American Journal of Nephrology最新文献

Introduction: Time in target range of systolic blood pressure (SBP-TTR) is the percentage of time that the SBP remains within 110-130 mm Hg. The association between the SBP-TTR and clinical outcomes in patients with chronic kidney disease (CKD) remains unclear. We evaluated the risks of cardiovascular disease (CVD), all-cause mortality, and renal events across the SBP-TTR groups.

Methods: Overall, 193,289 patients with CKD who underwent at least two health checkups between 2012 and 2015 were selected from the Korean National Health Insurance Database. The patients were categorized into three categories based on their SBP-TTR levels: 76-100%, 26-75%, and 0-25%. The primary outcome was CVD risk and the secondary outcomes were all-cause mortality and progression to end-stage kidney disease (ESKD) according to SBP-TTR using Cox regression analysis.

Results: Compared with patients with SBP-TTR of 76-100%, the adjusted hazard ratios (HRs) for CVD were 1.07 (95% confidence interval [CI], 1.03-1.10) and 1.09 (95% CI: 1.06-1.13) for patients with SBP-TTR of 26-75%, and 0-25%, respectively. The adjusted HR for all-cause mortality was 1.04 (95% CI: 1.003-1.07) and 1.37 (95% CI: 1.28-1.46) for patients with SBP-TTR of 26-75% and 0-25%, respectively. The adjusted HRs for ESKD progression increased gradually: 1.14-fold (95% CI: 1.07-1.21) for the SBP-TTR 26-75% group and 1.37-fold (95% CI: 1.28-1.46) for the SBP-TTR 0-25% group. For patients not taking antihypertensive medications, a lower SBP-TTR was associated with a higher risk of CVD events and ESKD progression than in those taking antihypertensive medications.

Conclusion: Among patients with CKD, those with a lower SBP-TTR had a higher risk of cardiovascular events, mortality, and progression to ESKD.

Introduction: Patients with end-stage kidney disease develop cognitive impairment due to comorbidities and dialysis dependence. Among community-dwelling older adults, cognitive (CT) and exercise training (ET) are promising interventions to preserve cognition; these interventions may be tailored for adults undergoing in-center hemodialysis.

Methods: Adult (≥18 years) English-speaking patients undergoing hemodialysis (within 3 months to 3 years of initiation) were enrolled in a 2 × 2 factorial randomized controlled trial: Interventions Made to Preserve Cognitive Function Trial (IMPCT). Participants (n = 121) were block-randomized (September, 2018-February, 2023) into 4 arms: control (SC) (n = 26), intradialytic web-based CT (n = 31), ET using foot peddler (n = 29), and combined CT+ET (n = 35). Participants underwent assessments at baseline and 3 months for executive function, global cognitive function, clinical outcomes, and patient-centered outcomes. We estimated 3-month executive function change (primary outcome) and secondary outcomes using linear regression.

Results: There were no differences in 3-month executive function change by arm. Participants exhibited improvement in 3-month global cognitive function in CT+ET arm (Montreal Cognitive Assessment score difference = 2.1, 95% CI: 0.4-3.9), and self-reported 3-month improvement in perceived health change (score difference = 0.8, 95% CI: 0.2-1.4) in ET arm.

Conclusion: Clinicians may encourage CT+ET for hemodialysis patients to improve short-term global cognitive function and perceived health. The long-term benefits of these interventions warrant further study.

Introduction: Erythropoietin and roxadustat are commonly used to manage anemia in hemodialysis-dependent chronic kidney disease (CKD) patients, but the comparative safety and effectiveness are unknown.

Methods: This is a retrospective cohort study. Data were extracted from Tianjin Healthcare and Medical Big Data Platform. We screened all patients with CKD stage G5 and anemia (hemoglobin <100 g/L) who were treated with either erythropoietin or roxadustat between January 1, 2015, and December 31, 2021. The primary endpoints included expanded composite of major adverse cardiovascular events (MACE+), cardio-cerebrovascular events, and thromboembolic events in the peridialytic period, defined as the duration from the time of estimated glomerular filtration rate decrease to <15 mL/min × 1.73 m2 to 3 months after dialysis initiation. A propensity score-matched analysis (1:1 ratio; caliper width: 0.02) was conducted to minimize the impact of confounding factors.

