[Health risk assessment of heavy metals and metalloid in drinking water in a region of Huaihe River Basin from 2015 to 2019].

OBJECTIVE: To evaluate the chronic health risk of heavy metals and metalloid in drinking water through oral ingestion in a typical area. METHODS: Monitoring data of seven heavy metals and metalloid elements(Hg, As, Pb, Ni, Mn, Cr~(6+) and Cd) in drinking water in a typical area of Huaihe River Basin were collected from 2015 to 2019. The health risks of heavy metals and metalloid in drinking water in the area were assessed using the classic four-step health risk assessment model. RESULTS: The average concentrations of Hg, As, Pb, Ni, Mn, Cr~(6+) and Cd in drinking water in the typical area of Huaihe River Basin were(0.13±0.45), (0.49±0.49), (0.34±0.99), (1.10±2.49), (32.29±126.64), (2.13±0.50) and(0.03±0.04) µg/L, respectively. In which, Hg, Mn and Ni exceeded the limit of the Standard for Drinking Water(GB 5749-2006), the exceedance rates were 2.14%, 6.79% and 0.3%, respectively, and the maximum exceedance times were 2.61, 8.90 and 0.34, respectively. The chronic non-carcinogenic risks of Hg, As, Pb, Ni, Mn, Cr~(6+) and Cd were 1.32×10~(-2), 4.99×10~(-2), 2.97×10~(-3), 1.68×10~(-3), 7.04×10~(-3), 2.17×10~(-2) and 1.83×10~(-3), respectively. The carcinogenic risks of As, Pb, Cr~(6+) and Cd were 2.24×10~(-5), 8.82×10~(-8), 3.25×10~(-5) and 5.86×10~(-7), respectively. CONCLUSION: Hg, Mn and Ni in drinking water exceeded the standard in a typical area of Huaihe River Basin from 2015 to 2019. The chronic non-carcinogenic risks of Hg, As and other 7 heavy metals and metalloid are at an acceptable level(HQ≤1), while As and Cr~(6+) have certain carcinogenic risks(10~(-6)≤CR≤10~(-4)).

Plasma sMer, sAxl and GAS6 levels correlate with disease activity and severity in lupus nephritis.

OBJECTIVE: The purpose of this study is to determine whether TAM receptors and ligands associated with the activity and severity of lupus nephritis. METHODS: Clinical data were statistically analysed and studied in 122 SLE patients, diagnosed from 2013 to 2016 in First Hospital Affiliated to Harbin Medical University. Levels of TAM receptors and ligands in the plasma of 122 SLE patients were measured by ELISA. Renal biopsies were performed to confirm lupus nephritis (LN) by histopathology in 68 patients. The associations of TAM receptors and ligands with clinical and serological parameters were analysed in 68 LN patients. RESULTS: Amongst patients with SLE, those with LN had significantly higher plasma sMer, sAxl and GAS6 levels than those without renal involvement (P < 0.01 for all comparisons). Additional comparisons on the renal function-associated clinical parameters confirmed an indicative role of the sMer, sAXL and GAS6 levels in the cohort of patients with more severe nephritis. Patients with higher sMer, sAXL and GAS6 levels of LN patients tended to suffer from proliferative glomerulonephritis. The sAXL and GAS6 levels had a strong positive correlation with activity index (AI) in LN patients. Furthermore, there was a significant drop of the sMer, sAXL and GAS6 concentrations from the time of the biopsy to month t6, but no further decrease from months t6 to t12. CONCLUSIONS: These results suggest that plasma sMer, sAxl and GAS6 can be an additional clinical marker related to the disease activity and severity in LN.

Phosphatidylserine on microparticles and associated cells contributes to the hypercoagulable state in diabetic kidney disease.

