Progression Of Renal Disease Research Articles

Abstract 4133830: Uncovering the Gaps: Analyzing Prescribing Patterns of Combination Therapy with SGLT2-inhibitors and GLP-1 Receptor Agonists in Established Atherosclerotic Cardiovascular Disease (ASCVD) and Type 2 Diabetes (T2DM)

Introduction: Combination therapy with SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1RA) reduces major cardiovascular events (MACE) and improves HbA1c, blood pressure, weight, and renal disease progression. The European Society of Cardiology recommends this therapy for ASCVD and T2DM, independent of HbA1c. This study evaluates prescribing patterns in the Internal Medicine Residency Clinics for patients with ASCVD and T2DM. Aims: To investigate demographic and social determinants of health (SDOH) influencing the prescription of combination therapy versus no therapy in an outpatient population and identify factors affecting prescribing patterns and guideline adherence. Methods: We reviewed 828 electronic records of T2DM and ASCVD patients from March 2024. Patients were grouped into combination therapy (SGLT2i and GLP1RA) and no therapy groups. Data on demographics (Table 1) and SDOH (Table 2) were analyzed. Patients on monotherapy or those who did not complete the SDOH questionnaire were excluded. Descriptive statistics were used to summarize demographics. Welch’s t-test compared continuous variables, and chi-square or Fisher’s exact tests compared categorical variables. Analyses were done with SAS 9.4 with significance at 0.05. Results: Age significantly differed between groups (t = 4.56, p < .05), with older patients less likely to receive therapy. Sex was also significant (p < .05); more females were in the no therapy group. No significant association was found between SDOH and combination therapy (p > .05). Conclusion: Over 90% of patients with T2DM and ASCVD were not on optimal medical therapy to reduce MACE, with nearly half on no medications. This highlights the need for increased awareness and targeted interventions to improve outcomes. Future research will explore insurance status and physician awareness to address prescription discrepancies. Limitations: Patients with a GFR <30 are precluded from SGLT2i usage but were not excluded from this study.

Natural History of Auditory Function in Patients with Alport Syndrome: A Case Series Study

Background: Alport syndrome (AS) is a genetic disorder characterized by progressive renal disease, ocular abnormalities, and sensorineural hearing loss. However, the audiological profile of patients with AS remains elusive. Thus, this study aims to evaluate the natural history of auditory function in patients with AS. Methods: Exome or targeted sequencing for deafness genes was performed to confirm the pathogenic variants in patients with AS. Results: We identified fifteen individuals with AS who carried pathogenic variants of COL4A3, COL4A4, or COL4A5. Among fifteen, twelve (80%) showed hematuria, and six (40%) showed proteinuria. The patients exhibited bilateral sensorineural hearing loss, which was progressive and symmetric. The hearing thresholds increased according to age and plateaued at the level of 53 dB HL, indicating the hearing loss did not reach the severe-to-moderate level. The auditory dysfunction showed a distinct natural history depending on the inheritance pattern, but there was no remarkable difference between males and females among X-linked AS. Conclusions: Auditory dysfunction in AS is progressive up to the level of moderate hearing loss. Precise auditory rehabilitation for patients with AS is warranted depending on the inheritance pattern and genetic predisposition.

Telmisartan potentiates the ITE-induced aryl hydrocarbon receptor activity in human liver cell line.

