Progression Of Kidney Disease Research Articles

Neutrophil-to-lymphocyte ratio associated with renal function in type 2 diabetic patients

BACKGROUND Type 2 diabetes mellitus (T2DM) is a leading risk factor for the development and progression of chronic kidney disease (CKD). However, an accurate and convenient marker for early detection and appropriate management of CKD in individuals with T2DM is limited. Recent studies have demonstrated a strong correlation between the neutrophil-to-lymphocyte ratio (NLR) and CKD. Nonetheless, the predictive value of NLR for renal damage in type 2 diabetic patients remains understudied. AIM To investigate the relationship between NLR and renal function in T2DM patients. METHODS This study included 1040 adults aged 65 or older with T2DM from Shanghai's Community Health Service Center. The total number of neutrophils and lymphocytes was detected, and NLR levels were calculated. CKD was defined as an estimated glomerular filtration rate ≤ 60 mL/min/1.73 m². Participants were divided into four groups based on NLR levels. The clinical data and biochemical characteristics were compared among groups. A multivariate logistic regression model was used to analyze the association between NLR levels and CKD. RESULTS Significant differences were found in terms of sex, serum creatinine, blood urea nitrogen, total cholesterol, and low-density lipoprotein cholesterol among patients with T2DM in different NLR groups (P < 0.0007). T2DM patients in the highest NLR quartile had a higher prevalence of CKD (P for trend = 0.0011). Multivariate logistic regression analysis indicated that a high NLR was an independent risk factor for CKD in T2DM patients even after adjustment for important clinical and pathological parameters (P = 0.0001, odds ratio = 1.41, 95% confidence intervals: 1.18-1.68). CONCLUSION An elevated NLR in patients with T2DM is associated with higher prevalence of CKD, suggesting that it could be a marker for the detection and evaluation of diabetic kidney disease.

Elevated apolipoprotein C3 augments diabetic kidney disease and associated atherosclerosis in type 2 diabetes.

Diabetes increases the risk of both cardiovascular disease and kidney disease. Notably, most of the excess cardiovascular risk in people with diabetes is in those with kidney disease. Apolipoprotein C3 (APOC3) is a key regulator of plasma triglycerides, and it has recently been suggested to play a role in both type 1 diabetes-accelerated atherosclerosis and kidney disease progression. To investigate if APOC3 plays a role in kidney disease in people with type 2 diabetes, we analyzed plasma levels of APOC3 from the Veterans Affairs Diabetes Trial (VADT). Elevated baseline APOC3 levels predicted a greater loss of renal function. To mechanistically test if APOC3 plays a role in diabetic kidney disease and associated atherosclerosis, we treated BTBR wildtype (WT) and leptin-deficient (OB; diabetic) mice, a model of type 2 diabetes, with an antisense oligonucleotide (ASO) to APOC3 or a control ASO (cASO), all in the setting of human-like dyslipidemia. Silencing APOC3 prevented diabetes-augmented albuminuria, renal glomerular hypertrophy, monocyte recruitment, and macrophage accumulation, partly driven by reduced ICAM1 expression. Furthermore, reduced levels of APOC3 suppressed atherosclerosis associated with diabetes. This suggests that targeting APOC3 might benefit both diabetes-accelerated atherosclerosis and kidney disease. .

Inducible deletion of microRNA activity in kidney mesenchymal cells exacerbates renal fibrosis

