American Journal of Nephrology最新文献

Introduction: Kidney dysfunction (KD) is a major metabolic risk factor for cardiovascular disease (CVD) and has been playing an increasingly significant role in the global burden of disease. However, there is still a lack of comprehensive, long-term, and systematic research assessing the global burden of CVD attributable to KD.

Methods: Using data from the Global Burden of Disease (GBD) 2021 database, we extracted burden indicators related to KD-associated CVD, including the number of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and their corresponding age-standardized rates, and evaluated annual trends using estimated annual percentage change. We performed decomposition analysis to identify three main drivers of burden changes-population, aging, and epidemiological change; and applied an autoregressive integrated moving average model to project future trends from 2022 to 2050.

Results: From 1990 to 2021, the global absolute numbers of deaths, DALYs, YLLs, and YLDs caused by KD-related CVD increased, while the corresponding age-standardized rates generally declined. Males exhibited a higher disease burden compared to females, and the elderly population, particularly those aged 75-84 years, represented the primary burden group. Middle-SDI countries experienced the highest burden, while inequality remained pronounced in low-SDI countries. Decomposition analysis revealed that, however, the increase in burden was primarily driven by population and aging, epidemiological change showed improvement. Forecasting results indicated that by 2050, the total number of cases will continue to rise, age-standardized rates will keep declining, but the YLD among females is expected to increase.

Conclusion: The burden of CVD attributable to KD is expected to continue rising in the future, characterized by increasing absolute numbers and declining age-standardized rates. This trend suggests that stratified prevention strategies may be needed across countries with varying SDI levels, with particular attention to older populations and integrated heart-kidney disease management to reduce the global burden of the disease.

Introduction: Intradialytic hypertension (IH) is associated with elevated ambulatory blood pressure (BP), volume overload, and endothelial dysfunction, which may contribute to its increased morbidity/mortality. There is a paucity of data on cardiac structural and functional abnormalities in IH patients.

Methods: In a cross-sectional analysis among 83 Veterans on maintenance hemodialysis with transthoracic echocardiograms (TTEs), we analyzed all intradialytic BP measurements from 3 treatments before and 3 treatments after the TTE and defined IH as an intradialytic BP slope >0 mm Hg/min averaged over these treatments. We compared systolic and diastolic dysfunction prevalence, ejection fraction (EF), left ventricular mass index (LVMI), left atrial volume index (LAVI), and early transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') and used logistic regression to determine if IH is independently associated with E/e' >14, a key criteria for diagnosing diastolic dysfunction and assessing elevated filling pressure.

Results: Mean age was 67.4 (±9.2) years. Most were men (n = 81), and 71% had diabetes. IH was present in 25 patients (30%), and they had higher prevalence of systolic dysfunction (52% vs. 17%, p = 0.003) and grade III diastolic dysfunction (16% vs. 2%, p = 0.03) reported on TTE compared to non-IH patients. IH patients had higher E/e' (18.5 [14-24] vs. 15.5 [11-19], p = 0.03), greater LVMI (137 [43] vs. 113 [38] mg/m2, p = 0.009), greater LAVI (52.7 [39-59] vs. 41.0 (33-48] mL/m2, p = 0.005), and lower EF (45.6% [17] vs. 55.7% [11], p = 0.002). IH associated with E/e' >14 in multiple models controlling for demographics, EF, mean intradialytic BP or CV comorbidities (OR 3.59-3.85, p < 0.05 for all); but in the model with LVMI, the association was blunted (OR 2.86, p = 0.1).

Conclusions: IH patients had a higher prevalence of TTE-reported systolic dysfunction and more severe diastolic dysfunction with more abnormalities than those without IH. IH independently associated with E/e' >14, even controlling for EF, intradialytic BP burden, and comorbid CV disease. Clinicians should consider TTE in IH patients to evaluate these abnormalities and optimize dialysis prescriptions and preventative pharmacologic therapies.

Introduction: Chronic kidney disease (CKD) is a public health and economic burden with serious adverse health outcomes and extremely low awareness. Current evidence on independent correlates of CKD awareness is inconsistent and recent data examining time trends of CKD awareness in the USA are dated. The aims of our study are to examine time trends in CKD awareness from 1999 to 2020 and examine independent correlates of CKD awareness in US adults with CKD.

Methods: We analyzed data from the National Health and Nutrition Examination Survey (1999-2020). The study sample consisted of 9,825 US adults with CKD. The primary outcome was CKD awareness. Independent correlates included sociodemographic, comorbidity and clinical variables. Unadjusted and adjusted logistic regression models were used to examine the association of CKD awareness and covariates.