Telmisartan is an angiotensin receptor blocker (ARB) approved by the Food and Drug Administration of the US for the treatment of hypertension. It possesses unique pharmacologic properties, including the longest half-life among all ARBs; this leads to a 24-h sustained reduction of blood pressure. Besides well-known antihypertensive and cardioprotective effects, there is also strong clinical evidence that telmisartan confers renoprotection. Aryl hydrocarbon receptor (AhR) belongs to the steroid receptor family. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous ligand of AhR. Cytochrome P450 (CYP) 1A1 is an AhR-target gene. In this article, we demonstrated that telmisartan (2.5-60μM) enhanced CYP1A1 promoter activity and expressions of mRNA and protein. Telmisartan-induced CYP1A1 expression was blocked by the AhR antagonist CH-223191 in liver cell lines and was negligible in the AhR signaling-deficient mutant cells. In addition, telmisartan induced transcriptional activity mediated by aryl hydrocarbon response element in both human and mouse cells, and was able to induce AhR translocation into the nucleus. Accordingly, telmisartan is an AhR agonist. It also acted synergistically with ITE to further enhance the expression of CYP1A1 mRNA and protein. This synergistic effect was more pronounced in cells with AhR overexpression compared to those without. AhR activity has strong association with the progression of chronic renal disease. Our study demonstrated that telmisartan is an AhR agonist and has synergistic effect with ITE, an indole derivative, to potentiate the effect on AhR. This finding may provide additional clues about the mechanism of the protective effect of telmisartan on the kidney.

Systemic inflammation in patients with atherosclerotic cardiovascular and chronic kidney disease in Spain: a population-based study using electronic medical records from a primary care database

Abstract Background Systemic inflammation (SI) is recognized as a critical driver of atherosclerotic cardiovascular disease (ASCVD), and it is frequently observed in ASCVD patients with comorbid chronic kidney disease (CKD). Elevated C-reactive protein (CRP) levels, a common biomarker for SI, have been associated with poor prognosis in ASCVD and CKD patients, increased risk of major adverse cardiovascular events and renal disease progression, as well as greater mortality. Purpose To estimate the prevalence of SI in patients with ASCVD in Spain overall and by CKD status, and to describe patients’ clinical characteristics. Methods In this population-based observational study, data from THIN Spain, a database of electronic medical records from a large network of general practitioners, were used to identify adult patients with a diagnosis code of ASCVD (atherosclerotic coronary or cerebrovascular event, peripheral arterial disease, or other atherosclerotic vascular event) and ≥1 eligible CRP measurement between January 1st 2014 to July 31st 2023 (latest data available at time of data extraction).[Figure] SI was defined as CRP ≥ 2mg/L. Point prevalence of SI at the end of the study (among patients alive with ≥1 CRP in the prior 18 months) and the proportion of patients with evidence of SI during the study period (2014-2023) were estimated overall and by CKD status (defined as CKD stage 3+, or eGFR <60 mL/min/1.73m², or urinary albumin-to-creatinine ratio ≥30 mg/g). Patients’ comorbidities (defined using primary care diagnoses), and laboratory values were reported by SI status at first CRP measurement during the study period. Results Among 76,423 patients with ASCVD diagnosis, 15,798 patients (20.7%) were included in the study (mean age: 71.1 years; 43% females), of whom 5,111 (34%) had CKD at first eligible CRP (n=975 with unknown CKD status). Mean CRP in ASCVD patients with CKD was 24% higher than in those without CKD (4.36 vs 3.53 mg/L, p<0.001). The proportion of ASCVD patients with SI at first CRP measurement was 58% overall (65% among CKD patients; 55% among patients without CKD; p<0.001). The point prevalence of SI at the end of the study was 56% among ASCVD patients overall (62% among CKD patients; 52% among patients without CKD; p<0.001), while 64% of ASCVD patients had evidence of SI at any time during the study period (72% among CKD patients; 59% among patients without CKD; p<0.001). Compared to ASCVD patients without SI, higher proportion of SI patients were smokers and with comorbidities. Also, ASCVD patients with SI had lower baseline eGFR levels and higher levels of LDL-C and triglycerides than ASCVD patients without SI.[Table] Conclusions SI prevalence is high among patients with ASCVD in Spain, especially among patients with comorbid CKD. Strategies to target SI may have beneficial effects in prevention of cardiovascular events and mortality in ASCVD patients.