MicroRNAs (miRNAs) are sequence-specific inhibitors of post-transcriptional gene expression. However, the physiological functions of these non-coding RNAs in renal interstitial mesenchymal cells remain unclear. To conclusively evaluate the role of miRNAs, we generated conditional knockout (cKO) mice with platelet-derived growth factor receptor-β (PDGFR-β)-specific inactivation of the key miRNA pathway gene Dicer. The cKO mice were subjected to unilateral ureteral ligation, and renal interstitial fibrosis was quantitatively evaluated using real-time polymerase chain reaction and immunofluorescence staining. Compared with control mice, cKO mice had exacerbated interstitial fibrosis exhibited by immunofluorescence staining and mRNA expression of PDGFR-β. A microarray analysis showed decreased expressions of miR-9-5p, miR-344g-3p, and miR-7074-3p in cKO mice compared with those in control mice, suggesting an association with the increased expression of PDGFR-β. An analysis of the signaling pathways showed that the major transcriptional changes in cKO mice were related to smooth muscle cell differentiation, regulation of DNA metabolic processes and the actin cytoskeleton, positive regulation of fibroblast proliferation and Ras protein signal transduction, and focal adhesion-PI3K/Akt/mTOR signaling pathways. Depletion of Dicer in mesenchymal cells may downregulate the signaling pathway related to miR-9-5p, miR-344g-3p, and miR-7074-3p, which can lead to the progression of chronic kidney disease. These findings highlight the possibility for future diagnostic or therapeutic developments for renal fibrosis using miR-9-5p, miR-344g-3p, and miR-7074-3p.

MiR-486-5p protects against rat ischemic kidney injury and prevents the transition to chronic kidney disease and vascular dysfunction.

Acute kidney injury (AKI) increases the risk for progressive chronic kidney disease (CKD). MicroRNA (miR)-486-5p protects against kidney ischemia reperfusion (IR) injury in mice, although its longterm effects on the vasculature and development of CKD are unknown. We studied whether miR-486-5p would prevent the AKI to CKD transition in rat, and affect vascular function.Methods:Adult male rats were subjected to bilateral kidney IR followed by i.v. injection of liposomal-packaged miR-486-5p (0.5 mg/kg). Kidney function and histologic injury were assessed after 24 h and 10 weeks. Kidney endothelial protein levels were measured by immunoblot and immunofluorescence, and mesenteric artery reactivity was determined by wire myography.Results:In rats with IR, miR-486-5p blocked kidney endothelial cell increases in intercellular adhesion molecule-1 (ICAM-1), reduced neutrophil infiltration and histologic injury, and normalized plasma creatinine (p<0.001). However, miR-486-5p attenuated IR-induced kidney endothelial nitric oxide synthase (eNOS) expression (p<0.05). At 10 weeks, kidneys from rats with IR alone had decreased peritubular capillary density and increased interstitial collagen deposition (p<0.0001), and mesenteric arteries showed impaired endothelium-dependent vasorelaxation (p<0.001). These changes were inhibited by miR-486-5p. Delayed miR-486-5p administration (96 h, 3 weeks after IR) had no impact on kidney fibrosis, capillary density, or endothelial function.Conclusion:In rats, administration of miR-486-5p early after kidney IR prevents injury, and protects against CKD development and systemic endothelial dysfunction. These protective effects are associated with inhibition of endothelial ICAM-1 and occur despite reduction in eNOS. miR-486-5p holds promise for the prevention of ischemic AKI and its complications.

Predicting the Progression of Chronic Kidney Disease: A Systematic Review of Artificial Intelligence and Machine Learning Approaches

Predicting the Progression of Chronic Kidney Disease: A Systematic Review of Artificial Intelligence and Machine Learning Approaches

RUNX3 alleviates mitochondrial dysfunction and tubular damage by inhibiting TLR4/NF-κB signalling pathway in diabetic kidney disease.