Results: The initial screen identified a total of 40,324 patients; 1,092 were included in the propensity score-matched analysis (546 in each group). In comparison to the roxadustat group, the erythropoietin group had a lower rate of MACE+ events within 6 months (13.4% vs. 21.2%, p < 0.001) and 12 months of treatment initiation (17.0% vs. 24.0%, p = 0.004), as well as within 3 months of hemodialysis initiation (12.9% vs. 28.7%, p < 0.001). The rate of cardio-cerebrovascular events was also lower in the erythropoietin group within 6 months (38.5% vs. 50.7%, p < 0.001) and 12 months of treatment initiation (49.1% vs. 56.2%, p < 0.001). The rate of thromboembolic events did not differ between the two groups.

Conclusion: Peridialytic erythropoietin was associated with a more favorable cardiovascular safety profile versus roxadustat in hemodialysis-dependent CKD patients.

Background: Paraneoplastic glomerular diseases are triggered by substances secreted by tumor cells, such as tumor antigens, rather than direct tumor invasion.

Summary: These conditions frequently manifest as glomerular disorders, particularly in the elderly, with membranous nephropathy being the most observed lesion. They often present with proteinuria, hematuria, and/or varying levels of kidney dysfunction. In some cases, the initial presentation may precede the diagnosis of malignancy and can be indistinguishable from the idiopathic glomerulopathies, requiring a high level of clinical suspicion to accurately identify a paraneoplastic origin. Although the exact pathophysiologic mechanisms underlying paraneoplastic glomerulopathy are not fully understood, they are thought to involve an immune-mediated response to tumor antigens in most cases.

Key message: Recognizing paraneoplastic glomerulopathies is of significant clinical importance as their management is distinct and has substantial implications for the treatment of the associated malignancy.

Background: Electrolyte disorders are common in cancer patients and have significant impacts on treatment outcomes and quality of life. The frequency, severity, complexity, and etiology of fluid and electrolyte disorders are different among cancer patients when compared to the general population.

Summary: This review describes the key electrolyte imbalances and pathogenesis, including sodium disorders, potassium disorders, and abnormalities in magnesium, calcium, and phosphorus levels, within the context of cancer therapies. Cancer-specific therapies reviewed surgical and radiologic therapies, cellular therapies, use of checkpoint inhibitors, and traditional cytotoxic chemotherapy that can result in specific patterns of electrolyte derangements.

Key message: The objective of this article is to highlight clinical presentations and to discuss management of some cancer-specific electrolyte disturbances. This article underscores the importance of regular electrolyte monitoring and timely intervention in managing cancer patients.

Background: Kidney transplant is the treatment of choice for end-stage kidney disease, with longer survival and better quality of life posttransplant. However, long-term immunosuppression comes with an increased risk of cancer and infection. Cancer is one of the leading causes of death after kidney transplant. While novel cancer therapies become available, transplant recipients are usually excluded from clinical trials.

Summary: In this review, we summarize the updated knowledge on immunosuppression management in kidney transplant recipients treated with immune checkpoint inhibitors (ICIs), bispecific T-cell engager therapy, and chimeric antigen receptor (CAR)-T-cell therapies.

Key messages: Transplant nephrologists should be empowered to participate in the decision-making of cancer treatment together with patients, care partners, and oncologists, by managing immunosuppression.

Background: Immune checkpoint inhibitors (ICIs) have been increasingly used over the past decade for treatment of several cancer types. Despite the excellent cancer response they provide, their use has been associated with serious immune-related adverse events affecting multiple systems including the kidney. Currently, limited data are available to guide treatment of acute kidney injury secondary to ICI use (ICI-AKI) due to tubulointerstitial nephritis or glomerulonephritis. Another huge obstacle is the safety of resuming ICI following an episode of ICI-AKI.

