American Journal of Nephrology最新文献

Background: Acute kidney injury (AKI) is a common clinical condition where cellular senescence plays a crucial role in its progression. Previous studies have suggested that DOT1L plays a pivotal role in cellular senescence, yet its specific mechanisms in regulating AKI cellular senescence remain unclear.

Methods: This study utilized a glycerol-induced in vivo AKI model and employed the DOT1L-specific inhibitor EPZ004777 (EPZ) to suppress DOT1L function. Aging staining, PAS staining, and Masson staining were employed to assess renal aging, injury, and interstitial fibrosis. In vitro experiments utilized doxorubicin-treated human kidney tubular epithelial (HK-2) cells to establish an AKI cellular senescence model. EPZ was used to inhibit DOT1L, evaluating its impact on cellular senescence. High-throughput miRNA sequencing was performed to analyze differential expression of miRNAs downstream of DOT1L, and DOT1L overexpression and dual luciferase reporter gene experiments were conducted to explore interactions among DOT1L, miR-222-5p, and WNT9B.

Results: The results demonstrated that in vivo inhibition of DOT1L significantly reduced cellular senescence and improved renal tubular injury and interstitial fibrosis. In the doxorubicin -induced HK-2 cell model, DOT1L inhibition markedly decreased cellular senescence and lowered mRNA and protein levels of senescence markers, while alleviating cell cycle arrest. DOT1L inhibition notably upregulated miR-222-5p expression and suppressed WNT9B expression, with opposite effects observed with DOT1L overexpression.

Conclusion: DOT1L regulates cellular senescence through the miR-222-5p/WNT9B pathway in AKI. These findings suggest that DOT1L may serve as a potential therapeutic target to mitigate the progression of AKI to chronic kidney disease.

Objective: To investigate the potential of diffusion kurtosis imaging (DKI) in monitoring the improvement of liver and kidney injury in cirrhotic rats after bone marrow derived mesenchymal stem cells (BMSCs) treatment.

Methods: Thirty rats were induced with liver cirrhosis via subcutaneous injection of carbon tetrachloride. Six rats were randomly selected for DKI scanning and subsequently euthanized for biochemical and histological analysis. The remaining 24 rats were randomly divided into a BMSC group (n=12) and control group (n=12). In the BMSC group, six rats underwent dynamic DKI scans and were sacrificed after 13, 14, 15, and 16 weeks, while the other 6 rats were sacrificed after being scanned in the 14th week. The control group followed the same protocol as the BMSC group. Additionally, six normal rats were euthanized after undergoing DKI scanning to provide baseline data. Liver and kidney DKI parameters, biochemical markers, liver fibers, kidney hematoxylin-eosin (HE) score, and alpha smooth muscle actin (α-SMA) were analyzed.

Results: Compared to baseline, there was a significant increase in liver fibers and kidney HE scores by week 12. At weeks 13, 14, 15,and 16, the mean kurtosis (MK) of the liver in the BMSC group was significantly lower than that at week 12 and in the control group. At week 16, the mean diffusion (MD) in the BMSC group was significantly higher than that at week 12 and in the control group. The apparent diffusivity coefficient (ADC) values in the BMSC group were higher than those at week 12 and in the control group at weeks 13, 14, and 16. All regions of kidney showed decreased MK values from weeks 14 to 16 compared to week 12 and the control group. Liver fiber was moderately or highly correlated with all DKI parameters. MK and ADC of the renal cortex (CO) and outer stripe of the outer medulla (OSOM) showed moderate correlation with HE scores and α-SMA.

Conclusion: DKI can serve as a non-invasive means to effectively monitor the process of liver and kidney injury improvement in cirrhotic rats treated with BMSCs.

Introduction Previous studies have shown that there is a higher incidence of men initiating kidney replacement therapy (KRT) in comparison to women. However, the contribution of gender disparity may well differ among the different types of kidney disease, and over time. Utilising a nationwide Registry, we examined disease- and gender-specific trends in incident kidney failure required KRT. Methods Registry-based analysis of all incident patients commencing KRT in Australia using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. All patients who initiated dialysis in Australia from January 1971 to 31 December 2021 were included. Confidence intervals around rates were calculated and compared using Poisson distributions. Results During the study period a total of 31834 women and 47718 men were recorded in ANZDATA to have commenced KRT in Australia, a male to female ratio of 1.51 [1.49-1.53]. The male to female ratio increased over time from 1.05 [0.83-1.34] in 1971 to 1.78 [1.66-1.92] in 2021. There was a progressive increase in the male:female ratio with age; for those starting in 2017-21 this rose from 1.37 [95% CI 1.26-1.50] among 25-44 years olds to 4.38 [2.47-5.53] among those ≥85 years at KRT start. Conclusions Men had a significantly higher rate of starting KRT in Australia compared with women, and this difference is increasing over time. This disparity also varied between types of primary kidney disease but was higher among older age groups. It is still seen for causes (such as polycystic kidney disease) that have equal gender disease distribution, suggesting differences in propensity to commence KRT as well as differences in underlying disease processes.

