Cause Of Chronic Renal Failure Research Articles

#1440 Analysis of risk factors for the development of coronary events in patients with chronic kidney disease stage 5

Abstract Background and Aims To analyze the number and presence of certain risk factors for the development of coronary events in patients with chronic kidney disease receiving program hemodialysis. Method To achieve this goal, we first conducted an information search in electronic databases of articles: in English - in PubMed, the search depth was from 2010 to 2020, after which we selected the most common risk factors for the development of coronary events in the conditions of Uzbekistan (Table 1). The study and recruitment of patients took place in the department of nephrology and hemodialysis of the Republican Specialized Scientific and Practical Medical Center for Nephrology and Kidney Transplantation in 2023. The study involved 73 (42.95%) men and 97 (57.05%) women; the average age of the patients was 54.00 ± 13.72 years. The main causes of chronic renal failure in the structure of the overall morbidity of the prospective study were: diabetic nephropathy - 41% (69), chronic glomerulonephritis - 40% (68), chronic pyelonephritis - 12.9% (22). Results All 170 patients were assessed for risk factors for the development of coronary events according to Table 1. Based on the current literature, we selected 30 risk factors for the development of coronary events. The most common risk factors for the development of coronary events were, that is, 2/3: albumin, body mass index, calcium, cardiovascular diseases, clinical and ambulatory blood pressure, chronic heart failure, diastolic blood pressure, hemoglobin, left ventricular hypertrophy, mean arterial pressure, systolic blood pressure, diuretic (urea), years with hypertension. The least significant risk factors for the development of coronary events were, that is, 1/3: diabetes, diabetic nephropathy, dyslipidemia, coronary heart disease, left ventricular end-diastolic volume, metabolic syndrome, parathyroid hormone, peripheral vascular disease, phosphorus, potassium, pulse pressure, sodium (in plasma), sodium-potassium ratio, smoking, total cholesterol. Conclusion In 2/3 of the studied patients of the main group, the presence of 15 risk factors for the development of coronary events was noted, in 1/3 of the patients, 21 risk factors for the development of coronary events were identified. The above risk factors together increase the incidence of coronary events in patients with stage 5 CKD several times. Coronary events are the leading causes of death in all groups. The most common were: acute left ventricular failure and sudden cardiac death. And predictors of the risk factor for death for coronary events include: blood albumin levels, BMI, blood hemoglobin, LVH, SBP, DAS, CHF, blood calcium, years since hypertension.

Macrohematuria in children and adolescents

Hematuria is usually only noticed early in the case of macrohematuria. In around half of affected children, macrohematuria is caused by aurinary tract infection. In all other cases, acareful diagnosis is required. In addition to adetailed medical history, this builds upon aprecise examination of the urine (microscopy, quantitative determination of proteinuria [mgalbumin/gcreatinine in spontaneously voided urine]) and measurement of blood pressure. The work-up usually includes sonography as the primary imaging modality. Invasive diagnostic tests using cystoscopy are only necessary in exceptional cases. If there is evidence of glomerulonephritis, akidney biopsy may be indicated. Careful attention should be given to persisting microhematuria (> 6months) and Alport syndrome should be confirmed or ruled out. Heterozygotic Alport syndrome can also be apossible cause of chronic renal failure.

Efficacy of prednisone combined with mycophenolate mofetil for immunoglobulin A nephropathy with moderate-to-severe renal dysfunction.

