Renal Failure Research Articles

Financial Benefits of Renal Dose-Adjusted Dipeptidyl Peptidase-4 Inhibitors for Patients with Type 2 Diabetes and Chronic Kidney Disease.

Dipeptidyl peptidase-4 (DPP4) inhibitors are frequently prescribed for patients with type 2 diabetes; however, their cost can pose a significant barrier for those with impaired kidney function. This study aimed to estimate the economic benefits of substituting non-renal dose-adjusted (NRDA) DPP4 inhibitors with renal dose-adjusted (RDA) DPP4 inhibitors in patients with both impaired kidney function and type 2 diabetes. This retrospective cohort study was conducted from January 1, 2012 to December 31, 2018, using data obtained from common data models of five medical centers in Korea. Model 1 applied the prescription pattern of participants with preserved kidney function to those with impaired kidney function. In contrast, model 2 replaced all NRDA DPP4 inhibitors with RDA DPP4 inhibitors, adjusting the doses of RDA DPP4 inhibitors based on individual kidney function. The primary outcome was the cost difference between the two models. In total, 67,964,996 prescription records were analyzed. NRDA DPP4 inhibitors were more frequently prescribed to patients with impaired kidney function than in those with preserved kidney function (25.7%, 51.3%, 64.3%, and 71.6% in patients with estimated glomerular filtration rates [eGFRs] of ≥60, <60, <45, and <30 mL/min/1.73 m2, respectively). When model 1 was applied, the cost savings per year were 7.6% for eGFR <60 mL/min/1.73 m2 and 30.4% for eGFR <30 mL/min/1.73 m2. According to model 2, 15.4% to 51.2% per year could be saved depending on kidney impairment severity. Adjusting the doses of RDA DPP4 inhibitors based on individual kidney function could alleviate the economic burden associated with medical expenses.

Mathematical Analysis and Numerical Simulation on Free-Living Leptospira: A Mathematical Modeling Perspective

A bacterial disease called leptospirosis is very typical in both tropical and subtropical regions. It is a well-known animal-borne illness that is brought on by spiral-shaped bacteria (Leptospira spp.). Both directly and indirectly, the disease can spread to humans through the urine of sick animals or polluted water, soil, or food. Two phases might appear in leptospirosis symptoms. The patient will have symptoms such as fever, chills, headache, muscle aches, vomiting, or diarrhea during the first phase, which is known as the Septicemic phase. In the meantime, the Immune phase, the second, is more severe. Meningitis, liver failure, renal failure, or both could be fatal for the patient. This study aimed to create a mathematical model of leptospirosis disease using free-living bacteria. In the model, interactions occur between people, free-living Leptospira, animal hosts, and animal vectors. The population's characteristics are used to build the model, and the actual issue is used to identify the disease's transmission paths. While the endemic equilibrium is investigated numerically, the disease-free equilibrium is analyzed theoretically. The paper demonstrates that for the established mathematical model with an epidemic threshold $R_0$, analytical and numerical solutions produced the same outcome.

Pediatric TAFRO syndrome: A multi-institution case series illustrating clinical challenges and excellent outcomes.

A rare lymphoproliferative disorder involving thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), renal dysfunction (R), and organomegaly (O), called TAFRO syndrome, was first reported in 2010. Considered a variant of idiopathic multicentric Castleman's disease, the recent discovery and rarity of this syndrome pose challenges to diagnosis and management. Herein, we review three pediatric cases, including an infant, that illustrate the heterogeneity of TAFRO syndrome. Despite differences in presentation and treatment responses, all patients experienced excellent outcomes. This multi-institutional case series highlights the need to work toward earlier diagnosis and improved long-term management recommendations for patients with TAFRO syndrome.

Stroke in sickle cell patients, epidemiology, pathophysiology, systemic and surgical treatment options and prevention strategies