The impaired function of tubular mitochondria is critical in diabetic kidney disease (DKD) progression. RUNX3 is down-regulated in DKD models. We intend to explore the effects of RUNX3 on mitochondrial dysfunction and renal tubule injury in DKD and related mechanisms. The development of diabetes models involved injecting mice with streptozotocin while treating HK-2 cells with high glucose (HG). By using immunohistochemical techniques, the renal localizations of RUNX3 were identified. Levels of adenosine triphosphate (ATP), mitochondrial membrane potential, and biochemical index were detected by appropriate kits. Reactive oxygen species (ROS) generation was assessed with dihydroethidium and MitoSOX Red staining. Apoptosis was assessed by flow cytometry and TUNEL. RUNX3 ubiquitination was measured. RUNX3 was mainly present in renal tubules. Overexpressing RUNX3 increased Mfn2, Mfn1, ATP levels, and mitochondrial membrane potential, reduced Drp1 and ROS levels and cell apoptosis, as well as Cyt-C release into the cytoplasm. RUNX3 overexpression displayed a reduction in urinary albumin to creatinine ratio, Hemoglobin A1c, serum creatinine, and blood urea nitrogen. Overexpressing TLR4 attenuated the inhibitory effect of RUNX3 overexpression on mitochondrial dysfunction and cell apoptosis. HG promoted RUNX3 ubiquitination and SMURF2 expression. RUNX3 knockdown cancelled the inhibitory effect of SMURF2 on mitochondrial dysfunction and cell apoptosis. SMURF2 interference inhibits RUNX3 ubiquitination and TLR4/NF-κB signalling pathway, thereby alleviating renal tubule injury.

NET-Related Gene as Potential Diagnostic Biomarkers for Diabetic Tubulointerstitial Injury

Background: Tubulointerstitial injury plays a pivotal role in the progression of diabetic kidney disease (DKD), yet the link between neutrophil extracellular traps (NETs) and diabetic tubulointerstitial injury is still unclear.Methods: We analyzed microarray data (GSE30122) from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) associated with DKD’s tubulointerstitial injury. Functional and pathway enrichment analyses were conducted to elucidate the involved biological processes (BP) and pathways. Weighted gene coexpression network analysis (WGCNA) identified modules associated with DKD. LASSO regression and random forest selected NET-related characteristic genes (NRGs) related to DKD tubulointerstitial injury.Results: Eight hundred ninety-eight DEGs were identified from the GSE30122 dataset. A significant module associated with diabetic tubulointerstitial injury overlapped with 15 NRGs. The hub genes, CASP1 and LYZ, were identified as potential biomarkers. Functional enrichment linked these genes with immune cell trafficking, metabolic alterations, and inflammatory responses. NRGs negatively correlated with glomerular filtration rate (GFR) in the Neph v5 database. Immunohistochemistry (IHC) validated increased NRGs in DKD tubulointerstitial injury.Conclusion: Our findings suggest that the CASP1 and LYZ genes may serve as potential diagnostic biomarkers for diabetic tubulointerstitial injury. Furthermore, NRGs involved in diabetic tubulointerstitial injury could emerge as prospective targets for the diagnosis and treatment of DKD.

A Pilot Comparative Study between Creatinine- and Cystatin-C-Based Equations to Estimate GFR and Kidney Ultrasound Percentiles in Children with Congenital Anomalies of the Kidney and Urinary Tract

Congenital anomalies affecting the kidneys present significant challenges in pediatric nephrology, needing precise methods for assessing renal function and guiding therapeutic intervention. Bedside Schwartz formula with the cystatin-C-based Full Age Spectrum formula and Chronic Kidney Disease in Children (CKiD) U 25 formula used in estimating glomerular filtration rate (eGFR) and also to assess if the eGFR in association with kidney length percentiles can be a monitoring parameter for the progression of chronic kidney disease in children with congenital anomalies of the kidney and urinary tract (CAKUT). A total of 64 pediatric patients (median age at diagnostic was 12 months with an interquartile range of 2 to 60) were diagnosed with congenital anomalies in the kidney and urinary tract between June 2018 and May 2023 at “Louis Turcanu” Emergency Hospital for Children in Timisoara, Romania. Baseline characteristics, CAKUT types, associated pathologies, CKD staging, and eGFR using creatinine and cystatin C were analyzed. The mean age at the moment of examination was 116.50 months; (65, 180). Chronic kidney disease staging revealed a predominance of patients in CKD stages G1 and A1. Analysis of eGFR methods revealed a small mean difference between eGFR estimated by creatinine and cystatin C, with a moderate-strong positive correlation observed between the eGFR and ultrasound parameters. Using cystatin-C-based formulas for eGFR, in conjunction with ultrasound measurements, may offer reliable insights into renal function in pediatric patients with congenital anomalies affecting the kidney and urinary tract. However, the economic aspect must be taken into consideration because cystatin C determination is approximately eight times more expensive than that of creatinine. An interdisciplinary approach is crucial for managing patients with CAKUT.

