Renal Failure Research Articles

Accurate statistical methods to cover the aspects of the increase in the incidence of kidney failure: A survey study in Ha'il -Saudi Arabia.

Chronic kidney disease (CKD) has become more common in recent decades, putting significant strain on healthcare systems worldwide. CKD is a global health issue that can lead to severe complications such as kidney failure and death. The purpose of this study was to investigate the actual causes of the alarming increase of kidney failure cases in Saudi Arabia using the supersaturated design analysis and edge design analysis. A cross-sectional questionnaire was distributed to the general population in the KSA, and data were collected using Google Forms. A total of 401 responses were received. To determine the actual causes of kidney failure, edge and supersaturated designs analysis methods were used, which resulted in statistical significance. All variables were studied from factor h1 to factor h18 related to the causes of kidney failure. The supersaturated analysis method revealed that the reasons for the increase in kidney failure cases are as follows: h9(Bad diet), h8(Recurrent urinary tract infection), h1 (Not drinking fluids), h6 (Lack of exercise), h14 (drinking from places not designated for valleys and reefs), h18 (Rheumatic diseases), h10 (Smoking and alcohol consumption), h13 (Direct damage to the kidneys), h2 (take medications), h17 (excessive intake of soft drinks), h12 (Infection), h5 (heart disease), h3 (diabetes), h4 (pressure disease), h15 (Dyes used in X-rays), and h11 (The presence of kidney stones) are all valid. The design analysis method by edges revealed that the following factors contributed to an increase in kidney failure cases: h8 (Recurrent urinary tract infection), h6 (Lack of exercise), h7 (Obesity), and h11. The findings showed that there were causes of kidney failure that led to the statistical significance, which is h8 (Recurrent urinary tract infection) and h11 (The presence of kidney stones).

Endoplasmic reticulum stress promotes oxidative stress, inflammation, and apoptosis: A novel mechanism of citrinin-induced renal injury and dysfunction

Citrinin (CTN) has been reported to induce renal failure and structural damage, but its nephrotoxic effects and mechanisms are not fully understood. Therefore, we established a model by orally administering CTN (0, 1.25, 5, or 20 mg/kg) to mice for 21 consecutive days. Histological and biochemical analyses revealed that CTN caused structural damage to renal tubules, increased inflammatory cell infiltration, and elevated levels of serum markers of renal function (creatinine, urea, and uric acid). Moreover, mRNA transcript levels of the inflammatory factors TNF-α, IL-1β, and IL-6 were increased, indicating the occurrence of an inflammatory response. Furthermore, exposure to CTN induced renal oxidative stress by decreasing antioxidant GSH levels, antioxidant enzyme (SOD, CAT) activities, and increasing oxidative products (ROS, MDA). In addition, CTN increased the expression of proteins associated with endoplasmic reticulum (ER)stress and apoptotic pathways. ER stress has been shown to be involved in regulating various models of kidney disease, but its role in CTN-induced renal injury has not been reported. We found that pretreatment with the ER stress inhibitor 4-PBA (240 mg/kg, ip) alleviated CTN-induced oxidative stress, NF-κB pathway mediated inflammatory response, and apoptosis. Interestingly, 4-PBA also partially alleviated renal structural damage and dysfunction. Thus, ER stress may be a novel target for the prevention and treatment of CTN-induced renal injury.

Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Perspectives

Long-lasting COVID-19 (long COVID) diseases constitute a real life-changing burden for many patients around the globe and, overall, can be considered societal and economic issues. They include a variety of symptoms, such as fatigue, loss of smell (anosmia), and neurological–cognitive sequelae, such as memory loss, anxiety, brain fog, acute encephalitis, and stroke, collectively called long neuro-COVID-19 (long neuro-COVID). They also include cardiopulmonary sequelae, such as myocardial infarction, pulmonary damage, fibrosis, gastrointestinal dysregulation, renal failure, and vascular endothelial dysregulation, and the onset of new diabetes, with each symptom usually being treated individually. The main unmet challenge is to understand the mechanisms of the pathophysiologic sequelae, in particular the neurological symptoms. This mini-review presents the main mechanistic hypotheses considered to explain the multiple long neuro-COVID symptoms, namely immune dysregulation and prolonged inflammation, persistent viral reservoirs, vascular and endothelial dysfunction, and the disruption of the neurotransmitter signaling along various paths. We suggest that the nucleoprotein N of SARS-CoV-2 constitutes a “hub” between the virus and the host inflammation, immunity, and neurotransmission.