AbstractBackgroundA hereditary haemoglobinopathy known as sickle cell disease (SCD) affects over 100 000 people in the United States severely. Cerebrovascular disease is a prominent consequence of SCD. By the age of 30, 53% of patients have silent cerebral infarcts (SCIs) (a stroke that occurs without any obvious symptoms because it damages a small part of the brain that isn't responsible for any essential functions), and by the age of 40, 3.8% have overt strokes.Main bodyThe multidimensional burden of cerebrovascular illness in SCD is reviewed in detail in this article, which includes both clinical strokes and the frequently asymptomatic SCIs. The intricate pathophysiology of SCD and stroke is explored. With SCD, there are currently very few methods for preventing primary and secondary stroke; the most common ones are hydroxyurea and blood transfusion. Nevertheless, not enough research has been done on the possible contributions of anticoagulation and aspirin to strokes linked to SCD. Promising evidence is also highlighted in the study, suggesting that new drugs intended to treat SCD may be able to alleviate leg ulcers and renal impairment in addition to reducing unusually high transcranial Doppler flow velocity – a crucial component of cerebrovascular events. Given that these novel medications specifically target haemolysis and vaso‐occlusion, the two main causes of strokes in this population, more research is desperately needed to determine whether they are effective in avoiding strokes in people with SCD. The literature review also emphasizes how common healthcare inequities are and how they hinder advancements in SCD research and management in the United States.ConclusionTo successfully address these inequities, the evaluation recommends more funding for both SCD management and research, as well as for patient and clinician education. This multimodal viewpoint highlights the intricate terrain of cerebrovascular problems associated with SCD and the urgent need for all‐encompassing and fair strategies to improve patient outcomes and advance research.

Concomitant Wilms tumor and autosomal dominant polycystic kidney disease.

Concomitant Wilms tumor (WT) and autosomal dominant polycystic kidney disease (ADPKD) is exceedingly rare, presenting a diagnostic and technical challenge to pediatric surgical oncologists. The simultaneous workup and management of these disease processes are incompletely described. We performed a retrospective analysis of patients treated at our institution with concomitant diagnoses of WT and ADPKD. We also review the literature on the underlying biology and management principles of these conditions. We present three diverse cases of concomitant unilateral WT and ADPKD who underwent nephrectomy. One patient had preoperative imaging consistent with ADPKD with confirmatory testing postoperatively, one was found to have contralateral renal cysts intraoperatively with confirmatory imaging post nephrectomy, and one was diagnosed in childhood post nephrectomy. All patients are alive at last follow-up, and the patient with longest follow-up has progressed to end-stage kidney failure requiring transplantation and dialysis in adulthood. All patients underwent germline testing and were found to have no cancer predisposition syndrome or pathogenic or likely pathogenic variants for WT. Concomitant inheritance of ADPKD and development of WT are extremely rare, and manifestations of ADPKD may not present until late childhood or adulthood. ADPKD is not a known predisposing condition for WT. When ADPKD diagnosis is made by family history, imaging, and/or genetic testing before WT diagnosis and treatment, the need for extensive preoperative characterization of cystic kidney lesions in children and increased risk of post-nephrectomy kidney failure warrant further discussion of surgical approach and perioperative management strategies.

Relationship Between Complications and Readmissions in Type 2 Diabetes Mellitus Patients in Aceh, Indonesia

Introduction: Complications in diabetes mellitus patients are among the causes of hospital readmissions. Readmissions negatively impact patients’ quality of life and increase health and care costs. This study aims to explore the relationship between complications and readmissions in type 2 diabetes mellitus patients. Methods: A correlational study was utilized with a cross-sectional design. A total of 184 readmission patients with type 2 diabetes mellitus were selected as the sample using the accidental sampling technique. Data were collected through a questionnaire consisting of the Diabetes Early Readmission Risk Indicators (DERRI™) and the Readmission Questionnaire providing 4 answer choices, i.e. ≤ 30 days; &gt; 30–60 days; &gt; 60–90 days; and &gt; 90 days. The Chi-square test was employed for data analysis. Results: Of all respondents, the majority are in late adulthood (50-61 years), totaling 70 individuals (38.0%) with a mean age of 57.3 years; 111 individuals (60.3%) are male; 99 (53.8%) have completed elementary education; 102 (55.4%) work as farmers/laborers/fishermen; and 67 (36.4%) use Humalog as their insulin. Moreover, 69 respondents (37.5%) have experienced the third readmission, which is the highest number of readmissions. The bivariate analysis reveal that there is a significant relationship between complications of type 2 diabetes mellitus and patient readmission (p=0.000). Conclusion: The findings demonstrate complications as a factor associated with readmissions of type 2 diabetes mellitus patients. The complications leading to the readmissions include hypoglycemia, hypertension, heart problems, kidney problems, diabetic ulcers, and strokes. Also, age contributes as a factor increasing the readmission risk of patients with type 2 diabetes mellitus. The results emphasize the need to re-evaluate health service strategies and nursing interventions by providing effective discharge planning to prevent complications or reduce readmissions in type 2 diabetes mellitus patients.

