Abstract: Introduction: The urinary sodium-to-potassium ratio is an indicator of dietary sodium intake and has been associated with reduced kidney function. However, less is known about its association with albuminuria, the other key component of chronic kidney disease, in the community-dwelling adult population. We examined the association of the spot urinary sodium-to-potassium ratio with albuminuria and compared spot urinary and dietary sodium-to-potassium ratios.Methods: We quantified the association of the urinary sodium-to-potassium ratio with albuminuria in 6,274 Japanese adults (age, 40–97 years; 50.9% women) based on spot urine samples. We performed linear and logistic regression modeling to account for potential confounders. Elevated albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥ 30 mg/g. We secondarily evaluated the dietary sodium-to-potassium ratio based on a food-frequency questionnaire.Results: The median spot urinary and dietary sodium-to-potassium ratios were 2.70 (interquartile interval, 1.87–3.83) and 1.50 (1.21–1.84), respectively. The median ACR was 11.0 (6.0–24.0) mg/g. In a multivariable linear regression model, the spot urinary sodium-to-potassium ratio (per increment) was significantly associated with the natural logarithm of the ACR (regression coefficient, 0.023 [95% confidence interval [95% CI], 0.007–0.038]). This result was consistent in a multivariable logistic regression model (adjusted odds ratio, 1.08 [95% CI, 1.04–1.12]). The corresponding estimates for the dietary sodium-to-potassium ratio were 0.139 (95% CI, 0.087–0.191) and 1.28 (95% CI, 1.14–1.45), respectively.Conclusions: Both spot urinary and dietary sodium-to-potassium ratios were associated with elevated albuminuria in community-dwelling Japanese adults. Our findings further support the potential usefulness of the spot urinary sodium-to-potassium ratio as an indicator of sodium intake and suggest a link between sodium intake and kidney damage.
Abstract: Introduction: The angiotensin-converting enzyme 2 (ACE2) as well as the transmembrane protease serine type 2 (TMPRSS2) have been found to play roles in cell entry for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing Coronavirus disease 2019 (COVID-19). SARS-CoV-2 infection risk and severity of COVID-19 might be indicated by the expression of ACE2 and TMPRSS2 in the lung. Methods: A high salt diet rat model and RAAS blockade were used to test whether these factors affect ACE2 and TMPRSS2 expression of the lung. A normal (0.3% NaCl), a medium (2% NaCl), or a high (8% NaCl) salt diet was fed to rats for 12 weeks, along with enalapril or telmisartan, before examining the lung for histopathological alteration. Using immunofluorescence and qRT-PCR, the localization as well as mRNA expression of ACE2 and TMPRSS2 were investigated. Results: The findings provide evidence that both TMPRSS2 and ACE2 are highly expressed in bronchial epithelial cells as well as ACE2 was also expressed in alveolar type2 (AT2) cells. High salt diet exposure in rats leads to elevated ACE2 expression on protein level. Treatment with RAAS blockers had no effect on lung tissue expression of ACE2 and TMPRSS2. Conclusions: These findings offer biological support regarding the safety of these drugs that are often prescribed to COVID-19 patients with cardiovascular co-morbidity. High salt intake on the other hand might adversely affect COVID-19 outcome. Our preclinical data should stimulate clinical studies addressing this point of concern.
Abstract: Background：Currently, the interaction between proton pump inhibitors (PPI) and their effects on hemodialysis (HD) patients has not been clarified. Here, we aimed to explore the association between PPI and adverse outcomes in HD patients.Methods：A search was performed on the PubMed, Embase, Cochrane Library, and Web of Science databases for relevant articles published up to April 10, 2022. Studies examining the association (odds ratio [OR]) between PPI and side effects were identified. The study followed guidelines prescribed in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), and was registered with PROSPERO (CRD42021291177).Results: A total of 12 studies comprising 4,227,497 HD patients with PPI were identified. Results showed that PPI use was associated with increased risk of bone fracture and hip fracture in the HD patients (pooled OR = 1.29, 95% CI = 1.21-1.37, p PubDate: Mon, 25 Jul 2022 10:16:12 +020
Abstract: Background: Gitelman’s and Bartter’s syndromes (GS/BS) are rare genetic tubulopathies characterized by electrolyte imbalance and activation of the renin angiotensin aldosterone system (RAAS). These syndromes have intriguing biochemical and hormonal abnormalities that leads them to be protected from hypertension, cardiovascular and renal remodeling.Summary: In this review we explore the biochemical/molecular mechanisms induced by the activation of the RAAS and its counterregulatory arm which is particularly activated in GS/BS patients, in the context of blood pressure regulation. In addition, we report our findings in the context of COVID-19 pandemic where we observed GS/BS subjects being protected from infection. Key Messages: The intracellular pathways induced by Ang II starting from induction of oxidative stress and vasoconstriction, are crucial for the progression toward cardiovascular-renal remodeling and might be useful targets in order to reduce/halt the progression of Ang II/oxidative stress-induced cardiovascular-renal morbidity in several diseases.