Role of baseline soluble tumor necrosis factor receptor 2 as a biomarker in primary podocytopathy: Implications for renal impairment and disease progression

BackgroundPodocytopathies, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and collapsing glomerulopathy (CG), are kidney diseases that damage glomerular podocytes, leading to heavy proteinuria and nephrotic syndrome (NS). Inflammation plays a critical role in the progression of chronic kidney disease (CKD), with recent studies linking inflammatory biomarkers to declining kidney function. Tumor necrosis factor-alpha (TNF-α), an essential inflammatory cytokine, interacts with its circulating receptors, TNFR1 and TNFR2. The TNF-α pathway has been implicated in the pathogenesis of FSGS and MCD. Increased circulating TNFR2 levels have been associated with worsening renal function in podocytopathies, suggesting that the TNF-α inflammatory pathway significantly contributes to disease progression.MethodsWe conducted a study involving 53 patients with biopsy-proven MCD or FSGS and 53 healthy, age- and gender-matched controls. All patients were followed for 18 months. We analyzed serum and urine TNFR2 levels and gene expression at baseline and after three months. To assess the ability of TNFR2 to predict persistent decline in estimated glomerular filtration rate (eGFR < 30 mL/min/1.73m2), remission, and relapse, we employed Cox regression analysis. Additionally, we evaluated its prognostic utility for predicting progression to stage 4 CKD using ROC curve analysis.ResultsSerum and urine TNFR2 levels were significantly elevated in patients compared to controls. Serum TNFR2 was a significant predictor in univariate Cox regression analysis for persistent eGFR decline (HR 1.017, 95% CI: 1.003 to 1.032, p = 0.018), remission (HR 0.995, 95% CI: 0.992 to 0.999, p = 0.006), and relapse (HR 1.005, 95% CI: 1.001 to 1.010, p = 0.029). The ROC curve analysis demonstrated that serum TNFR2 levels had a strong prognostic ability for predicting progression to stage 4 CKD, with an AUC of 0.848 (95% CI: 0.737—0.960), sensitivity of 81%, and specificity of 71%.ConclusionThis study underscores the critical role of circulating TNFR2 in kidney injury among patients with primary podocytopathy. Elevated TNFR2 levels are significant predictors of persistent eGFR decline and disease relapse, highlighting their potential as biomarkers for disease progression and prognosis.

CH6824025, potent and selective DDR1 inhibitor, reduces kidney fibrosis in UUO mice.

Discoidin domain receptor 1 (DDR1) is a collagen receptor with tyrosine kinase activity, and its expression is enhanced in various disease conditions. Although previous research suggests that DDR1 contributes to renal disease progression, DDR1 inhibitors for renal fibrosis have yet to be developed. In this study, we used unilateral ureteral obstruction (UUO) mice to investigate whether CH6824025, a strong and selective DDR1 phosphorylation inhibitor, can improve renal fibrosis. Furthermore, we performed 10x Visium spatial transcriptomics (ST) analysis on the kidney. CH6824025 suppressed the phosphorylation of DDR1 in the kidney, and the amount of hydroxyproline, the Sirius red- and the F4/80-positive area, and the mRNA expression of fibrosis and inflammation-related genes in the kidney were significantly decreased. 10x Visium ST analysis suggested that DDR1 is mainly expressed in distal nephrons under normal conditions, but that its expression appears to increase in the injured proximal tubules in UUO mice. Comparing mRNA expression in DDR1 positive spots in the Vehicle and the CH6824025 group, oxidative phosphorylation and mitochondrial dysfunction might be improved, and pathways involved in fibrosis tended to be inhibited in the CH6824025 administration group. Downstream analysis would suggest that mRNA expression changes in the CH6824025 group contribute to the inhibition of cell movement. Taken together, our findings suggest that CH6824025 inhibited kidney fibrosis in UUO mice, which might be due to the inhibition of the migration of inflammatory cells to the injury site and the reduction of inflammation. DDR1 inhibitors are expected to be a promising treatment for renal fibrosis. Significance Statement The novel DDR1 inhibitor CH6824025 could ameliorate fibrosis and inflammation in UUO mice. CH6824025 would inhibit cell motility (e.g., migration) that prevents the progression of fibrosis and improves mitochondrial function in UUO mice. CH6824025 could provide a significant benefit to patients with kidney fibrosis.