Results: CKD awareness did not change significantly from 1999 (9.4%) to 2020 (10.8%). Fully adjusted model showed male sex (OR 1.41, 95% CI [1.09, 1.84]), non-Hispanic black race/ethnicity (OR 1.73, 95% CI [1.36, 2.20]), multimorbidity (OR 2.92, 95% CI [2.01, 4.25]), having high-risk CKD (OR 2.06, 95% CI [1.57, 2.70]), and very high-risk CKD (OR 5.38, 95% CI [3.99, 7.25]) were associated with higher likelihood of CKD awareness. However, age, education, and insurance were not significantly associated with CKD awareness.

Discussion: During the 2 decades examined in this study, CKD awareness remains extremely low. More prospective studies are needed to understand patient-level barriers to CKD awareness and provider-level barriers to CKD screening, CKD education, and knowledge transfer.

Background: Fluid monitoring is critical for patients on maintenance hemodialysis. Bioimpedance enables estimation of fluid volumes from measures of electrical tissue properties. However, empirical equations are needed to approximate key variables, especially in wrist-to-ankle bioimpedance measurements, introducing potential errors.

Summary: Here, we provide a technical overview of electrical impedance, derivation of fluid volumes from different bioimpedance methods and electrode setups, as well as sources of error including the assumption of constant resistivity, constant body temperature, and vendor-specific equations to derive fluid overload. We summarize the validity of bioimpedance methods in hemodialysis and conclude that irrespective of error sources reported above, segmental bioimpedance, where limbs and the trunk are measured separately, may be more accurate compared to the convenient wrist-to-ankle measurement. We argue that insufficient correction for variable body shape in wrist-to-ankle measurements jeopardizes this methodology, reporting here our analyses by means of theory and data simulation, where we found that conventional wrist-to-ankle bioimpedance underestimated extracellular fluid volume with increasing body fat percentage. The error could be reduced by using subject-specific body shape correction based on high-resolution 3D models. Finally, we attempt to provide guidance for identifying and mitigating common issues of wrist-to-ankle bioimpedance.

Key messages: While more convenient than segmental measurements, wrist-to-ankle bioimpedance may underestimate fluid volumes in obesity when body shape is not properly accounted for. Novel techniques, including smartphone-based 3D scans of the body, could potentially facilitate individualizing body shape correction to improve fluid volume estimates.

Introduction: Endothelin-1 (ET-1) is a potent vasoconstrictor and is implicated in the pathogenesis of proteinuria and progressive chronic kidney disease (CKD). With the development of ET-1 receptor antagonists, there is interest in whether higher ET-1 concentrations are associated with a greater risk of adverse cardio-kidney events among high-risk patients, e.g., those with established CKD and type 2 diabetes mellitus (T2DM).

Methods: ET-1 concentrations were measured in a random subset of TREAT (n = 997 [25%] of the original 4,038 patients with CKD, T2DM, and anemia) using an automated ELISA assay on the Ella analyzer (ProteinSimple). We used unadjusted and adjusted Cox regression models to explore the association of baseline serum ET-1 (log-transformed and quartiles) with kidney events (composite of kidney failure or doubling of serum creatinine), heart failure (HF), and cardiovascular and all-cause death.

Results: At baseline, mean age was 67 ± 10 years and 56% were female. The mean eGFR was 34 ± 11 mL/min/1.73 m2; median urine protein/creatinine ratio was 0.4 (0.1, 1.7) g/g; median ET-1 was 2.4 (1.9, 3.0) pg/mL. During a median follow-up of 2.4 years, there were 225 kidney events, 99 HF events, 124 cardiovascular deaths, and 188 all-cause deaths. Each log-unit higher ET-1 was associated with a higher adjusted risk of the kidney composite (HR: 1.61; 95% CI: 1.08, 2.39), HF (HR: 2.61; 95% CI: 1.42, 4.81), but not with cardiovascular death (HR: 1.06; 95% CI: 0.65, 1.75) or all-cause death (HR: 1.33; 95% CI: 0.86, 2.04). Compared with the lowest quartile, categorical analyses suggested a higher risk of kidney events (HR 1.69; 95% CI 1.08, 2.64), HF events (HR: 2.35; 95% CI: 1.16, 4.80), and all-cause death (HR: 1.81; 95% CI: 1.09, 3.00) for the highest quartile of ET-1.

Conclusions: Among patients with established CKD, T2DM, and anemia, higher baseline ET-1 was associated with a higher subsequent risk of kidney outcomes, HF events, and all-cause death. Whether higher ET-1 predicts responsiveness to ET receptor antagonism warrants further investigation.