Immunoglobulin A nephropathy (IgAN) is a common form of chronic glomerulonephritis. Currently, IgAN is one of the main causes of chronic renal failure in China; its prognosis varies greatly between patients, with renal function at the time of diagnosis and prognosis being strongly correlated. Mycophenolate mofetil (MMF) is a drug with a good immunomodulatory effect and is commonly used clinically. However, its effects in IgAN have not yet been clearly demonstrated. Therefore, herein, we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment. To evaluate the effectiveness and safety of prednisone and MMF in treating IgAN with moderate-to-severe renal dysfunction. Between January 2011 and December 2020, 200 patients with moderate-to-severe IgAN were included in this study, all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University. All patients underwent a renal puncture biopsy, which revealed primary IgAN with a glomerular filtration rate (GFR) of 30-60 mL/min. The patients were divided into a glucocorticoid therapy group (GTG) and an immunosuppressive therapy group (ITG) according to the different treatment regimens, with 100 patients in each group. Based on general treatments, such as angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers, patients in the GTG were administered prednisone 0.5-0.8 mg/ (kg·d-1) for 4-8 wk, which was reduced by 5 mg every two weeks until the maintenance(30 mg/d) dose was reached and maintained for 12 mo. In the ITG, MMF was administered at 1.0 g/d for 6-12 mo, followed by a maintenance dosage of 0.5 g/d for 12 mo. Age, sex, blood pressure, 24-h urinary egg white measurement, serum creatinine (Scr), blood uric acid, blood albumin, blood potassium (K), hemoglobin, GFR, alanine aminotransferase, total cholesterol (T-CHO), fasting blood glucose, and body mass index were recorded. The 24-h urinary protein, Scr, and GFR levels were recorded 3, 6, 9, and 12 mo after treatment. Follow-up data were also collected. No discernible differences existed between the two groups in terms of age, sex, blood pressure, creatinine, 24-h urinary protein level, GFR, or other biochemical indicators at the time of enrollment. Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function. Nine months after treatment, the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG. By the 12th month of treatment, the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month. In addition, the overall response rate in the ITG was significantly higher than that in the GTG. The occurrence of side effects did not vary significantly between the two regimens; however, endpoint events were significantly more common in the GTG than in the ITG. The follow-up time for the GTG was noticeably lower than that for the ITG. Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.

Kidney Intrinsic Mechanisms as Novel Targets in Renovascular Hypertension.

Almost a hundred years have passed since obstruction of the renal artery has been recognized to raise blood pressure. By now chronic renovascular disease (RVD) due to renal artery stenosis is recognized as a major source of renovascular hypertension and renal disease. In some patients, RVD unaccompanied by noteworthy renal dysfunction or blood pressure elevation may be incidentally identified during peripheral angiography. Nevertheless, in others, RVD might present as a progressive disease associated with diffuse atherosclerosis, leading to loss of renal function, renovascular hypertension, hemodynamic compromise, and a magnified risk for cardiovascular morbidity and mortality. Atherosclerotic RVD leads to renal atrophy, inflammation, and hypoxia but represents a potentially treatable cause of chronic renal failure because until severe fibrosis sets in the ischemic kidney, it retains a robust potential for vascular and tubular regeneration. This remarkable recovery capacity of the kidney begs for early diagnosis and treatment. However, accumulating evidence from both animal studies and randomized clinical trials has convincingly established the inadequate efficacy of renal artery revascularization to fully restore renal function or blood pressure control and has illuminated the potential of therapies targeted to the ischemic renal parenchyma to instigate renal regeneration. Some of the injurious mechanisms identified as potential therapeutic targets included oxidative stress, microvascular disease, inflammation, mitochondrial injury, and cellular senescence. This review recapitulates the intrinsic mechanisms that orchestrate renal damage and recovery in RVD and can be harnessed to introduce remedial opportunities.

Renal Failure, Types, Causes and Etiology: A Review Article

Renal failure is the most important disease that causes losing in the efficiency of kidney and is renal failure or may called end stage kidney disease where capacity for kidney become 15% less than the normal levels .This disease can be classified into two types : first (acute kidney failure ) which may resolve and it rapidly developed .Second (chronic kidney failure) : it slowly developed and may become a permanent condition Symptoms of Renal failure include vomiting; swelling in the legs; a loss of appetite; confusion and tiredness. Several complications occurred which include high blood potassium ; volume overload and uremia in acute condition while high blood pressure; anemia and heart disease in the chronic condition. There are several factors that may lead to the progress of acute renal failure conditions such as hypotension, a blockage of the urinary tract, hemolytic uremic syndrome and some medications.While diabetes ,hypertension, polycystic renal disease and nephrotic syndrome represent the major causes of chronic renal failure . Signs that help in identification of acute and chronic renal failure based on mishmash of several factors and help in distinguish between its types such as increasing of creatinine levels and decreasing of urine production are the signs of acute failure while decrease the rate of glomerular filtration to below of 15 or therapy with renal replacement are the signs of chronic renal failure. Acute failure can be treated depending on the main causes , on the other hand may use dialysis (hemodialysis or peritoneal dialysis) or kidney transplant in order treating chronic failure.

