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The Difference Between Cystatin C- and Creatinine- Based Assessment of Renal Function in Heart Failure Patients: Insights From PARADIGM-HF and RELAX-AHF

The Difference Between Cystatin C- and Creatinine- Based Assessment of Renal Function in Heart Failure Patients: Insights From PARADIGM-HF and RELAX-AHF

Alberto Pinsino

Columbia University Medical Center

31 August 2021

Background•   Among heart failure (HF) patients, estimating kidney function accurately is of paramount importance for several reasons, such as dosing medications correctly and identifying patients with kidney disease. •   Creatinine is a chemical waste molecule that is generated from muscle metabolism and filtered by the kidneys. Creatinine is measured in routine blood works and reflects kidney function - as the kidneys become impaired, creatinine levels in the blood will rise. Since creatinine is a waste product of muscle and HF patients have lower muscle mass compared to healthy individuals, creatinine may be falsely low despite impairment of kidney function.•   Cystatin C is an alternative blood test to estimate kidney function whose levels, similarly to creatinine, rise with kidney impairment. However, unlike creatinine, cystatin C levels are not affected by muscle mass. Prior studies have found that cystatin C more accurately reflects kidney function than creatinine. Moreover, the difference between cystatin C and creatinine has been used as a surrogate marker for muscle mass - the larger the difference, the lower the muscle mass. HF patients with lower muscle mass may have worse prognosis.•   Mineralocorticoid receptor antagonists (MRA) are medications which have been shown to reduce the risk of death and hospital admission in HF patients. However, MRA can cause potentially life-threatening side effects (high blood levels of potassium and dialysis), in particular among patients with kidney impairment.Research questions1.   What is the difference in estimated kidney function between cystatin C and creatinine in HF patients?2.   Can the difference between cystatin C and creatinine be used to find HF patients who have decreased muscle mass and, ultimately, worse prognosis?3.   Can cystatin C help identify patients who will experience side effects (high potassium, dialysis) when receiving MRA?Our studyWe plan to analyze data from 3 different studies, which were previously performed in patients with either chronic stable HF or worsening HF requiring admission to the hospital. All these trials measured cystatin C and creatinine at different time points. We hypothesize that:1)   Kidney function based on cystatin C would be worse than what estimated using creatinine due to the loss of muscle mass.2)   The difference between cystatin C and creatinine will serve as a surrogate marker of muscle mass, and help identifying patients who have muscle wasting and therefore worse prognosis.3)   Patients with severe kidney impairment as defined by cystatin C will be more likely to experience side effects when receiving MRA.Implications of our research Our research study may contribute to change the current standard of care for the assessment of kidney function in HF patients. Cystatin C may provide a more accurate measure of kidney function, prevent the side effects of HF medications like MRA and, when used in conjunction with creatinine, indicate muscle wasting and worse prognosis.

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Statistical Analysis Plan

A.Pinsino, M.R. Carey, S.Husain et al The Difference Between Cystatin C- and Creatinine-Based eGFR in Heart Failure With Reduced Ejection Fraction: Insights From PARADIGM-HF American Journal of Kidney Diseases April 20, 2023
DOI: https://doi.org/10.1053/j.ajkd.2023.03.005