Abstract: Background: Diabetic kidney disease is a major cause of global end-stage renal diseases. Ectopic lipid deposition in the renal tissues of diabetic kidney disease is one major factor leading to renal fibrosis and chronic kidney disease. Pterostilbene has been reported to display lipid-lowing activity and participate in many kidney diseases. However, the influence of pterostilbene on the ectopic lipid deposition is unclear. We intend to explore the influence of pterostilbene on the ectopic lipid deposition in the kidney of mice induced by high fat.Methods: A high-fat diet-induced diabetic mouse model was established to detect the alleviative effect of pterostilbene on the ectopic lipid deposition in the kidney of diabetic mice. Biochemical analysis was performed to examine the level of urine albumin, urine creatinine, serum creatinine and blood urea nitrogen in mice after pterostilbene treatment. Histological analysis was conducted to detect the degree of renal injury and fibrosis. Oil red O staining and immunohistochemical staining were carried out to evaluate lipid droplets and the expression of adipose differentiation-related protein (ADRP) in renal tissues of the mice treated by pterostilbene. The protein levels were assessed by western blotting.Results: Pterostilbene inhibits the expression of the TGF-β1 and p-smad3 and suppresses the protein levels of SREBP-1 and FAS, and ultimately reduces the ectopic lipid deposition and alleviates the renal tubular damage and renal fibrosis in the kidneys of diabetic mice induced by high fat, and improved kidney function.Conclusion: Pterostilbene alleviates renal fibrosis and ectopic lipid deposition in the kidneys of diabetic mice induced by high fat diet by inhibiting the TGF-β1/smad3 signaling.
Abstract: AbstractIntroduction Kidney transplantation has surpassed dialysis as the optimal therapy for end-stage kidney disease (ESKD). Yet, most patients could suffer from a slow but continuous deterioration of kidney function leading to graft loss mostly due to chronic allograft nephropathy (CAN) after KT. The dysregulated gene expression for CAN is still poorly understood. Methods To explore the pathogenesis of genomics in CAN, we analyzed the differentially expressed genes (DEGs) of kidney transcriptome between CAN and non-rejecting patients by downloading gene expression microarrays from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene co-expression network analysis (WGCNA) to analyze the co-expression of DEGs to explore key modules, hub genes, and transcription factors in CAN. Functional enrichment analysis of key modules was performed to explore pathogenesis. ROC curve analysis was used to validate hub genes.Results As a result, 3 key modules and 15 hub genes were identified by WGCNA analysis. 3 key modules had 21 mutual Gene Ontology (GO) term enrichment functions. Extracellular structure organization, extracellular matrix organization, and extracellular region were identified as significant functions in CAN. Furthermore, transcription factor 12 was identified as the key transcription factor regulating key modules. All 15 hub genes: Yip1 interacting factor homolog B, membrane trafficking protein(YIF1B), toll like receptor 8 (TLR8), neutrophil cytosolic factor 4 (NCF4), glutathione peroxidase 8 (GPX8), mesenteric estrogen dependent adipogenesis (MEDAG), decorin(DCN), serpin family F member 1 (SERPINF1), integrin subunit beta like 1 (ITGBL1), SRY-box transcription factor 15 (SOX15), trophinin associated protein (TROAP), SRY-box transcription factor 1 (SOX1), metallothionein 3 (MT3), lysosomal protein transmembrane (5LAPTM5), FERM domain containing kindlin 3 (FERMT3), cathepsin S (CTSS) had a great diagnostic performance (AUC>0.7). Conclusion This study updates information and provides a new perspective for understanding the pathogenesis of CAN by bioinformatics means. More research is needed to validate and explore the results we have found to reveal the mechanisms underlying CAN.
