lncRNA NORAD alleviates dysfunction of renal proximal tubular epithelial cells during the sepsis-associated acute kidney injury by modulating the miR-155-5p-PDK1 axis.

The sepsis-associated acute kidney injury (Sa-AKI) is closely related to high mortality rates worldwide. Injury to the renal proximal tubular epithelial cells (RPTECs), caused by pathological conditions, is a major cause of acute kidney injury (AKI). The lncRNA NORAD has been reported to be positively associated with kidney cancers. However, the biological roles and underlying mechanisms of NORAD in RPTECs during AKI are still unclear. In this study, we found that NORAD was significantly downregulated in RPTECs from AKI tissues. Overexpression of NORAD alleviated RPTECs injury induced by lipopolysaccharide (LPS). Additionally, glucose metabolism was significantly impaired during AKI, and LPS treatment inhibited glucose metabolism in RPTECs. We demonstrated that NORAD rescued the LPS-induced inhibition of glucose metabolism in RPTECs. Furthermore, miRNA-155-5p was significantly upregulated in RPTECs from AKI. Through bioinformatics analysis, RNA pull-down, RNA IP, and luciferase assays, we showed that NORAD directly associated with miR-155-5p to downregulate its expression. Moreover, overexpression of miR-155-5p inhibited glucose metabolism by directly targeting the 3'UTR of the glucose metabolism enzyme, pyruvate dehydrogenase kinase 1 (PDK1). Finally, rescue experiments validated that NORAD's protective effect on RPTECs injury was mediated through modulation of the miR-155-5p-PDK1-glucose metabolism pathway. In summary, these results reveal that lncRNA NORAD can alleviate RPTECs dysfunction by targeting the miR-155-5p-PDK1 axis, suggesting that NORAD has the potential to contribute to the development of therapeutic approaches against Sa-AKI.

Proliferative glomerulonephritis with monoclonal IgG Lambda deposits caused by plasmablastic lymphoma: a case report.

INTRODUCTION: As a very rare form of B-cell lymphoma, plasmablastic lymphoma (PBL) typically occurs in patients with underlying immunosuppression, including human immunodeficiency virus (HIV), organ transplantation, and autoimmune diseases. For HIV-positive patients, PBL normally originates in the gastrointestinal tract, especially from the oral cavity in most cases. It is extremely rare to find abdominal cavity involvement in PBL, and there has been no previously reported instance of proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) attributed to monoclonal IgG (MIgG) lambda secreted by PBL. CASE PRESENTATION: We report the case of an HIV-negative female with nephrotic syndrome, renal insufficiency, and multiple swollen lymph nodes. Ascitic fluid cytology revealed a high level of plasmablast-like lymphocytes with the restriction of lambda light chains. Besides, the renal biopsy revealed PGNMID, which could presumably be secondary to MIgG-lambda-secreting by PBL. MIgG-lambda-restricted expression was discovered earlier in the kidney tissue than in the blood. CONCLUSION: The diagnostic landscape for PBL is notoriously intricate, necessitating a multifaceted and nuanced approach to mitigate the risks of erroneous identification.

Clinical effects of continuous veno-venous hemofiltration combined with hemoperfusion for the treatment of multiple myeloma complicated with acute kidney injury.

Objective: To evaluate the clinical efficacy of continuous veno-venous hemofiltration (CVVH) combined with hemoperfusion for the treatment of multiple myeloma (MM) complicated with acute kidney injury (AKI). Methods: Medical records of 73 patients with MM complicated with AKI admitted to the First People's Hospital of Huzhou from January 2019 to January 2021 were retrospectively analyzed. According to the treatment records, 35 patients received simple chemotherapy (control group), and 38 patients received CVVH combined with HP on the basis of chemotherapy (observation group). We compared the clinical efficacies, renal function indexes, and the serum globulin and erythrocyte sedimentation rate (ESR) values between the two groups. Results: After the treatment, the total efficacy of the observation group was significantly higher (81.58%) than that in the control group (57.14%; p <0.05). Serum cystatin C (CysC), urea nitrogen (BUN), ß2 macroglobulin (ß2-MG) and creatinine (SCr) levels were significantly lower in the observation group than in the control group (p <0.05). Serum globulin level and ESR values in the observation group after the treatment were also significantly lower than in the control group (p <0.05). Conclusions: The outcomes of patients with MM complicated with AKI treated with CVVH and hemoperfusion differ significantly from those of the patients treated only with CVVH. Combining CVVH and hemoperfusion helps to improve the efficacy of the treatment, promotes renal function recovery, and improves the levels of serum globulin and ESR.