Research progress in the pathogenesis and treatment of diabetic nephropathy

Diabetic nephropathy (DN) is one of the most common, frequent, age-related diseases, and it is also an important cause of chronic renal failure and end-stage renal diseases. It has always been one of the research hotspots. The high cost of treatment will bring a great burden to society and families. Therefore, it is very important to study the pathogenesis and treatment methods of DN. At present, many methods have been put forward for clinical diagnosis and treatment like Thiazolidinediones, renin inhibitor drug -aliskiren, tregs cells. These methods have their own advantages and disadvantages. However, the etiology of diabetic nephropathy is complicated and the course of the disease is long, and current treatments cannot achieve the expected target. Scholars also have studied many symptomatic treatment methods for different pathogenesis. However, the specific pathogenesis of DN has not yet been fully elucidated, and there is no special medicine for DN yet. This article briefly reviews the pathogenesis and treatments of DN based on the existing kinds of literature and new advances to provide some references for its clinical diagnosis and treatment.

Risk factors associated with the development of secondary hyperparathyroidism in dialysis patients.

Aim To determine risk factors associated with the development and severity of secondary hyperparathyroidism in dialysis patients. Methods A cross-sectional study at the Clinical Centre of the University of Tuzla (March 2022) included 104 adult patients (males 51.9%, females 48.1%) with chronic kidney diseases under dialysis treatment. Based on parathyroid hormone (PTH) values, patients were divided into two groups: study group (45/104, PTH >792pg/mL) and control group (59/104, PTH 176-792 pg/ mL). The analysis aimed to resolve whether there was a connection between the duration of dialysis, the type of therapy treatment administered, the underlying kidney disease, and the presence of comorbidities with the values of PTH, and a wide spectrum of monitored laboratory parameters. Results The most common causes of chronic renal failure were undefined kidney diseases (32.7%), followed by diabetic nephropathy (18.3%) and chronic glomerulonephritis (16.3%). In the examined biochemical parameters, a significant difference was found in mean values of alkaline phosphatase (p<0.001). The correlation was proved between the duration of dialysis (p=0.028), the values of phosphorus (p=0.031), and alkaline phosphatase (p<0.001) with absolute values of PTH. The most common present comorbidity was hypertension (78.8%), followed by cardiovascular diseases (40.4%) and diabetes (22.1%). Conclusion A number of factors contribute to the development and severity of SHPT. Modulation of therapy and better control of risk parameters can prolong and reduce the frequency of SHPT in dialysis patients, as well as the occurrence of comorbidities.

Effects of modified Huangqi Chifeng decoction on the IL-17 signaling pathway in an IgA nephropathy rat model.

Immunoglobulin A nephropathy (IgAN) is an immune-related primary glomerular disease prevalent worldwide, with complicated clinical manifestations and an unclear pathogenesis. IgAN is the main cause of chronic renal failure and places a significant burden on patients and society. The modified Huangqi Chifeng decoction (MHCD) is an effective prescription for the clinical treatment of IgAN while its specific mechanism remains to be further elucidated. Based on the findings of previous network pharmacology-related method-based studies, this study aimed to further explore the mechanism of action of MHCD for IgAN treatment. IgAN rat model was established by bovine serum protein+carbon tetrachloride+lipopolysaccharide. After successful modeling, the rats in the original model group were divided into 5 group: model group, telmisartan group, and MHCD high-, medium- and low-dose groups by random number table (n=10 respectively). The corresponding drugs were applied for 8 weeks, and the experiment lasted for 21 weeks. At the end of the experiment, 24h urine protein quantification, serum biochemistry and IL-6 and IL-17A levels were measured. The pathological changes of kidney were observed by light microscope, immunofluorescence microscope and the changes of glomerular ultrastructure were observed by transmission electron microscope. The expression levels of IL-17 signaling pathway related proteins (HSP90, MMP9, NF-κB P65 and p-NF-κB P65) were detected by Western Blot and immunohistochemistry. Telmisartan and MHCD treatment can reduce the 24h urinary protein level and improved blood stasis states of IgAN rats, alleviate the renal pathological injury, decrease the serum levels of IL-6, IL-17A and the expression levels of HSP90, MMP9 and p-NF-κB P65 related proteins in IL-17 signaling pathway. MHCD can down-regulate the expression of IL-17 signaling pathway-related factors in IgAN model rats, improve the state of blood stasis, and alleviate the pathological damage of kidney in rats.