Association of Preterm Birth with Adverse Glomerular Disease Outcomes in Children and Adults.

While some studies of children with nephrotic syndrome have demonstrated worse outcomes in those born preterm compared with term, little data exists on associations of preterm birth with outcomes in adult-onset glomerular disease. Cardiovascular outcomes in those born preterm with glomerular disease are unknown. We performed a cross-sectional and longitudinal analysis of participants in the Cure Glomerulonephropathy (CureGN) cohort. Preterm (<37 weeks' gestation) was compared to term (≥37 weeks' gestation). A survival analysis and adjusted Cox proportional hazards model were used to examine a composite outcome of 40% decline in estimated glomerular filtration rate (eGFR) or progression to kidney failure. An adjusted logistic regression model was used to examine remission of proteinuria. There were 2,205 term and 235 preterm participants. APOL1 risk alleles were more common in those born preterm. More pediatric than adult participants in CureGN were born preterm: 12.8% vs. 7.69% (P<0.001). Adults born preterm as compared to term had a higher prevalence of Focal Segmental Glomerulosclerosis (FSGS) (35% vs. 25%, P=0.01) and APOL1 high-risk genotype (9.4% vs 4.2%, P=0.01). Participants born preterm had a shorter time interval to a 40% eGFR decline/kidney failure after biopsy (P=0.001). In adjusted analysis, preterm participants were 28% more likely to develop 40% eGFR decline/kidney failure (Hazard Ratio: 1.28 [1.07, 1.54], P=0.008) and 38% less likely to attain complete remission of proteinuria (Odds Ratio: 0.62 [0.45, 0.87], P=0.006). There was no significant difference in cardiovascular events. Preterm birth was a risk factor for adverse outcomes in this heterogenous cohort of children and adults with glomerular disease. Adults born preterm were more likely to have an APOL1 high-risk genotype and FSGS. In analyses adjusted for FSGS and APOL1 risk status, there was less remission and faster progression of kidney disease in those born preterm.

N1F(Improved-Nephropathy 1 Formula) Ameliorates Renal Interstitial Fibrosis via Inhibiting Extracellular Matrix Deposition and Regulating the FGF23/P38MAPK/Wnt Pathway.

Renal fibrosis is the primary pathway in the progression of chronic kidney disease (CKD) towards end-stage renal failure. The currently used drugs currently are ineffective, and their mechanisms of action remain unclear. This study aims to investigate the nephroprotective effect of Improved-Nephropathy 1 Formula (N1F) in a rat model of unilateral ureteral obstruction (UUO) and explore the potential mechanisms of N1F-containing serum in treating TGF-ß1-induced human renal tubular epithelial cells (HK-2). SD rats received 2-week continuous N1F gavage starting on day 2 after UUO. HK-2 cells were pretreated with a P38MAPK inhibitor for 1 h in vitro, followed by induction of the cells with TGF-ß1 and treatment with N1F 48 h later. The chemical composition of N1F was analyzed using high-performance liquid chromatography-Q-Orbitrap high-resolution liquid mass spectrometry. Renal function was assessed by measuring serum creatinine (Scr), blood urea nitrogen (BUN) and urine protein (Upro) levels. Hematoxylin and eosin (HE) and Masson's trichrome (Masson) staining were used to evaluate the extent of renal tissue damage and fibrosis. Western blotting, immunohistochemistry, and immunofluorescence were used to detect the protein levels of relevant indices. The RNA levels of the relevant indices were detected using real-time fluorescence quantitative PCR (RT-qPCR). We identified 361 chemical components in the water extract of N1F. These chemical components of N1F significantly reduced the area associated with interstitial fibrosis in the kidneys of UUO rats and the levels of serum creatinine, urea nitrogen, and urinary protein. Additionally, N1F decreased the protein levels of FGF23, Wnt1, ß-catenin and p-P38MAPK/P38MAPK, along with the expression of renalfibrosis-associated proteins, α-SMA, FN, Collagen III, and Vimentin in the renal tissues of the UUO rats, while enhancing klotho and DKK1 protein levels. In vitro experiments revealed that inhibition of P38MAPK signaling significantly suppressed the expression of proteins related to the Wnt signaling pathway, with a concomitant decrease in the expression of FGF23 and an increase in the expression of Klotho. Notably, the P38MAPK inhibitor (SB203580) had similar effects to N1F in altering the above-mentioned indices in vitro. N1F may exhibit potential therapeutic efficacy against renal fibrosis by inhibiting the FGF23/P38MAPK/Wnt signaling pathway, consequently inhibiting extracellular matrix deposition due to renal injury.