A ecological study of galamsey activities in Ghana and their physiological toxicity

Background: Small-Scale Small-Scale Gold Mining (ASGM), locally known as "galamsey," has emerged as a pervasive issue in Ghana characterized with environmental degradation, land and water resource depletion, health hazards for miners, social and economic impacts. This comprehensive review explores the ecological and health effects of galamsey operations across different regions of the country. Methods: The study employs a systematic analysis method to examine the available literature from 2000 to 2023. Various academic databases, including PubMed, Google Scholar, JSTOR, and relevant government publications, were searched to gather relevant information. Findings: The review reveals that galamsey has had significant ecological consequences, including deforestation, habitat destruction, water pollution, and soil degradation, which have adversely affected Ghana's natural beauty. These environmental challenges pose a threat to local ecosystems and resources, particularly in the Ashanti, Western, and Central regions of Ghana. Moreover, the study highlights the physiological health issues faced by galamsey miners, such as accidents, physical strain, mental strain, kidney problems, respiratory disorders, and metabolic diseases. The presence of elevated levels of mercury, cyanide, arsenic, and cadmium in both the environment and the human body are directly linked to ASGM in Ghana. About seventy percent (70%) of the houses in ASGM community relied on surface water, and all of the homes utilized the fields or bush as their main toilet. Conclusion: Implementing remote sensing, geospatial technologies, promoting clean mining technologies, integrating environmental conservation, occupational safety and public health awareness are key technical and innovative measures to mitigate galamsey in Ghana. Novelty/Originality of this article: This study proposes an integrated approach to address the impacts of galamsey, combining remote sensing and geospatial technologies with public health and environmental conservation programs. The model can provide a comprehensive understanding of the spatial and temporal impacts of ASGM and enable more targeted interventions.

Endovascular Treatment for Renal Vein Embolism by a Renal Calculus After Percutaneous Nephrolithotomy.

This report presents the endovascular strategies adopted to treat a kidney calculus venous embolism after percutaneous nephrolithotomy and the versatility of endovascular techniques to manage even the most unexpected renovascular complications after urological intervention. According to the literature available in PubMed, Cochrane, SciELO, and Science.gov repositories, this is the first case to our knowledge of renal vein calculus embolism as a complication of percutaneous treatment of kidney stones. A 62-year-old woman underwent percutaneous nephrolithotomy to treat a left kidney 2.8-cm staghorn calculi. The stone cracked, leaving a residual fragment in the ureteropelvic junction. Abdominal computed tomography revealed a 0.9-mm extrarenal calculus located inside the left retroaortic renal vein. Calculus was captured using a basket catheter system through a 6F 45-cm sheath positioned in the left common femoral vein (CFV) and accessed by dissection to safely conclude the calculus extraction by venous cut down. The patient was asymptomatically discharged 48 hours after the endovascular procedure, under a rivaroxaban anticoagulation regimen, with no symptoms or renal function impairment until the 6 months of follow-up. The endovascular strategy proposed in this case was effective for calculus rescue and venous flow restoration. This case reinforces the adaptability of endovascular therapy in an unexpected scenario. A potentially life-threatening extremely rare adverse event following a common urological procedure could be treated with minimally invasive hybrid treatment, preserving renal function and maintaining venous vascular patency. This report may add a discussion of procedures to manage similar events and bring to the literature a possible strategy to solve the problem.

Can Apigenin Be an Effective Therapeutic Agent Against Experimental Renal Ischemia-Reperfusion Injury?

Aim: This study aims to reveal the effects of two doses of apigenin (API) against renal ischemia-reperfusion injury (R I/R). Material and Methods: For this purpose, 5 and 10 mg/kg doses of API were preferred in our study, and the groups were designed as sham, R I/R, 5 mg/kg API, and 10 mg/kg API groups for the implementation of the experimental protocol. In the R I/R model, 1-hour ischemia and 24-hour reperfusion periods were preferred. Oxidative and inflammatory markers were measured biochemically in samples taken at the end of the experiment. Results: Biochemical results showed that oxidative and inflammatory markers increased significantly in the R I/R group, but antioxidant activities decreased significantly. In the 5 and 10 mg/kg API groups, R I/R damage was alleviated considerably, with these markers approaching the sham group values. Conclusion: As a result, the study's results determined that two different doses of API were effective against R I/R-induced kidney damage.