Urinary RBP as an Independent Predictor of Renal Outcome in Diabetic Nephropathy.

Background: Renal tubular impairment is prevalent in diabetic nephropathy (DN) and the histological severity predicted renal outcome. Biomarkers of tubular injury also increased in the urine of DN patients. The retrospective study aimed to assess the prognostic value of clinically widely applied urinary tubular injury markers, retinol-binding protein (RBP), ß2-microglobulin (ß2-MG) and N-acetyl-ß-D-glucosaminidase (NAG) in DN. Method: A total of 305 patients with biopsy-proven DN were enrolled. The baseline urine total protein and components including albumin, IgG, RBP, ß2-MG and NAG were retrieved from medical records. The primary outcome was end stage renal disease (ESRD). Cox proportional hazard analysis and restricted cubic splines were performed to evaluate the association of parameters with ESRD. Nomograms were constructed and concordance index (C-index) was used to measure the prediction ability. Result: The levels of urinary RBP, ß2-MG and NAG were positively correlated with the severity of interstitial fibrosis and tubular atrophy (IFTA). Positive correlations were also observed among ß2-MG, NAG and mesangial expansion. Urinary RBP was not correlated with any glomerular lesions. Urinary RBP, ß2-MG and NAG were risk factors for ESRD in hazard analysis with adjustment for age, gender and body mass index (BMI). The hazard ratios increased with the increment of baseline levels. In the multivariate Cox model including serum creatinine (SCr), total urinary protein, urinary albumin, urinary IgG and the tubular injury biomarkers, urinary RBP (with every g/mol.Cr increase: HR 1.06, 95% CI 1.03-1.10, p =0.001) remained as an independent risk factor for ESRD in DN patients. Patients were divided by the medium value of urinary RBP into the low RBP and high RBP groups. Survival analysis showed that significantly more patients in the high RBP progressed to ESRD compared to those in the low RBP group (p =0.02) when urinary total protein was less than 3.5 g/g. The C-index of the nomogram incorporating age, gender, BMI, SCr and total urine protein was 0.757. The value increased to 0.777 after adding urinary RBP to the model. Conclusions: Urinary RBP excretion was only correlated with the severity of IFTA and independently predicted ESRD in DN patients.

Personalized discovery of altered pathways in clear cell renal cell carcinoma using accumulated normal sample data.

PURPOSE: To identify altered pathways in an individual with clear cell renal cell carcinoma (ccRCC) using accumulated normal sample data. METHODS: Gene expression data of E-GEOD-40435 was downloaded from the ArrayExpress database. Gene-level statistics of genes in tumor and normal samples were computed. Then, the Average Z method was applied to calculate the individual pathway aberrance score (iPAS). Subsequently, the significantly altered pathways in a ccRCC sample were identified using T-test based on the pathway statistics values of normal and ccRCC samples. Moreover, the identified altered pathways were verified through two methods: one was assessing classification capability for microarray data samples, and the other was computing the changed percentage of each pathway in ccRCC samples. RESULTS: Based on the threshold, 886 altered pathways were identified in all samples. The most significant pathways were potassium transport channels, proton-coupled monocarboxylate transport, beta oxidation of octanoyl-CoA to hexanoyl-CoA, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. Additionally, iPAS separated ccRCC from normal controls with an accuracy of 0.980. Moreover, a total of 5 significant pathways with change in 100% ccRCC samples were extracted including proton-coupled monocarboxylate transport, antigen presentation: folding, assembly and peptide loading of class I MHC, and so on. CONCLUSIONS: iPAS is useful to predict marker pathways for ccRCC with a high accuracy. Pathways of proton-coupled monocarboxylate transport, and antigen presentation: folding, assembly and peptide loading of class I MHC might play crucial roles in ccRCC progression.