Introduction: Peritonitis occurring within the first months on peritoneal dialysis (PD) has been associated with poorer PD outcomes. Whether early peritonitis is a risk factor for transfer to haemodialysis in the long term is a matter of investigation.

Methods: This retrospective study was conducted using data from the French Language PD Registry of incident PD patients between 2002 and 2018. Early-onset peritonitis (EOP) was defined as peritonitis occurring during the first 3 months on PD. Our hypothesis was that EOP was associated with an increased risk of transfer to haemodialysis during the first months on PD but that it was no longer associated with an increased risk of transfer to haemodialysis several months after the start of PD. The associations between EOP and the different outcomes were explored via time-dependent coefficient Cox regression and Fine and Gray regression.

Results: EOP was associated with an increased risk of PD cessation by transfer to haemodialysis within the first 12 months of PD and beyond (<12 months cs-HR 1.50, 95% CI: 1.36-1.66 and >12 months cs-HR 1.17, 95% CI: 1.06-1.28, respectively).

Conclusion: EOP is associated with a greater risk of PD cessation due to transfer to haemodialysis, especially within the first year after peritonitis occurrence, and with a persistent effect in the long term. Reducing or delaying EOP, notably through its systematic reporting and monitoring as a KPI to help in the implementation of QIPs, could have a favourable impact on patient-level outcomes.

Introduction We evaluated the association between iron-related biomarkers-key indicators of iron metabolism and inflammation, and crucial in the management of anemia in patients undergoing hemodialysis-and all-cause mortality. This study aimed to clarify the nuanced relationship between these biomarkers and mortality outcomes, addressing the limitations of traditional cutoff-based analyses. Methods We conducted a prospective cohort analysis of patients undergoing dialysis across Japan using data from the Japan Renal Database collected between 2019 and 2020. Patients who had been on dialysis for at least 3 months by the end of 2019 were considered eligible. The associations between iron-related biomarkers and all-cause within 1 year were analyzed using Cox proportional hazards models. The relationship between each biomarker and outcome was illustrated using restricted cubic spline curves, while the combined association of serum ferritin and TSAT with mortality was shown using contour plots. Results A total of 215,927 patients were included in the analysis. During the follow-up period, 17,803 (8.24%) deaths were recorded. Contour plots demonstrated increased mortality risk in areas with low ferritin and TSAT levels. Additionally, even in regions with high TSAT levels, there was a trend toward increased mortality risk with increasing ferritin levels. Conversely, in areas with low ferritin levels, there was a trend toward a decreased risk of death. Conclusions Our findings highlight the complex interplay between serum ferritin and TSAT levels, emphasizing the limitations of relying on single cutoff values for clinical decision-making. The study underscores the need for individualized approaches to iron management in patients undergoing hemodialysis.

Introduction: Podocyte injury has been proven to be a major cause for poor renal outcomes after acute kidney injury (AKI). However, clinical trial data are still limited. This study aimed to explore the clinical correlations between podocyte injury and renal outcomes in hospitalized AKI patients.

Method: This retrospective study analyzed data on 52 AKI patients who were histologically diagnosed with acute tubular necrosis or acute interstitial nephritis from six centers throughout China between January 2012 and June 2023. Patients were classified into two groups based on the degree of foot process fusion: ≤50% (mild podocyte injury group) and >50% (severe podocyte injury group). The outcomes were post-AKI new-onset proteinuria and incident CKD.

Results: Among 52 AKI patients (14 male; median age, 49 [30, 56] years), 28 (53.8%) had mild podocyte injury; 24 (46.2%) had severe podocyte injury. After 12-month follow-up, 16 (57.1%) had post-AKI new-onset proteinuria, and 5 (17.9%) had post-AKI incident CKD in mild podocyte injury group. Twenty (83.3%) had post-AKI new-onset proteinuria, and 14 (58.3%) had post-AKI incident CKD in severe podocyte injury group. Patients with more severe foot process fusion exhibited significantly higher incidences of post-AKI new-onset proteinuria (83.3% vs. 57.1%, p = 0.041) and incident CKD (58.3% vs. 17.9%, p = 0.003) at 12 months following AKI. The degree of foot process fusion (95% CI 1.013∼3.88, p = 0.048) and proteinuria at 3 months (95% CI 1.309∼5.443, p = 0.015) were identified as independent risk factors for post-AKI new-onset proteinuria at 12 months. The degree of foot process fusion (95% CI 1.026∼14.196, p = 0.048), and the presence of partial renal pathological features, including tubular atrophy (95% CI 1.012∼5.958, p = 0.030), interstitial inflammation (95% CI 1.005∼6.846, p = 0.039), interstitial fibrosis (95% CI 1.110∼6.075, p = 0.043) were independent risk factors for post-AKI incident CKD at 12 months. Kaplan-Meier analysis shows severe podocyte injury group had worst renal survival, including post-AKI new-onset proteinuria (p = 0.0066) and incident CKD (p = 0.0455).

