Songmin Huang

Amelioration of rhabdomyolysis-induced renal mitochondrial injury and apoptosis through suppression of Drp-1 translocation

INTRODUCTION Mitochondrial dysfunction plays an important role in acute kidney injury (AKI). Mitochondrial fission regulated by dynamin-related protein 1 (Drp-1) impairs the function of the mitochondria and the survival of cells. This study was conducted to explore the effects of suppression of Drp-1 accumulation in the mitochondria, on mitochondrial function and renal tubular cell apoptosis in rhabdomyolysis (RM)-induced AKI. METHODS An RM model was induced by intramuscular injection of glycerol in Sprague Dawley rats. Twenty-four and 48 hours after intraperitoneal injections of mitochondrial division inhibitor 1 (Mdivi-1), we observed the functions of the kidney, changes in pathology, expressions of Drp-1 in tubular tissues (by immunohistochemistry and Western blot) and accumulation of Drp-1 and mitofusin 2 in tubular mitochondria (by Western blot). Mitochondrial function (ATP and ROS) and tubular epithelial cell apoptosis (by TUNEL) were also measured. RESULTS RM induced Drp-1 accumulation, decreased ATP production and increased ROS in mitochondria. With increasing cytochrome c expression, cell apoptosis increased, whereas kidney function decreased. These changes were time-dependent. At different time points, despite not significantly influencing the overall expression of Drp-1, Mdivi-1 suppressed the accumulation of Drp-1, inhibited the insertion of proapoptotic Bax in mitochondria and inhibited the release of cytochrome c, thus ameliorating cell apoptosis. CONCLUSIONS To conclude, in RM-induced AKI, suppression of Drp-1 accumulation in mitochondria favors the maintenance of mitochondrial function and reduces the apoptosis of tubular cells. Regulation of the mitochondrial fusion-fission balance may offer a novel strategy for the prevention and treatment of RM-induced AKI.

Renal pathological implications in type 2 diabetes mellitus patients with renal involvement

AIMS To investigate the renal pathological implications in type 2 diabetes mellitus patients with renal involvement. METHODS A total of 328 type 2 diabetes mellitus (T2DM) patients with renal involvement who underwent a renal biopsy and received follow-up for at least one year were recruited in our study. The patients were divided into the diabetic nephropathy (DN), non-diabetic renal disease (NDRD), and NDRD superimposed on DN groups based on the pathological diagnosis. Renal outcomes were defined by the initiation of renal replacement therapy or doubling of the serum creatinine. Kaplan-Meier analysis was used to compare renal survival, and Cox proportional hazard analysis was used to determine the predictors of renal outcomes in the DN group. RESULTS Renal biopsy findings revealed that 188 patients (57.32%) had pure DN, 121 patients (36.89%) had NDRD alone, and 19 patients (5.79%) had NDRD superimposed on DN. The most frequent subclassification of NDRD was membranous nephropathy (MN). Compared with the NDRD and NDRD superimposed on DN groups, patients with pure DN had poorer renal function and lower renal survival rates. In the DN group, the five-year renal survival rates of glomerular classes of I, IIa, IIb, III and IV were 100%, 84.62%, 60%, 47.5% and 33.33%, respectively. Multivariate Cox proportional hazard analysis showed that the glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes, while interstitial fibrosis/inflammation and arteriolar hyalinosis were not independently associated with renal outcomes in the DN group. CONCLUSIONS Making an accurate pathologic diagnosis by renal biopsy is crucial for diabetes mellitus (DM) patients with renal involvement. The findings of our present study indicated that patients with pure DN had poorer renal outcomes than patients with NDRD or NDRD superimposed on DN. The classification of glomerular lesions, proteinuria and serum creatinine were independent risk factors for renal outcomes in the DN group. More studies with large samples and longer time follow-up are needed to evaluate the relationship between pathological changes and clinical characteristics in T2DM patients who have renal involvement.

Spontaneous retroperitoneal hemorrhage after hemodialysis involving anticoagulant agents.

In this paper, we described the symptoms and treatment of a patient with diabetic nephropathy accompanied by spontaneous retroperitoneal hemorrhage after hemodialysis. An elderly female patient with diabetic nephropathy presented with severe pain, numbness, and an increasing swelling in the left hip and left thigh after six sessions of hemodialysis involving the use of an antiplatelet drug and an anticoagulant agent. Her hemoglobin decreased to 46 g/L. An abdominal ultrasound showed a hematoma in the left retroperitoneal space, and computed tomography (CT) findings revealed a 6 cm×8 cm×10 cm hematoma in the left psoas muscle. After aggressive supportive therapy [the administration of packed red blood cell transfusion, carbazochrome sodium sulfonate injection, and continuous venovenous hemofiltration (CVVH)], the patient’s vital signs stabilized and her hemoglobin increased to 86 g/L. Repeat CT showed that the hematoma had been partially absorbed after two weeks. Eventually, the patient was discharged with stable vital signs. Physicians should be aware of the possibility of spontaneous retroperitoneal hemorrhage, particularly in patients with diabetic nephropathy undergoing hemodialysis involving the use of anticoagulant agents.