Evaluation of serum Chemerin level in non-diabetic, Hemodialized patients

Background: Chronic Renal Failure (CRF) or chronic kidney disease (CKD) is the state which resultsfrom a permanent and usually progressive reduction in renal function and leads to many complicationsover a period of time. The most common complications include cardiovascular, cerebrovascular andperipheral vascular diseases. Most common causes of CRF are diabetes mellitus (diabetic nephropathy)and hypertention. Adipose tissue is now considered as an active endocrine gland secretes manymetabolically active adipocytokines such as chemerin, visfatin, resistin and others that have importantroles in complications and progression of metabolic diseases such as diabetes mellitus and other diseaseslike CRF and cardiovascular diseases (CVD). Aim: The aim of this study was to evaluate serum chemerinlevel and other biochemical and clinical markers in non-diabetic hemodialized patients, to determine therisk of CVD in non diabetic hemodialyzed patients. Materials and methods: This study was conductedfor a sample composed of 50 patients with end stage renal disease (ESRD) or on hemodialysis (HD) and acontrol group consists of 50 apparently normal healthy subjects. Estimation of serum chemerin level byELIZA, lipid profile, Blood urea, serum creatinine, serum albumin, serum electrolytes, serum uric acidand serum malondialdehyde (MDA) were done for both patients and control. Body mass index (BMI) andglomerular filtration rate (GFR) were calculated for both patients and control. Atherogenic index, CADrisk %, were also calculated for both HD patients and control. Results: The results of this study showedthat the level of serum chemerin was significantly increased in CKD patients on hemodialysis comparedto control. Blood urea, creatinine , TG, T-C, LDL-C,VLDL-C, MDA, uric acid, K+, BMI and atherogenicindex of plasma (AIP) levels were significantly increased in diabetic nephropathy patients compared tocontrol, while, HDL-C, CAD risk %, Na+, Ca+2, PCV%, Hb and albumin levels were significantlydecreased in ESRD patients compared to control. There was a non- significant difference of bloodglucose for HD patients and control.

Identification of transcription factors related to diabetic tubulointerstitial injury

BackgroundDiabetic nephropathy (DN) is a main cause of chronic renal failure. Despite decades of extensive study, the molecular mechanisms underlying diabetic tubulointerstitial injury remain unclear. We aim to identify key transcription factor genes involved in diabetic tubulointerstitial injury.MethodsA microarray dataset (GSE30122) from Gene Expression Omnibus (GEO) was downloaded. A total of 38 transcription factor genes based on 166 differentially expressed genes (DEGs) were identified by UCSC_TFBS.ResultsThe regulatory network showed connections between the top 10 transcription factors and their target DEGs. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of targeted DEGs indicated that extracellular space, extracellular exosome, cell surface and complement and coagulation cascades were most significantly enriched. Utilizing Nephroseq v5 online platform, the mRNA expression pattern analysis of transcription factor genes demonstrated that mRNA expression of CDC5, CEBPA, FAC1, HFH1, IRF1, NFE2 and TGIF1 increased in renal tubulointerstitium of DN patients compared with normal controls while that of CEBPB and FOXO4 decreased in renal tubulointerstitium of DN patients compared with normal controls. Correlation analysis between mRNA expression of transcription factor genes in renal tubulointerstitium and clinical features showed that AP1, BACH1, CDC5, FAC1, FOXD1, FOXJ2, FOXO1, FOXO4, HFH1, IRF1, POU3F2, SOX5, SOX9, RSRFC4, S8 and TGIF1 may be related to diabetic tubulointerstitial injury.Conclusions(1) CDC5, FAC1, FOXO4, HFH1, IRF1 and TGIF1 may be key transcription factor genes. (2)Transcription factors involved in diabetic tubulointerstitial injury may become prospective targets for diagnosis and treatment of DN.

