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Comparative risk assessment of cardiovascular and kidney outcomes in patients with type 2 diabetes using cystatin C and creatinine in DECLARE-TIMI 58

Year: 2026
Type: article
Abstract: Background: The relationship between cystatin C and cardiovascular and kidney outcomes is not well explored in individuals with type 2 diabetes (T2D) and normal or mild kidney dysfunction. Methods: and classified according to Kidney Disease Improving Global Outcomes (KDIGO) risk categories. Hazard ratios were estimated for a composite of cardiovascular death and hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE), and a kidney-specific composite outcome (persistent ≥40% decrease in eGFR, end-stage renal disease, or renal death). Results: Among 1899 placebo-treated patients, higher baseline CysC was associated with higher risk for CVD/HHF, MACE, and the kidney-specific composite outcome. A gradient of risk across quartiles was observed for CVD/HHF [Q4 v Q1: 1.33 (0.98-1.80), p-trend = 0.016]; MACE [1.34 (1.06-1.69), p-trend = 0.013]; and kidney-specific composite outcome [1.95 (0.95-3.99), p-trend = 0.036]. When compared with creatinine, CysC showed more pronounced and statistically significant risk gradients (CVD/HHF: KDIGO-CysC p-trend < 0.001 vs. p-trend Cr 0.34; MACE: CysC p-trend < 0.001 vs. Cr p-trend 0.52). No heterogeneity was observed in the effect of dapagliflozin across CysC concentrations (p-interactions >0.05). Conclusion: In patients with T2D and predominantly preserved Cr-based eGFR, CysC was associated with increased cardiovascular and kidney risk. Although discrimination assessed by c-statistic was similar for CysC and Cr, risk gradients seen with CysC became attenuated and no longer statistically significant when using Cr-based analogs. The effect of dapagliflozin was consistent irrespective of baseline CysC. Trial registration: ClinicalTrials.gov Identifier: NCT01730534.
DOI: 10.1016/j.ahjo.2026.100929
Authors: Andre M. Small, David D. Berg, Itamar Raz, Petr Jarolim, Erica L. Goodrich, Filipe A. Moura, Ofri Mosenzon, Avivit Cahn, Deepak L. Bhatt, Jamie P. Dwyer, Lawrence A. Leiter, John P.H. Wilding, Ingrid Gause-Nilsson, Marc S. Sabatine, David A. Morrow, Stephen D. Wiviott
Institutions: Brigham and Women's Hospital, Harvard University, Thrombolysis in Myocardial Infarction Study Group, Hebrew University of Jerusalem, Hadassah Medical Center, Mount Sinai Health System, Icahn School of Medicine at Mount Sinai, University of South Carolina, St. Michael's Hospital, University of Toronto, University of Liverpool, AstraZeneca (Sweden)
Language: English
Subfield: Nephrology
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,810
Funders: AstraZeneca United States, Amgen, Pfizer, AstraZeneca, Vertex Pharmaceuticals, Kowa Company, Novo Nordisk, National Heart, Lung, and Blood Institute
OpenAlex ID: W7220409326
FWCI:
Cites: 25
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Related to: 10