Journal of Nephrology最新文献

Background: The incidence of acute type B aortic dissection is higher than that of acute type A aortic dissection among patients on dialysis. However, the impact of being on chronic dialysis on outcomes after type B aortic dissection remains unknown. This study aimed to investigate the trends in in-hospital mortality after type B aortic dissection and the association between body mass index (BMI) and survival paradox on dialysis.

Methods: This study included 48,889 type B aortic dissection hospitalizations in Japan from 2010 to 2020 based on data from a nationwide administrative database. Logistic regression was used to examine mortality risks and restricted cubic spline to investigate the non-linear association between mortality and BMI.

Results: There were 2,116 in-hospital deaths, and the mortality rates were 8.0% in patients receiving chronic dialysis and 4.3% in patients not receiving dialysis. Patients not receiving dialysis had decreased trends of absolute mortality. Meanwhile, patients receiving chronic dialysis had a higher mortality rate from 2010 to 2020. The mortality risk was high in patients receiving chronic dialysis who were underweight and had normal BMI, but not in those who were overweight. Restricted cubic spline analysis showed that a higher BMI was associated with a lower mortality risk in dialysis patients. This finding contrasted the U-shape observed in patients not receiving dialysis.

Conclusions: A lower BMI was associated with a higher risk of in-hospital mortality after type B aortic dissection among dialysis patients, thereby illustrating the obesity paradox. Our findings provide insights that can enhance the management strategies for dialysis patients facing type B aortic dissection.

Trial emulation, also known as target trial emulation, has significantly advanced epidemiology and causal inference by providing a robust framework for deriving causal relationships from observational data. This approach aims to reduce biases and confounding factors inherent in observational studies, thereby improving the validity of causal inferences. By designing observational studies to mimic randomized controlled trials (RCTs) as closely as possible, researchers can better control for confounding and bias. Key components of trial emulation include defining a clear time-zero, simulating random assignment using techniques like propensity score matching and inverse probability treatment weighting, assessing group comparability by standardized mean differences and establishing a clear comparison strategy. The increasing availability of large-scale real-world databases, such as research cohorts, patient registries, and hospital records, has driven the popularity of target trial emulation. These data sources offer information on patient outcomes, treatment patterns, and disease progression in real-world settings. By applying the principles of target trial emulation to these rich data sources, researchers can design studies that provide robust causal inferences about the effects of interventions, informing clinical guidelines and regulatory decisions. Despite its advantages, trial emulation faces challenges like data quality, unmeasured confounding, and implementation complexity. Future directions include integrating trial emulation with machine learning techniques and developing methods to address unmeasured confounding. Overall, trial emulation represents a significant advancement in epidemiology, offering a valuable tool for deriving accurate and reliable causal inferences from observational data, ultimately improving public health outcomes.

Background: Chronic kidney disease (CKD) increases cardiovascular risk, however, traditional cardiovascular risk factors cannot entirely explain it. A real-world investigation examined the concept that renal function decline is linked to carotid total plaque area progression, which strongly confirms cardiovascular risk. We analyzed CKD patients in stages 1-3 to find risk factor relationships before the onset of severe CKD.

Methods: We monitored 328 patients for 16 ± 5 months. Participants were classified at baseline by estimated glomerular filtration rate (eGFR) stage: G1 (≥ 90), G2 (60-89), and G3 (30-59 ml/min/1.73m²). Ultrasound-guided total plaque area tracked atherosclerosis. Age, sex, blood pressure, lipids, and HbA1c were covariates. Total plaque area and variables were measured on day 1 and at the conclusion of observation. We used a multilevel mixed effects model to assess biological and behavioral factors on total plaque area progression in the general population. For validation, this research was conducted on 73 CKD patients with optimal traditional cardiovascular risk factor management during 15 ± 5 months.

Results: Multiple analyses showed an inverse relationship between eGFR decline and total plaque area progression [β-exponent = 0.99 (95% CI = 0.98-0.99)], regardless of age, lipid profile, blood pressure, smoking, diabetes, or hypertension. The correlation remained significant in the 73-patient sample with optimal traditional cardiovascular risk factor management (β-exponent = 0.99; 95% CI 0.97-0.99). Although traditional cardiovascular risk factor management was excellent, total plaque area increased considerably in G2-G3 patients compared to G1.