Background: Relatively little is known about the role of phosphatidylserine (PS) in procoagulant activity (PCA) in patients with diabetic kidney disease (DKD). This study was designed to evaluate whether exposed PS on microparticles (MPs) and MP-origin cells were involved in the hypercoagulability in DKD patients. Methods: DKD patients (n = 90) were divided into three groups based on urinary albumin excretion rate, defined as normoalbuminuria (No-A) (<30 mg/24 h), microalbuminuria (Mi-A) (30-299 mg/24 h) or macroalbuminuria (Ma-A) (>300 mg/24 h), and compared with healthy controls (n = 30). Lactadherin was used to quantify PS exposure on MPs and their original cells. Healthy blood cells (BCs) and human umbilical vein endothelial cells (HUVECs) were treated with 25, 5 or 2.5 mmol/L glucose as well as 3-12 mg/dL uric acid and cells were evaluated by clotting time and purified coagulation complex assays. Fibrin production was determined by turbidity. PS exposure and fibrin strands were observed using confocal microscopy. Results: Using flow cytometry, we found that PS+ MPs (derived from platelets, erythrocytes, HUVECs, neutrophils, monocytes and lymphocytes) and BCs were significantly higher in patients than in controls. Furthermore, the number of PS+ MPs and BCs in patients with Ma-A was significantly higher than in patients with No-A. Similarly, we observed markedly elevated PS exposure on HUVECs cultured with serum from patients with Ma-A versus serum from patients with Mi-A or normoalbuminuria. In addition, circulating PS+ MPs cooperated with PS+ cells, contributing to markedly shortened coagulation time and dramatically increased FXa/thrombin generation and fibrin formation in each DKD group. Confocal microscopy images demonstrated colocalization of fibrin with PS on HUVECs. Moreover, blockade of exposed PS on MPs and cells with lactadherin inhibited PCA by ∼80%. In vitro, BCs and endothelial cells exposed more PS in hypoglycemia or hyperglycemia. Interestingly, reconstitution experiments showed that hypoglycemia-treated cells could be further activated or injured when recovery is obtained reaching hyperglycemia. Moreover, uric acid induced PS exposure on cells (excluding platelets) at concentrations >6 mg/dL. Linear regression analysis showed that levels of PS+ BCs and microparticles were positively correlated with uric acid and proteinuria, but negatively correlated with glomerular filtration rate. Conclusions: Our results suggest that PS+ MPs and MP-origin cells play procoagulant roles in patients with DKD. Blockade of PS could become a novel therapeutic modality for the prevention of thrombosis in these patients.

Deferiprone attenuates inflammation and myocardial fibrosis in diabetic cardiomyopathy rats.

We attempted to investigate the therapeutic effects of deferiprone on DC rats and explore the underlying mechanism. Total 24 6-week-old male Wistar rats (weighing from 180 g to 220 g) were subjected to DC model construction and then randomly divided to three groups (8 rats per group): DC group, DC + 50 mg, and DC + 100 mg deferiprone treatment group. The 8 normal rats were considered as controls. After deferiprone treatment for 20 weeks, the blood samples were collected for the biochemical parameters test, including fasting glucose, HOMA-IR (homeostasis model assessment of the insulin resistance), serum iron, ferritin and transferrin saturation (TS). The oxidative stress was assessed by detecting the level of malondialdehyde (MDA) and superoxide dismutase (SOD). Histopathologic changes were determined by Masson's trichrome staining and electron microscopy imaging. The expression levels of NF-κB (nuclear factor kappa B), COX2 (cytochrome c oxidase), tenascin C, collagen IV were measured by RT-PCR and western blotting. The expression of nitrotyrosine and MCP-1 (monocyte chemotactic protein 1) were determined by immunohistochemistry. Deferiprone treatment reduced iron deposition and IR in DC rats except for blood glucose. After deferiprone treatment, MDA level was significantly decreased and SOD level was increased significantly. The level of NF-κB, cyclooxygenase-2, tenascin C, collagen IV MCP-1 and nitrotyrosine were significantly reduced. There was no significant difference in the effect of deferiprone at 50 and 100 mg doses. Deferiprone showed therapeutic effects on DC by regulating the pro-inflammatory and pro-fibrotic factors.

Urinary Volatile Organic Compounds as Potential Biomarkers in Idiopathic Membranous Nephropathy.