Isoliquiritigenin Alleviates Diabetic Kidney Disease via Oxidative Stress and the TLR4/NF-κB/NLRP3 Inflammasome Pathway.

Diabetic kidney disease (DKD) is the primary factor that causes chronic kidney disease and causes increasing mortality and morbidity due to its severe consequences. Isoliquiritigenin (ISL) is the primary element of licorice root that is physiologically active and has antifree radical, antioxidation, and antiapoptotic properties. However, the effect of ISL on DKD is still unclear and needs to be further improved. This study aims to evaluate the renoprotective effects of ISL on diabetes-induced renal injury and explores the underlying mechanisms involved. Male C57BL/6 mice are fed a high-fat diet and then injected with streptozotocin for 2 consecutive days to establish a diabetic model, and high-glucose-treated NRK-52E cells are used to investigate the renoprotective effects of ISL in DKD. The results show that ISL significantly preserves renal function and architecture in DKD. ISL suppresses oxidative stress and reduces ROS levels, inhibiting the activation of the NF-κB and the NLRP3 inflammasome and the occurrence of pyroptosis. Moreover, the study finds that ISL can inhibit the mitochondrial apoptotic pathway. In addition, the study confirms the inhibitory effect of ISL on the TLR4/NF-κB/NLRP3 inflammasome pathway. These observations demonstrate that the natural flavonoid compound ISL can be a promising agent for the treatment of DKD.

A translational model of chronic diabetic nephropathy in the Nile grass rat.

Diabetic nephropathy (DN) is a major healthcare challenge for individuals with diabetes and associated with increased cardiovascular morbidity and mortality. The existing rodent models do not fully represent the complex course of the human disease. Hence, developing a translational model of diabetes that reproduces both the early and the advanced characteristics of DN and faithfully recapitulates the overall human pathology is an unmet need. Here, we introduce the Nile grass rat (NGR) as a novel model of DN and characterize key pathologies underlying DN. NGRs spontaneously developed insulin resistance, reactive hyperinsulinemia, and hyperglycemia. Diabetic NGRs evolved DN and the key histopathological aspects of the human advanced DN, including glomerular hypertrophy, infiltration of mononuclear cells, tubular dilatation, and atrophy. Enlargement of the glomerular tufts and the Bowman's capsule areas accompanied the expansion of the Bowman's space. Glomerular sclerosis, renal arteriolar hyalinosis, Kimmelsteil-Wilson nodular lesions, and protein cast formations in the kidneys of diabetic NGR occurred with DN. Diabetic kidneys displayed interstitial and glomerular fibrosis, key characteristics of late human pathology as well as thickening of the glomerular basement membrane and podocyte effacement. Signs of injury included glomerular lipid accumulation, significantly more apoptotic cells, and expression of KIM-1. Diabetic NGRs became hypertensive, a known risk factor for kidney dysfunction, and showed decreased glomerular filtration rate. Diabetic NGRs recapitulate the breadth of human DN pathology and reproduce the consequences of chronic kidney disease, including injury and loss of function of the kidney. Hence, NGR represents a robust model for studying DN-related complications and provides a new foundation for more detailed mechanistic studies of the genesis of nephropathy, and the development of new therapeutic approaches.

Bardet-Biedl syndrome improved diagnosis criteria and management: Inter European Reference Networks consensus statement and recommendations.

Four European Reference Networks (ERN-EYE, ERKNet, Endo-ERN, ERN-ITHACA) have teamed up to establish a consensus statement and recommendations for Bardet-Biedl syndrome (BBS). BBS is an autosomal recessive ciliopathy with at least 26 genes identified to date. The clinical manifestations are pleiotropic, can be observed in utero and will progress with age. Genetic testing has progressively improved in the last years prompting for a revision of the diagnostic criteria taking into account clinical Primary and Secondary features, as well as positive or negative molecular diagnosis. This consensus statement also emphasizes on initial diagnosis, monitoring and lifelong follow-up, and symptomatic care that can be provided to patients and family members according to the involved care professionals. For paediatricians, developmental anomalies can be at the forefront for diagnosis (such as polydactyly) but can require specific care, such as for associated neuro developmental disorders. For ophthalmology, the early onset retinal degeneration requires ad hoc functional and imaging technologies and specific care for severe visual impairment. For endocrinology, among other manifestations, early onset obesity and its complications has benefited from better evaluation of eating behaviour problems, improved lifestyle programs, and from novel pharmacological therapies. Kidney and urinary track involvements warrants lifespan attention, as chronic kidney failure can occur and early management might improve outcome. This consensus recommends revised diagnostic criteria for BBS that will ensure certainty of diagnosis, giving robust grounds for genetic counselling as well as in the perspective of future trials for innovative therapies.

