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Background: Monitoring of serum alkaline phosphatase (ALP) is recommended in the management of chronic kidney disease (CKD)-mineral bone disorder (MBD) because of associations with poor outcome among dialysis patients. However, such associations may have changed with several advances in the management of CKD-MBD over the last decade.

Methods: Baseline data for 241,670 dialysis patients (mean age, 69 ± 12 years; male, 65.9%; median dialysis duration, 68 months) were extracted from a nationwide dialysis registry in Japan at the end of 2019. Outcomes, including all-cause and cardiovascular (CV) mortality and hip fracture, were evaluated using the registry at the end of 2020 and 2021. All-cause mortality was assessed using Cox regression analysis, whereas CV mortality and new hip fracture were assessed using competing-risks regression analysis. Multiple imputation for missing values was performed.

Results: Within the 2-year study period, a total of 40,449 patients (16.7%) died, including 13,562 (5.6%) CV deaths. Of the 168,836 patients with no history of hip fracture at the end of 2019, 4,136 (2.4%) suffered hip fracture within 2 years. Higher serum ALP was independently associated with higher all-cause and CV mortality and new hip fracture, but the association with CV mortality was marginal (hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.18-1.24; sub-HR [SHR] 1.07, 95%CI 1.03-1.12; and SHR 1.28, 95%CI 1.19-1.38, respectively). There is a linier association between serum ALP and all-cause mortality among the lower- parathyroid hormone (PTH) group, whereas lower serum ALP tended to have higher all-cause mortality than intermediate serum ALP among patients in the higher-PTH group.

Conclusions: Higher serum ALP was independently and linearly associated with higher all-cause and CV mortality and new hip fracture in Japanese dialysis patients. Higher serum ALP and higher intact PTH were synergistic in increasing all-cause and CV mortality but not with new hip fracture.

The lack of non-invasive urine and blood-based biomarkers for the diagnosis of acute kidney injury (AKI) in patients with cancer is an area of significant unmet clinical need. Traditional non-invasive diagnostic tools that are currently utilized in the clinic, such as creatinine and cystatin C-based eGFR measurements, urinalysis, urine sediment exam, urine protein quantification, and urine electrolyte measurement, lack the sensitivity and specificity to distinguish between the various underlying etiologies of AKI in patients with cancer. Imaging-based diagnostics can be helpful to rule out urinary obstruction, but also lack sensitivity and specificity to diagnose the etiology of AKI. Kidney biopsy is often required for definitive diagnosis. As our scientific understanding of the biological pathways that are dysregulated in AKI has advanced, there has been considerable interest in developing new biomarkers for AKI. For example, the diagnosis of acute interstitial nephritis (AIN), which can occur in patients treated with immune checkpoint inhibitors (ICIs), promises to be revolutionized by the incorporation of urinary testing for inflammatory biomarkers such as C-X-C motif ligand 9 (CXCL9), tumor necrosis factor alpha (TNF-α), and interleukin 9 (IL-9). In the case of cisplatin administration, biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) may improve prognostication, differentiating between persistent AKI resulting from acute tubular injury versus pre-renal azotemia. The development and validation of blood, urine and imaging biomarkers into widely utilized diagnostic tests will require a concerted effort, but could improve diagnosis, management and prognostication for a growing group of patients who are at high risk of developing AKI during the course of their illness.

Background: Many patients with newly created arteriovenous fistulas (AVF) may die before the AVF is needed for hemodialysis. However, formal competing risks frameworks are rarely used to report AVF patency, which may lead to biased estimates. We sought to identify the proportion of newly created AVF experiencing primary non-function and to describe long-term patency using a competing risk framework.

Methods: We did a prospective observational study in 257 adults with newly created AVF in Alberta, Canada. The primary outcome was primary non-function. Secondary outcomes included loss of primary-patency, loss of assisted primary-patency, and loss of secondary functional-patency. Results were presented using icon-array plots to form the basis for future decision aids.

Results: Participants were 63.0% male with mean age 62.3 years and median follow-up of 18.5 months (range 0.02-180 months). Of 257 participants, 50 could not be assessed for function or primary non-function, usually due to death. Of the remaining 207, 102 (49.3%) had primary non-function, and function was ultimately established for 142 (68.6%). Thus, only 142 of the 257 participants (55.3%) ultimately used the AVF for hemodialysis. High rates of competing risks led to biased results from Kaplan-Meier analyses of lost patency. When accounting for competing risks, loss of primary-patency among AVF with established function was 36.6%, 65.5% and 66.2%, at 1y, 3y and 5y respectively.

Conclusions: Only 55% of fistulas were ultimately used for hemodialysis when accounting for competing risks and primary non-function. These results and the icon-array plots may inform discussions surrounding vascular access options for patients.