OBJECTIVE: To detect urinary volatile organic compounds (VOCs) in patients with idiopathic membranous nephropathy (iMN) and normal controls, and to examine whether or not urinary VOCs can act as biomarkers for the diagnosis of iMN independent of renal biopsy. MATERIALS AND METHODS: Gas chromatography/mass spectrometry (GC/MS) was used to assess the urine collected from 63 iMN patients and 15 normal controls. The statistical methods of principal component analysis and partial least squares discriminant analysis were performed to process the final data in Common Data Format which were converted from GC/MS data. RESULTS: Six VOCs in the urine samples of iMN patients exhibited significant differences from those of normal controls: carbamic acid monoammonium salt, 2-pentanone, 2,4-dimethyl-pentanal, hydrogen azide, thiourea, and 4-heptanone were significantly higher than in controls (p < 0.05). CONCLUSIONS: Six urinary VOCs were isolated from patients with iMN using GC/MS. The analysis of urinary VOCs using GC/MS could be developed into a non-invasive method for the detection of iMN.

Efficacy and safety of Abelmoschus manihot for primary glomerular disease: a prospective, multicenter randomized controlled clinical trial.

BACKGROUND: Abelmoschus manihot, a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess its efficacy and safety in patients with primary glomerular disease. STUDY DESIGN: Prospective, open-label, multicenter, randomized, controlled, clinical trial. SETTING & PARTICIPANTS: From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. INTERVENTIONS: A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50mg/d. The duration of intervention was 24 weeks. OUTCOMES & MEASUREMENTS: The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. RESULTS: Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot, losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2, respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of -508, -376, and -545 mg/d, respectively (P=0.003 for A manihot vs losartan and P<0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups (P>0.05), and there were no severe adverse events in any group. LIMITATIONS: Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. CONCLUSIONS: A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.

Relationship between hypoalbuminemia, hyperlipidemia and renal severity in patients with lupus nephritis: a prospective study.

AIM OF THE STUDY: The purpose is to evaluate the relationship between hypoalbuminemia, hyperlipidemia, nephrotic and renal severity in patients with lupus nephritis. MATERIAL AND METHODS: Autoantibodies and serological parameters were measured and analyzed in 429 patients with lupus nephritis in a single centre. RESULTS: The prevalence for anti-dsDNA, anti-nucleosome and anti-histone was higher in the nephrotic syndrome (NS) patients than that in non-NS patients (p < 0.0001 for all comparisons). The NS patients had a higher proportion of diffuse proliferative renal lesions (69.05%) and membranous lesions (68.00%). Serum total cholesterol and albumin levels were associated with activity and severity of renal disease. The levels of proteinuria and serum albumin were positively correlated with activity and chronicity index (p < 0.001 for all correlations). The incidence of a poor renal outcome (p = 0.0461) in the NS patients was significantly increased. On the other hand, the remission rate (p = 0.0002) was significantly reduced and recurrence rate (p = 0.0027) was significantly increased in NS patients. CONCLUSIONS: This paper highlights that nephrotic-range proteinuria, elevated total cholesterol level and decreased serum albumin levels may reflect the activity and severity of renal damage in SLE patients.

Simultaneous positivity for anti-DNA, anti-nucleosome and anti-histone antibodies is a marker for more severe lupus nephritis.

OBJECTIVE: The purpose of this study is to examine autoantibody profile of systemic lupus erythematosus (SLE) patients with lupus nephritis (LN) and to establish the correlation between the antibody reactivity and disease activity of LN. METHODS: Autoantibodies and serological parameters were measured and analyzed in 589 SLE patients. The associations of the co-positivity of anti-dsDNA, -nucleosome and -histone antibodies (3-pos) with clinical, serological and outcome parameters were analyzed. RESULTS: At the study entry, the prevalence for anti-dsDNA (61.52 % vs. 34.11 %, P < 0.0001), anti-nucleosome (56.09 % vs. 37.21 %, P = 0.0002) and anti-histone (49.35 % vs. 33.33 %, P = 0.0013) antibodies in patients with LN were significantly higher than that in patients without LN. Patients with 3-pos had a higher proportion of proliferative renal lesions (class III + IV). The incidence of a poor renal outcome (7.14 % vs. 2.52 %, P = 0.0174) in LN patients with 3-pos was significantly higher than those without 3-pos. Moreover, the rate of remission (73.63 % vs. 82.37 %, P = 0.0245) was significantly reduced and recurrence increased (58.90 % vs. 23.44 %, P < 0.0001) in 3-pos patients as compared to that in non 3-pos within the LN group. CONCLUSION: Our data indicate a strong association between the 3-pos and renal disease activities, especially proliferative glomerulonephritis. The ability of 3-pos to predict renal flares may lead to major additional benefits in the follow-up of these patients.