Hubungan Hipertensi dengan Kejadian Gagal Ginjal Kronik di RSUD DR. Djasamen Saragih Kota Pematang Siantar Tahun 2020

Background: Chronic renal failure (CRF) had became a concern because of the increasing globally for incidence, prevalence, and mortality and hypertension was one of the main causes of CRF. magnitude of the risk of hypertension with chronic renal failure. This study aims to assess the magnitude of the risk of hypertension with chronic kidney failure at Dr. Djasamen Saragih City of Pematang Siantar.Methods: This research was an analytic observational study with a case control design. The research subjects were 260 kidney failure patients who were treated at RSUD Dr. Djasamen Saragih Kota Pematang Siantar with as many as 52 cases of patients diagnosed with chronic kidney failure by doctors who can be seen from medical records. As many as 208 hospital controls were patients without CRF (gastritis, gastroenteritis, hernia, and trauma or minor infections). The inclusion criteria of the study subjects were ≥ 18 years of age and had completed medical record data. The exclusion criteria for study subjects were if they had a history of kidney transplantation or a history of kidney transplantation and patients with incomplete medical records.Results: the results of the analysis of bivariate hypertension variables, patients aged &gt; 45 years, patients with diabetes, patients with anemia, patients with gout, and patients with a history of kidney stones showed a relationship with the incidence of kidney failure. The multivariate results showed that the incidence of hypertension in patients with chronic renal failure was 5.52 times higher than those without chronic renal failure with an OR of 5.52 (95% CI: 2.10-14.53).Conclusion: Hypertension has a relationship with the incidence of chronic renal failure with an OR value of 5,52 (95% CI: 2.10-14.53).

Transgelin-2 as an Early Detection for Diabetic Nephropathy Through Inflammation, Periostin and E-cadherin by STAT3 Signaling Through ANXA2.

Diabetic nephropathy (hereinafter referred to as DN) is one of the important causes of chronic renal failure, with great harm. We aimed to elucidate the role of transgelin-2, a key early detection for diabetic ne-phropathy. The serum samples of 12 DN patients and 12 normal volunteers were collected for this experiment. Mice of the model group were injected intraperitoneally with streptozotocin following a high fat diet. Mouse podocyte (MPC5) cells were induced with 20 mmol/L d-glucose. Transgelin-2 was highly expressed in DN patients with diabetic nephropathy both at the expression levels of mRNA and protein. Transgelin-2 expression was correlated with blood sugar in patients with DN. Transgelin-2 gene up-regulation enhanced inflammation and periostin levels, and reduced E-cadherin activity level in mice with DN. Over-expression of transgelin-2 increased inflammation and periostin levels, and reduced E-cadherin activity level in the in vitro model. Down-regulation of Transgelin-2 reduced inflammation and periostin levels and induced E-cadherin activity level in the in vitro model. Transgelin-2 induced ANXA2/ STAT3 signaling in a mouse model or an in vitro model. ANXA2 was one of the regulatory factors for the effects of transgelin-2 with inflammation, periostin, and E-cadherin in a model of DN. Taken together, these findings demonstrated that transgelin-2 promoted inflammation and periostin levels, and suppressed E-cadherin levels in DN by STAT3 signaling through ANXA2.

Effect of crocin and losartan on biochemical parameters and genes expression of FRMD3 and BMP7 in diabetic rats.

