Renal Failure Research Articles

What every clinician needs to know about chronic kidney disease: Detection, classification and epidemiology.

Chronic kidney disease (CKD) is a major healthcare challenge, affecting >800 million people worldwide. Implications for population health result from the strong associations of CKD with increased rates of cardiovascular disease, heart failure, progressive CKD leading to kidney failure, acute kidney injury (AKI), and mortality. In addition to a single disease perspective, CKD commonly coexists alongside other long-term conditions, in particular type 2 diabetes and cardiovascular disease. CKD is therefore an important component of multimorbidity that influences individual management and impacts prognosis. CKD is defined by abnormalities of kidney structure or function of any cause with implications for health that are present for longer than 3 months. The diagnosis is usually made on the basis of an abnormal glomerular filtration rate (GFR < 60 mL/min/1.73 m2) and/or the presence of proteinuria (urine albumin to creatinine ratio > 30 mg/g or >3 mg/mmol). GFR is usually estimated from serum creatinine concentration using a variety of validated equations. However, serum creatinine is closely related to muscle mass and may therefore not be an accurate marker of GFR in people with high or low muscle mass (sarcopaenia). Cystatin C is an alternative endogenous marker of GFR that is increasingly being used but also has limitations. An estimate of GFR based on both creatinine and cystatin C is the most accurate. Diagnosis should be followed by classification and risk stratification to guide the development of a risk-based, personalized care plan. Improved detection and widespread implementation of optimal CKD management has the potential to bring major benefits to population health.

Elevated Serum KIM-1 in Sepsis Correlates with Kidney Dysfunction and the Severity of Multi-Organ Critical Illness

The kidney injury molecule (KIM)-1 is shed from proximal tubular cells in acute kidney injury (AKI), relaying tubular epithelial proliferation. Additionally, KIM-1 portends complex immunoregulation and is elevated after exposure to lipopolysaccharides. It thus may represent a biomarker in critical illness, sepsis, and sepsis-associated AKI (SA-AKI). To characterise and compare KIM-1 in these settings, we analysed KIM-1 serum concentrations in 192 critically ill patients admitted to the intensive care unit. Irrespective of kidney dysfunction, KIM-1 serum levels were significantly higher in patients with sepsis compared with other critical illnesses (191.6 vs. 132.2 pg/mL, p = 0.019) and were highest in patients with urogenital sepsis, followed by liver failure. Furthermore, KIM-1 levels were significantly elevated in critically ill patients who developed AKI within 48 h (273.3 vs. 125.8 pg/mL, p = 0.026) or later received renal replacement therapy (RRT) (299.7 vs. 146.3 pg/mL, p &lt; 0.001). KIM-1 correlated with markers of renal function, inflammatory parameters, hematopoietic function, and cholangiocellular injury. Among subcomponents of the SOFA score, KIM-1 was elevated in patients with hyperbilirubinaemia (&gt;2 mg/dL, p &lt; 0.001) and thrombocytopenia (&lt;150/nL, p = 0.018). In univariate and multivariate regression analyses, KIM-1 predicted sepsis, the need for RRT, and multi-organ dysfunction (MOD, SOFA &gt; 12 and APACHE II ≥ 20) on the day of admission, adjusting for relevant comorbidities, bilirubin, and platelet count. Additionally, KIM-1 in multivariate regression was able to predict sepsis in patients without prior (CKD) or present (AKI) kidney injury. Our study suggests that next to its established role as a biomarker in kidney dysfunction, KIM-1 is associated with sepsis, biliary injury, and critical illness severity. It thus may offer aid for risk stratification in these patients.