Epidemiology and risk factors for chronic kidney disease in patients with ischaemic stroke.

BACKGROUND: There is growing evidence for an association between chronic renal disease (CKD) and adverse cerebrovascular events because of the overlap of several risk factors. The purpose of this study is to examine the epidemiology of CKD and the characteristics of risk factors for CKD in the population with ischaemic stroke. METHODS: This retrospective study included 571 patients with ischaemic stroke. Estimated glomerular filtration rate (eGFR) was calculated by the Modification of Diet in Renal Disease (MDRD) study equation. Renal function was assessed according to the Kidney Disease Outcomes Quality Initiative (K/DOQI)-CKD classification. RESULTS: Study demonstrated that the major factors associated with CKD in the ischaemic stroke patients were age, diabetes mellitus, hypertension, systolic blood pressure, LDL cholesterol and serum uric acid. Diabetes mellitus (OR 4·146, 95% CI 1·047-16·418, P = 0·043), hypertension and diabetes mellitus (OR 3·574, 95% CI 1·248-10·234, P = 0·018), serum uric acid (OR 1·010, 95% CI 1·006-1·013, P < 0·001) and LDL cholesterol (OR 1·431, 95% CI 1·063-1·928, P = 0·018) were independent risk factors associated with CKD in the patients with ischaemic stroke. CONCLUSIONS: The patients with ischaemic stroke may be considered as a high-risk population for CKD and be aggressively managed for CKD prevention. The high prevalence of CKD in population with ischaemic stroke prompts the need for greater public awareness about risks of CKD.

Serum levels and activity of indoleamine2,3-dioxygenase and tryptophanyl-tRNA synthetase and their association with disease severity in patients with chronic kidney disease.

OBJECTIVE: This study aims to test the serum levels and activity of indoleamine2,3-dioxygenase(IDO) and tryptophanyl-tRNA synthetase (TTS) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity. METHOD: Serum concentrations of IDO and TTS in 61 patients with CKD and 16 healthy volunteers were tested by ELISA. Tryptophan and kynurenine concentrations were measured by high-performance liquid chromatography (HPLC). RESULTS: Patients with CKD showed higher serum levels of IDO and TTS in comparison to healthy controls (p = 0.001). Patients with CKD showed lower serum levels of tryptophan and higher serum levels of kynurenine in comparison to healthy controls (p < 0.001). The kyn/Trp ratio significantly correlated with the disease severity in CKD patients (r = 0.721; p < 0.001). CONCLUSIONS: IDO and TTS may play critical roles in the immune pathogenesis of CKD. The activity of IDO correlated with the disease severity of CKD.

Characterization of interleukin-33 and soluble ST2 in serum and their association with disease severity in patients with chronic kidney disease.

INTRODUCTION: This study aims to test the serum levels of interleukin-33 (IL-33) and soluble ST2 (sST2) in patients with chronic kidney disease (CKD) and to evaluate their association with disease severity. METHODS: Sixty-nine patients with CKD were enrolled, disease severity was assessed, and clinical data were collected. Twelve healthy volunteers served as healthy individuals. Serum IL-33 and sST2 were tested by enzyme-linked immunosorbent assay. RESULTS: The patients were classified into five categories based on their estimated glomerular filtration rate (eGFR). No difference was found as to the serum concentration of IL-33 between CKD patients and healthy individuals (p = 0.656), while a higher serum level of sST2 was found in CKD patients (p = 0.003). The correlation analysis revealed a significant correlation between the serum level of sST2 and disease severity (r = 0.586; p < 0.001). A higher level of sST2 was found in CKD patients with elevated parathyroid hormone (p = 0.001). Serum sST2 correlated with parathyroid hormone (r = 0.412; p < 0.001), serum phosphorus (r = 0.545; p < 0.001), and serum calcium (r = -0.494; p < 0.001). CONCLUSION: An elevated concentration of serum sST2 is found in CKD patients and correlates with disease severity. Serum sST2 may be also associated with parathyroid hormone disorder of CKD. The sST2 may have an important role in the development of CKD or as a marker of disease severity.