PENGARUH DZIKIR TERHADAP KECEMASAN DAN KOPING RELIGIUS PASIEN HEMODIALISIS

Chronic Kidney Failure is a progressive and irreversible kidney function disorder where the body is unable to maintain fluid and electrolyte balance, resulting in uremia. In general, cases of chronic kidney failure undergoing hemodialysis are increasing every year, especially in developing countries. The anxiety and decreased coping experienced by patients suffering from chronic kidney failure undergoing hemodialysis is due to a lack of support and enthusiasm from the family, funding for treatment and costs to meet living needs.A literature search was carried out based on articles published between 2018-2023 according to the inclusion and exclusion criteria that had been determined using 1 data base, namely Google Schoolar. This literature search uses the PRISMA guideline in carrying out the screening process. From the search results, 200 articles were obtained. After carrying out the screening process, there were 8 articles that met the criteria and will be analyzed.Based on a study of 8 pieces of literature, it was found that the hemodialysis process affects clients' religious anxiety and coping.From the results of a literature review of 8 journals, it was found that dhikr was able to reduce anxiety levels because the client felt calmer Keywords: Dhikr, anxiety, religious coping

Early Detection and Noninvasive Staging of Kidney Dysfunction by a PEGylated Conventional Fluorophore via GFR-Sensitive Renal Transport.

Noninvasive fluorescence imaging of renal function is a valuable technique for understanding kidney disease progression and the development of renal medicine. This technique requires sensitive imaging probes for reporting renal dysfunction accurately at early stage. Herein, a molecularly engineered imaging probe (800CW-PEG45-COOH) was synthesized by simply PEGylating conventional near-infrared fluorophore IRDye800CW with NH2-PEG45-COOH (molecular weight ∼2100 Da) for early detection and staging of renal dysfunction through noninvasive real-time kidney imaging. 800CW-PEG45-COOH not only cleared through the kidney efficiently (>90% injection dosage at 24 h postinjection) but was also found to be freely filtered by glomeruli without renal tubular reabsorption and secretion. Despite this simple construction strategy, the transport of 800CW-PEG45-COOH within the kidneys was extremely sensitive to the alteration of the glomerular filtration rate (GFR), which enabled it to detect renal dysfunction much earlier than commonly used serum biomarkers and stage kidney function impairments (mild vs severe dysfunction) via imaging-based kidney clearance kinetics. This work not only provides a promising optical imaging probe for the noninvasive evaluation of kidney function but also highlights the utility of PEGylation in enhancing the performance of conventional organic dyes in biomedical applications.

A Novel Formulation of Ketorolac Tromethamine (NTM-001) in Continuous Infusion in Adults with and without Renal Impairment: A Randomized Controlled Pharmacologic Study.

There is a medical need for a safe, effective nonopioid postoperative analgesic for older subjects, including those with mild to moderate renal impairment. Participants (≥ 65years) were stratified by no, mild, or moderate renal impairment defined as creatinine clearance 60-89mL/min for mild and 30-59mL/min for moderate. Subjects were randomized to receive a loading dose of 6.25mg of ketorolac tromethamine drug candidate NTM-001 followed by a 1.75mg/h continuous intravenous (IV) infusion over 24h or an IV bolus injection of ketorolac tromethamine (KETO-BOLUS) of 15mg every 6h. There were four treatment periods of 24h for each subject with a minimum 7-day washout between them. This was a crossover study so subjects served as their own controls. Blood drawn from the subjects was used to plot concentration-time profiles against target profiles. Adverse events were monitored. Thirty-nine subjects enrolled. Concentration-time profiles showed low intersubject variability. Model-predicted curves for those with renal impairment closely matched observed plasma concentrations. Continuous infusion maintained higher mean plasma concentrations than the bolus regimen. No serious or unexpected adverse events were observed. No deaths occurred. NTM-001 was considered safe and well tolerated in this population of participants ≥ 65years, including in those with mild or moderate renal impairment. There were fewer adverse events in the continuous infusion group. The predictable pharmacologic properties and blood concentration levels suggest that continuous IV infusion of ketorolac can be used as an effective postoperative pain reliever in older subjects.