Risk evaluation and recipient selection in adult liver transplantation: A mixed-methods survey

Background: Liver transplant (LT) is the definitive treatment for end-stage liver disease. Limited resources and important post-operative implications for recipients compel judicious risk stratification and patient selection. However, little is known about the factors influencing physicians’ assessment regarding patient selection for LT and risk evaluation. Methods: We conducted a mixed-methods, cross-sectional survey involving Canadian hepatologists, anesthesiologists, LT surgeons, and French anesthesiologists. The survey contained quantitative questions and a vignette-based qualitative substudy about risk assessment and patient selection for LT. Descriptive statistics and qualitative content analyses were used. Results: We obtained answers from 129 physicians, and 63 participated in the qualitative substudy. We observed considerable variability in risk assessment prior to LT and identified many factors perceived to increase the risk of complications. Clinicians reported that the acceptable incidence of at least 1 severe post-operative complication for a LT program was 20% (95% CI: 20-30%). They identified the presence of any comorbidity as increasing the risk of different post-operative complications, especially acute kidney injury and cardiovascular complications. Frailty and functional disorders, severity of the liver disease, renal failure and cardiovascular comorbidities prior to LT emerged as important risk factors for post-operative morbidity. Most respondents were willing to pursue LT in patients with grade III acute-on-chronic liver failure but were less often willing to do so when faced with the uncertainty of a clinical example. Conclusions: Clinicians had a heterogeneous appraisal of the post-operative risk of complications following LT, as well as factors considered in risk assessment.

Association between renal dysfunction and outcomes of lung cancer: A systematic review and meta‑analysis

Association between renal dysfunction and outcomes of lung cancer: A systematic review and meta‑analysis

Tirzepatide’s innovative applications in the management of type 2 diabetes and its future prospects in cardiovascular health

Tirzepatide, a novel GLP-1/GIP dual receptor agonist, shows significant advantages in glycemic management and weight control. By summarizing the results of the SURMOUNT and SURPASS clinical trials, we evaluate the efficacy and safety of tirzepatide in reducing blood glucose and weight. These trials indicate that tirzepatide significantly lowers HbA1c levels (with a maximum reduction of 2.24%) and promotes weight loss (up to 11.2 kg) with good tolerability. However, there are still some challenges in its clinical application, including high treatment costs and gastrointestinal discomfort. Additionally, the safety and efficacy of tirzepatide in special populations, such as patients with renal impairment, require further investigation. Future large-scale clinical trials, such as SURPASS-CVOT and SUMMIT, are expected to further verify the long-term benefits of tirzepatide in cardiovascular health management, providing stronger evidence for its comprehensive treatment of diabetes and its complications.

Mechanistic Differences between Torsemide and Furosemide.

Torsemide is proposed to have clinically important pharmacokinetic and pharmacodynamic advantages over furosemide. However, clinical outcomes did not differ in the Torsemide Comparison with Furosemide for Management of Heart Failure (TRANSFORM-HF) randomized trial. We conducted a multicenter mechanistic substudy of patients with heart failure randomized to oral furosemide or torsemide (TRANSFORM-Mechanism). At baseline and 30 days, participants underwent detailed assessments of pharmacokinetic and pharmacodynamic parameters. TRANSFORM-Mechanism enrolled 88 participants. Kidney bioavailability, or the proportion of dose delivered to the tubular site of action, was significantly less with torsemide compared to furosemide [median 17.1%, (IQR 12.3, 23.5%) vs. 24.8% (16.6, 34.1%), p < 0.001]. Furosemide had a longer duration of kidney drug delivery and duration of natriuresis (p≤0.004 for both). Prescribed doses of furosemide and torsemide in TRANSFORM-Mechanism were similar to TRANSFORM-HF, with providers on average using a 2:1 dose equivalence conversion between drugs. However, these doses resulted in a substantially greater natriuresis with torsemide (p<0.001). A dose equivalence of ∼4:1 resulted in similar natriuresis. Higher diuretic doses in the torsemide group resulted in mild perturbations in kidney function and significant increases in renin, aldosterone, and norepinephrine (p<0.05 for all). Plasma volume (p=0.52) and body weight (p=0.89) did not improve with torsemide vs. furosemide. We observed no meaningful pharmacokinetic/pharmacodynamic advantages for torsemide vs. furosemide. The greater natriuresis from higher diuretic doses in the torsemide group was offset by greater neurohormonal activation and kidney dysfunction.