Conclusion: The degree of podocyte injury is an independent risk factor for post-AKI new-onset proteinuria and incident CKD in patients, and patients with more severe podocyte injury exhibit a higher incidence of post-AKI new-onset proteinuria and incident CKD.

Introduction: Niacin is a non-statin lipid-lowering therapy that has been shown to lower triglycerides and improve other risk factors for renal outcomes. Despite these favorable data, the effect of niacin on long-term kidney outcomes remains unclear. The aim of this study was to examine the associations of niacin therapies with incident chronic kidney disease (CKD), end-stage renal disease (ESRD), and death in patients with estimated glomerular filtration rate (eGFR) of at least 60 mL/min/1.73 m2.

Methods: In a nationwide historic cohort of 1,139,630 United States (US) veterans with normal baseline eGFR, we examined the association of de novo prescription of niacin with incident CKD (defined as eGFR <60 mL/min/1.73 m2 on two occasions, separated by ≥90 days), ESRD (defined as the initiation of kidney replacement therapy), and death. Associations were examined in Cox proportional hazards models adjusted for demographics, major comorbidities, laboratory measurements, and medications. Prescription time-distribution matching was used to control for survival bias.

Results: We identified 133,450 new users of niacin. Overall, patients (n = 1,139,630) had a mean (standard deviation) age of 60 (13) years, with 6% female, 78% white, 16% black, and 6% Hispanic. Niacin users were more likely to be male, white, current, or former smokers, with higher frequencies of comorbidities and statin use. Niacin use (vs. nonuse) was associated with a higher risk of CKD (HR: 1.08, 95% confidence interval:1.07-1.10) but a lower risk of ESRD (0.82, 0.76-0.88) and death (0.90, 0.89-0.91).

Conclusions: In a large national cohort of US veterans with normal kidney function, niacin use was associated with a lower risk of ESRD and death but with a higher risk of incident CKD, which is potentially explained by acute effects on eGFR. Further studies are needed to corroborate the potential benefits of niacin on kidney function and survival.

Introduction: Zinc, an essential trace element, plays an important role in various cellular processes, and zinc deficiency is common in patients undergoing hemodialysis. Zinc has been shown to stimulate osteoblastic bone formation and mineralization and inhibit osteoclastic bone resorption. Although osteoporosis is highly prevalent among patients undergoing hemodialysis, the utility of areal bone mineral density (aBMD) measured using dual-energy X-ray absorptiometry (DXA) is limited because DXA cannot reveal bone microarchitectural alterations. The trabecular bone score (TBS) extracted from DXA images is a new texture measurement used to assess the bone microarchitecture. However, whether zinc status is associated with TBS in patients undergoing hemodialysis remains unclear. Therefore, we investigated the association between serum zinc levels and osteoporosis parameters (aBMD and TBS) in patients undergoing chronic hemodialysis.

Methods: This cross-sectional study included 316 outpatients undergoing hemodialysis at the Masuko Memorial Hospital in Japan. Serum zinc levels were measured, and aBMD and TBS were assessed using DXA.

Results: In total, 139 (41.0%) patients had zinc deficiency, defined as serum zinc levels <60 µg/dL. In multivariate linear regression analyses, high serum zinc levels were associated with high TBS (β = 0.146, p = 0.004) but not aBMD values (total hip aBMD: β = -0.0200, p = 0.63; lumbar spine aBMD: β = 0.0478, p = 0.34). In multiple logistic regression analysis, zinc deficiency was associated with degraded bone microarchitecture according to the TBS (odds ratio, 2.27; 95% confidence interval, 1.22-4.22; p = 0.009). No association was found between the serum zinc status and aBMD thresholds for osteoporosis.

Conclusion: These results suggest that zinc plays a protective role in bone metabolism by inhibiting chronic kidney disease-induced changes in the bone microarchitecture.

Introduction: Dry weight management in dialysis patients is crucial but often subjective, primarily based on symptoms. Due to continuous fluid removal in peritoneal dialysis (PD) and intermittent ultrafiltration in hemodialysis (HD), symptom-based assessments may be biased, leading to varying results. Surprisingly, no direct comparison of dry weight changes between PD and HD has been conducted. This study aimed to evaluate the impact of transitioning from PD to HD on body weight and related clinical parameters.

Methods: This retrospective cohort study included 127 stable PD patients who transitioned to HD. Changes in body weight, echocardiographic parameters, albumin, and hemoglobin levels were analyzed over a 1-year period post-transition.

Results: The mean patient age was 57.1 ± 15.5 years, with an average PD vintage of 5.8 ± 4.9 years. Most patients had hypertension. After transitioning to HD, body weight decreased significantly, with a reduction of -2.8 kg at 1 month, -5.3 kg at 3 months, and -7.5 kg 1 year post-transition. Echocardiographic parameters showed no significant changes. However, serum albumin and hemoglobin levels increased slightly but significantly after the transition, and the number of antihypertensive medications was also reduced.

Conclusion: The transition from PD to HD results in significant reductions in body weight. These findings underscore the often-overlooked issue of fluid overload in PD patients and its potential impact on patient outcomes.