Diabetes is a multifactorial and growing disease, one of the severe complications of which is diabetic nephropathy (DN), which is the most common cause of chronic renal failure. FERM domain containing 3 (FRMD3) is responsible for maintaining the shape and integrity of nephron cells, and bone morphogenetic protein 7 (BMP7) helps maintain function and reduce kidney damage. This study aimed to evaluate the effect of crocin and losartan on biochemical parameters and the expression of FRMD3 and BMP7 genes in streptozotocin (STZ)-induced diabetic rats. Forty male Wistar rats were randomly divided into five experimental groups as healthy, diabetic control (D), crocin, losartan, and diabetic rats treated with losartan-crocin (n = 8). A single dose of STZ (50 mg/kg intraperitoneally injection) was used to induce diabetes. Four weeks after induction of diabetes, rats received crocin (50 mg/kg) and losartan (25 mg/kg) daily for four weeks orally. Rats were sacrificed at the end of the intervention, and blood samples were taken to determine serum levels of glucose, urea, creatinine (Cr), malondialdehyde (MDA), and thiol. Real-time polymerase chain reaction (PCR) was used to assess the expression of the FRMD3 and BMP7 genes in the kidney samples. Diabetes induction increased serum levels of glucose, Cr, urea, MDA, and thiol, but decreased BMP7 and FRMD3 genes expression. Treatment with crocin and losartan decreased these biochemical parameters and increased the expression of the BMP7 and FRMD3 genes. Crocin may be a promising therapeutic agent for preventing and improving diabetes-related kidney disease due to its antidiabetic and antioxidant properties.

Role of vitamin D in diabetic nephropathy

Diabetic nephropathy (DN) or Diabetic kidney disease (DKD) is one of the major microvascular complications of diabetes mellitus (DM). DN is observed in approximately 20–40% of diabetic patients. DN is also an important risk factor for DM patient’s death. Nowadays, DN has become the leading cause of chronic renal failure (CRF) in most countries without effective therapeutic methods. Recently, the renoprotective effects mediated by vitamin D have been evidenced. Currently available evidence showed that vitamin D is effective in reducing proteinuria in DN patients. A recent meta-analysis demonstrated the therapeutic effect of vitamin D, on urinary albumin excretion, in DN patients. This review summarized the multiple roles of vitamin D in mechanism of renopretective effect of vitamin D to explore much more and effective therapeutic methods for DN.

Chronic Renal Failure in Hemodialysis Patients

Objective: This study was a retrospective cross-sectional examination. Methods: The study enrolled 301 patients in 2018 who were referred to dialysis clinic. Data is collected through a series of questions about demographics (gender, age, education, employment, housing, marital status) and a checklist for causes of chronic renal failure (hypertension, diabetes, kidney disease, etc.). The Chi-square test, Fisher's exact test, analysis of variance (ANOVA), and SPSS version 24 were utilized to carry out inferential statistics. Results: Patients on hemodialysis typically develop chronic renal failure due to high blood pressure, although kidney disease and diabetes also play a role. Among the many potential factors that led to ESRD in these patients, the most common were: other/unspecified causes (15.3%), surgical history (6.3%), anemia (5%), trauma (4.3%), shock (7.7%) (2%), viral diseases (2%), drug use and congenital causes (1.3%), and poisoning during pregnancy and lupus (0.3%). Conclusions: According to the results of this study, promoting screening procedures for patients who are at risk may help to lower the prevalence of end-stage renal failure.

Factors associated with the progression of mesangial lesions in IgA nephropathy: A comparative analysis of renal re-biopsies.

