Renal Failure最新文献

Background and hypothesis: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a major genetic contributor to end-stage kidney disease (ESKD). Current evidence on tolvaptan primarily focuses on slowing estimated glomerular filtration rate (eGFR) decline and kidney volume growth. However, direct confirmation of its effectiveness in reducing the need for hemodialysis in ESKD remains limited.

Methods: We included ADPKD patients aged ≥18 years using TriNetx data from Sep 2, 2018, to Sep 3, 2023. Propensity score matching (PSM) ensured baseline comparability (standardized mean difference (SMD) <0.1). Hazard ratios (HRs) with 95% confidence intervals (CIs) evaluated outcomes, and subgroup analyses were performed.

Results: After 1:1 PSM, both groups comprised 673 patients. The average age was 45, with generally good health (3-5% diabetes, 2-3% ischemic heart disease). Baseline eGFR averaged ∼55 ml/min/1.732m². Post-matching, all SMDs were <0.1, indicating successful matching. Tolvaptan users exhibited lower eGFR (51.45 ± 30.09 vs. 57.37 ± 33.65, p < 0.001) and higher risk of stage 4-CKD (HR: 2.436, 95% CI:1.649, 3.599) compared to non-users. However, tolvaptan users showed significantly reduced chances of initiating hemodialysis (HR:0.362, 95%CI:0.176, 0.745), experiencing urinary tract infections (HR:0.581, 95%CI:0.354, 0.956), and all-cause mortality (HR:0.355, 95% CI:0.180, 0.700). Kaplan-Meier curves for hemodialysis initiation indicated higher survival rates among tolvaptan users across age and number of medication refill subgroups.

Conclusions: This real-world study, employing precise matching, reveals tolvaptan's role in reducing hemodialysis initiation risk in ADPKD, despite initial hemodynamic-induced lower eGFR.

Renal fibrosis is the major pathological changes of Chronic kidney disease (CKD). Piezo1, a mechanical sensitive ion channel, is implicated in organ fibrosis. However, the precise role of Piezo1 in CKD fibrosis is unknown. The aims of this study were to identify that the role of Piezo1 in CKD fibrosis and its potential involvement of mitochondrial dysfunction. We performed the study with the Piezo1 agonist Yoda1, Bax inhibitor BAI1, Piezo1 inhibitor GsMTx4 and detected the injury, fibrosis, apoptosis markers and mitochondrial dysfunction. The results showed that the levels of apoptosis, mitochondrial dysfunction, injury and fibrosis increased in TCMK-1 cells after treatment with Yoda1. However, these changes that induced by Yoda1 were relieved by BAI1. Similarly, inhibition Piezo1 with GsMTx4 also partly relieved the renal injury, renal fibrosis, apoptosis and mitochondrial dysfunction in vivo and vitro. In conclusion, we found Piezo1 promoted the initiation and development of renal fibrosis and inhibiting Piezo1 improved the fibrosis.

Introduction: Early diagnosis of acute kidney injury (AKI) is limited with current tools. MicroRNAs (miRNAs) are implicated in AKI pathogenesis in preclinical models, but less is known about their role in humans. We conducted a systematic review to identify dysregulated miRNAs in humans with AKI.

Methods: We searched Ovid MEDLINE, Embase, Web of Science, and CENTRAL (August 21, 2023) for studies of human subjects with AKI. We excluded reviews and pre-clinical studies without human data. The primary outcome was dysregulated miRNAs in AKI. Two reviewers screened abstracts, reviewed full texts, performed data extraction and quality assessment (Newcastle Ottawa Scale).

Results: We screened 2,456 reports and included 92 for synthesis without meta-analysis. All studies except one were observational. Studies were grouped by etiology of AKI: cardiac surgery-associated (CS-AKI, n = 13 studies), sepsis (n = 25), nephrotoxic (n = 9), kidney transplant (n = 26), and other causes (n = 19). In total, 128 miRNAs were identified to be dysregulated across AKI studies (45 miRNAs upregulated, 55 downregulated, 28 both). miR-21 was the most frequently reported (n = 17 studies) and it was increased in all etiologies except CS-AKI where it was decreased (n = 3 studies). Study limitations included bias due to targeted approaches, absence of clinical data/controls, and miRNA normalization methods. Overall study quality was fair (median 5/9, range 2-8 points).

