In many cells and tissues including the glomerular filtration barrier (GFB), scaffold proteins are critical in optimizing signal transduction by enhancing structural stability and functionality of their ligands. Recently, mutations in scaffold protein Membrane-Associated Guanylate Kinase Inverted 2 (MAGI-2) encoding gene were identified among the etiology of steroid-resistant nephrotic syndrome (SRNS). MAGI-2 interacts with core proteins of multiple pathways such as TGF-β signaling, planar cell polarity pathway, and Wnt/β-catenin signaling in podocyte and slit diaphragm. Through the interaction with its ligand, MAGI-2 modulates the regulation of apoptosis, cytoskeletal reorganization, and glomerular development. This review aims to summarize recent findings on the role of MAGI-2 and some other scaffold proteins such as nephrin and synaptopodin in the underlying mechanisms of glomerulopathy.
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Background: Activation of renin-Angiotensin system in hypertension was believed to be major determinant in endothelial dysfunction, micro-inflammation, and reactive oxygen species generation. This study aimed to investigate the interaction of increased blood pressure with cardiovascular risk factors in chronic kidney disease (CKD). Materials & methods: The study was an observational study with cross-sectional design that consecutively enrolled CKD patients in Universitas Airlangga Hospital and two other hospitals in Surabaya, Indonesia. The resting blood pressure and kidney functions of the participants were examined. Malondialdehyde (MDA) and total antioxidant capacity (TAC) was measured in serum and used as oxidative stress markers. Serum hs-C-reactive protein (CRP), lymphocyte-to-monocyte ratio and platelet-to-lymphocyte ratio were utilized as inflammatory markers, while urine albumin-to-creatinine ratio (ACR) was used as renal disease marker. The participants were grouped based on their systolic and diastolic blood pressure (SBP and DBP). The difference of marker levels between groups was tested using Mann-Whitney test. The correlation between SBP and DBP with inflammation, oxidative stress, and albuminuria was determined using Spearman’s test. Results: As many as 71 patients with CKD were enrolled in this study. As much as 37% of the participants had high SBP and 14% had high DBP. High SBP positively associated with MDA (P<0.05), hs-CRP (P<0.05), platelet-to-lymphocyte ratio (P<0.05), and ACR (P<0.0001) and negatively with lymphocyte-to-monocyte ratio (P<0.05) and TAC (P<0.0001). High DBP associated positively with ACR (P<0.05) and negatively with TAC (P<0.05). Conclusions: High systolic or diastolic blood pressure was significantly associated with inflammation, oxidative stress and albuminuria. Optimal blood pressure control may be one of strategies to prevent inflammation and oxidative stress among CKD patients. J MEDICINE JUL 2019; 20 (1) : 12-18
BACKGROUND: Sleep deprivation is strongly associated with cardiovascular disease (CVD) via sympathetic overstimulation and systemic inflammation in general population. However, the significance of poor sleep quality in chronic kidney disease (CKD) is still underexplored.METHODS: This study assessed the sleep quality of 39 with non-dialysis CKD (ND CKD) patients and 25 hemodialysis CKD (HD CKD) patients using the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Poor sleeper was defined as individual with PSQI > 5.RESULTS: The prevalence of poor sleeper (30% vs. 60%, p=0.029) and the cummulative PSQI (ND CKD 4.5±4.4, HD CKD 8±6, p=0.038) are different between ND CKD and HD CKD groups. Among the ND CKD, there are association between short sleep duration (< 5 hours per day) with elevated diastolic blood pressure groups (r=0.421, p<0.05); habitual sleep efficiency with platelet-to-lymphocyte ratio (r= 0.532, p<0.0001); daytime dysfunction with increased hs-CRP (r=0.345, p=0.032) and neutrophil-to-lymphocyte ratio (r=0.320, p=0.046). In HD CKD group, a requirement to use sleep medication was associated with elevated highsensitivity C-reactive protein (hs-CRP) level (r=0.434, p=0.030) and decreased monocyte-to-lymphocyte ratio (r=- 0.410, p=0.042); daytime dysfunction was associated with serum hs-CRP (r=0.452, p=0.023).CONCLUSION: This study revealed that some features of poor sleep quality in CKD patients including low sleep efficiency, daytime dysfunction and requirement to use sleep medication were associated with increased diastolic blood pressure, hs-CRP and blood-count-based inflammatory predictors. Thus, this finding prompt to pay closer attention to sleep complaints in the management of CVD risk factors in CKD patients.KEYWORDS: sleep quality, chronic kidney disease, blood pressure, inflammation
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