SGLT2 inhibition to target kidney aging

Abstract Anti-aging therapy is the latest frontier in the world of medical science, especially for widespread diseases, such as chronic kidney disease (CKD). Both renal aging and CKD are characterized by increased cellular senescence, inflammation and oxidative stress. A variety of cellular signaling mechanisms are involved in these processes, which provide new potential targets for therapeutic strategies aimed at counteracting the onset and progression of CKD. At the same time, sodium-glucose cotransporter 2 inhibitors (SGLT2is) continuously demonstrate large beneficial effects at all stages of the cardiorenal metabolic continuum. The broad-spectrum benefits of SGLT2is have led to changes in several treatment guidelines and to growing scientific interest in the underlying working principles. Multiple mechanisms have been studied to explain these great renal benefits, but many things remain to be solved. With this in mind, we provide an overview of the experimental evidence for the effects of SGLT2is on the molecular pathway able to modulate senescence, aging and parenchymal damage especially at the kidney level. We propose to shed some light on the role of SGLT2is in kidney care by focusing on their potential to reduce the progression of kidney disease across the spectrum of aging and dysregulation of senescence.

A Bayesian Joint Model of Longitudinal Kidney Disease Progression, Recurrent Cardiovascular Events, and Terminal Event in Patients with Chronic Kidney Disease

AbstractNearly 15% (37 million) of adults in the United States (US) have chronic kidney disease (CKD). The longitudinal decline of kidney function is intricately related to the development of cardiovascular disease (CVD) and eventual “terminal” event (kidney failure and mortality) in patients with CKD. Understanding the mechanism and risk factors underlying the three key outcome processes, (1) CKD progression, (2) CVD, and (3) subsequent terminal event in the CKD patient population remains incomplete. Thus, in this work, we develop a novel trivariate joint model to study the risk factors associated with the interdependent outcomes of kidney function (as measured by longitudinal estimated glomerular filtration rate), recurrent cardiovascular events, and the terminal event. Efficient estimation and inference is proposed within a Bayesian framework using Markov Chain Monte Carlo and Bayesian P-splines for hazard functions. The proposed Bayesian framework is directly generalizable beyond trivariate outcome processes to accommodate other potential modeling of complex multi-disease processes. The method is applied to study the aforementioned trivariate processes using data from the Chronic Renal Insufficiency Cohort Study, an ongoing prospective cohort study, established by the National Institute of Diabetes and Digestive and Kidney Diseases to address the rising epidemic of CKD in the US.

Is there a role for uric acid in polycystic kidney disease progression?

Is there a role for uric acid in polycystic kidney disease progression?

Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data

ObjectiveTo compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice.DesignCohort study...

Mineralocorticoid receptor antagonists and reno-protection: What's the evidence & where do they fit? A guide for non-specialists.

