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Observational Study
. 2025 Jan 1;10(1):50-58.
doi: 10.1001/jamacardio.2024.4578.

Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy

Adam Ioannou  1 , Yousuf Razvi  1 , Aldostefano Porcari  1   2 , Muhammad U Rauf  1 , Ana Martinez-Naharro  1 , Lucia Venneri  1 , Salsabeel Kazi  1 , Ali Pasyar  1 , Carina M Luxhøj  1 , Aviva Petrie  3 , William Moody  4   5 , Richard P Steeds  4   5 , Brett W Sperry  6 , Ronald M Witteles  7 , Carol Whelan  1 , Ashutosh Wechalekar  1 , Helen Lachmann  1 , Philip N Hawkins  1 , Scott D Solomon  8 , Julian D Gillmore  1 , Marianna Fontana  1
Affiliations
Observational Study

Kidney Outcomes in Transthyretin Amyloid Cardiomyopathy

Adam Ioannou et al. JAMA Cardiol. .

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 < .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 < .001; troponin T: 0.060 ng/mL [0.042-0.086] vs 0.052 ng/mL [0.033-0.074]; P < .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 = .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 < .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 = .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 = .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 < .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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Moody reported a joint working collaborative agreement with his institution and advisory board and lecture fees from Alnylam Pharmaceuticals and Pfizer; advisory board or lecture fees from Ionis Pharmaceuticals (formerly Akcea), Bayer/BridgeBio, and Bristol Myers Squibb; and receiving financial support to attend medical conferences from AstraZeneca outside the submitted work. Dr Sperry reported personal fees from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, and Pfizer and grants from Pfizer outside the submitted work. Dr Witteles reported personal fees from Alexion, Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, Novo Nordisk, and Pfizer outside the submitted work. Dr Solomon reported grants to his institution from Alexion, Alnylam Pharmaceuticals, Applied Therapeutics, AstraZeneca, Bayer, Bellerophon, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Edgewise, Eidos/BridgeBio, Gossamer, GSK, Ionis, Lilly, the US National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI and personal consulting fees from Abbott, Action, Akros, Alexion, Alnylam Pharmaceuticals, American Regent, Amgen, Anacardio, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Cardurion, CellProThera, Corvia, Cytokinetics, Dinaqor, GSK, Lexicon, Lilly, Moderna, Novartis, Quantum Genomics, Roche, Sarepta, Sanofi Pasteur, Tenaya, Theracos, Tremeau, and Valo outside the submitted work. Dr Gillmore reported consultancy fees from Alnylam Pharmaceuticals, ATTRalus, AstraZeneca, BridgeBio, Ionis, Intellia, and Pfizer outside the submitted work. Dr Fontana reported consultancy or advisory board fees from Alnylam Pharmaceuticals, Alexion/Caelum Biosciences, AstraZeneca, Attralus, Bayer, BridgeBio/Eidos, Cardior, Intellia Therapeutics, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Lexeo Therapeutics, Mycardium, Novo Nordisk, Pfizer, and Prothena; research grants from Alnylam Pharmaceuticals, AstraZeneca, BridgeBio, and Pfizer; salary from the British Heart Foundation Intermediate Fellowship; and share options in LexeoTherapeutics and Mycardium outside the submitted work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kidney Progression and Survival
Landmark Kaplan-Meier curves demonstrating the association between decline in kidney function at 1 year and subsequent survival.
Figure 2.
Figure 2.. Risk of Mortality Associated With Decline in Kidney Function in Transthyretin Amyloid Cardiomyopathy
The first P value for interaction is the interaction between decline in kidney function and genotypes and the second is the interaction between decline in kidney function and disease stages. HR indicates hazard ratio; NAC, National Amyloidosis Centre.
Figure 3.
Figure 3.. Combined Decline in Kidney Function and N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Progression
Landmark Kaplan-Meier curves demonstrating the association between decline in kidney function and NT-proBNP progression at 1 year and subsequent survival.
Figure 4.
Figure 4.. Combined Decline in Kidney Function, N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) Progression, and Outpatient Diuretic Intensification
Landmark Kaplan-Meier curves demonstrating the association between markers of disease progression at 1 year and subsequent survival.
See this image and copyright information in PMC

References

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