The sphingosine-1-phosphate receptor agonist FTY720 prevents the development of anti-glomerular basement membrane glomerulonephritis.

The sphingosine-1-phosphate (S1P) agonist FTY720 prolongs the survival of organ allograft and attenuates autoimmune-mediated injury in experimental models. Most cases of glomerulonephritis (GN) in human appear to be immunologically initiated. In this study, we evaluated the potential therapeutic role of FTY720 in GN via a mouse anti-glomerular basement membrane (GBM) model. Mice were immunized with rabbit IgG in complete Freund's adjuvant (CFA) followed by an intravenous injection of a rabbit anti-mouse GBM serum. Disease and immune responses were assessed on day 14. Mice were treated with FTY720 (0.3 or 3 mg/kg) and prednisone (10 mg/kg) from days 0 to 14. The S1P modulator reduced proteinuria, serum creatinine, crescent formation and serum IgG level. The expressions of splenic S1P receptor and renal Th-1 cytokine were also inhibited at the transcription stage. Treatment with FTY720 increased splenocyte production of protective Th2 cytokine IL-4 and promoted the apoptosis of splenic CD4+ T cells in the animal models, which suggests that FTY720 played a protective role at the induction stage of GN by inhibiting mRNA expressions of splenic S1P receptor 1, S1P receptor 2, and S1P receptor 5.

Treatment of 5/6 nephrectomy rats with sulodexide: a novel therapy for chronic renal failure.

AIM: Sulodexide, a glycosaminoglycan, could reduce albuminuria in diabetic patients. The aim of this study was to determine whether sulodexide could be used to treat chronic kidney failure in rats. METHODS: Sixty Wistar rats undergone 5/6 nephrectomy, then were randomly divided into 4 groups: the model group, sulodexide group (sulodexide 5 mg/kg per day, im), irbesartan group irbesartan (20 mg/kg per day, ig) and sulodexide plus irbesartan group. Another 12 rats were enrolled into the sham operation group. After the treatments for 4, 8 and 12 weeks, urinary protein and serum creatinine levels were measured. After 12 weeks, serum cholesterin and triglycerides levels were measured, and the degrees of glomerular sclerosis and renal tubulointerstitial fibrosis were scored. The expression of aminopeptidase P (JG-12) in the renal tissue was examined using immunohistochemical staining. The renal expressions of endothelial nitric oxide synthase (eNOS) and tissue type plasminogen activator (tPA) were detected with RT-PCR and Western blot. RESULTS: Proteinuria was markedly attenuated in the sulodexide-treated groups. After 4 and 8 weeks only the sulodexide-treated groups showed significant reduction in serum creatinine; while after 12 weeks all the three treatment groups showed significant reduction in serum creatinine. Furthermore, all the three treatment groups showed significant reduction in the scores of glomerular sclerosis and tubulointerstitial fibrosis. The glomerular expression of JG-12 was increased in both the sulodexide group and the sulodexide plus irbesartan group, but not in the irbesartan group. The eNOS mRNA and protein expression was decreased and the tPA mRNA and protein expression was significantly increased in the model group compared with Sham group. Sulodexide, irbesartan, and their combination reversed the decrease of eNOS expression but increased the tPA expression much more compared with model group. CONCLUSION: Sulodexide was similar to irbesartan that can decrease proteinuria and attenuate renal lesions in 5/6 nephrectomy rats. The renal protection by sulodexide might be achieved via its impact on renal vascular endothelial cells.

[Atorvastatin attenuates parathyroid hormone 1-34 induced cardiomyocytes hypertrophy through downregulating K-Ras-ERK1/2 pathway].