LAPAROSCOPIC TREATMENT OF RIGHT INGUINAL HERNIA RE-RECURRENCE

Abstract We report the case of an 81-year-old man presenting with a right inguinal hernia re-recurrence. He had undergone a laparoscopic transabdominal preperitoneal hernioplasty in 2001. The recurrence occurred in 2021, and therefore, he had to be treated with an open approach. Past medical history included arterial hypertension, COPD, coronary artery stenting for ischemic heart disease, stage II chronic renal failure. Previous surgeries consisted of bilateral iliac arteries, percutaneous angioplasty and stenting with a right femoral arterial access, laminectomy of L3–L5, and laparoscopic cholecystectomy. Surgical procedure Laparoscopy confirmed a right hernia re-recurrence. Herniated ileal loop was completely reduced. Peritoneal incision was performed with a lateral-to-medial approach. The mesh was dissected away from the pre-peritoneal fat. The shrunk mesh was pulled downwards to allow the identification of the epigastric vessels, which were then dissected according to a cranial-to-caudal approach. The large hernia sac was completely reduced thus exposing the re-recurrence orifice. Dissection was carried out towards the Bogros’ space. Epigastric vessels were detached from the mesh thus allowing to expose the medial part of the myopectineal orifice. Cooper’s ligament and pubic symphysis were therefore identified. The epigastric and spermatic vessels were freed from the mesh only after the critical view of the myopectineal orifice (MPO) was achieved. The mesh was completely mobilized from the peritoneum and removed. A “landing zone” was obtained, a 15 × 10 cm self-fixating mesh positioned around the re-recurrence orifice. Peritoneum closure was performed by means of a 3–0 running barbed suture from medial to lateral.

Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases

Kidney diseases pose a significant global health issue, frequently resulting in the gradual decline of renal function and eventually leading to end-stage renal failure. Abnormal iron metabolism and oxidative stress-mediated cellular dysfunction facilitates the advancement of kidney diseases. Iron homeostasis is strictly regulated in the body, and disturbance in this regulatory system results in abnormal iron accumulation or deficiency, both of which are associated with the pathogenesis of kidney diseases. Iron overload promotes the production of reactive oxygen species (ROS) through the Fenton reaction, resulting in oxidative damage to cellular molecules and impaired cellular function. Increased oxidative stress can also influence iron metabolism through upregulation of iron regulatory proteins and altering the expression and activity of key iron transport and storage proteins. This creates a harmful cycle in which abnormal iron metabolism and oxidative stress perpetuate each other, ultimately contributing to the advancement of kidney diseases. The crosstalk of iron metabolism and oxidative stress involves multiple signaling pathways, such as hypoxia-inducible factor (HIF) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. This review delves into the functions and mechanisms of iron metabolism and oxidative stress, along with the intricate relationship between these two factors in the context of kidney diseases. Understanding the underlying mechanisms should help to identify potential therapeutic targets and develop novel and effective therapeutic strategies to combat the burden of kidney diseases.

Exploring the mechanism of cardiorenal protection with finerenone based on network pharmacology.

Large prospective trials have demonstrated that finerenone could reduce the risk of cardiovascular death and progression of renal failure among patients with chronic kidney disease (CKD) associated heart failure (HF) and/or type 2 diabetes mellitus (T2DM). The aim of this study was to explore the molecular mechanism of finerenone in the treatment of cardiorenal diseases through network pharmacology. The STITH, SwissTargetPrediction, PharmMapper, DrugBank and ChEMBL databases were used to screen the targets of finerenone. The diseases-related targets were retrieved from the DisGeNET, GeneCards, CTD, OMIM and MalaCards databases. The protein-protein interaction (PPI) network was conducted with STRING database and Cytoscape software. The clusterProfiler R package was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The interactions of key targets and finerenone were analyzed by molecular docking in Autodock software. Diabetes mellitus was induced by intraperitoneal injection of streptozotocin. Histopathology of myocardial and renal tissues were observed by hematoxylin-eosin (HE) staining, and detection of protein expressions was conducted using western blotting. A total of 111 potential cardiorenal targets of finerenone were identified. The main mechanisms of action may be associated with lipid and atherosclerosis, fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications and diabetic cardiomyopathy. The hub targets demonstrated by the PPI network were CASP3, ALB, MMP9, EGFR, ANXA5, IGF1, SRC, TNFRSF1A, IL2 and PPARG, and the docking results suggested that finerenone could bind to these targets with high affinities. HE staining revealed the cardiorenal protection of finerenone on diabetic mice. In addition, the protein expressions of CASP3 and EGFR were increased while ALB was decreased in myocardial and renal tissues in diabetic mice compared with control mice, which were reversed by finerenone. This study suggested that finerenone exerts cardiorenal benefits through multiple targets and pathways.