B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.

B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality. The induced MM mimics human disease, exhibiting features like clonal plasma cell expansion, paraproteinemia, anemia, and kidney and bone failure, as well as critical immunosurveillance strategies that promote a tumor-supportive microenvironment. This research elucidates the differential impacts of RANK activation in B1- and B2-cells and underscores the distinct roles of single versus combined oncogenes in B-cell malignancies. We also demonstrate that human MM cells express RANK and that inhibiting RANK signaling can reduce MM progression in a xenotransplantation model. Our study provides a rationale for further investigating the effects of RANK signaling in B-cell transformation and the shaping of a tumor-promoting microenvironment.

A real-world pharmacovigilance study of KRAS G12C mutation inhibitors based on the food and drug administration adverse event reporting system

IntroductionSotorasib and adagrasib have been widely used for the non-small cell lung cancer (NSCLC) patients harboring Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation. It's necessary to assess their safety profiles in the real-world population.MethodsA retrospective pharmacovigilance was conducted to examine adverse events (AEs) associated with sotorasib and adagrasib therapies using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was performed employing Venn analysis and four data-mining algorithms, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS).ResultsThe most commonly reported system organ classes (SOCs) for both adagrasib and sororasib were general, gastrointestinal, and investigations disorders. Notably, sotorasib exhibited significant signals for neoplasms and hepatobiliary disorders in four algorithms. Specifically, AEs related to neoplasms were predominantly associated with lung malignancies, all of which were consistent with the therapeutic indications of KRAS G12C mutation inhibitor. A total of 19 common AEs were identified in sotorasib and adagrasib, spanning gastrointestinal, general, hepatobiliary, investigations, metabolism, musculoskeletal, neoplasms, and respiratory disorders. 4 severe AEs (SAEs) were identified in sotorasib, with 3 SAEs displaying significant signals in four algorithms, including drug-induced liver injury, pancreatitis, and hepatic failure. In adagrasib, only 2 SAEs were detected, with renal failure showing significant signals in four algorithms.ConclusionThis study offers a comprehensive evaluation of the major safety signals associated with sotorasib and adagrasib, providing valuable information for clinicians regarding drug selection and safety considerations, thereby facilitating the design of future prospective safety studies.

Sonographic Appearance of Hemodialysis Reliable Outflow Graft (HeRO Graft)

HeRO Graft (Hemodialysis Reliable Outflow Graft) consists of 3 components; an arterial graft component, a titanium connector and a venous outflow component. It is implanted under the skin of end-stage renal failure patients as a subcutaneous permanent access. It is a vascular graft that traverses central venous stenosis and has no venous anastomosis, thus providing blood flow from an artery direct into the central venous system. Ultrasound imaging of the 3 components of the HeRO graft is performed and described in this article. Equipment used include Phillips ultrasound machines CX-50, iU22, and EPIQ 7 with linear transducers of frequency 3 to 15 MHz and curvilinear transducers of frequency 1 to 5 MHz. HeRO graft is often the last hemodialysis access available for patients on long-term dialysis who would have typically exhausted all other hemodialysis options like the native arterio-venous fistula (AVF) and arterio-venous graft (AVG). As long-term dialysis patients run out of typical AVF/AVG accesses coupled with the increasing longevity of persons in countries where advanced medical technology is available, subcutaneously implanted grafts such as the HeRO graft may become more commonplace. Description of the sonographic appearance of the various components of the HeRO graft may help sonographers who are not familiar with the graft to image the components.