OBJECTIVE: To investigate the effects of atorvastatin on parathyroid hormone 1-34 (PTH1-34) induced neonatal rat cardiomyocytes hypertrophy and on the expression changes of small GTP-binding protein (K-Ras) and extracellular signal regulated protein kinases 1/2 (ERK1/2). METHODS: Neonatal rat cardiomyocytes hypertrophy was established with 10(-7) mol/L rPTH1-34 in the presence or absence of 10(-5) mol/L atorvastatin or 10(-4) mol/L mevalonic acid (MVA). Cardiomyocyte diameter was measured by Motic Images Advanced 3.0 software, the synthetic rate of protein in cardiomyocytes was determined by (3)H-leucine incorporation and single-cell protein content was measured by BCA. The concentration of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined by ELISA. Protein expression of ERK1/2, p-ERK1/2 and K-Ras was detected by Western blot. RESULTS: Compared to PTH1-34 group, cellular diameter was decreased 12.07 µm, (3)H-leucine incorporation decreased 1622 cpm/well and single-cell protein content decreased 84.34 pg, ANP or BNP concentration reduced 7.13 µg/L or 20.04 µg/L, protein expression of K-Ras, ERK1/2 or p-ERK1/2 downregulated 0.81, 0.19 and 1.44 fold, respectively, in PTH1-34 plus atrovastatin co-treated cardiomyocytes (all P < 0.05). Compared to PTH1-34 plus atrovastatin co-treated group, cardiomyocyte diameter increased 4.95 µm, (3)H-leucine incorporation increased 750 cpm/well and single-cell protein content increased 49.08 pg, ANP or BNP increased 3.12 µg/L or 9.35 µg/L and protein expression of K-Ras, ERK1/2 or p-ERK1/2 upregulated 0.52, 0.06 and 1.19 fold (all P < 0.05) in MVA, PTH1-34 and atrovastatin co-treated cardiomyocytes. CONCLUSIONS: Atrovastatin attenuates PTH1-34 induced neonatal rat cardiomyocytes hypertrophy through downregulating K-Ras and ERK1/2 pathway.

Long COVID: The Nature of Thrombotic Sequelae Determines the Necessity of Early Anticoagulation.

Many discharged COVID-19 patients affected by sequelae experience reduced quality of life leading to an increased burden on the healthcare system, their families and society at large. Possible pathophysiological mechanisms of long COVID include: persistent viral replication, chronic hypoxia and inflammation. Ongoing vascular endothelial damage promotes platelet adhesion and coagulation, resulting in the impairment of various organ functions. Meanwhile, thrombosis will further aggravate vasculitis contributing to further deterioration. Thus, long COVID is essentially a thrombotic sequela. Unfortunately, there is currently no effective treatment for long COVID. This article summarizes the evidence for coagulation abnormalities in long COVID, with a focus on the pathophysiological mechanisms of thrombosis. Extracellular vesicles (EVs) released by various types of cells can carry SARS-CoV-2 through the circulation and attack distant tissues and organs. Furthermore, EVs express tissue factor and phosphatidylserine (PS) which aggravate thrombosis. Given the persistence of the virus, chronic inflammation and endothelial damage are inevitable. Pulmonary structural changes such as hypertension, embolism and fibrosis are common in long COVID. The resulting impaired lung function and chronic hypoxia again aggravates vascular inflammation and coagulation abnormalities. In this article, we also summarize recent research on antithrombotic therapy in COVID-19. There is increasing evidence that early anticoagulation can be effective in improving outcomes. In fact, persistent systemic vascular inflammation and dysfunction caused by thrombosis are key factors driving various complications of long COVID. Early prophylactic anticoagulation can prevent the release of or remove procoagulant substances, thereby protecting the vascular endothelium from damage, reducing thrombotic sequelae, and improving quality of life for long-COVID patients.

Circulating Microparticles in the Pathogenesis and Early Anticoagulation of Thrombosis in COVID-19 With Kidney Injury.