Molecular Aspects of Cardiometabolic Diseases: From Etiopathogenesis to Potential Therapeutic Targets

Cardiometabolic diseases (CMDs) encompass a range of prevalent, often preventable, non-communicable illnesses, including myocardial infarction, stroke, cardiac insufficiency, arterial hypertension, obesity, type 2 diabetes mellitus, insulin resistance, chronic renal dysfunction, non-alcoholic fatty liver disease, and rare metabolic disorders [...]

Evaluation of split renal dysfunction using radiomics based on magnetic resonance diffusion-weighted imaging.

Accurate and noninvasive assessment of split renal dysfunction is crucial, while there is lack of corresponding method clinically. To investigate the feasibility of using diffusion-weighted imaging (DWI)-based radiomics models to evaluate split renal dysfunction. We enrolled patients with impaired and normal renal function undergoing renal DWI examination. Glomerular filtration rate (GFR, mL/min) was measured using 99mTc-DTPA scintigraphy, which is reference standard of GFR measurement. The kidneys were classified into normal (GFR ≥40), mildly impaired (20≤ GFR<40), moderately impaired (10≤ GFR<20), and severely impaired (GFR<10) renal function groups. Optimized subsets of radiomics features were selected from renal DWI images and radiomics scores (Rad-score) calculated to discriminate groups with different renal function. The radiomics model (Rad-score based) was developed in a training cohort and validated in a test cohort. Evaluations were conducted on the discrimination, calibration, and clinical application of the method. The final analysis included 330 kidneys. Logistic regression was used to develop three radiomics models, model A, B, and C, which were used to distinguish normal from impaired, mild from moderate, and moderate from severe renal function, respectively. The area under the curve of the three models were 0.822, 0.704, and 0.887 in the training cohort and 0.843, 0.717, and 0.897 in the test cohort, respectively, indicating efficient discrimination performance. DWI-based radiomics models have potential for evaluating split renal dysfunction and discriminating between normal and impaired renal function groups and their subgroups.

Heterogeneity in the definition of major adverse kidney events: a scoping review.

Acute kidney injury (AKI) is associated with persistent renal dysfunction, the receipt of dialysis, dialysis dependence, and mortality. Accordingly, the concept of major adverse kidney events (MAKE) has been adopted as an endpoint for assessing the impact of AKI. However, applied criteria or observation periods for operationalizing MAKE appear to vary across studies. To evaluate this heterogeneity for MAKE evaluation, we performed a systematic scoping review of studies that employed MAKE as an AKI endpoint. Four major academic databases were searched, and we identified 122 studies with increasing numbers over time. We found marked heterogeneity in applied criteria and observation periods for MAKE across these studies, with some even lacking a description of criteria. Moreover, 13 different observation periods were employed, with 30 days and 90 days as the most common. Persistent renal dysfunction was evaluated by estimated glomerular filtration rate (34%) or serum creatinine concentration (48%); however, 37 different definitions for this component were employed in terms of parameters, cut-off criteria, and assessment periods. The definition for the dialysis component also showed significant heterogeneity regarding assessment periods and duration of dialysis requirement (chronic vs temporary). Finally, MAKE rates could vary by 7% [interquartile range: 1.7-16.7%] with different observation periods or by 36.4% with different dialysis component definitions. Our findings revealed marked heterogeneity in MAKE definitions, particularly regarding component assessment and observation periods. Dedicated discussion is needed to establish uniform and acceptable standards to operationalize MAKE in terms of selection and applied criteria of components, observation period, and reporting criteria for future trials on AKI and related conditions.

Chemotherapy plus therapeutic plasmapheresis with 4% human albumin solution in multiple myeloma patients with acute kidney injury: a prospective, open-label, proof-of-concept study

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median −12.12%, interquartile ranges (IQRs) −18.62 to −5.626) and creatine (median −46.91 μmol/L, IQR −64.70 to −29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03–25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.

Antineutrophil cytoplasmic antibody-associated vasculitis.