Conclusions: CKD, total plaque area, and eGFR are inversely correlated, independent of traditional cardiovascular risk factors, suggesting that non-traditional mechanisms are responsible for resistant atherosclerosis. The combination of eGFR and total plaque area may be useful in identifying high-risk patients.

Background: Anti-neutrophil cytoplasmic antibody (ANCA) Renal Risk Score has not been widely validated in Chinese patients with myeloperoxidase -ANCA-associated glomerulonephritis and its predictive ability needs to be improved.

Methods: Three hundred and forty patients with biopsy-proven myeloperoxidase-ANCA-associated glomerulonephritis were included in this study. They were divided into an oliguric group (urine volume < 400 ml/24 h) and a non-oliguric group (urine volume ≥ 400 ml/24 h). The ANCA Renal Risk Score and Berden classes were used to predict the risk of end-stage kidney disease (ESKD), and Cox regression analysis was performed to evaluate the impact of oliguria on ESKD risk.

Results: The predictive performance of ANCA Renal Risk Score was significantly higher than that of Berden classes (AUC: 0.79 vs. 0.709, P = 0.003). Thirty-six (10.6%) patients presented with oliguria. Patients in the oliguric group had significantly lower levels of baseline estimated glomerular filtration rate (eGFR) [6.51(4.55-7.72) vs. 21.22(11.49-36.63) ml/min/1.73 m², P < 0.001], hemoglobin (78.33 ± 16.75 vs. 92.47 ± 18.95 g/L, P < 0.001), serum albumin (32.01 ± 5.92 vs. 36.22 ± 4.84 g/L, P < 0.001), and a lower percentage of normal glomeruli [6.86(0-17.39)% vs. 18.18(9.09-35)%, P < 0.001]. Consistently, the oliguric group had a higher percentage of patients that progressed to ESKD (83.3% vs. 36.2%, P < 0.001). Multivariate Cox regression analysis showed that oliguria was an independent risk factor for ESKD [HR = 2.38(1.39-4.06), P = 0.002]. Oliguria scores (3 points for presence and 0 for absence) were incorporated into the ANCA Renal Risk Score, resulting in ANCA Renal Risk Score-U. The patients were then categorized into four risk groups: low-(0-2 points), moderate-(3-7 points), high-(8-11 points) and very high-(12-14 points). The incidences of ESKD in these groups were 11.1%, 30%, 72.2% and 95.8%, respectively. The predictive efficacy of ANCA Renal Risk Score-U in predicting ESKD risk was significantly higher than that of the ANCA Renal Risk Score (AUC: 0.812 vs. 0.79, P = 0.025).

Conclusions: This study has validated the ANCA Renal Risk Score for predicting kidney outcomes among Chinese patients with myeloperoxidase-ANCA-associated glomerulonephritis. Furthermore, the ANCA Renal Risk Score-U model with oliguria as a variable can further improve the prediction of ESKD risk in patients with myeloperoxidase-ANCA-associated glomerulonephritis.

IgA nephropathy is the commonest pattern of primary glomerular disease in the world, with high rates of progression to kidney failure. As IgA nephropathy commonly causes kidney failure at a young age, kidney transplantation is commonly used to treat kidney failure. However, high rates of recurrent disease in the allograft remain a common management challenge. The prevalence of post-transplant recurrence approaches 15% at ten years post-transplant and is associated with poor allograft function and high rates of allograft loss. Post-transplant IgA nephropathy has also been described de novo in some case series. Treatment of recurrent IgA nephropathy has been challenging but with the rapid growth of new treatments for IgA nephropathy it is likely that many of these treatments will, over time, transition to the treatment of recurrent disease. In this narrative review, our aim is to evaluate post-transplant IgA nephropathy in terms of epidemiology, risk factors, underlying pathophysiology, diagnosis and management strategies.