IgA nephropathy (IgAN) is the most common primary glomerular disease, and is the leading cause of chronic renal failure. Because mesangial lesions are the main pathological changes seen in IgAN, we investigated factors associated with the progression of mesangial lesions in IgAN. We enrolled participants with IgAN who underwent repeat renal biopsies. Based on the progression of mesangial proliferative lesions, the participants were divided into progressive and stable groups. The progression group included participants with a ratio of mesangial cell proliferation score ≥ 1.1 (i.e., proliferation of > 10%) in the second biopsy specimen compared to the first biopsy specimen. The stable group included participants who did not fulfill the aforementioned criteria. We recorded the laboratory parameters, expression of renin-angiotensin system (RAS) receptors (angiotensin II type 1 receptor [AT1R], angiotensin II type 2 receptor [AT2R], Mas receptor [MasR], and the Mas-related G protein-coupled receptor, member D [MrgD]) and mesangial matrix proteins (collagen [Col] IV, fibronectin [FN] and laminin) at the first and second renal biopsies, and the use of immunosuppressive therapy and/or RAS blockers after the first biopsy. We enrolled 24 patients with IgAN who underwent repeat renal biopsies. Half of patients showed progression of mesangial lesions on repeat renal biopsy after a median of 4.3 (1-6) years. The progression group had significantly higher expression levels of AT1R and mesangial matrix proteins (Col IV and FN), and significantly lower expression of AT2R and MasR, compared to the stable group. Multivariate analysis showed that the use of RAS blockers (hazard ratio [HR], 0.27; 95% CI, 0.08-0.97; p < 0.05) and the level of proteinuria (HR, 1.8; 95% CI, 1.04-3.12; p < 0.05) were associated with progression of mesangial lesions. Additionally, the progression group exhibited a more rapid decline of renal function compared to the stable group (0.38 and 0.012 ml/min/1.73 m2/month, respectively; p = 0.004). Continuous activation of the intrarenal RAS and massive proteinuria correlate with histological progression of mesangial lesions in IgAN patients, which may further accelerate the deterioration of renal function.

Network Pharmacology and Molecular Docking Analysis to Explore the Mechanism of Huaiqihuang-Mediated Alleviation of Henoch-Schönlein Purpura Nephritis.

Henoch-Schönlein purpura nephritis (HSPN) is considered a major cause of chronic renal failure and is the most common secondary glomerular disease in children. Huaiqihuang (HQH), a traditional Chinese herbal formula, exhibits therapeutic effects against HSPN in clinical practice. However, the potential molecular targets and mechanisms underlying HSPN treatment remain unclear. By constructing a protein-protein interaction (PPI) network, core targets related to HQH and HSPN were identified. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathways were analyzed to identify the main pathways related to HSPN based on the core targets. To screen the main active ingredients of HQH against HSPN, an ingredient-target-pathway network was constructed using the top 10 main pathways associated with HSPN. Then, molecular docking was performed to explore the interactions and binding patterns between molecules and proteins. Clinical data showed that HQH combined with conventional medicine significantly reduced 24-hour urine protein excretion, urine microalbumin levels, and erythrocyte counts in the urine sediment of HSPN patients. By constructing PPI models, 15 potential core targets were identified. The top 10 main pathways showed higher enrichment ratios, including the cytokine-cytokine receptor interaction and signaling pathways related to NOD-like receptor, IL-17, etc. Through the ingredient-target-pathway network and molecular docking, we revealed that five active ingredients of HQH had good affinities with three core targets, AKT1, MMP9, and SERPINE1, which may be vital in treating HSPN. The study preliminarily explored the active ingredients, targets, and pathways involved in HQH therapy for HSPN. The mechanism of HQH therapy may be attributed to the modulation of inflammatory response, immune response, and oxidative stress. Combined with clinical data, our results indicate that HQH is highly effective in treating HSPN.

Relationship of proliferative diabetic retinopathy and severe stages of chronic renal failure

Diabetic nephropathy, as a frequent complication in patients with diabetes mellitus (DM), is increasing due to the rapid increase in the prevalence of diabetes, which is considered one of the leading causes of chronic renal failure (CRF). Diabetic retinopathy (DR) and diabetic nephropathy are the two main microvascular complications of DM. Studies show that the prevalence and severity of visual pathology is significantly higher among patients with severe stages of CRF, which is associated with the following risk factors: hypertension, metabolic disorders, uremia, anemia, and the use of anticoagulant therapy. The leading forms of eye pathology in patients with DR and CRF are proliferative DR, macular edema, and vitreous hemorrhage. The main structural changes in the choroid and retina in patients with CRF are the thickness of the choroid, accompanied by a decrease in the density of vessels and the volume of perfusion in the surface capillary layer of the choriocapillaries, which is aggravated with the aggravation of the stage of the disease and is interconnected with impaired renal function. Literature data indicate a positive effect of the hemodialysis procedure on DR. It should be borne in mind that in patients with end-stage chronic renal failure, a hemodialysis session may be accompanied by pain in the eye associated with an increase in blood pressure. Interdisciplinary collaboration between nephrologists and ophthalmologists will ensure improved and adequate treatment of patients with CRF and proliferative DR.