Drug-drug interactions in hospitalized urological patients: a retrospective cohort study.

Exposure to potential drug-drug interactions (pDDIs) can be a notable source of avoidable drug-related harm that requires adequate management to prevent medical errors. We aimed to evaluate pDDIs and associated factors in hospitalized urological patients on admission, during hospitalization, and on discharge. A retrospective cohort study was conducted at the Clinic of Urology of the University Clinical Centre Kragujevac, Serbia. To detect pDDIs we used Lexicomp, which categorizes pDDIs as follows: X (Avoid combination), D (Consider therapy modification), C (Monitor therapy), B (No action needed) and A (No known interaction). Multiple linear regression analysis was used to identify factors associated with the number of pDDIs. More than half of the 220 included patients had at least one pDDI on admission and discharge (57.3% and 63.6%, respectively), whereas 95.0% had at least one pDDI during hospitalization. The total number and number of X, D, C, and B categories of pDDIs were the highest during hospitalization and the lowest on admission. Duration of hospitalization, arrhythmias, dementia, renal failure, cancer, surgery during hospitalization, number of prescribed drugs, and various pharmacological drug classes were risk factors for a higher number of pDDIs, while age, ischemic heart disease, hypertension, and development of infection during hospitalization were protective factors in at least one of the stages. The impact of renal colic depended on the stage and category of pDDI. More than half of the urological patients were exposed to at least one pDDIs at all stages. Medical professionals should regularly screen for pDDIs, particularly in patients with risk factors.

Co-Administration of Amiodarone Increases Bleeding by Affecting Rivaroxaban Pharmacokinetics in Patients with Atrial Fibrillation

This study aimed to investigate the impact of the drug–drug interaction between rivaroxaban and amiodarone on the clinical outcomes in patients with non-valvular atrial fibrillation (NVAF), focusing on pharmacokinetic and pharmacodynamic (PK/PD) aspects. A prospective study enrolling 174 patients with NVAF who were treated with rivaroxaban was conducted. The patients were divided into two groups based on postoperative antiarrhythmic and anticoagulation strategies: the rivaroxaban group (Control group) and the rivaroxaban plus amiodarone group (Riv/Amio group). The trough plasma concentrations (Ctrough) of rivaroxaban, activated partial thromboplastin time (APTT), prothrombin time (PT), and the clinical outcomes between the two groups were compared. Patients receiving 20 mg of rivaroxaban in the Riv/Amio group had a higher concentration of rivaroxaban Ctrough than those in the Control group (p = 0.009). Furthermore, in patients with moderate to severe renal impairment, rivaroxaban Ctrough was significantly increased in the Riv/Amio group. There was no significant difference in PT and APTT between the two groups. Regarding the clinical outcomes, the combination of rivaroxaban and amiodarone medication was associated with a higher incidence of bleeding events (p = 0.041; HR = 2.83, 95% CI 1.05–7.66) and clinically relevant non-major bleeding (p = 0.021; HR = 3.65, 95% CI 1.21–10.94). Finally, independent risk factors for bleeding in NAVF patients treated with rivaroxaban were identified as its combination with amiodarone (p = 0.044; OR = 2.871, 95% CI 1.028–8.023). The combination of rivaroxaban and amiodarone led to changes in rivaroxaban pharmacokinetics and an elevated risk of bleeding events. Therefore, physicians prescribing rivaroxaban medications should assess the potential bleeding risk associated with the concurrent use of amiodarone, particularly in patients with renal impairment.

TEMPI syndrome: difficult to diagnose, "easy" to treat?

TEMPI syndrome is a rare, acquired disorder with multisystemic manifestations. It is classified as a plasma cell disorder and is characterized by telangiectasias, erythrocytosis, monoclonal gammopathy, perinephric fluid collections and intrapulmonary shunt. Even though TEMPI's pathophysiology remains elusive, it responds to anti-myeloma therapy indicating that the monoclonal protein or clone plays a key role. We present a challenging case of a 73-year-old man with erythrocytosis and deteriorating renal function with nephrotic-range proteinuria in whom after extensive work up, the diagnosis of TEMPI syndrome was made. He was received treatment with daratumumab-bortezomib-cyclophosphamide and dexamethasone (Dara-VCD) and achieved a hematological and clinical response. We also report preliminary data on a multiplex assay for cytokines and growth factors for two patients with TEMPI syndrome and note lower levels for non-specific innate immunity related cytokines. A direct link between renal impairment and TEMPI syndrome is not currently established; cytokine deregulation could potentially be involved in the ischemic changes observed in the renal biopsy of our patient.

