Research progress on exosomes in podocyte injury associated with diabetic kidney disease

Diabetic kidney disease (DKD), a common cause of end-stage renal disease, is a serious complication that develops with the progression of chronic diabetes. Its main clinical manifestations are persistent proteinuria and/or a progressive decline in the estimated glomerular filtration rate. Podocytes, terminally differentiated glomerular visceral epithelial cells, constitute the glomerular filtration barrier together with the basement membrane and endothelial cells, and the structural and functional barrier integrity is closely related to proteinuria. In recent years, an increasing number of studies have confirmed that podocyte injury is the central target of the occurrence and development of DKD, and research on exosomes in podocyte injury associated with DKD has also made great progress. The aim of this review is to comprehensively describe the potential diagnostic value of exosomes in podocyte injury associated with DKD, analyze the mechanism by which exosomes realize the communication between podocytes and other types of cells and discuss the possibility of exosomes as targeted therapy drug carriers to provide new targets for and insights into delaying the progression of and treating DKD

Containing anti-PLA2R IgG antibody induces podocyte injury in idiopathic membranous nephropathy

AbstractBackground: Idiopathic membranous nephropathy is widely recognized as an autoimmune kidney disease that is accompanied by the discovery of several autoantibodies, and the antibody subclass in the circulation of patients with iMN is mainly IgG. However, the direct pathogenic effect of the containing anti-PLA2R IgG antibody on podocytes is not clear.Method: A protein G affinity chromatography column was used to purify serum IgG antibodies. Containing anti-PLA2R IgG antibodies from iMN patients and IgG from healthy controls were also obtained. Based on the established in vitro podocyte culture system, purified IgG antibodies from the two groups were used to stimulate podocytes, and the expression of essential podocyte proteins (podocin), the levels of inflammatory cytokines in the cell supernatant, cytoskeletal disorders, and podocyte apoptosis were analyzed.Results: Compared with that in the normal IgG group, the expression of podocin and podocin mRNA was reduced (p = 0.016 and p = 0.005, respectively), the fluorescence intensity of podocin on the surface of podocytes was reduced, the cytoskeleton of podocytes was disordered and reorganized, and the ratio of podocyte apoptosis was increased in the iMN group (p = 0.008).Conclusion: The containing anti-PLA2R IgG antibody might have a direct damaging effect on podocytes in idiopathic membranous nephropathy

Association between microalbuminuria and subclinical atherosclerosis evaluated by carotid artery intima-media in elderly patients with normal renal function

<p>Abstract</p> <p>Background</p> <p>Moderate to severe renal insufficiency and albuminuria have been shown to be independent risk factors for atherosclerosis. However, little is known about the direct association between subclinical atherosclerosis evaluated by carotid artery intima-media thickness (IMT) and microalbuminuria in elderly patients with normal renal function.</p> <p>Methods</p> <p>Subjects were 272 elderly patients (age  ≥ 60 years) with normoalbuminuria (n = 238) and microalbuminuria (n = 34). Carotid IMT was measured by means of high-resolution B-mode ultrasonography. Estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m² was defined as normal renal function. Those who had macroalbuminuria and atherosclerotic vascular disease were not included.</p> <p>Results</p> <p>Compared to subjects with normoalbuminuria, subjects with microalbuminuria had higher mean carotid IMT (1.02 ± 0.38 vs. 0.85 ± 0.28 mm; P < 0.01) and maximal IMT (1.86 ± 0.86 vs. 1.60 ± 0.73 mm; P = 0.06). By a multiple linear regression, microalbuminuria positively correlated with mean carotid IMT after adjusting for traditional cardiovascular disease risk factors including age, sex, hypertension, diabetes, smoking, total cholesterol, pulse pressure, waist circumference, serum uric acid. As a categorical outcome, the prevalence of the highest mean cariotid IMT quartile (increased IMT ≥ 1.05 mm) was compared with the lower three quartiles. After adjusted for potential confounders, microalbuminuria was associated with increased carotid IMT, with an odds ratio of 2.95 [95 % confidence interval, 1.22 – 7.10]. eGFR was not significantly associated with mean carotid IMT in our analysis.</p> <p>Conclusions</p> <p>A slight elevation of albuminuria is a significant determinant of carotid IMT independent of traditional cardiovascular risk factors in our patients. Our study further confirms the importance of intensive examinations for the early detection of atherosclerosis when microalbuminuria is found in elderly patients, although with normal renal function.</p

Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients

AbstractBackground Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 μg, 2.5 μg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 μg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 μg and placebo group was 8.81 mm (p = .110). Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5μg, 38.6% in 2.5 μg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus

Associations between genetic variants of NADPH oxidase-related genes and blood pressure responses to dietary sodium intervention: The GenSalt study

BACKGROUND The aim of this study was to comprehensively test the associations of genetic variants of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related genes with blood pressure (BP) responses to dietary sodium intervention in a Chinese population. METHODS We conducted a 7-day low-sodium intervention followed by a 7-day high-sodium intervention among 1,906 participants in rural China. BP measurements were obtained at baseline and each dietary intervention using a random-zero sphygmomanometer. Linear mixed-effect models were used to assess the additive associations of 63 tag singlenucleotide polymorphisms in 11 NADPH oxidase-related genes with BP responses to dietary sodium intervention. Gene-based analyses were conducted using the truncated product method. The Bonferroni method was used to adjust for multiple testing in all analyses. RESULTS Systolic BP (SBP) response to high-sodium intervention signifcantly decreased with the number of minor T allele of marker rs6967221 in RAC1 (P = 4.51 × 10). SBP responses (95% confdence interval) for genotypes CC, CT, and TT were 5.03 (4.71, 5.36), 4.20 (3.54, 4.85), and 0.56 (-1.08, 2.20) mm Hg, respectively, during the high-sodium intervention. Gene-based analyses revealed that RAC1 was signifcantly associated with SBP response to high-sodium intervention (P = 1.00 × 10) and diastolic BP response to low-sodium intervention (P = 9.80 × 10). CONCLUSIONS These fndings suggested that genetic variants of NADPH oxidaserelated genes may contribute to the variation of BP responses to sodium intervention in Chinese population. Further replication of these fndings is warranted