Preclinical Detection of Early Glomerular Injury in Children with Kidney Diseases—Independently of Usual Markers of Kidney Impairment and Inflammation

Glomerular kidney diseases typically begin insidiously and can progress to end stage kidney failure. Early onset of therapy can slow down disease progression. Early diagnosis is required to ensure such timely therapy. The goal of our study was to evaluate protein biomarkers (BMs) for common nephropathies that have been described for children with Alport syndrome. Nineteen candidate BMs were determined by commercial ELISA in children with congenital anomalies of the kidneys and urogenital tract, inflammatory kidney injury, or diabetes mellitus. It is particularly essential to search for kidney disease BMs in children because they are a crucial target group that likely exhibits early disease stages and in which misleading diseases unrelated to the kidney are rare. Only minor differences in blood between affected individuals and controls were found. However, in urine, several biomarker candidates alone or in combination seemed to be promising indicators of renal injury in early disease stages. The BMs of highest sensitivity and specificity were collagen type XIII, hyaluronan-binding protein 2, and complement C4-binding protein. These proteins are unrelated to inflammation markers or to risk factors for and signs of renal failure. In conclusion, our study evaluated several strong candidates for screening for early stages of kidney diseases and can help to establish early nephroprotective regimens.

Vascular wall microenvironment: Endothelial cells original exosomes mediated melatonin-suppressed vascular calcification and vascular ageing in a m6A methylation dependent manner

Vascular calcification and vascular ageing are “silent” diseases but are highly prevalent in patients with end stage renal failure and type 2 diabetes, as well as in the ageing population. Melatonin (MT) has been shown to induce cardiovascular protection effects. However, the role of MT on vascular calcification and ageing has not been well-identified. In this study, the aortic transcriptional landscape revealed clues for MT related cell-to-cell communication between endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) in vascular calcification and vascular ageing. Furthermore, we elucidated that it was exosomes that participate in the information transportation from ECs to VSMCs. The exosomes secreted from melatonin-treated ECs (MT-ECs-Exos) inhibited calcification and senescence of VSMCs. Mechanistically, miR-302d-5p was highly enriched in MT-ECs-Exos, while depletion of miR-302d-5p blocked the ability of MT-ECs-Exos to suppress VSMC calcification and senescence. Notably, Wnt3 was a bona fide target of miR-302d-5p and modulated VSMC calcification and senescence. Furthermore, we found that maturation of endothelial derived exosomal miR-302d-5p was promoted by WTAP in an N6-methyladenosine (m6A)-dependent manner. Interestingly, MT alleviated vascular calcification and ageing in 5/6-nephrectomy (5/6 NTP) mice, a chronic kidney disease (CKD) induced vascular calcification and vascular ageing mouse model. MT-ECs-Exos was absorbed by VSMCs in vivo and effectively prevented vascular calcification and ageing in 5/6 NTP mice. ECs-derived miR-302d-5p mediated MT induced anti-calcification and anti-ageing effects in 5/6 NTP mice. Our study suggests that MT-ECs-Exos alleviate vascular calcification and ageing through the miR-302d-5p/Wnt3 signaling pathway, dependent on m6A methylation.

Predictive value of perioperative NT-proBNP levels for acute kidney injury in patients with compromised renal function undergoing cardiac surgery: a case control study.