1,2,3,4,6‑penta‑O‑galloyl‑β‑D‑glucose alleviates inflammation and oxidative stress in diabetic nephropathy rats through MAPK/NF‑κB and ERK/Nrf2/HO‑1 signaling pathways.

Diabetic nephropathy (DN) is one of the main causes of chronic renal failure, which is also the final cause of mortality in ~30% of diabetic patients. 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose (PGG) from Galla rhois has anti-inflammation, anti-oxidation and angiogenesis effects. The present study aimed to explore the protective effects on diabetic nephropathy rats by alleviating inflammation and oxidative stress and the underlying mechanism. High-fat diet/STZ induced rats and high glucose (HG) induced podocytes (MPC5) were used to simulate the DN in vivo and in vitro. The blood glucose level was measured using a blood glucose meter and renal function was determined by an automatic biochemical analyzer. The pathological changes and renal fibrosis were observed through hematoxylin and eosin, periodic acid-Schiff and Masson staining. The expression of nephrin in tissues, fibrosis-related proteins in tissues, MAPK/NF-κB and ERK/nuclear factor erythroid-derived 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) signaling pathway related proteins in tissues and apoptosis related proteins in tissues and podocytes was detected by western blotting. The inflammatory response and oxidative stress in tissues and podocytes were determined by respective commercial kits and apoptosis in tissues and podocytes was detected by TUNEL assay. The viability of podocytes treated with PGG with or without HG was analyzed by CCK-8 assay. As a result, the blood glucose level, urinary albumin/creatinine ratio, blood urea nitrogen and serum creatinine in blood were all increased and nephrin expression was decreased. The pathological changes and renal fibrosis were aggravated and the inflammation, oxidative stress and apoptosis in renal tissues were enhanced. The above effects were reversed by PGG treatment dose-dependently. MAPK/NF-κB and ERK/Nrf2/HO-1 signaling pathways were activated in DN rats and were suppressed by PGG treatment. The reduced viability and increased apoptosis, inflammation and oxidative stress in MPC5 cells were shown in HG induction, which was reversed by PGG treatment. However, P79350 (p38 agonist) and LM22B-10 (ERK1/2 agonist) weakened the effect of PGG. In conclusion, PGG protects against DN kidney injury by alleviating inflammation and oxidative stress by suppressing the MAPK/NF-κB and ERK/Nrf2/HO-1 signaling pathways.

Changes in Expression of the Connective Tissue Growth Factor in the Kidneys of Diabetic Rats During Aging

Background: Diabetic nephropathy (DN) is the most common cause of chronic renal failure in the world. There appears to be different pathogenetic, hemodynamic and metabolic processes leading to the pathologic mechanisms in DN. We studied the expression of connective tissue growth factor (CTGF) in the kidneys of diabetic rats over time.Methods: Male Sprague-Dawley rats were injected with 55mg/kg streptozotocin (STZ) (diabetes mellitus (DM) group) or with citrate buffer (control group). The rat kidneys were harvested 2 weeks, 2 months, 6 months and 12 months following the STZ challenge, and sectioned into three different kidney structures: glomeruli, proximal convoluted tubule (PCT) and distal convoluted tubule (DCT). Sections were immunohistochemically stained to monitor the expression of CTGF. Results:Significant differences in CTGF expression were observed 2 weeks and 2 months after the STZ challenge, with higher CTGF expression in diabetic rats. Two weeks post DM onset, high CTGF expression was demonstrated in the distal tubules of the diabetic rats. The expression of CTGF in the glomeruli of diabetic rats washighest 12 months after diabetes induction, with a complete absence of CTGF expression in the control groups throughout the study.Conclusions:The major change in expression of CTGF occurs within the first 2 months of DM, particularly in the DTC, implying an early onset of pathophysiological changes in diabetic kidneys, which would normally occur with aging. These findings help to contribute to our understanding of changes associated with DN and guide towards potentially appropriate treatment modalities.Key words: diabetes mellitus (DM), nephropathy, chronic renal failure, connective tissue growth factor (CTGF)