Role of Emerging Urinary Biomarkers in Predicting Progressive Deterioration of Kidney Function in Congenital Anomalies of Kidney and Urinary Tract: Trefoil Family Factor 3, Alpha Soluble Klotho and Urinary Microalbuminuria

IntroductionChronic kidney disease is an irreversible fate of many CAKUT (Congenital Abnormalities of the Kidneys and Urinary Tract) patients. Biomarkers involved in the disease progression are raised early in the disease process and aid in identifying the individuals at risk of progressive renal function decline. AimsTo determine and compare the initial levels of urinary biomarkers in patients of CAKUT with asymptomatic controls and to correlate the same with progression of renal disease. ResultsThis study includes 66 children with CAKUT and 22 healthy controls. Initial levels of three urinary Biomarkers: Trefoil family factor 3 (TFF3), Alpha soluble Klotho and Albumin-to-creatinine ratio (ACR) was recorded. Kidney function was assessed initially and at the end of 1 y follow up. Progressive deterioration of renal disease was noted in 26 (fall in GFR by >10 ml/min/m2). Median levels of urinary TFF3, alpha soluble Klotho and ACR was higher in patients with CAKUT (263, 18, 56 mcg/gCr) as compared to controls (15, 5, 6 mcg/gCr) and was further higher in patients having a progressive kidney disease (586, 40, 182 mcg/gCr). The cut-off value of the TEF3 to diagnose progressive renal disease was 178 mcg/g Cr with sensitivity and specificity of 95 % and 96 %, respectively. Using a cut-off of 29 mg/g Cr for ACR, sensitivity and specificity were 97 and 96 %, respectively.Urinary soluble Klotho was a relatively poor urinary biomarker with sensitivity and specificity of only 70 and 78 %, respectively, at a cut-off value of 18 mcg/g Cr. ConclusionTFF3 and ACR are useful biomarkers which can be included in the biomarker panel to identify patients having a progressive renal disease and are at a risk of developing CKD.

Preventing Progression of Renal Disease: A New Method for Monitoring Body Fat Percentage in Pre-Dialysis Chronic Kidney Disease Patients.

Preventing Progression of Renal Disease: A New Method for Monitoring Body Fat Percentage in Pre-Dialysis Chronic Kidney Disease Patients.

The use of artificial intelligence, numerical algorithms and expert approach in selected nephrology problems

Background: The integration of AI, numerical algorithms, and expert approaches in nephrology shows promise for enhancing patient care. Traditionally, nephrology relied on clinician expertise, but the growing volume of data requires innovative methods. AI, fueled by vast datasets, can uncover patterns and improve diagnostic accuracy and treatment optimization. Numerical algorithms enable computational modeling of renal physiology and disease progression, aiding in treatment prediction and optimization. Expert systems codify nephrologists' knowledge into decision support tools, aiding in diagnosis and treatment selection. Embracing these technologies can revolutionize nephrological practice, improving patient outcomes.Aim of the study: The aim of the research is to review scientific works on the use of artificial intelligence (AI), numerical algorithms, and expert algorithms in diagnosis, decision support and prediction of selected disease states and issues related to nephrology.Material and methods: The study rigorously retrieved relevant publications from esteemed academic databases, Scopus and PubMed, and screened them based on predefined criteria. Through keyword-based searches, it analyzed the intersection of nephrology and artificial intelligence, offering insights into emerging trends and advancements. This approach facilitated a comprehensive exploration of the integration of artificial intelligence in nephrology research, paving the way for future developments in the field.Results: Artificial intelligence in nephrology and medicine uses various technologies such as machine learning, deep learning and natural language processing to improve diagnosis, treatment and patient care. Analyzes clinical, laboratory, imaging and genetic data to accelerate the identification of kidney diseases. By integrating health information systems and research data, artificial intelligence enables pattern recognition, outcome prediction and treatment optimization, ultimately having the potential to permanently improve patient care.Conclusions: Numerical algorithms, artificial intelligence, and expert algorithms show promise in nephrology, improving patient care and research.