As more is learned about the pathophysiological mechanisms of COVID-19, systemic thrombosis has been recognized as being associated with more severe clinical manifestations, mortality and sequelae. As many as 40% of patients admitted to the hospital due to COVID-19 have acute kidney injury, with coagulation abnormalities the main cause of impaired function. However, the mechanism of renal thrombosis and the process leading to kidney injury are unclear. Microparticles (MPs) are membrane bubbles released in response to activation, injury or apoptosis of cells. The phosphatidylserine (PS) exposed on the surface of MPs provides binding sites for endogenous and exogenous FXase complexes and prothrombin complexes, thus providing a platform for the coagulation cascade reaction and facilitating clot formation. In the context of COVID-19 infection, viral attack leads immune cells to release cytokines that damage circulating blood cells and vascular endothelial cells, resulting in increased MPs levels. Therefore, MPs can be used as a risk factor to predict renal microthrombosis and kidney injury. In this paper, we have summarized the latest data on the pathophysiological mechanism and treatment of renal thrombosis caused by MPs in COVID-19, revealing that the coagulation abnormality caused by MP and PS storms is a universal progression that aggravates the mortality and sequelae of COVID-19 and potentially other pandemic diseases. This paper also describes the risk factors affecting renal thrombosis in COVID-19 from the perspective of the Virchow's triad: blood hypercoagulability, vascular endothelial injury, and decreased blood flow velocity. In summary, given the serious consequences of thrombosis, current guidelines and clinical studies suggest that early prophylactic anticoagulant therapy reduces mortality and improves clinical outcomes. Early anticoagulation, through inhibition of PS-mediated coagulopathy, allows maintenance of unobstructed blood circulation and oxygen delivery thereby facilitating the removal of inflammatory factors, viruses, MPs, and dead or damaged cells, and expediting patient rehabilitation.

Associations between m-type phospholipase A2 receptor,human leukocyte antigen gene polymorphisms and idiopathic membranous nephropathy.

Primary membranous nephropathy, also known as idiopathic membranous nephropathy, is an autoimmune disease. As an autoimmune disease, genetic factors are essential in the pathogenesis of IMN. People pay more and more attention to genetics and bioinformatics. With the continuous improvement and development of high-throughput gene sequencing and genotyping technology, it has been confirmed that many genes and their single nucleotide polymorphisms are strongly correlated with IMN disease susceptibility. However, there are few studies on HLA-DQA1 and PLA2R gene polymorphisms and IMN susceptibility in China. The purpose of this study was to investigate whether PLA2R rs2715928 and rs16844715 are related to IMN, the correlation between five SNP loci of PLA2R and HLA-DQA1 and IMN, and the effect of gene-gene interaction among different genotypes of each locus on disease. In this study, 86 patients with IMN confirmed by renal biopsy in the first hospital of Harbin Medical University and 90 healthy controls were selected. All subjects were excluded from secondary membranous nephropathy, pregnant or breastfeeding women, severe primary disease of vital organs, severe infection, major surgery, and severe trauma. Seven selected SNP loci were genotyped using the IMLDR multiple SNP typing kit. Chi-square test and logistic regression were used to analyze the correlation between each SNP and IMN. The general clinical data and laboratory indicators of each subject were recorded, and the relationship between different genotypes and clinical manifestations was analyzed. Among the 7 SNP loci included in the study, except HLA-DQA1 rs2187668, the other 6 loci all met Hardy-Weiberg equilibrium test (P > 0.05). The allele distribution of PLA2R rs2715928 and rs16844715 was significantly different between the IMN group and the healthy control group, and it was closely related to IMN (P < 0.05). There was no statistical difference in the distribution of alleles of rs2715918 between the IMN group and the control group (P* > 0.05), and there was also statistical difference in the distribution of alleles of rs35771982, rs3749117, and rs4664308 between the IMN group and the healthy control group (P < 0.05).The C allele of rs16844715 (OR = 2.03, 95%CI: 1.29-3.19, P* = 0.0140) and the A allele of rs2715928 (OR = 3.18, 95%CI: 1.94-5.24, P* = 3.54E-5), G allele of rs35771982 (OR = 4.07, 95%CI: 2.34-7.08, P* = 4.96E-6), T allele of rs3749117 (OR = 4.07, 95%CI: 2.34-7.08, P* = 4.96E-6), the A allele of rs4664308 (OR = 2.63, 95%CI: 1.54-4.49, P* = 0.0028) was the risk gene of IMN.Through the establishment of different genetic models, we found that,in the additive model, the three SNPs of PLA2R rs2715928 (OR = 5.40, 95%CI: 1.77-16.50, P* = 0.0217) and rs35771982 (OR = 15.15, 95%CI: 2.92-78.48, P* = 0.0084), rs3749117 (OR = 15.15, 95%CI: 2.92-78.48, P* = 0.0084) had a strong correlation with IMN. In the stealth model,homozygous gene risk type of the five SNPs,PLA2R rs16844715 (OR = 2.52, 95%CI: 1.38-4.61, P* = 0.0189) and rs2715928 (OR = 4.30, 95%CI: 2.31-8.03, P* = 3.14E-5), rs35771982 (OR = 4.85, 95%CI: 5.53-9.31, P* = 1.42E-5), rs3749117 (OR = 4.85, 95%CI: 5.53-9.31, P* = 1.42E-5) and rs4664308 (OR = 3.16, 95%CI: 1.67-5.97, P* = 0.0028) had a strong correlation with IMN. The distribution of GT haplotypes and CC haplotypes of rs35771982 and rs3749117 and CA haplotypes and TG haplotypes of rs16844715 and rs4664308 were significantly different between IMN group and control group (P < 0.05). When GMDR software was used to establish a model to analyze the interaction between various SNP sites, it was found that the combination of GG genotype at rs35771982 and AA genotype at rs2715928 was the highest risk of disease. The risk genotypes of rs16844715, rs2715928 and rs4664308 had no effect on the clinical manifestations of IMN (P > 0.05). PLA2R rs2715928 and rs16844715 are associated with susceptibility to IMN. The C allele of rs16844715, the A allele of rs2715928, the G allele of rs35771982, the T allele of rs3749117, and the A allele of rs4664308 are the dangerous genes of IMN. The combination of GG genotype at rs35771982 and AA genotype at rs2715928 poses the greatest risk of disease. Haplotype may affect susceptibility to IMN. The risk genotype had no effect on the clinical manifestations of IMN.