Background: The Human Protein Atlas, with more than 10 million immunohistochemical images showing tissue- and cell-specific protein expression levels and subcellular localization information, is widely used in kidney research. The Human Protein Atlas contains comprehensive data on multi-tissue transcript and protein abundance, allowing for comparisons across tissues. However, while visual and intuitive to interpret, immunohistochemistry is limited by its semi-quantitative nature. This can lead to mismatches in protein expression measurements across different platforms.

Methods: We performed a comparison of the Human Protein Atlas' kidney-specific RNA sequencing and immunohistochemistry data to determine whether the mRNA and protein abundance levels are concordant.

Results: Our study shows that there is a discordance between mRNA and protein expression in the kidney based on the Human Protein Atlas data. Using an external validation mass spectrometry dataset, we show that more than 500 proteins undetected by immunohistochemistry are robustly measured by mass spectrometry. The Human Protein Atlas transcriptome data, on the other hand, exhibit similar transcript detection levels as other kidney RNA-seq datasets.

Conclusions: Discordance in mRNA-protein expression could be due to both biological and technical reasons, such as transcriptional dynamics, translation rates, protein half-lives, and measurement errors. This is further complicated by the heterogeneity of the kidney tissue itself, which can increase the discordance if the cell populations or tissue compartment samples do not match. As such, shedding light on the mRNA-protein relationship of the kidney-specific Human Protein Atlas data can provide context to our scientific inferences on renal gene and protein quantification.

Background: The relationship between kidney and vascular health is acknowledged, but detailed information is still missing. This study examines the relationship of estimated glomerular filtration rate (eGFR) and carotid intima media thickness, providing insights into the association between atherosclerosis and kidney function.

Methods: Participants older than 50 years of age who were part of the PolyIran-L study, a trial nested in the Golestan Cohort Study, were included. The maximal intima media thickness of both common carotid arteries was evaluated using B-mode ultrasonography. Four different cut-off values for abnormal carotid intima media thickness were considered. Correlation of carotid intima media thickness and eGFR was assessed with linear correlation and multivariable binary logistic regression models after adjusting for several confounders.

Results: In total, 1562 participants (750 females, 48%) were included in this population-based study. Assuming the eGFR < 45 [mL/min/1.73 m²] group as reference in the crude analysis, those with eGFR ≥ 45 and < 60 [mL/min/1.73 m²] showed an association of being less likely to have carotid intima media thickness above the 0.8 cutoff. However, the fully adjusted analysis showed no significant statistical association between carotid intima media thickness and eGFR.

Conclusion: This study did not support the independent association of eGFR and different carotid intima media thickness cutoffs. This pattern may be different in patients with severely decreased eGFR, a subset of cases in which it should be further investigated.

Background: Chronic kidney disease (CKD)-associated pruritus is a condition that strongly impacts CKD patients and is associated with increased morbidity/mortality, and worse health-related quality of life (HRQoL). Difelikefalin is currently the only drug approved in Europe specifically for treating moderate to severe CKD-associated pruritus in patients undergoing hemodialysis. The KALM-1 and KALM-2 trials showed better efficacy of difelikefalin vs placebo and best supportive care. The aim of this study was to investigate the cost-effectiveness of difelikefalin according to the Italian National Health Service (NHS) perspective.

Methods: A cohort model represented by four health states (No, Mild, Moderate, and Severe pruritus) was adapted to the Italian setting. The model used data from the KALM-1 and -2 trials for efficacy, integrated with other publications for HRQoL estimations. To assess the cost of disease management, a recent Italian publication on CKD-associated pruritus was used and a price of €27 per difelikefalin vial was assumed. The base case analysis over a 15-year time horizon, and an additional 10-year scenario analysis, were established. Additionally, both deterministic univariate analysis and probabilistic multivariate sensitivity analyses were developed. Discount rates of 3% were applied. An acceptability threshold of 40,000 €/quality-adjusted life-year (QALY) was considered.

Results: The results show that difelikefalin plus best supportive care is cost-effective vs best supportive care alone, with an incremental cost-effectiveness ratio, in the base case, of €35,823/QALY. Both the scenario and sensitivity analyses confirmed the strength of the results.

Conclusions: Difelikefalin was found to be a cost-effective treatment for the Italian NHS. These results support its reimbursement and its inclusion in routine clinical practice.