Mitophagy Regulates Kidney Diseases

Background: Mitophagy is a crucial process involved in maintaining cellular homeostasis by selectively eliminating damaged or surplus mitochondria. As the kidney is an organ with a high dynamic metabolic rate and abundant mitochondria, it is particularly crucial to control mitochondrial quality through mitophagy. Dysregulation of mitophagy has been associated with various renal diseases, including acute and chronic kidney diseases, and therefore a better understanding of the links between mitophagy and these diseases may present new opportunities for therapeutic interventions. Summary: Mitophagy plays a pivotal role in the development of kidney diseases. Upregulation and downregulation of mitophagy have been observed in various kidney diseases, such as renal ischemia-reperfusion injury, contrast-induced acute kidney injury, diabetic nephropathy, kidney fibrosis, and several inherited renal diseases. A growing body of research has suggested that PINK1 and Parkin, the main mitophagy regulatory proteins, represent promising potential therapeutic targets for kidney diseases. In this review, we summarize the latest insights into how the progression of renal diseases can be mitigated through the regulation of mitophagy, while highlighting their performance in clinical trials. Key Message: This review comprehensively outlines the mechanisms of mitophagy and its role in numerous kidney diseases. While early research holds promise, most mitophagy-centered therapeutic approaches have yet to reach the clinical application stage.

Determinants of Disease Progression in Autosomal Dominant Polycystic Kidney Disease.

Despite its severity, there has been a lack of adequate study on autosomal dominant polycystic kidney disease (ADPKD) in Ethiopia. This study assessed the clinical profile and determinant factors contributing to renal disease progression. A retrospective study was conducted on 114 patients for 6 years in Addis Ababa. Patients with ADPKD who had follow-up visits at two health centers were included. The mean age at diagnosis was 42.7 ± 12.7 years, with 43% reporting a positive family history of ADPKD. Approximately 22 patients (20%) developed end-stage renal disease, and 12 patients died. The mean estimated glomerular filtration rate at the initial visit was 72.4 mL/min/1.73 m2. The key risk factors associated with disease progression included younger age at diagnosis [adjusted Odds Ratio (aOR): 0.92, 95% CI: 0.87-0.98; p = 0.007], male gender (aOR: 4.5, 95% CI: 1.3-15.95, p = 0.017), higher baseline systolic blood pressure (aOR: 1.05, 95% CI: 1.01-1.10, p = 0.026), and the presence of comorbidities (aOR: 3.95, 95% CI: 1.10-14.33, p = 0.037). The progression of renal disease in ADPKD patients significantly correlates with age at diagnosis, gender, presence of comorbidities, and higher baseline systolic blood pressure. These findings underscore the importance of early detection and management of hypertension and comorbidities in ADPKD patients to mitigate disease progression and improve treatment outcomes.

The Analysis Study of Association of Intestinal Microbiota and Kidney Disease: A Comprehensive Systematic Review

Background: Disruptions in gut microbiota compositiosn (dysbiosis) in kidney diseases can lead to worsened kidney function. Dysbiosis may increase intestinal permeability and systemic inflammation, allowing bacterial toxins to enter the bloodstream and exacerbate CKD and its complications. This systematic review aims to evaluate the association of intestinal microbiota and kidney disease by analyzing available studies of the last 10 years. Methods: The study adhered to PRISMA 2020 standards, examining English literature from 2014 to 2024. It excluded editorials, reviews from the same journal, and submissions without a DOI. PubMed, SagePub, SpringerLink, and Google Scholar were utilized as literature sources. Result: Initially retrieving 360 articles from online databases (PubMed, SagePub, SpringerLink and Google Scholar) eight relevant papers were selected after three rounds of screening for full-text analysis. Conclusion: Gut microbiota alterations are closely linked to chronic kidney disease (CKD) and end-stage renal disease (ESRD), impacting inflammation and disease progression. Microbial shifts offer potential diagnostic and therapeutic insights, though further research is needed for clinical application.

