Serum Insulin-like Growth Factor-1 to Albumin Ratio as a Biomarker for Sarcopenia Severity in End-Stage Renal Disease Patients on Hemodialysis

Sarcopenia, defined as a progressive and generalized loss of skeletal muscle mass, strength, and function, represents a formidable comorbidity in patients with End-Stage Renal Disease (ESRD) undergoing maintenance dialysis (Cruz-Jentoft et al., 2019). Its prevalence in this population is alarmingly high, exceeding 50% in some cohorts, and it is independently associated with increased mortality, hospitalization rates, frailty, and diminished quality of life (Kim et al., 2021; Souza et al., 2017). The pathophysiology of sarcopenia in ESRD is multifactorial, driven by a synergistic interplay of chronic inflammation, metabolic acidosis, anorexia, hormonal derangements (including growth hormone resistance), and the catabolic effects of dialysis itself (Lecker et al., 2006).

The diagnosis of sarcopenia, as per the 2019 European Working Group on Sarcopenia in Older People (EWGSOP2) consensus, requires assessment of muscle strength, muscle quantity/quality, and physical performance (Cruz-Jentoft et al., 2019). In clinical nephrology practice, widespread implementation of these criteria is hindered by the need for specialized equipment (e.g., bioimpedance analysis [BIA], dynamometers), time constraints in dialysis units, and variability in test performance due to fluid shifts. Consequently, there is a critical unmet need for a reliable, easily obtainable serum biomarker that can serve as a surrogate or screening tool for identifying and stratifying patients at risk of severe sarcopenia.

Insulin-like Growth Factor-1 (IGF-1) is a pivotal anabolic hormone mediating the effects of growth hormone on muscle protein synthesis. In ESRD, hepatic production of IGF-1 is reduced, and its bioactivity is impaired due to the accumulation of inhibitory binding proteins and uremic toxicity, contributing to the anabolic resistance characteristic of uremic sarcopenia (Huang et al., 2002). Serum albumin is the classical biomarker of nutritional status and a negative acute-phase reactant; low levels reflect both malnutrition and chronic inflammation, two core drivers of muscle wasting (Carrero et al., 2021). However, albumin alone has limited specificity for sarcopenia.

We hypothesize that the IGF-1/Albumin ratio integrates two key pathophysiological axes of uremic sarcopenia: the anabolic deficit (low IGF-1) and the catabolic/inflammatory state (low albumin). This composite ratio may therefore provide a more comprehensive and robust biochemical reflection of the net balance between muscle synthesis and breakdown than either marker alone. While IGF-1 and albumin have been studied independently in CKD, the diagnostic and prognostic utility of their ratio specifically for sarcopenia severity in dialysis patients remains unexplored. This cross-sectional study aims to investigate the association between the serum IGF-1/Albumin ratio and the presence and severity of sarcopenia, as defined by EWGSOP2 criteria, in a stable outpatient dialysis population.

Inclusion criteria

• 1. Adult patients (age ≥ 18 years). 2. Diagnosis of ESRD on maintenance hemodialysis for > 3 months. 3. Clinically stable (no hospitalization or active infection in the past 4 weeks).

• Willing and able to provide informed consent.

Exclusion criteria

• 1. Active malignancy or recent chemotherapy/radiotherapy. 2. Decompensated liver cirrhosis (Child-Pugh B or C). 3. Major limb amputation or severe neuromuscular disease precluding functional assessment.

• Acute inflammatory conditions (e.g., systemic lupus erythematosus flare, vasculitis).

• Pregnancy.