Introduction: Immune checkpoint inhibitors (ICIs) have improved cancer treatment; however, their use can be limited by immune-mediated adverse events, such as kidney damage. Diagnostic limitations of nephrotoxicity may lead to worsening of the patient's prognosis. This study aimed to validate a panel of urinary biomarkers as diagnostic tools for kidney damage in patients treated with ICIs.

Methods: A prospective study was conducted on patients scheduled to receive ICIs. Those who subsequently developed kidney damage were considered cases; and those who did not were considered controls. A battery of biomarkers was assessed in urine samples at PRE-1, before the first treatment cycle; PRE-3, before the third cycle; and POST-3, 1 week after the third treatment cycle.

Results: A total of 46 patients participated in the study. At PRE-1, increased urinary excretion of IGFBP7, NAG, TIMP-2 × IGFBP7, and transferrin was observed in the case group, suggesting that these markers could be useful for early risk stratification of developing kidney damage. Furthermore, increased urinary excretion of albumin and NGAL was observed at PRE-3, suggesting that these markers could be of diagnostic utility to identify patients that could develop kidney damage once treatment is initiated. All of the aforementioned biomarkers demonstrated significant discriminatory ability between cases and controls, as verified by ROC curve analysis.

Conclusion: The proposed biomarker battery could be used as a preventive tool for decision-making in the management of oncology patients at risk for kidney damage associated with ICIs. Furthermore, its use would allow personalized adjustment of therapy that would minimize the probability of renal complications even before starting the first cycle of treatment.

Background: Methotrexate (MTX) is an antimetabolite anticancer agent that has been used at doses ranging from 20 mg/m2 of body surface area to 33,000 mg/m2. High-dose methotrexate (HDMTX), defined as doses higher than 500 mg/m2, is used to treat acute lymphoblastic leukemia, non-Hodgkin lymphoma, osteosarcoma, brain cancers, leptomeningeal spread of carcinomas, and other cancers. Depending on the dose and other factors, acute kidney injury occurs in 2%-39% of HDMTX courses and severe (Acute Kidney Injury Network grade 2 or higher) nephrotoxicity in approximately 2%, though incidence varies widely. Prompt recognition and treatment of delayed MTX elimination and renal dysfunction which includes increased hydration, high-dose leucovorin, and sometimes glucarpidase, is crucial to prevent life-threatening toxicities such as myelosuppression, mucositis, renal failure, and dermatitis.

Summary: In this article, we emphasize the importance of MTX pharmacokinetics and pharmacodynamics, highlight the cellular mechanisms of MTX anticancer activity, review the pathophysiology of MTX-induced renal injury, and explore strategies to prevent and manage MTX nephrotoxicity.

Key messages: Prompt recognition and effective treatment of renal and non-renal toxicities of HDMTX can improve outcomes, cancer prognosis, and survival.

Introduction: Prognostic value of glomerular hematuria in primary membranous nephropathy (PMN) patients with nephrotic syndrome (NS) has not been well understood. We investigated the earlier improvement of hematuria in PMN patients with NS receiving immunosuppressive (IS) therapies to illuminate its prediction capacity for the treatment response and remission status at 12 months.

Methods: This is a single-center retrospective study. From 1 January 2021 to 30 June 2024, patients with biopsy-proven PMN and NS starting IS therapy after renal biopsy were recruited. The main exposures were baseline hematuria and hematuria disappearing at 6 months. The outcome was nephrotic remission status at 12 months. Binary logistic regression models were used to estimate the relationship between exposures and outcomes. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive performance of exposures.

Results: Overall, 127 patients met the eligibility criteria. Overall, 112 patients (88.2%) had glomerular hematuria at the renal biopsy. Patients with hematuria had higher ages (57.2 ± 12.4 vs. 47.9 ± 12.7, p = 0.007), higher serum h-CRP levels (1.14 [0.66, 2.11] vs. 0.41 [0, 0.91], p = 0.004), and lower remission rate at 12 months (66/112 [58.9%] vs. 13/15 [86.67%], p = 0.037). In the subgroup of patients with glomerular hematuria, baseline hematuria levels were 18 (8, 25) RBC/μL. No significant correlations were found between baseline hematuria levels and other clinical indexes. At 6 months, 31 out of 112 (27.7%) patients had negative conversion of hematuria, and they had lower baseline PLA2R Ab titer (43.6 [0, 78.2] vs. 67.5 [10.8, 191.4], p = 0.025) and higher nephrotic remission rates at 12 months (26/31 [83.9%] vs. 40/81 [49.4%], p = 0.037), compared with those without. There were no significant differences among IS agents between the groups. Binary logistic regression demonstrated that hematuria disappearance at 6 months was an independent predictor for nephrotic remission at 12 months (OR = 0.211, 95% CI: 0.070-0.635, p = 0.006). ROC curve analysis revealed that the area under the curve for forecasting nephrotic remission at 12 months was 0.643 (p = 0.010) independently by the hematuria disappearance at 6 months and 0.781 (p < 0.001) combined with PLA2R Ab titer and IS therapeutic programs.