Background: Prevention is a cornerstone for management of recurrent urinary stone disease. Current guidelines recommend metabolic evaluation, lifestyle modification, and medical treatment for patients with urinary stone disease. Nephrologists are uniquely qualified to evaluate stone risk and formulate treatment strategies to reduce that risk. The objective of this study was to determine the frequency of nephrology visits after a urinary stone diagnosis, a key window of opportunity to assess stone risk.

Methods: We used nationwide data from the United States Veterans Health Administration to identify patients who had an incident stone diagnosis between 2016 and 2018. We examined the proportion of patients who visited a nephrology clinic within 6 months of stone diagnosis.

Results: We identified 42,927 Veterans with urinary stone disease. Only 2432 (5.6%) visited a nephrology clinic within six months of the index diagnosis. The proportion of patients who visited a nephrology clinic after their stone diagnosis ranged between 0.7 and 20.7% across 104 VHA sites, with a median of 4.6% (25%, 75% range 3.4-7.0%). The median rate ratio for a nephrology follow-up visit after a stone diagnosis was 1.72. Veterans with chronic kidney disease were significantly more likely to visit a nephrology clinic relative to Veterans without chronic kidney disease (OR 5.19; 95% CI 4.69, 5.74).

Conclusions: Nephrologists are infrequently and variably involved in the care of patients after a urinary stone diagnosis, suggesting potential for quality improvement.

The Autosomal Dominant Polycystic Kidney Disease (ADPKD) Centers of Excellence Program, launched by the Polycystic Kidney Disease Foundation in 2022, aims to bridge the gap in specialized care for individuals with ADPKD. This program seeks to enhance the availability of specialized clinicians and simplify the process for patients seeking expert care. It is founded on three pillars: improving care for all individuals with ADPKD, educating and empowering the community, and advancing PKD research. The program draws inspiration from successful models in other diseases, such as cystic fibrosis and muscular dystrophy, which have demonstrated the effectiveness of standardized care centers in improving patient outcomes. Patient and clinician stakeholder interviews have identified key areas where a national program could make a significant impact, including the need for a core care team with defined referral processes, mentorship and shared care models, patient navigation services, and education around expert consensus and care guidelines. The program introduces two designations: "Center of Excellence" and "Partner Clinic" to accommodate diverse care settings and enhance patient access to specialists. The Partner Clinic designation ensures that patients in smaller community practices have access to specialized care through mentorship and guidance from experts at Centers of Excellence. The program also emphasizes the importance of specialized services, especially in underserved communities experiencing health disparities, to manage the complexities of ADPKD care. Patient focus groups have highlighted the need for care navigation services, centralized sources of knowledge, and access to local care. The program aims to address these needs by providing a structured framework for care coordination, enhancing patient self-advocacy, and improving overall outcomes for individuals with ADPKD.

Background: National strategies to address chronic kidney disease (CKD) are crucial to support kidney health. Lack of political support in the form of policy decisions and funding leads to fragmentation of kidney care and catastrophic health expenditure. This study used data from the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to obtain a global overview of the existence and reach of national strategies for kidney care.

Methods: We leveraged data from an international survey of stakeholders (clinicians, policymakers, and patient advocates) conducted by the ISN between July and September 2022. Data were extracted on existence and scope of national non-communicable disease (NCD) and/or CKD-specific strategies and policies, as well as recognition of kidney disease as a national health priority through participant perception and existence of CKD advocacy groups.

Results: Overall, stakeholders from 167 countries responded to the survey representing 97.4% of the global population. National strategies for NCDs were reported by 56% of countries. In 29% of countries CKD was addressed within an NCD strategy while 25% of countries reported CKD-specific strategies. Countries with CKD-specific strategies were more likely to address all CKD populations (non-dialysis dependent CKD, chronic dialysis and kidney transplantation) compared to those with NCD strategies only (51.2% versus 19%). Of the 54% of countries with any CKD strategy 89% reported public funding of the full spectrum of CKD care compared to 64% of those with no CKD strategy. KF, CKD and AKI were reported to be recognized as national health priorities by 63%, 48% and 19% of countries respectively.

Conclusions: The inclusion of CKD and kidney failure within national health strategies is frequently lacking. Countries with CKD-specific policies tend to include a broader spectrum of kidney disease populations and to fund kidney care more than those with CKD policies integrated within NCD strategies. Greater global and national prioritization of kidney health are required to reduce global inequities in access to kidney care.

Background: Elevated levels of fibroblast growth factor 23 (FGF23) are associated with left ventricular hypertrophy and heart failure (HF) in individuals with and without kidney disease. Prior studies investigated the association of FGF23 and structural cardiac changes using conventional echocardiography, which is limited in its ability to detect early cardiac dysfunction. We investigated the relationship between FGF23 levels and cardiac dynamics using two-dimensional speckle tracking echocardiography (2D-STE), a novel imaging modality.