Benefits of SGLT2 inhibitors on renal and cardiovascular protection, in diabetic patients

Introduction: Type 2 Diabetes Mellitus is major risk factors for both cardiovascular and renal diseases. Managing cardiovascular risk and the progression of renal disease is therefore essential in treating diabetic patient. Sodium-glucose cotransporter-2 inhibitors have been linked to a substantial decrease in cardiovascular and renal mortality, reduced hospitalizations for heart failure and slower progression of renal damage and albuminuria. Objectives: Our study aimed to evaluate the impact of SGLT2i on cardiovascular and renal protection in diabetic patients. Methods: Our study involved elderly patients, with type 2 diabetes, who were divided in two groups, one group received SGLT2i, while the other did not. Data were collected at the start of treatment, as well as at 3, 6, 9 and 12 months thereafter. During each evaluation, we assessed HbA1C, BMI, GFR and renal parameters, uric acid, NTproBNP, echocardiography, and both PAS and PAD values, in both groups. Results: Out of 300 elderly diabetic patients included in the study, 200 were started on dapagliflozin 10 mg. At 12 months, HbA1c, weight, systolic blood pressure, NTproBNP, uric acid, albuminuria, were decreases in group with dapagliflozin versus the other group without it, and estimated glomerular filtration rate was higher (75.3 – 87.19mL/min/1.73m2; p&lt;0.005). Follow up in patients with SGLT2i showed a significant decrease in left ventricular end-diastolic dimension (LV-EDD) (62.86 mm to 54.85 mm; P&lt; 0.001) and improvement in LV-EF. Conclusions: The use of Dapagliflozin demonstrated metabolic benefits in patients with T2DM, including notable decreases in HbA1c, blood pressure, weight, uric acid, and NTproBNP. Additionally, cardiovascular and renal benefits were observed. Therefore, SGLT2i have a significant impact on both cardiovascular and renal protection in diabetic patients.

A One-Month Advanced Glycation End Products-Restricted Diet Improves CML, RAGE, Metabolic and Inflammatory Profile in Patients with End-Stage Renal Disease Undergoing Haemodialysis.

Exogenous and endogenous advanced glycation end products (AGEs) contribute to the pathogenesis and progression of renal disease. This is a one-month controlled dietary counseling trial that restricts nutritional AGEs in patients with end-stage renal disease (ESRD) undergoing haemodialysis (n = 22 participants in the intervention and n = 20 participants in the control group). Haematological, biochemical markers, the soluble form of the receptor for AGEs (sRAGE), and carboxymethyl lysine (CML) were measured at baseline and at follow-up. Mononuclear cells were isolated and the protein expression of RAGE and the inflammatory marker COX-2 was measured using Western immunoblotting. The intervention group presented a lower increase in CML compared to the control group (12.39% median change in the intervention vs. 69.34% in the control group, p = 0.013), while RAGE (% mean change -56.54 in the intervention vs. 46.51 in the control group, p < 0.001) and COX-2 (% mean change -37.76 in the intervention vs. 0.27 in the control group, p < 0.001) were reduced compared to the control group. sRAGE was reduced in both groups. In addition, HbA1c (at two months), total cholesterol, and triglycerides were reduced in the intervention versus the control group. The adoption of healthy cooking methods deserves further research as a possible way of modulating inflammatory markers in patients with CKD.

Enhancing prognostic guidance in renal light-chain amyloidosis: a new staging system incorporating pathological characters.