Activation of the lectin complement pathway on human renal glomerular endothelial cells triggered by high glucose and mannose-binding lectin

This study aimed to investigate the roles of high glucose and mannose-binding lectin (MBL) on the activation of the lectin complement pathway (LCP) on human renal glomerular endothelial cells (HRGECs) in vitro . Flow cytometry analysis, immunofluorescence staining and Western blot were used to detect the cell surface deposition of MBL, C3 and the membrane attack complex (MAC), as well as the code position of MBL and C3 (MBL+C3). Electrophoretic mobility shift assay (EMSA) was used to measure the activation of nuclear factor-kappaB (NF-κB). These results show that cell surface deposition of MBL, C3 and MBL+C3 after exposure to high glucose increased in both time- and dosedependent manner (P < 0.05). Moreover, MBL, C3 and MBL+C3 deposition stimulated by exogenous recombinant human MBL (rhuMBL) were also observed in both time- and dose-dependent manner, peaking at 4 h and then decreasing (P < 0.05). Inhibition experiments indicated that the inhibitory monoclonal antibody 3F8 against human MBL (MAb 3F8) significantly abrogated the cell surface deposition of MBL, C3 and MBL+C3, attenuated MAC staining, and inhibited NF-κB activation in HRGECs (P < 0.05). In conclusion, high glucose and MBL played an important role on the LCP activation of HRGECs, and MAb 3F8 may represent a novel potential therapeutic strategy to block LCP activation on HRGECs. Key words: High glucose, mannose-binding lectin, complement activation, human renal glomerular endothelial cells.

Involvement of parathyroid hormone-related protein in vascular calcification of chronic haemodialysis patients

Aims:  To investigate the role of parathyroid hormone‐related protein (PTHrP) in vascular calcification of patients with chronic hemodialysis.

Atrial Fibrillation is Associated With Poor Outcomes in Thrombolyzed Patients With Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

AbstractThe influence of atrial fibrillation (AF) on the clinical outcomes of patients with ischemic stroke (IS) has not been completely determined. We aimed to perform a systematic review and meta-analysis to assess the relationship between AF and adverse events in patients with acute IS treated with thrombolysis.PubMed, EMBASE, and the Cochrane Library were searched for relevant studies regarding the association between AF and the outcomes of patients with IS treated with thrombolysis. Random and fixed effect models were used for pooling data.Twelve cohort studies involving 14,801 patients with acute IS were included. Meta-analysis revealed that patients with AF were more likely to die within 90 days after thrombolysis (odds ratio [OR], 2.13; 95% confidence interval [CI]: 1.68–2.70, P < 0.001), whereas this association was not observed in hospitalized patients (OR, 1.50; 95% CI, 0.86–2.60; P = 0.150). AF was associated with a reduced incidence of favorable outcomes (modified Rankin Scale ⩽ 2) (OR, 1.95; 95% CI: 1.33–2.85, P = 0.001) and an increased risk of symptomatic intracerebral hemorrhage (OR, 1.28; 95% CI: 1.08–1.52, P = 0.006). No evident publication bias was found by Beggs test or Eggers test.Comorbidity of AF may increase the risk of adverse outcomes for patients with IS undergoing thrombolysis. Further well-designed trials are warranted to confirm this association.

Influence of HbA1c on short-term blood pressure variability in type 2 diabetic patients with diabetic nephropathy.

The aim of this study was to understand the characteristics of blood pressure (BP) variability in subjects with diabetic nephropathy (DN), and identify the probable predictors affecting BP variability. Fifty-one chronic kidney disease (CKD)-hypertensive patients without diabetes (NDN group) and sixty type 2 diabetic patients with overt DN (DN group) were enrolled in this study. The values of short-term BP variability were obtained from 24 h ambulatory BP monitoring (ABPM). Variance analysis or nonparametric analysis revealed that 24-h systolic BP variability and nighttime systolic BP variability of the DN group were significantly higher than those of the NDN group [(12.23±3.66) vs. (10.74±3.83) mmHg, P<0.05; (11.23±4.82) vs. (9.48±3.69) mmHg, P<0.05]. Then the patients of the DN group were divided into two groups according to glycated hemoglobin (HbA1c) level: Group A (HbA1c<7%) and Group B (HbA1c≥7%), and the t-test showed that patients in Group B had larger 24-h diastolic, daytime diastolic, and nighttime systolic/diastolic BP variability compared with Group A. In the DN group, partial correlation analysis revealed that HbA1c exhibited a strong association with 24-h diastolic, daytime diastolic, nighttime systolic and diastolic BP variability (P<0.001, P<0.001, P<0.05, and P<0.001, respectively). Taken together, larger short-term BP variability was detected in hypertensive type 2 diabetic patients with overt nephropathy and renal insufficiency. It may imply that the optimal BP variability level could benefit from a better glycaemic control.

A case of focal segmental glomerulosclerosis syndrome secondary to high-altitude polycythemia

Abstract In recent years, focal segmental glomerulosclerosis has become the commonest cause of the nephrotic syndrome seen in adults. Secondary focal segmental glomerulosclerosis is observed when glomerular workload is increased. We report a case of focal segmental glomerulosclerosis with nephrotic syndrome secondary to high-altitude polycythemia (HAPC). Our case points out that for patients with focal segmental glomerulosclerosis, who presented with nephrotic syndrome secondary to HAPC, treatments for HAPC are crucial for the reduction of proteinuria and renal protection instead of glucocorticoid and immunosuppressive drugs.

Atorvastatin attenuates experimental contrast-induced acute kidney injury: a role for TLR4/MyD88 signaling pathway

Abstract Objectives: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. Results: After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p < .05) and ameliorated the contrast-induced acute kidney injury (p < .05) and significantly reduced Toll-like receptor 4 (TLR4), Myeloid differentiation factor 88 (Myd88), and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) protein expression and relative mRNA expression levels (p < .05) and significantly decreased expression levels of downstream inflammatory factors (p < .05). Conclusion: Different atorvastatin doses have protective effects on contrast-induced acute renal tubular injury in rats, possibly by targeting TLR4, suppressing TLR4 expression, regulating the TLR4/Myd88 signaling pathway, and inhibiting the expression of downstream inflammatory factors.