Summary: Acute tubulointerstitial nephritis (ATIN) is the most common pathology associated with ICI-AKI, followed by other less common forms of glomerulonephritis. Management of this disorder is very challenging. Corticosteroids therapy remains the mainstay treatment for patients with ICI-ATIN. Use of other immunosuppressants for ICI-ATIN and recurrent ICI-ATIN has been also described in the literature. In patients with ICI-related glomerulonephritis, the use of rituximab is the more common approach reported in the literature. Regarding the safety to resume ICI following an episode of ICI-AKI, this decision should be made following a multidisciplinary approach on a case-by-case basis.

Key messages: Limited evidence is available to guide management in patients with ICI-AKI. More prospective studies are needed in the future to better guide treatment of cancer patients with ICI-AKI.

Introduction: The early diagnosis and appropriate treatment of monogenic glomerular diseases can reduce kidney failure, avoid unnecessary investigations such as kidney biopsies and ineffective treatment with immunosuppressants, guide transplant decisions, and inform the genetic risks of their family members. Yet, genetic testing for kidney disease is underutilized in Singapore. We aimed to implement a nephrologist-led genetic service and evaluate the acceptance, adoption, utility, and cost-effectiveness of genetic testing for monogenic glomerular disease in Singapore.

Methods: We will perform a prospective, multi-centre, type II hybrid effectiveness-implementation study with a post-design to evaluate both implementation and clinical outcomes of nephrologist-led genetic testing for suspected genetic glomerular kidney diseases. The multi-disciplinary implementation team will train "genetic nephrologists" to provide pre- and post-test counselling, order targeted exome panel sequencing for suspected glomerular kidney diseases (persistent microscopic haematuria and/or albuminuria or proteinuria in the absence of known causes, steroid-resistant primary nephrotic syndrome, apparent familial IgA nephropathy, or chronic kidney disease with no apparent cause), and interpret genetic test results; create workflows for patient referral, evaluation and management, and discuss genetic results at regular genomic board meetings. The outcomes are acceptance, appropriateness and adoption among patients and nephrologists, utility (proportion of patients who received genetic testing and have a confirmed diagnosis of genetic glomerular disease), and cost-effectiveness.

Conclusion: This study will create and evaluate a nephrologist-led genetic service, develop an efficient variant curation process, and inform future recommendations on the optimal referral and genetic testing strategy for monogenic glomerular disease in Singapore. This will facilitate the future mainstreaming of genetic testing that will enable precision medicine in kidney care.

Introduction: Peritoneal dialysis (PD) is an effective home therapy for end-stage kidney disease. However, continuous exposure to PD fluids with high glucose concentration and recurrent peritonitis may lead to the activation of cellular and molecular processes of peritoneal damage, including inflammation and fibrosis. In particular, recent studies have highlighted the role of neutrophils in chronic inflammation. This study explores how neutrophil extracellular traps (NETs) affect peritoneal membrane function and contribute to technical failures in PD patients.

Methods: We conducted a prospective observational study involving 250 noninfectious and 30 acute peritonitis patients. NETs were measured using nucleosome and myeloperoxidase DNA levels in PD fluids. Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-8 (MMP-8) were also measured to assess peritoneal inflammation and damage.

Results: A significant increase in peritoneal NETs, as determined by nucleosome and myeloperoxidase DNA levels, was observed in patients with acute peritonitis compared to patients without peritonitis. Even in noninfectious samples, NET levels were widely distributed and closely correlated with levels of MCP-1 and MMP-8. Higher levels of peritoneal NETs were closely associated with increased 4-h dialyzate/peritoneal (D/P) creatinine ratio and 1-h D/P sodium levels, indicating a higher prevalence of fast transport and limited free water transport. These factors were associated with a higher risk of technical failure. During a mean follow-up of 34 months, 39.2% (98 patients) switched from PD to hemodialysis, with higher NET levels significantly increasing the risk by 1.9 times (95% confidence interval: 1.27-2.83, p = 0.020).

Conclusion: This study suggests the importance of peritoneal NETs not only as markers of acute inflammation but also as significant immunological predictors of chronic peritoneal membrane inflammation and dysfunction and as potential risk factors for technical failure.