Abstract: Introduction: Setting dry weight (DW) in haemodialysis (HD) patients is still an hard issue. Several clinical, haematochimical and instrumental parameters have been considered. In the last years bioelectrical impedance vector analysis (BIVA) became the main method to evaluate body composition and water body percentage. However it is still difficult to assess the nutritional status and identify a correct DW in HD patients.Aim: to set DW and nutritional status, combining BIVA with phase angle (PhA) and serum brain natriuretic peptide (BNP) in HD patients.Methods: we evaluated PhA and BNP modifications before (T0), after HD section (T1) and after 60 days (T2), in all patients treated in our HD centre. Results: A total of 50 patients (36 males) with a mean age of 70.1 ± 8.85 years, were recruited. We did not report significant changes in BNP and PhA between T0 and T1, while they were significantly different between T0 and T2. We also reported a significant difference between T0 and T2 in ECW / TBW, while we did not show significant variations in ECM / BMC between T0, T1 and T2 indicating a stability of the nutritional status. PhA, BNP and ECW / TBW, returned to a normal value in patients in which we reached a DW, also considering clinical parameters such as blood pressure and antihypertensive therapy. The weight loss obtained with the evaluation of the BIVA and the BNP was 1.2-5.7 kg, greater than that calculated empirically which stood at around 0.9-4.3 Kg.Conclusion: We suggest to carry out BIVA with PhA combined with BNP to assess an adequate DW and evaluate a correct nutritional status in HD patients.
Abstract: Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a cluster of potentially life-threatening disorders often involving the kidney with a necrotizing crescentic glomerulonephritis with scanty deposition of immunoglobulins and complement. Historically the role of complement has been considered ancillary. Recently, an anti-myeloperoxidase (MPO) AAV model in complement-deficient mice has shown an involvement for the complement cascade in the development of the renal injuries. Further animal studies showing that in contrast to mice deficient for factor B and C5 animals deficient for C4 were susceptible to AAV development by injection of anti-MPO antibodies emphasized the specific involvement of the alternative pathway. Consonantly, the C5a receptor (Cd88) blockade was found to protect mice from MPO AAV. CCX168, i.e., Avacopan, a powerful inhibitor of C5a receptor that can be administered orally, was shown to reduce the pro-inflammatory effects of C5a and abolish the activation of neutrophils, their migration and adherence to endothelium, and the vascular endothelial cell retraction that increases permeability. Summary: Avacopan was found to be safe in healthy volunteers given a wide range of doses in a Phase 1 clinical trial. The Phase 2 trial CLEAR assessed the possibility to decrease dose or entirely replace glucocorticosteroids in the Standard of Care (SoC) therapy of AAV. Avacopan, added to CYC or RTX either in combination with GCs or not, shortened the time to remission in patients with either newly diagnosed or relapsing AAV. The Phase 3 ADVOCATE study compared the ability of an Avacopan-associated regimen to induce and sustain remission in AAV patients vs a conventional GC-associated scheme. Remission at week 26 was observed in 72.3% of patients given Avacopan and in 70.1% of those given prednisone. Sustained remission at week 52 (second primary endpoint) was obtained in 65.7% of patients given Avacopan and in 54.9% receiving prednisone. The Avacopan-associated regimen was non-inferior at week 26, and superior at week 52 in sustaining remission as compared to the GC-based scheme. Key point: The results of the ADVOCATE trial opened new prospects for the treatment of AAV and also other immune-mediated diseases with renal involvement. The possible position of Avacopan in a routinary clinical setting and its possible indications in specific subsets of patients with AAV are extensively discussed.
Abstract: AbstractBackground: It has been noted in observational and interventional studies that individuals exposed to fenofibrate can exhibit a rise in serum creatinine (sCr) concentration. However, it is not known to what extent this phenomenon impacts kidney function in patients who are referred to a nephrology clinic for consultation for chronic kidney disease (CKD). Methods: We conducted a prospective observational study of patients referred to our nephrology clinic for a new evaluation of a rise in sCr or worsening CKD and who were on fenofibrate therapy. We examined the effect of discontinuation of fenofibrate on kidney function, change in sCr and estimated glomerular filtration (eGFR) at 3, 6 and 12 months. Results: A total of 22 patients (59% women, 86% white, 59% with type 2 diabetes, 18% with peripheral arterial disease) were captured over 2.5 years. Median sCr at the time of fenofibrate discontinuation was 1.9 (1.1–3.3) mg/dL and eGFR 32 (17–57) ml/min; proteinuria was absent in 17 (77%). Upon discontinuation of fenofibrate, median sCr decreased to 1.5 (0.9–2.4), 1.4 (1.0–2.5) and 1.4 (1.0–2.3) mg/dL at 3, 6, and 12 months respectively (p PubDate: Tue, 24 May 2022 09:20:20 +020
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