Advancements in treatment regimens have led to improved outcomes in renal Immunoglobulin light-chain amyloidosis. Nevertheless, a subset of patients may still experience renal adverse events despite achieving hematologic very good partial response or better. This discrepancy may be attributed to the deposition pattern of amyloid in renal tissue. To enhance prognostic assessment, a staging system that incorporates both pathological characteristics and clinical indicators should be developed. Patients newly diagnosed through renal biopsy between January 1, 2017, and December 31, 2022, were included. The renal pathology of patients was evaluated according to amyloid score (AS). Risk factors for end-stage renal disease or renal progression were identified by thecompeting risk model, then to develop a renal staging system. The Concordance index (C-index), internal cross-validation and Decision Curve Analysis (DCA) were used to evaluate the performance of the new staging system. 74 patients were included, and 16 (21.6%) patients had end-stage renal disease or renal progression within 24.7 (11.9, 50.7) months. AS and estimated glomerular filtration rate (eGFR) were identified as independent risk factors and the staging system based on them, which the C-index was 0.81 (95%CI, 0.73-0.89), had greater improvement than previous staging systems. The internal cross-validation and DCA also confirmed its great clinical benefits. The AS demonstrated its prognostic significance in Chinese patients, and the novel renal staging system based on AS and eGFR may provide great prognostic guidance for these patients.

Investigating quantitative histological characteristics in renal pathology using HistoLens

HistoLens is an open-source graphical user interface developed using MATLAB AppDesigner for visual and quantitative analysis of histological datasets. HistoLens enables users to interrogate sets of digitally annotated whole slide images to efficiently characterize histological differences between disease and experimental groups. Users can dynamically visualize the distribution of 448 hand-engineered features quantifying color, texture, morphology, and distribution across microanatomic sub-compartments. Additionally, users can map differentially detected image features within the images by highlighting affected regions. We demonstrate the utility of HistoLens to identify hand-engineered features that correlate with pathognomonic renal glomerular characteristics distinguishing diabetic nephropathy and amyloid nephropathy from the histologically unremarkable glomeruli in minimal change disease. Additionally, we examine the use of HistoLens for glomerular feature discovery in the Tg26 mouse model of HIV-associated nephropathy. We identify numerous quantitative glomerular features distinguishing Tg26 transgenic mice from wild-type mice, corresponding to a progressive renal disease phenotype. Thus, we demonstrate an off-the-shelf and ready-to-use toolkit for quantitative renal pathology applications.

Unveiling the bidirectional role of MMP9: A key player in kidney injury

Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteolytic metalloenzymes that are involved in numerous pathological conditions, including nephropathy. MMP9, a member of the MMPs family, is categorized as a constituent of the gelatinase B subgroup, and its involvement in extracellular matrix (ECM) remodeling and renal fibrosis highlights its importance in the development and progression of renal diseases. The exact role of MMP9 in the development of kidney diseases is still controversial. This study investigated the dual role of MMP9 in kidney injury, discussing its implications in the pathogenesis of kidney diseases and investigating the design and mechanism of MMP9 inhibitors based on previous studies. This study provides an effective basis for the development of novel and selective MMP9 inhibitors for treating renal diseases.

High systemic inflammatory response index (SIRI) is an independent risk factor for poor outcome in IgA nephropathy patients.

