a promising class of agents, possess the potential to act as renal protectors, effectively slowing the progression of DKD. Other agents, including pentoxifylline (PTF), selonsertib, and baricitinib hold great promise as potential therapies for DKD due to their anti-inflammatory and antifibrotic properties. Multidisciplinary treatment, encompassing lifestyle modifications and drug therapy, can effectively decelerate the progression of DKD. Based on the treatment of heart failure, it is recommended to use multiple drugs in combination rather than a single-use drug for the treatment of DKD. Unearthing the mechanisms underlying DKD is urgent to optimize the management of DKD. Inflammatory and fibrotic factors (including IL-1, MCP-1, MMP-9, CTGF, TNF-a and TGF-β1), along with lncRNAs, not only serve as diagnostic biomarkers, but also hold promise as therapeutic targets. In this review, we delve into the potential mechanisms and the current therapies of DKD. We also explore the additional value of combing these therapies to develop novel treatment strategies. Drawing from the current understanding of DKD pathogenesis, we propose HIF inhibitors, AGE inhibitors, and epigenetic modifications as promising therapeutic targets for the future.

Sex differences in kidney metabolism may reflect sex-dependent outcomes in human diabetic kidney disease.

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females. Male human PTECs showed increased glucose and glutamine fluxes to the TCA cycle, whereas female human PTECs showed increased pyruvate content. The male human PTEC phenotype was enhanced by dihydrotestosterone and mediated by the transcription factor HNF4A and histone demethylase KDM6A. In mice where sex chromosomes either matched or did not match gonadal sex, male gonadal sex contributed to the kidney metabolism differences between males and females. A blood metabolomics analysis in a cohort of adolescents with or without diabetes showed increased TCA cycle metabolites in males. In a second cohort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did males with or without DKD. Serum pyruvate concentrations positively correlated with the estimated glomerular filtration rate, a measure of kidney function, and negatively correlated with all-cause mortality in this cohort. In a third cohort of adults with CKD, male sex and diabetes were associated with increased plasma TCA cycle metabolites, which correlated with all-cause mortality. These findings suggest that differences in male and female kidney metabolism may contribute to sex-dependent outcomes in DKD.

Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study

Background and aimDiabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. MethodsA hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman’s rank correlation was used to evaluate the relationship between the categorical variables. ResultsThe median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= −0.486, p<0.001). ConclusionPlasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.

Clinical and Epidemiological Study of IgA Nephropathy in the Bulgarian Population: Insights into Disease Presentation and Potential Biomarkers.

IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and a leading cause of chronic kidney disease and renal failure. However, the Bulgarian population has limited epidemiological data and biomarkers for IgAN. In this retrospective monocentric analysis, we investigated all the patients with biopsy-proven IgAN over 10 years in a tertiary Bulgarian institution. From the analysis of 762 kidney biopsies, the diagnosis of primary IgAN was established in 125, with an average age of 35.94 ± 11.91 years. Our study aimed to assess the clinical characteristics, histological features, and potential biomarkers of IgAN in the Bulgarian population. We evaluated parameters such as proteinuria, hematuria, serum creatinine, and glomerular filtration rate (GFR). In fifty IgAN patients and 30 healthy controls, serum levels of Gd-IgA1, IgA, C3, BAFF, and APRIL using ELISA were examined. The results revealed significant differences in serum concentrations of Gd-IgA1 (p < 0.001), Gd-IgA1/IgA (p = 0.022), IgA (p = 0.014), and IgA/C3 (p = 0.047) between patients and controls. However, no correlation was found between Gd-IgA1, IgA, Gd-IgA1/IgA, and IgA/C3 and chronic kidney disease progression. Our study reports evidence of the diagnostic value of Gd-IgA1 and contributes to the understanding of IgAN in the Bulgarian population and suggests potential biomarkers for disease diagnosis and prognosis.