Conclusions: Patients with PMN and NS have high prevalence of glomerular hematuria. Patients without hematuria or negative conversion of hematuria at 6 months after IS treatment have higher nephrotic remission rates at 12 months. For patients with hematuria, hematuria disappearance at 6 months was an independent predictor for nephrotic remission at 12 months.

Introduction: Cardiovascular-kidney-metabolic (CKM) syndrome represents an integrated pathophysiological framework encompassing cardiovascular disease, kidney dysfunction, and metabolic disorders. The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) may reflect pathophysiological processes beyond kidney function, yet its prognostic significance across CKM syndrome stages remains poorly understood.

Methods: We examined records from 4,382 adult participants diagnosed with CKM syndrome (stages 0-3) extracted from the National Health and Nutrition Examination Survey database (1999-2004), with mortality surveillance continuing through December 2019. eGFRdiff was calculated using both absolute difference (eGFRabdiff) and the ratio (eGFRrediff) between cystatin C- and creatinine-based calculations. To investigate associations with overall and cardiovascular mortality outcomes, we employed Cox proportional hazard regression models with adjustments for demographic factors, clinical parameters, and biochemical indicators.

Results: Throughout a median surveillance period spanning 201.8 months, we documented 1,034 fatalities (15.69% of the cohort), with cardiovascular events accounting for 230 deaths (22.2% of all deaths, representing 3.24% of the entire cohort). After comprehensive adjustment in our statistical models, participants exhibiting a negative absolute eGFRdiff (eGFRabdiff <-15 mL/min/1.73 m2) demonstrated significantly elevated all-cause mortality risk (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.34-2.29) compared to those with intermediate eGFRabdiff values (-15 to 15 mL/min/1.73 m2). Conversely, subjects with positive eGFRabdiff (≥15 mL/min/1.73 m2) showed a protective association (HR 0.65, 95% CI: 0.54-0.80). Quantitatively, each standard deviation reduction in eGFRabdiff corresponded to a 42% mortality risk increase (HR 1.42, 95% CI: 1.28-1.59) and 57% higher cardiovascular mortality (HR 1.57, 95% CI: 1.36-1.82). The relative difference metric yielded similar patterns, with eGFRrediff <1 associated with elevated risks for both all-cause (HR 1.79, 95% CI: 1.48-2.17) and cardiovascular mortality (HR 1.71, 95% CI: 1.23-2.38) versus eGFRrediff ≥1. Notably, these associations were significant in CKM syndrome stages 2-3 but not in stages 0-1.

Conclusion: eGFRdiff is inversely associated with all-cause and cardiovascular mortality in populations with CKM syndrome stages 0-3, with stronger associations in more advanced stages. eGFRdiff may serve as a valuable prognostic marker in CKM syndrome, potentially reflecting underlying inflammatory, oxidative stress, and endothelial dysfunction processes that contribute to adverse outcomes.

Introduction: Parathyroid hormone (PTH) induces browning of adipose tissue, leading to increased resting energy expenditure and loss of adipose and muscle tissues in animal models of kidney failure. However, its clinical significance in humans remains unclear. This study aimed to investigate whether PTH-lowering therapy with upacicalcet, a novel injectable calcimimetic, affects serum albumin levels as a surrogate marker of protein-energy wasting in patients on hemodialysis with secondary hyperparathyroidism (SHPT).

Methods: This was a post hoc analysis of a phase 3, double-blind, placebo-controlled study of upacicalcet for the treatment of SHPT in patients on hemodialysis. Participants were randomized in a 2:1 ratio to receive either upacicalcet or placebo after each hemodialysis session for 24 weeks. Longitudinal changes in serum albumin levels were compared between groups using mixed-effects models for repeated measures. The rate of change (slope) in serum albumin over time was also estimated using a linear mixed-effects model.

Results: A total of 99 patients in the upacicalcet group and 46 patients in the placebo group were included in the analysis. While serum albumin levels tended to decline in the placebo group, they remained relatively stable in the upacicalcet group, with a significant treatment-by-time interaction. In the linear mixed-effects model, the slope was less steep in the upacicalcet group than in the placebo group, although the between-group difference (0.09 g/dL per year; 95% CI, -0.04 to 0.23) did not reach statistical significance.

Conclusion: These findings raise the hypothesis that PTH suppression with upacicalcet mitigates the gradual decline in serum albumin levels over time. Further studies are warranted to investigate the long-term impact of PTH control on protein-energy wasting and related clinical outcomes.