Conclusion: Dysregulated miRNAs, particularly miR-21, have potential as AKI biomarkers. These results should be interpreted cautiously due to methodological limitations. Standardized methods and unbiased approaches are needed to validate candidate miRNA biomarkers.Registration: International Prospective Register of Systematic Reviews (PROSPERO CRD42020201253).

Background: Low protein intake (LPI) has been suggested as a treatment for chronic kidney disease (CKD). However, protein intake is essential for bone health.

Methods: We studied the database of the National Health and Nutrition Examination Survey, 2005-2010. Basic variables, metabolic diseases, and bone density of different femoral areas were stratified into four subgroups according to different protein intake (DPI) (that is, <0.8, 0.8-1.0, 1.0-1.2, and >1.2 g/kg/day).

Results: Significant differences were found among all lumbar area bone mineral density (BMD) and T-scores (p < 0.0001). There was an apparent trend between a decreasing BMD in the CKD groups with increasing DPI in all single lumbar spines (L1, L2, L3, and L4) and all L spines (L1-L4). Compared with DPI (0.8-1.0 g/day/kg), higher risks of osteoporosis were noticed in the subgroup of >1.2 g/day/kg over L2 (relative risk (RR)=1.326, 95% confidence interval (CI)=1.062-1.656), subgroup >1.2 g/day/kg over L3 (RR = 1.31, 95%CI = 1.057-1.622), subgroup <0.8 g/day/kg over L4 (RR = 1.276, 95%CI = 1.015-1.605), subgroup <0.8 g/day/kg over all L spines (RR = 11.275, 95%CI = 1.051-1.548), and subgroup >1.2 g/day/kg over all L spines (RR = 0.333, 95%CI = 1.098-1.618). However, a higher risk of osteoporosis was observed only in the non-CKD group. There was an apparent trend of higher DPI coexisting with lower BMD and T scores in patients with CKD. For osteoporosis (reference:0.8-1.0 g/day/kg), lower (<0.8 g/day/kg) or higher DPI (>1.2 g/day/kg) was associated with higher risks in the non-CKD group, but not in the CKD group.

Conclusions: In the CKD group, LPI for renal protection was safe without threatening L spine bone density and without causing a higher risk of osteoporosis.

Diabetic nephropathy (DN) is one of the most serious and frequent complications among diabetes patients and presently constitutes vast the cases of end-stage renal disease worldwide. Tubulointerstitial fibrosis is a crucial factor related to the occurrence and progression of DN. Oridonin (Ori) is a diterpenoid derived from rubescens that has diverse pharmacological properties. Our previous study showed that Ori can protect against DN by decreasing the inflammatory response. However, whether Ori can alleviate renal fibrosis in DN remains unknown. Here, we investigated the mechanism through which Ori affects the Wnt/β-catenin signaling pathway in diabetic rats and human proximal tubular epithelial cells (HK-2) exposed to high glucose (HG) levels. Our results revealed that Ori treatment markedly decreased urinary protein excretion levels, improved renal function and alleviated renal fibrosis in diabetic rats. In vitro, HG treatment increased the migration of HK-2 cells while reducing their viability and proliferation rate, and treatment with Ori reversed these changes. Additionally, the knockdown of β-catenin arrested cell migration and reduced the expression levels of Wnt/β-catenin signaling-related molecules (Wnt4, p-GSK3β and β-catenin) and fibrosis-related molecules (α-smooth muscle actin, collagen I and fibronectin), and Ori treatment exerted an effect similar to that observed after the knockdown of β-catenin. Furthermore, the combination of Ori treatment and β-catenin downregulation exerted more pronounced biological effects than treatment alone. These findings may provide the first line of evidence showing that Ori alleviates fibrosis in DN by inhibiting the Wnt/β-catenin signaling pathway and thereby reveal a novel therapeutic avenue for treating tubulointerstitial fibrosis.