This review focuses on latest developments in managing antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a systemic autoimmune condition characterized by inflammation and necrosis of small blood vessels due to circulating autoantibodies that target neutrophilic granules. Our understanding of AAV pathogenesis has evolved in the past decades highlighting the central pathogenic roles of autoantibodies and complement activation. In parallel, the appreciation for glucocorticoid toxicity has led the research on crucial steroid-sparing therapeutic alternatives. Complement inhibitors (like avacopan) that have emerged are associated with better preservation of kidney function in AAV patients with severe kidney impairment. The role of plasma-exchange (PLEX) was revisited in updated guidelines that recommended its potential use in the context of diffuse alveolar hemorrhage associated hypoxia and severe kidney involvement, particularly with a serum creatinine level above 3.4 mg/dl. The ANCA Kidney Risk Score risk prediction and Glucocorticoid Toxicity Index score aid in identifying high-risk patients and individualizing management plans. Kidney involvement in AAV requires prompt diagnosis and initiation of immunosuppression to prevent irreversible nephron loss. Newer therapeutic targets are on the horizon and offer hope for personalized treatment strategies.

Once-per-week haemodialysis in a financial crisis: Predictors of interdialytic weight gain.

Several countries are experiencing challenges in maintaining standard haemodialysis services for people with kidney failure. This study aimed to investigate the health profile of people receiving haemodialysis and to identify factors associated with interdialytic weight gain. A cross-sectional study. A total of 166 adults with kidney failure and receiving haemodialysis for at least 3 months were included. A structured chart audit form collected, demographic and haemodialysis treatment characteristics, recent biochemical and haematological results, and prescribed treatment regimens from clinical records. Data were analysed descriptively. Odds ratios (OR) were calculated to identify independent risk factors for interdialytic weight gain. Mean age was 52 years (SD = 12.5), over half were male (60.2%, n = 100), and most were receiving 4 h of haemodialysis once per week (87.3%, n = 145). Approximately half (51.8%, n = 86) had an interdialytic weight gain >2%. Being female (OR = 3.39; 95% CI, 1.51-7.61), increased comorbidities (OR = 1.50; 95% CI, 1.22-1.84) and having BMI outside of the normal range (overweight/obese [OR = 8.49; 95% CI, 3.58-20.13] or underweight [OR = 4.61; 95% CI, 1.39-15.31]) were independent risk factors for increased interdialytic weight gain. Most patients were receiving 4 h of haemodialysis once per week although only modest alterations in potassium, phosphate, and fluid status were observed. Understanding the patient profile and predictors of interdialytic weight gain will inform the development of self-management interventions to optimise clinician support.

Heroin Overdose Complicated by Compartment Syndrome, Rhabdomyolysis, and Acute Renal Failure

Heroin Overdose Complicated by Compartment Syndrome, Rhabdomyolysis, and Acute Renal Failure

Prognostic factors of idiopathic hypereosinophilic syndrome: A nationwide survey in Japan.

Idiopathic hypereosinophilic syndrome (iHES) is a condition wherein persistent hypereosinophilia associated with end-organ damage occurs without any known causes. Due to the rarity of the disease, insufficient knowledge has been accumulated. We therefore conducted a retrospective, multicentre, nationwide survey on iHES in Japan. A total of 57 patients were identified. For 43 patients who received any treatment, all cases were first treated with corticosteroids. An eosinophil percentage of less than 30% in the bone marrow and the absence of oedema were identified as factors associated with steroid dependency. The 5-year overall survival was 88.2%, and five patients died during follow-up; factors associated with worse overall survival were age >50, haemoglobin <12 g/dL, activated partial thromboplastin time >34 s, the presence of dyspnoea, the presence of thrombotic tendency and the presence of renal failure. Given the rarity of fatalities in our cohort, time-to-next-treatment (TTNT) was further analysed; the presence of renal failure, splenomegaly and lung abnormalities were associated with worse TTNT. Our nationwide study not only demonstrated clinical characteristics and the outcome of patients with iHES but also for the first time revealed clinical factors associated with steroid dependency and duration of first-line corticosteroid efficacy.