The role of aldosterone has yet to be well appreciated in chronic kidney disease (CKD). Two variables define CKD: an estimated glomerular filtration rate of <60 ml/min/1.73 m2 and a spot urine albumin-creatinine ratio of >30 mg/g. Both are needed for an accurate diagnosis. The presence of CKD at this level is associated with an elevated risk of cardiovascular death and a greater risk of CKD progression to kidney failure and subsequent dialysis. This paper presents an overview of aldosterone's importance in CKD and its contribution to the inflammatory processes involved in CKD development. Data on outcomes, both surrogate and hard, related to outcomes on CKD progression will also be discussed in the context of mineralocorticoid blockade. Based on recent epidemiological data as well as data examining markers of diabetic kidney disease progression, it is clear that use of both renin-angiotensin system inhibitors and aldosterone receptor antagonists have a significant role in altering the natural history of kidney disease progression itself, as well as reducing the risk of cardiovascular events that generally accompany long-standing kidney disease. This paper will discuss these issues and the management of consequent hyperkalaemia when both steroidal and non-steroidal mineralocorticoid receptor antagonists are used in detail.

EXPRESS: Association of suPAR, ST2, and Galectin-3 with eGFR Decline and Mortality in Patients with Advanced Heart Failure with Reduced Ejection Fraction.

Patients with heart failure with reduced ejection fraction (HFrEF) are at risk for chronic kidney disease (CKD). Elevated levels of circulating biomarkers soluble urokinase plasminogen activator receptor (suPAR), galectin-3, soluble suppression of tumorigenicity 2 (ST2), and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) are associated with CKD progression and mortality. The predictive value of these biomarkers in a population with HFrEF and kidney disease is relatively unknown. We sought to determine whether these biomarkers were associated with longitudinal trajectory of eGFR in HFrEF and assess their association with mortality using a joint model to account for competing risks of ventricular assist device (VAD) implantation and heart transplantation. We included participants from the Registry Evaluation of Vital Information for Ventricular Assist Devices in Ambulatory Life with repeated eGFR measures over 2 years. Of 309 participants mean age was 59 years, median eGFR 60 ml/min/1.73m2, 45 participants died, 33 received VAD, and 25 received OHT. Higher baseline serum standardized suPAR [β coefficient =-0.36 √(ml/min/1.73m2), 95% CI (-0.48, -0.24), P<0.001], standardized galectin-3 [-0.14 √(ml/min/1.73m2) (-0.27, -0.02), P=0.02], and log NT-proBNP [-0.23 √(ml/min/1.73m2) (-0.31, -0.15), P<0.001], were associated with eGFR decline. ST2 and log NT-proBNP were associated with mortality. Higher baseline suPAR, galectin-3, and NT-proBNP are associated with eGFR decline in patients with HFrEF. Only ST2 and NT-proBNP are associated with greater mortality after controlling for other factors including change in eGFR. These biomarkers may provide prognostic value for kidney disease progression in HFrEF and inform candidacy for advanced heart failure therapies.

Renal replacement therapy in critical ill patients

Acute kidney injury (AKI), especially when caused or accompanied by sepsis, is associated with prolonged hospitalization, progression of chronic kidney disease (CKD), financial burden on the health care system, and increases mortality in various entities. Extended renal replacement therapy (CRRT) is the predominant form of renal replacement therapy (RRT) in intensive care units (ICU) by providing hemodynamic stability in critically ill patients, more precise control of fluid balance, correction of acid-base imbalances, electrolyte disorders and achieving a stable level of osmolarity correction, including in multimorbid patients. This article examines the various aspects of CRRT in critically ill patients with severe AKI with high comorbidity, as well as in patients with sepsis and multiple organ failure. An analytical evaluation of the choice of CRRT over intermittent/intermittent hemodialysis (IHD) in selected clinical settings is being conducted. Filter/dialyzer life is assessed, including assessment of filtration fraction, use of anticoagulation options including regional citrate anticoagulation (RCA), dose of CRRT prescribed and delivered, vascular access management, general criteria, timing of initiation and cessation of CRRT, and initiation of renal replacement therapy for nonrenal indications. with AKI and/or sepsis.