Epidemiology and risk factors for progression in Chinese patients with IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is one of the main causes of primary glomerulonephritis worldwide, and it is also the main primary disease leading to chronic kidney disease. The purpose of this study is to evaluate the epidemiology and risk factors for progression in Chinese patients with IgAN. METHODS: In this retrospective study, 246 patients with renal biopsy-proven IgAN were enrolled from January 2012 to June 2018. The patients' data were divided into two groups according to eGFR at the end of follow-up: a high-eGFR group (eGFR≥60ml/min) and a low-eGFR group (eGFR<60ml/min). RESULTS: At the end of the study, we identified 49 (19.92%) patients with low-eGFR from 246 IgAN patients. Renal function, represented by serum creatinine, urea nitrogen and cystatin-C, was significantly decreased in the low-eGFR group (P<0.001 for all) at the time of renal biopsy. Compared with the high-eGFR group, the age, mean arterial blood pressure (MAP), proteinuria, cholesterol, triglycerides and serum uric acid were significantly higher (P<0.05 for all). According to the Oxford evaluation, the proportion of S1-2 (59.2%) and T1-2 (65.3%) was significantly increased (P<0.001 for both) and the proportion that had a MEST-C score ≥3 was statistically increased in the low-eGFR group (83.7%, P=0.001). CONCLUSIONS: Male, MAP, haematuria, Scr, cholesterol, hemoglobin, Lee classification more than 3 and C1-2 are independent risk factors for low-eGFR in Chinese IgAN patients.

[Expression and significance of CD80/CD86 in renal tissue of lupus nephritis].

OBJECTIVE: To measure the expression of CD80 and CD86 in renal tissue of lupus nephritis (LN) and explore its mechanism in the development of LN. METHODS: Forty-nine patients with active LN and 9 patients with minor glomerular abnormalities tissues as controls were studied. The expression of CD80 and CD86 in renal tissues was detected by immunohistochemical methods. RESULTS: CD86 was expressed extensively in glomerulus, periglomerular area, tubular epithelial cells and peritubular interstitium, while CD80 was expressed only in tubular epithelial cells and peritubular interstitium. Moreover, the percentage of CD80+ and CD86+ cells in tubular epithelial cells and peritubular interstitium showed a tendency to increase with tubulointerstitial damage. The expression of CD80 and CD86 in renal tissue correlated with the systemic lupus erythematosus (SLE) disease activity index score, the degree of proteinuria, creatinine clearance and anti-dsDNA antibody. CONCLUSIONS: This study shows that increased CD80 and CD86 expression with the progression of tubulointerstitial lesion might play an important role in the development of lupus nephropathy, and the tubulointerstitial expression of CD80 and CD86 could potentially serve as a surrogate marker of SLE disease activity. The co-stimulatory molecules CD80 and CD86 might play an important role in the pathogenesis of LN.