EFEKTIVITAS PENDIDIKAN KESEHATAN MENGGUNAKAN VIDEO TERHADAP KEPATUHAN PEMBATASAN CAIRAN PADA PASIEN HEMODIALISA DI KLINIK PANDAONI MEDIKA JAKARTA

Chronic kidney disease is a metabolic disease that can be seen in a decrease in kidney function. Patients with chronic kidney failure who do hemodialysis have a lot of fluid overload problems that cause an increase in IDWG. Patients who have excess fluids need to limit fluids. One effort to increase adherence is to provide education in advance to increase knowledge about the disease by providing health education using video. The purpose of this study was to determine the effectiveness of health education using video on compliance with fluid restrictions in hemodialysis patients at the Klinik Pandaoni Medika Jakarta. This study used a quantitative approach with a quasi-experimental design with two control groups for pre- and post-tests. The sampling technique used was purposive sampling on a total sample of 78 respondents. The analysis used is a paired sample t-test and an independent t-test. After the intervention was carried out and the results obtained, the intervention group experienced an average decrease indicating the influence of health education using video (p = 0.000), while in the control group the average compliance value increased with a value of p = 0.002, which indicated the influence of health education using video with a bad influence on the level of adherence to fluid restriction in the control group. There were differences in adherence to fluid restriction in the intervention group and the control group (p = 0.000).

Annexin-A5 monomer as a membrane repair agent for the treatment of renal ischemia-reperfusion injury.

Renal ischemia-reperfusion injury (IRI) is one of the causes of acute kidney injury. Annexin A5 (AnxA5), a calcium-dependent cell membrane-binding protein, shows protective effects in various organ IRI models. This study explored the therapeutic effect of exogenous AnxA5 monomer protein on renal IRI and its potential mechanism of action. Different doses of AnxA5 were injected intravenously to treat bilateral renal IRI in SD rats. This model confirmed the protective effects of AnxA5 on kidney structure and function. In vitro, HK-2 cells were subjected to hypoxia for 12h, followed by restoration of normal oxygen supply to simulate IRI. In vitro experiments demonstrated the mechanism of action of AnxA5 by measuring cellular activity and permeability. A comparison of the mutant AnxA5 protein M23 and the application of a calcium-free culture medium further validated the protective effect of AnxA5 by forming a network structure. Exogenous AnxA5 monomers prevented renal IRI by binding to the damaged renal tubular epithelial cell membrane, forming a two-dimensional network structure to maintain cell membrane integrity, and ultimately prevent cell death.

Vasodilator reactive oxygen species ameliorate perturbed myocardial oxygen delivery in exercising swine with multiple comorbidities.

Multiple common cardiovascular comorbidities produce coronary microvascular dysfunction. We previously observed in swine that a combination of diabetes mellitus (DM), high fat diet (HFD) and chronic kidney disease (CKD) induced systemic inflammation, increased oxidative stress and produced coronary endothelial dysfunction, altering control of coronary microvascular tone via loss of NO bioavailability, which was associated with an increase in circulating endothelin (ET). In the present study, we tested the hypotheses that (1) ROS scavenging and (2) ETA+B-receptor blockade improve myocardial oxygen delivery in the same female swine model. Healthy female swine on normal pig chow served as controls (Normal). Five months after induction of DM (streptozotocin, 3 × 50mgkg-1 i.v.), hypercholesterolemia (HFD) and CKD (renal embolization), swine were chronically instrumented and studied at rest and during exercise. Sustained hyperglycemia, hypercholesterolemia and renal dysfunction were accompanied by systemic inflammation and oxidative stress. In vivo ROS scavenging (TEMPOL + MPG) reduced myocardial oxygen delivery in DM + HFD + CKD swine, suggestive of a vasodilator influence of endogenous ROS, while it had no effect in Normal swine. In vitro wire myography revealed a vasodilator role for hydrogen peroxide (H2O2) in isolated small coronary artery segments from DM + HFD + CKD, but not Normal swine. Increased catalase activity and ceramide production in left ventricular myocardial tissue of DM + HFD + CKD swine further suggest that increased H2O2 acts as vasodilator ROS in the coronary microvasculature. Despite elevated ET-1 plasma levels in DM + HFD + CKD swine, ETA+B blockade did not affect myocardial oxygen delivery in Normal or DM + HFD + CKD swine. In conclusion, loss of NO bioavailability due to 5 months exposure to multiple comorbidities is partially compensated by increased H2O2-mediated coronary vasodilation.