Acute kidney injury (AKI) significantly increases morbidity and mortality following cardiac surgery, especially in patients with pre-existing renal impairments. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a marker of cardiac stress and dysfunction, conditions often exacerbated during cardiac surgery and prevalent in chronic kidney disease (CKD) patients. Elevated NT-proBNP levels can indicate underlying cardiac strain, hemodynamic instability and volume overload. This study evaluated the association between perioperative changes in NT-proBNP levels and the incidence of AKI in this particular patient group. This retrospective study involved patients with impaired renal function (eGFR 15-60ml/min/1.73m²) who underwent cardiac surgery from July to December 2022. It analyzed the association between the ratio of preoperative and ICU admittance post-surgery NT-proBNP levels and the development of AKI and AKI stage 2-3, based on KDIGO criteria, using multivariate logistic regression models. Restricted cubic spline analysis assessed non-linear associations between NT-proBNP and endpoints. Subgroup analysis was performed to assess the heterogeneity of the association between NT-proBNP and endpoints in subgroups. Among the 199 participants, 116 developed postoperative AKI and 16 required renal replacement therapy. Patients with AKI showed significantly higher postoperative NT-proBNP levels compared to those without AKI. Decreased baseline eGFR and increased post/preoperative NT-proBNP ratios were associated with higher AKI risk. Specifically, the highest quantile post/preoperative NT-proBNP ratio indicated an approximately seven-fold increase in AKI risk and a ninefold increase in AKI stage 2-3 risk compared to the lowest quantile. The area under the receiver operating characteristic curve for predicting AKI and AKI stage 2-3 using NT-proBNP were 0.63 and 0.71, respectively, demonstrating moderate accuracy. Subgroup analysis demonstrated that the positive association between endpoints and logarithmic transformed post/preoperative NT-proBNP levels was consistently robust in subgroup analyses stratified by age, sex, surgery, CPB application, hypertension, diabetes status and fluid balance. Perioperative NT-proBNP level changes are predictive of postoperative AKI in patients with pre-existing renal deficiencies undergoing cardiac surgery, aiding in risk assessment and patient management.

A longitudinal assessment of heat exposure and biomarkers of kidney function on heat shock protein 70 and antibodies among agricultural workers.

Exposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by hot temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body's cellular response to a hot environment. This longitudinal study investigated the impact of elevated temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala. We collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest. At the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices, heat index, and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (β: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest. These results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations.

Evaluation the Effectiveness of Nephelium Lappaceum (Nl) Peel Aqueous Extract Against Kidney Dysfunction Induced by Thioacetamide (TAA) in Male Albino Rats

Evaluation the Effectiveness of Nephelium Lappaceum (Nl) Peel Aqueous Extract Against Kidney Dysfunction Induced by Thioacetamide (TAA) in Male Albino Rats

Generalized Propensity Score Methods to Assess CKD-Associated Physiologic Factors and Risk of Kidney Failure in the Chronic Renal Insufficiency Cohort (CRIC) Study.

Epidemiologic studies have identified many biochemical risk factors for chronic kidney disease (CKD) progression that are correlates of kidney function, termed here 'CKD-associated physiologic factors'. Uncertainty remains if these factors are risk factors or risk markers accounting for aspects of kidney function not otherwise captured. We aimed to use flexible machine learning, a dynamic covariate history including kidney function informative markers, and generalized propensity score (GPS) weighting, to better control confounding for such exposures. We studied 3,052 adults with CKD in the Chronic Renal Insufficiency Cohort Study. We established a 2-year run-in period and assembled 90 variables that characterize variability and trends of selected CKD-associated physiologic factors and confounders. Using SuperLearner, we created a GPS for each CKD-associated physiologic factor and performed GPS-weighted Cox regressions. For context, we also evaluated results from traditional multivariable Cox proportional hazards models as in prior studies. Similar to traditional approaches, bicarbonate, calcium, potassium, hemoglobin, and PTH were each associated with risk of kidney failure using GPS weighting. The GPS approach detected non-linear associations in many factors, some of which were not detected with traditional models. We conclude that many associations between CKD-associated physiologic factors and kidney outcomes remain strong after GPS weighting.

Left ventricular outflow tract obstruction in Takotsubo syndrome with cardiogenic shock: prognosis and treatment

BackgroundPatients with Takotsubo syndrome (TTS) who develop cardiogenic shock may present with left ventricular outflow tract obstruction (LVOTO). The prognosis and treatment of this population have not been defined in...