Catalpol from Rehmannia glutinosa Targets Nrf2/NF-[Formula: see text]B Signaling Pathway to Improve Renal Anemia and Fibrosis.

Rehmannia glutinosa is widely recognized as a prominent medicinal herb employed by practitioners across various generations for the purpose of fortifying kidney yin. Within Rehmannia glutinosa, the compound known as catalpol (CAT) holds significant importance as a bioactive constituent. However, the protective effects of CAT on kidneys, including ameliorative effects on chronic kidney disease - most prominently renal anemia and renal fibrosis - have not been clearly defined. In this study, the kidney injury model of NRK-52E cells and C57BL/6N male mice was prepared by exposure to aristolochic acid I (AA-I), and it was discovered that CAT could ameliorate oxidative stress injury, inflammatory injury, apoptosis, renal anemia, renal fibrosis, and other renal injuries both in vivo and in vitro. Further treatment of NRK-52E cells with Nrf2 inhibitors (ML385) and activators (ML334), as well as NF-[Formula: see text]B inhibitors (PDTC), validated CAT's ability to target Nrf2 activation. Furthermore, the expression of phosphorylated NF-[Formula: see text]B p65, IL-6, and Cleaved-Caspase3 protein was inhibited. CAT also inhibited NF-[Formula: see text]B, and then inhibited the expression of IL-6, p-STAS3, TGF-[Formula: see text]1 protein. Therefore, CAT can regulate Nrf2/NF-[Formula: see text]B signaling pathway, significantly correct renal anemia and renal fibrosis, and is conducive to the preservation of renal structure and function, thus achieving a protective effect on the kidneys.

Emodin inhibits M1 macrophage activation that related to acute and chronic kidney injury through EGFR/MAPK pathway.

Macrophages are the main inflammatory cells involved in kidney injury and play a significant role in the development of acute kidney injury (AKI) and progression of chronic kidney disease (CKD). Emodin is believed to stabilize macrophage homeostasis under pathological conditions. The objective of this study aimed to explore the underlying mechanisms and effects of Emodin on M1 macrophages. Network pharmacology methods were used to predict target proteins associated with renal injury and identify the pathways affected by emodin. RAW264.7 macrophages were induced into M1 polarization using LPS and then treated with emodin at 20, 40, and 80 µM. The effects of emodin on cell viability, cytokines (IL-1β, IL-6, TNF-α), M1 macrophage markers (F4/80 + CD86+), and the EGFR/MAPK pathway were evaluated. Additionally, we transfected RAW264.7 cells with an EGFR shRNA interference lentivirus to assess its effects on RAW264.7 cells function and MAPK pathway. After RAW264.7 cells were passaged to expanded culture and transfected with EGFR-interfering plasmid, macrophages were induced to polarize towards M1 with LPS and then treated with 80 µM emodin. CKD modeling was performed to test how emodin is regulated during CKD. There are 15 common targets between emodin and kidney injury, of which the EGFR/MAPK pathway is the pathway through which emodin affects macrophage function. Emodin significantly reduced the levels of IL-6, IL-1β and TNF-α (p < 0.05) and the ratio of M1 macrophage surface markers F4/80 + CD86+ (p < 0.01) in the supernatant of RAW264.7 cells in a dose-dependent manner. Furthermore, the inhibitory effect of emodin on RAW264.7 cells was achieved by interfering with the EGFR/MAPK pathway. Moreover, emodin also affected the mRNA and protein expression of EGFR and Ras, leading to a decrease in the rate of M1 macrophages, thus inhibiting the pro-inflammatory effect of M1 macrophages. The addition of emodin reduced the rate of M1 macrophages in CKD and inhibited the further polarization of M1 macrophages, thus maintaining the pro-inflammatory and anti-inflammatory homeostasis in CKD, and these effects were achieved by emodin through the control of the EGRF/ERK pathway. Emodin attenuates M1 macrophage polarization and pro-inflammatory responses via the EGFR/MAPK signalling pathway. And the addition of emodin maintains pro- and anti-inflammatory homeostasis, which is important for maintaining organ function and tissue repair.