The systemic inflammatory response index (SIRI), a straightforward and easily accessible measure of inflammation and prognosis, has drawn more attention lately. It is unknown, however, if SIRI is important for IgA nephropathy (IgAN) patients' outcomes. To better clarify these concerns, we conducted this investigation. This retrospective study involved 981 patients with biopsy-confirmed IgAN from West China Hospital of Sichuan University between 2008 and 2019. The patients were divided into two groups based on the SIRI's optimal cut-off value calculated by the X-tile: the low SIRI group (SIRI ≤ 0.63, n = 312) and the high SIRI group (SIRI > 0.63, n = 669). Basic clinical characteristics at the time of renal biopsy were evaluated, and the relationship between SIRI and the combined endpoint was analyzed. We also used the Cox proportional hazard model and Kaplan‒Meier curve to evaluate the renal prognosis of IgAN. A total of 981 IgAN patients were included. During a median follow-up period of 56.7months (36.8-80.4months), 122 patients progressed to the combined endpoint (12.4%). Patients were divided into a low SIRI group (SIRI ≤ 0.63, n = 312) and a high SIRI group (SIRI > 0.63, n = 669) according to the optimal cut-off value of the systemic inflammatory response index (SIRI). Further analysis showed that a higher SIRI value was significantly associated with the risk of IgAN patients reaching the composite endpoint (HR 1.62, 95% CI 1.02-2.56, p = 0.041). High SIRI is a significant and independent risk factor for renal disease progression in IgAN patients.

SGLT-2 inhibitors: new horizons for rheumatologists.

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of medications initially developed for the treatment of diabetes, although their cardiac and renal protective benefits are far reaching. There has been marked interest in the rheumatology community to adopt these medications into our clinical practice, particularly for chronic kidney disease with persistent proteinuria. SGLT2 inhibitors have been approved for patients with type 2 diabetes mellitus, heart failure with reduced or preserved ejection fraction, atherosclerotic cardiovascular disease in the setting of type 2 diabetes mellitus, as well as chronic kidney disease with proteinuria. Large studies on SGLT2 inhibitors have largely excluded patients with proteinuric chronic kidney disease due to autoimmune glomerulonephritis due to concerns for confounding from immunosuppression. The Dapagliflozin and Prevention of Adverse Outcomes in CKD Trial (DAPA-CKD) showed that SGLT2 inhibition decreased progression of renal disease in patients with IgA nephropathy. Expanding this to other autoimmune glomerulonephropathies, several small studies have shown improvements in proteinuria in patients with lupus nephritis treated with SGLT2 inhibitors. A study evaluating safety of SGLT2 inhibitors in patients with lupus identified no specific concerns even with concomitant use of immunosuppression. Small studies have shown that SGLT2 inhibitors can been utilized safely and efficaciously in patients with lupus nephritis. Additional research is needed to identify where these medications fit into the rheumatology treatment armamentarium.

Targeting senescence to prevent diabetic kidney disease: Exploring molecular mechanisms and potential therapeutic targets for disease management.

As a microvascular complication, diabetic kidney disease is the leading cause of chronic kidney disease and end-stage renal disease worldwide. While the underlying pathophysiology driving transition of diabetic kidney disease to renal failure is yet to be fully understood, recent studies suggest that cellular senescence is central in disease development and progression. Consequently, understanding the molecular mechanisms which initiate and drive senescence in response to the diabetic milieu is crucial in developing targeted therapies that halt progression of renal disease. To understand the mechanistic pathways underpinning cellular senescence in the context of diabetic kidney disease, we reviewed the literature using PubMed for English language articles that contained key words related to senescence, inflammation, fibrosis, senescence-associated secretory phenotype (SASP), autophagy, and diabetes. Aberrant accumulation of metabolically active senescent cells is a notable event in the progression of diabetic kidney disease. Through autocrine- and paracrine-mediated mechanisms, resident senescent cells potentiate inflammation and fibrosis through increased expression and secretion of pro-inflammatory cytokines, chemoattractants, recruitment of immune cells, myofibroblast activation, and extracellular matrix remodelling. Compounds that eliminate senescent cells and/or target the SASP - including senolytic and senomorphics drugs - demonstrate promising results in reducing the senescent cell burden and associated pro-inflammatory effect. Here we evidence the link between senescence and diabetic kidney disease and highlight underlying molecular mechanisms and potential therapeutic targets that could be exploited to delay disease progression and improve outcomes for individuals with the disease. Trials are now required to translate their therapeutic potential to a clinical setting.