Detecting and managing the patient with chronic kidney disease in primary care: A review of the latest guidelines.

Chronic kidney disease (CKD) is a major global health problem, affecting about 9.5% of the population and 850 million people worldwide. In primary care, most CKD is caused by diabetes and/or hypertension, but a substantial proportion of cases may have alternative causes. During the early stages, CKD is asymptomatic, and many people are unaware that they are living with the disease. Despite the lack of symptoms, CKD is associated with elevated risks of cardiovascular disease, progressive kidney disease, kidney failure and premature mortality. Risk reduction strategies are effective and cost-effective but require early diagnosis through testing of the estimated glomerular filtration rate and albuminuria in high-risk populations. Once diagnosed, the treatment of CKD centres around lifestyle interventions, blood pressure and glycaemic control, and preventative treatments for cardiovascular disease and kidney disease progression. Most patients with CKD should be managed with statins, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. Additional treatment options to reduce cardiorenal risk are available in patients with diabetes, including glucagon-like peptide-1 receptor agonists and non-steroidal mineralocorticoid receptor antagonists. The Kidney Failure Risk Equation is a new tool that can support the identification of patients at high risk of progressive kidney disease and kidney failure and can be used to guide referrals to nephrology. This review summarizes the latest guidance relevant to managing adults with, or at risk of, CKD and provides practical advice for managing patients with CKD in primary care.

Causal association of plasma circulating metabolites with nephritis: a Mendelian randomization study

BackgroundNephritis is a pivotal catalyst in chronic kidney disease (CKD) progression. Although epidemiological studies have explored the impact of plasma circulating metabolites and drugs on nephritis, few have harnessed genetic methodologies to establish causal relationships.MethodsThrough Mendelian randomization (MR) in two substantial cohorts, spanning large sample sizes, we evaluated over 100 plasma circulating metabolites and 263 drugs to discern their causal effects on nephritis risk. The primary analytical tool was the inverse variance weighted (IVW) analysis. Our bioinformatic scrutiny of GSE115857 (IgA nephropathy, 86 samples) and GSE72326 (lupus nephritis, 238 samples) unveiled anomalies in lipid metabolism and immunological characteristics in nephritis. Thorough sensitivity analyses (MR-Egger, MR-PRESSO, leave-one-out analysis) were undertaken to verify the instrumental variables’ (IVs) assumptions.ResultsUnique lipoprotein-related molecules established causal links with diverse nephritis subtypes. Notably, docosahexaenoic acid (DHA) emerged as a protective factor for acute tubulointerstitial nephritis (ATIN) (OR1 = 0.84, [95% CI 0.78–0.90], p1 = 0.013; OR2 = 0.89, [95% CI 0.82–0.97], p2 = 0.007). Conversely, multivitamin supplementation minus minerals notably increased the risk of ATIN (OR = 31.25, [95% CI 9.23–105.85], p = 0.004). Reduced α-linolenic acid (ALA) levels due to lipid-lowering drugs were linked to both ATIN (OR = 4.88, [95% CI 3.52–6.77], p &amp;lt; 0.001) and tubulointerstitial nephritis (TIN) (OR = 7.52, [95% CI 2.78–20.30], p = 0.042). While the non-renal drug indivina showed promise for TIN treatment, the use of digoxin, hydroxocobalamin, and liothyronine elevated the risk of chronic tubulointerstitial nephritis (CTIN). Transcriptome analysis affirmed that anomalous lipid metabolism and immune infiltration are characteristic of IgA nephropathy and lupus nephritis. The robustness of these causal links was reinforced by sensitivity analyses and leave-one-out tests, indicating no signs of pleiotropy.ConclusionDyslipidemia significantly contributes to nephritis development. Strategies aimed at reducing plasma low-density lipoprotein levels or ALA supplementation may enhance the efficacy of existing lipid-lowering drug regimens for nephritis treatment. Renal functional status should also be judiciously considered with regard to the use of nonrenal medications.

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.