Budapest Nephrology School (BNS) could have celebrated its 30th event if it had not been interrupted by COVID pandemic for a few years. Yet, the organization of 27th BNS in August 2023 resumed its successful and traditional activities at Semmelweis University, in the beautiful central European city of Budapest. In over two decades, BNS has faithfully adapted to the changes and developments of medical science and clinical nephrology, the fact which has kept it unique and attractive for nephrologists from across the globe. With such a long history and representing the top international professors of nephrology, BNS has proved to be a successful one-week, in-person refreshing course which has attracted over 1600 medical doctors from more than 60 countries. It has well served as an academic meeting point suitable for networking and exchange of up-to-date knowledge presented by the best international experts in nephrology. The dedication and focus of these experts on education, research and patient care represent the very concept of translational medicine. The invaluable experience of the past 27 years has set the standards for BNS to contribute to the evolution of translational nephrology in Europe in the next decade.

Objective: To explore the relationship between lactate-to-albumin ratio (LAR) at ICU admission and prognosis in critically ill patients with acute kidney injury (AKI).

Methods: A retrospective analysis was conducted. Patients were divided into low (<0.659) LAR and high LAR (≥0.659) groups. Least absolute shrinkage and selection operator regression analysis was conducted to select variables associated with the 30-day prognosis. Cox regression analyses were performed to assess the association between LAR and mortality. Kaplan-Meier curves were plotted to compare cumulative survival rates between high and low LAR groups. Subgroup analysis was employed to assess the stability of the results. ROC curve was used to determine the diagnostic efficacy of LAR on prognosis.

Results: A nonlinear relationship was observed between LAR and the risk of 30-day and 360-day all-cause mortality in AKI patients (p < 0.001). Cox regulation showed that high LAR (≥ 0.659) was an independent risk factor for 30-day and 360-day all-cause mortality in patients with AKI (p < 0.001). The Kaplan-Meier survival curves demonstrated a noteworthy decrease in cumulative survival rates at both 30 and 360 days for the high LAR group in comparison to the low LAR group (p < 0.001). Subgroup analyses demonstrated the stability of the results. ROC curves showed that LAR had a diagnostic advantage when compared with lactate or albumin alone (p < 0.001).

Conclusion: High LAR (≥0.659) at ICU admission was an independent risk factor for both short-term (30-day) and long-term (360-day) all-cause mortality in patients with AKI.

Objectives: Peritoneal dialysis (PD) serves as a vital renal replacement therapy for patients with end-stage kidney disease (ESKD). γ-Gamma-glutamyl transferase (γ-GGT) is a recognized predictor of oxidative stress and mortality. This study aimed to assess the prognostic significance of γ-GGT in predicting all-cause and cardiovascular mortality among PD patients.

Methods: A retrospective study was conducted, enrolling 640 PD patients from a single center. The one-year, three-year, and five-year mortality rates for all causes and cardiovascular causes were evaluated. Kaplan-Meier survival analysis and multivariate Cox regression analysis were performed.

Results: Within five years of initiating PD, the observed all-cause mortality rates at one, three, and five years were 11.72%, 16.09%, and 23.44%, while cardiovascular mortality rates were 2.97%, 7.34%, and 11.09%, respectively. Lower γ-GGT levels were associated with decreased all-cause mortality during one-, three-, and five-year follow-ups, along with reduced cardiovascular mortality in the first and third years, as indicated by Kaplan-Meier analysis on median γ-GGT groupings. Multivariate Cox regression analysis showed significantly decreased hazard ratios (HRs) for one- to five-year all-cause mortality and cardiovascular mortality in the lower γ-GGT group compared to higher groups. However, when sex differences were eliminated using separate tertile groupings for males and females, only the one- and three-year all-cause mortality rates demonstrated significantly reduced hazard ratios (HRs) in the lower γ-GGT groups.

Conclusion: This retrospective study suggests that γ-GGT levels have prognostic significance in predicting one- and three-year all-cause mortality among PD patients when accounting for sex differences.