Methods: This was a cross-sectional analysis of data from the Cardiovascular Health Study, an ongoing prospective, population-based cohort study. The study population included 506 participants from CHS with available c-terminal (cFGF23) and intact FGF23 (iFGF23) measurements from 1996-1997 and 2D-STE images from 1994-1995. Forty two percent of the study population had CKD, defined as an eGFR < 60 ml/min/1.73m2, and the mean eGFR was 63 ml/min/1.73m2. The primary exposures were cFGF23 and iFGF23. The primary outcomes were six 2D-STE parameters performed at the 1994-1995 study visit. Linear regression models were used to examine the independent associations of FGF23 with six cardiac 2D-STE indices adjusting for demographics, cardiovascular risk factors, markers of kidney disease severity, and inflammation.

Results: cFGF23 levels were moderately correlated with iFGF23 levels in the CHS population. In fully adjusted models, cFGF23 was associated with left atrial dysfunction, but no other cardiac imaging parameter (β estimate -2.47; 95% Confidence Interval -4.68, -0.25; Table 2). iFGF23 was not associated with any of the six 2D-STE indices. Limitations include small sample size and noncurrent FGF23 measurements and 2D-STE imaging.

Conclusions: In a limited sample of individuals enrolled in the CHS with c- and i-FGF23 measurements, we did not find consistent associations between FGF23 levels and 2D-STE parameters. Further investigations in a larger population with concurrent 2D-STE are needed to better understand the associations of FGF23 with early changes in cardiac mechanics.

Background: Latinx individuals experience 2 times the incidence of kidney failure compared to non-Latinx individuals and are less likely to utilize home dialysis therapies. In this qualitative study, interdisciplinary home dialysis clinicians were interviewed to understand the key factors and strategies used by clinicians to improve home dialysis uptake among the Latinx community.

Methods: One-to-one, semi-structured interviews were conducted between November 2021 and March 2023 with 25 home dialysis interdisciplinary clinicians in Denver, Colorado and Houston, Texas. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.

Results: We identified three themes that focus on different levels of clinician advocacy in home dialysis uptake for the Latinx community: (1) Individual patient-level advocacy (helping patients overcome social challenges to home dialysis, cultivating personalized relationships, educating patients with in-person versus phone language interpretation, understanding cultural differences in communication), (2) Understanding patient influences on modality decision-making (acknowledging the importance of cultural concordance with clinician educator and patient peers, incorporating the patient lived experience, connecting with a patient's social support network, highlighting greater flexibility for employment, underscoring flexibility with culturally concordant foods) and (3) Changes to education at the dialysis facility level (standardizing routine and repeated modality education, promoting early and patient-centered education).

Conclusions: Clinicians outlined efforts to improve access to home dialysis for Latinx groups on the patient and system level; in particular, individual and system level advocacy was grounded in trusting relationships and personalized education. A future intervention that improves the quality and personalization of dialysis modality education incorporating Latinx cultural values may improve access to home dialysis for Latinx people with kidney disease.

Background: In acute kidney injury, macrophages play a major role in regulating inflammation. Classically activated macrophages (M1) undergo drastic metabolic reprogramming during their differentiation and upregulate the aerobic glycolysis pathway to fulfill their pro-inflammatory functions. NAD+ regeneration is crucial for the maintenance of glycolysis and the most direct pathway by which this occurs is via the fermentation of pyruvate to lactate, catalyzed by lactate dehydrogenase A (LDHA). Our previous study determined that LDHA is predominantly expressed in the proximal segments of the nephron in the mouse kidney and increases with hypoxia. This study investigates the potential of LDHA as a therapeutic target for inflammation by exploring its role in macrophage function in vitro.

Methods: Bone-marrow-derived macrophages (BMDMs) were isolated from myeloid-specific LDHA knockout mice derived from crossbreeding LysM-Cre transgenic mice and LDHA floxed mice. RNA sequencing and LC-MS/MS metabolomics analyses were used in this study to determine the effect of LDHA deletion on BMDM following stimulation with IFN-γ.

Results: LDHA deletion in IFN-γ BMDMs resulted in a significant alteration of the macrophage activation and functional pathways, and change in glycolytic, cytokine, and chemokine gene expression. Metabolite concentrations associated with pro-inflammatory macrophage profiles were diminished while anti-inflammatory-associated ones were increased in LDHA KO BMDMs. Glutamate and amino sugars metabolic pathways were significantly affected by the LDHA deletion. A combined muti-omics analysis highlighted changes in Rap1 signaling, cytokine-cytokine receptor interaction, focal adhesion, and MAPK signaling metabolism pathways.

Conclusions: Deletion of LDHA in macrophages results in a notable reduction in the pro-inflammatory profile and concurrent upregulation of anti-inflammatory pathways. These findings suggest that LDHA could serve as a promising therapeutic target for inflammation, a key contributor to the pathogenesis of acute kidney injury.