Urolithin A Ameliorates the TGF Beta-Dependent Impairment of Podocytes Exposed to High Glucose

Increased activity of transforming growth factor-beta (TGF-β) is a key factor mediating kidney impairment in diabetes. Glomerular podocytes, the crucial component of the renal filter, are a direct target of TGF-β action, resulting in irreversible cell loss and progression of chronic kidney disease (CKD). Urolithin A (UA) is a member of the family of polyphenol metabolites produced by gut microbiota from ellagitannins and ellagic acid-rich foods. The broad spectrum of biological activities of UA makes it a promising candidate for the treatment of podocyte disorders. In this in vitro study, we investigated whether UA influences the changes exerted in podocytes by TGF-β and high glucose. Following a 7-day incubation in normal (NG, 5.5 mM) or high (HG, 25 mM) glucose, the cells were treated with UA and/or TGF-β1 for 24 h. HG and TGF-β1, each independent and in concert reduced expression of nephrin, increased podocyte motility, and up-regulated expression of b3 integrin and fibronectin. These typical-for-epithelial-to-mesenchymal transition (EMT) effects were inhibited by UA in both HG and NG conditions. UA also reduced the typically elevated HG expression of TGF-β receptors and activation of the TGF-β signal transducer Smad2. Our results indicate that in podocytes cultured in conditions mimicking the diabetic milieu, UA inhibits and reverses changes underlying podocytopenia in diabetic kidneys. Hence, UA should be considered as a potential therapeutic agent in podocytopathies.

Hyperkalemia Management with Intravenous Insulin in Patients with Reduced Kidney Function

Background: Insufficient kidney function increases the risk of hyperkalemia and hypoglycemia, particularly in hemodialysis-dependent patients. Hypoglycemia is a common complication of insulin-based hyperkalemia treatment. This study aims to evaluate the efficacy and safety of hyperkalemia treatment in hemodialysis-dependent and -non-dependent patients and identify risk factors associated with hypoglycemia. Methods: A retrospective observational cohort study was conducted to assess the efficacy and safety of hyperkalemia treatment including patients with reduced kidney function and hyperkalemia treated with intravenous insulin. The decline rate of potassium and glucose levels were compared between hemodialysis-dependent and non-dependent patients. In addition, univariate and multivariable logistic regression analyses were performed to identify risk factors associated with hypoglycemia. Results: A total of 172 patients with hyperkalemia and reduced kidney function were included. The steepest reduction of serum potassium levels happened within the first 6 h after insulin administration, at 1.1 and 0.9 mmol/L for hemodialysis-dependent and non-dependent patients, respectively. The incidence of hypoglycemia was 18%, and no significant difference was found between cohorts. Hemodialysis-dependent patients were more likely to be readmitted within one month with hyperkalemia, while all-cause ICU admission was more likely for non-dependent patients. Older patients, and those who had heart failure or received a second dose of insulin to treat hyperkalemia, were more likely to experience hypoglycemia. Conclusions: Monitoring blood glucose levels following insulin administration is essential given the complexity of patients’ factors associated with hypoglycemia resulting from hyperkalemia treatment in patients with insufficient kidney function.

The novel peptide PEP-Z-2 potentially treats renal fibrosis in vivo and in vitro by regulating TGF-β/Smad/AKT/MAPK signaling

Renal fibrosis is a process in which excessive deposition of extracellular matrix leads to an increase in tissue hardness and gradual destruction of the renal parenchyma. Chronic kidney disease (CKD) commonly progresses to end-stage renal disease (ESRD), ultimately leading to renal failure. This disease has high incidence and mortality rates, but to date, effective treatment options are lacking. PEP-Z-2 is a collagen peptide isolated from redlip croaker scales and may have potential fibroprotective activity. In this study, PEP-Z-2 was found to alleviate unilateral ureteral obstruction (UUO)- and folic acid (FA)-induced kidney injury in a mouse model, reduce collagen deposition in tissues, normalize renal function, reduce the expression of fibrosis markers, reduce reactive oxygen species (ROS) production, and restore the balance of the oxidant/antioxidant system. In vitro experiments also demonstrated that PEP-Z-2 inhibits the TGF-β-induced differentiation of fibroblasts and renal tubular epithelial cells into myofibroblasts and reduces the production of extracellular matrix (ECM) proteins such as fibronectin, Col I, and α-SMA, demonstrating notable therapeutic effects on renal fibrosis. This effect is achieved by regulating the TGF-β/Smad/AKT/MAPK pathway. Our research suggested that PEP-Z-2 is a potential therapeutic drug for renal fibrosis, and peptides from aquatic organisms may constitute a new class of candidate drugs for the treatment of renal fibrosis and even other types of organ fibrosis.