PREVALENCE OF DIABETIC NEPHROPATHY AMONGST TYPE 2 DIABETIC PATIENTS ATTENDING TERTIARY HOSPITAL OF HYDERABAD, SINDH, PAKISTAN

Diabetic nephropathy (DN) is a common health problem; increasing with high proportion that results in significant reduction in life spawn of diabetic patients. This study was made in order to determine the prevalence of DN in patients having type 2 diabetes in major tertiary hospitals of Hyderabad and Adjoining areas. The progression of DN in Type 2 diabetic mellitus was gathered through pre-tested questionnaire from patients. During study period, 150 of DN patients were interviewed on the basis of their medical history including period of disease, blood sugar test, renal impairment, hypertension, cardiovascular and family background reports. While the measurement of albumin to creatinine ratio and uric acids in a random urine sample were evaluated with biochemical blood/urine test and immunological assays. It was found that out of 150 diabetes patients, 123 have DN and among them male and female ratio was 81: 42 respectively. According to the parameters, the diabetic mellitus were in both DN and non diabetic nephropathy (NDN) patients, as far as the circulating level of sugar level in both DN and NDN is concern it was noted that range of fasting blood sugar was high 232.86± 15.85 mg /dl as compared to the normal value 80-120. The level of blood glucose in the NDN it was 136,25 ± 10.85 around 100 mg/dl lesser than the values in DN patients. It was further observed that the smocking and hypertension played main role in the prevalence of the disorder.

Quercetin prevents kidney against diabetes mellitus (type 1) in rats by inhibiting TGF-β/apelin gene expression.

One of the main causes of diabetic nephropathy is oxidative stress induced by hyperglycemia. Apelin inhibits insulin secretion. Besides, renal expression of TGF-β is increased in diabetes mellitus (DM). The preventive effect of quercetin (Q) against renal functional disorders and tissue damage developed by DM in rats was assessed. Forty male Wistar rats were grouped into normal control (NC), normal + quercetin (NQ: quercetin, 50mg/kg/day by gavage), diabetic control (DC: streptozotocin, 65mg/kg, i.p.), diabetic + quercetin pretreatment (D + Qpre), and diabetic + quercetin post-treatment (D + Qpost). All samples (24-hour urine, plasma, pancreatic, and renal tissues) were obtained at the terminal of the experiment. Compared to NC and NQ groups, DM ended in elevated plasma and glucose levels, decreased plasma insulin level, kidney dysfunction, augmented levels of malondialdehyde, decreased level of reduced glutathione, reduced enzymatic activities of superoxide dismutase and catalase, elevated gene expression levels of apelin and TGF-β, also renal and pancreatic histological damages. Quercetin administration diminished entire the changes. However, the measure of improvement in the D + Qpre group was higher than that of the D + Qpost group. Quercetin prevents renal dysfunction induced by DM, which might be related to the diminution of lipid peroxidation, strengthening of antioxidant systems, and prevention of the apelin/ TGF-β signaling pathway.

IGFBP2 induces podocyte apoptosis promoted by mitochondrial damage via integrin α5/FAK in diabetic kidney disease.

Podocyte apoptosis or loss is the pivotal pathological characteristic of diabetic kidney disease (DKD). Insulin-like growth factor-binding protein 2 (IGFBP2) have a proinflammatory and proapoptotic effect on diseases. Previous studies have shown that serum IGFBP2 level significantly increased in DKD patients, but the precise mechanisms remain unclear. Here, we found that IGFBP2 levels obviously increased under a diabetic state and high glucose stimuli. Deficiency of IGFBP2 attenuated the urine protein, renal pathological injury and glomeruli hypertrophy of DKD mice induced by STZ, and knockdown or deletion of IGFBP2 alleviated podocytes apoptosis induced by high concentration of glucose or in DKD mouse. Furthermore, IGFBP2 facilitated apoptosis, which was characterized by increase in inflammation and oxidative stress, by binding with integrin α5 (ITGA5) of podocytes, and then activating the phosphorylation of focal adhesion kinase (FAK)-mediated mitochondrial injury, including membrane potential decreasing, ROS production increasing. Moreover, ITGA5 knockdown or FAK inhibition attenuated the podocyte apoptosis caused by high glucose or IGFBP2 overexpression. Taken together, these findings unveiled the insight mechanism that IGFBP2 increased podocyte apoptosis by mitochondrial injury via ITGA5/FAK phosphorylation pathway in DKD progression, and provided the potential therapeutic strategies for diabetic kidney disease.

Iron Deficiency in Newly Referred Patients With Chronic Renal Failure

Iron Deficiency in Newly Referred Patients With Chronic Renal Failure