PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 39550765

Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy.

Adam Ioannou·Yousuf Razvi·Aldostefano Porcari·Muhammad U Rauf·Ana Martinez-Naharro·Lucia Venneri·Salsabeel Kazi·Ali Pasyar·Carina M Luxhøj·Aviva Petrie·William Moody·Richard P Steeds·Brett W Sperry·Ronald M Witteles·Carol Whelan·Ashutosh Wechalekar·Helen Lachmann·Philip N Hawkins·Scott D Solomon·Julian D Gillmore·Marianna Fontana
View original source ↗Export metadata ↓

Abstract

IMPORTANCE: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Chronic kidney dysfunction is associated with worse outcomes, but the prognostic value of changes in kidney function over time has yet to be defined. OBJECTIVE: To assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) in a large cohort of patients with ATTR-CM. DESIGN, SETTING, AND PARTICIPANTS: This retrospective, observational, single-center cohort study evaluated patients diagnosed with ATTR-CM at the National Amyloidosis Centre (NAC) in the UK who underwent an eGFR baseline assessment and a follow-up assessment at 1 year between January 2000 and April 2024. Data analysis was performed in June 2024. MAIN OUTCOMES AND MEASURES: The primary outcome was the risk of all-cause mortality associated with decline in kidney function (defined as a decrease in eGFR >20%). RESULTS: Among 2001 patients, mean (SD) age was 75.5 (8.4) years, and 263 patients (13.1%) were female. The median (IQR) change in eGFR was -5 mlL/min/1.73 m2 (-12 to 1), and 481 patients (24.0%) experienced decline in kidney function. Patients who experienced decline in kidney function more often had the p.(V142I) genotype than patients with stable kidney function (99 [20.6%] vs 202 [13.3%]; P&#x2009;<&#x2009;.001) and had a more severe cardiac phenotype at baseline, as evidenced by higher median (IQR) concentrations of serum cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP]: 2949 pg/mL [1759-5182] vs 2309 pg/mL [1146-4290]; P&#x2009;<&#x2009;.001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; P&#x2009;<&#x2009;.001), while baseline median (IQR) kidney function was similar between the 2 groups (eGFR: 63 mL/min/1.73 m2 [51-77] vs 61 mL/min/1.73 m2 [49-77]; P&#x2009;=&#x2009;.41). Decline in kidney function was associated with a 1.7-fold higher risk of mortality (hazard ratio [HR], 1.71; 95% CI, 1.43-2.04; P&#x2009;<&#x2009;.001), with a similar risk across the 3 genotypes (wild type: HR, 1.64; 95% CI, 1.31-2.04; p.(V142I): HR, 1.70; 95% CI, 1.21-2.39; non-p.(V142I): HR, 1.51; 95% CI, 0.87-2.61) (P for interaction&#x2009;=&#x2009;.93) and the 3 NAC disease stages (stage 1: HR, 1.69; 95% CI, 1.22-2.32; stage 2: HR, 1.69; 95% CI, 1.30-2.18; stage 3: HR, 1.61; 95% CI, 1.11-2.35) (P for interaction&#x2009;=&#x2009;.97). Decline in kidney function remained independently associated with mortality after adjusting for increases in NT-proBNP and outpatient diuretic intensification (HR, 1.48; 95% CI, 1.23-2.76; P&#x2009;<&#x2009;.001). CONCLUSIONS AND RELEVANCE: In this retrospective cohort study, decline in kidney function was frequent in patients with ATTR-CM and was consistently associated with an increased risk of mortality, even after adjusting for established markers of worsening ATTR-CM. eGFR decline represents an independent marker of ATTR-CM disease progression that could guide treatment optimization in clinical practice.

Explore related subjects

HumansFemaleMaleAgedGlomerular Filtration RateRetrospective StudiesCardiomyopathiesRenal Insufficiency, ChronicAmyloid Neuropathies, FamilialPrognosisAged, 80 and overNatriuretic Peptide, BrainJournal ArticleObservational Study

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Adam Ioannou, Yousuf Razvi, Aldostefano Porcari, Muhammad U Rauf, Ana Martinez-Naharro, Lucia Venneri, Salsabeel Kazi, Ali Pasyar, Carina M Luxh&#xf8;j, Aviva Petrie, William Moody, Richard P Steeds, Brett W Sperry, Ronald M Witteles, Carol Whelan, Ashutosh Wechalekar, Helen Lachmann, Philip N Hawkins, Scott D Solomon, Julian D Gillmore, Marianna Fontana. 2025-01-01. Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy.. https://doi.org/10.1001/jamacardio.2024.4578

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2027

Global Genomic Surveillance.

Global genomic surveillance has emerged as a foundational pillar of public health in the twenty-first century, enabling real-time tracking of pathogen evolution and informing outbreak response. This chapter examines the strategic architecture of global genomic surveillance, focusing on its application to arboviruses such as chikungunya virus (CHIKV). It explores the integration of genomic data with epidemiological, clinical, and environmental information within a One Health framework, while addressing critical challenges in governance, equity, and interoperability. The discussion covers the entire genomic surveillance workflow, from sample collection and sequencing to bioinformatic analysis and phylogenetic inference, and highlights the transformative role of artificial intelligence (AI) in predictive surveillance. By analyzing global initiatives, operational barriers, and emerging technologies, this chapter underscores the necessity of sustainable, equitable, and interoperable genomic systems to proactively address current and future infectious disease threats.

Humans↗
PubMed2027

Systematic Dissection of Key Driver Perturbation Signatures in Single Cells via ECCITE-seq.

CRISPR screens, such as expanded CRISPR-compatible cellular indexing of transcriptomes and epitopes by sequencing (ECCITE-seq), enable the simultaneous measurement of transcriptomes, gRNA identity, and cell-surface protein expression at single-cell resolution to systematically interrogate gene function. This platform provides a powerful and scalable experimental approach for validating disease-associated regulators identified by large-scale association studies and other computational methods, including network-based analyses of multi-omics data. Here, as an example application, we describe an ECCITE-seq framework to characterize the transcriptomic consequences of perturbing multiple neuronal key driver genes associated with Alzheimer's disease (AD) in human-induced pluripotent stem cell (hiPSC)-derived neurons. More broadly, by integrating customized pooled gRNA libraries with different CRISPR effectors across multiple cell types, this approach allows for the assessment of the regulatory impact of candidate genes implicated in development and disease processes.

Humans↗
PubMed2027

Identification of Genome-Wide Chromatin Structural Aberration in Cancer by Hi-C Analysis.

Aberrant three-dimensional genome organization is a hallmark of cancer, often driving oncogene activation through mechanisms such as enhancer hijacking. High-throughput chromosome conformation capture (Hi-C) maps these interactions on a genome-wide scale. Unlike earlier dilution-based methods, in situ Hi-C performs proximity ligation within intact nuclei, minimizing random ligation noise and enabling fine-scale structure detection. This chapter describes an optimized in situ Hi-C protocol tailored for cancer cell lines using MboI digestion and biotin-mediated pull-down to generate high-complexity libraries. We further outline a computational workflow that extends beyond standard topological mapping of compartments and topologically associating domains to identify cancer-specific aberrations. Specifically, we focus on detecting chromosomal rearrangements (structural variants) and characterizing the distinct circular topology of extrachromosomal DNA. This integrated experimental and analytical framework provides the necessary tools to dissect the spatial dysregulation underlying tumor evolution.

Humans↗