Low Fischer’s ratio is associated with increased mortality in patients with kidney failure

Background Metabolic changes in kidney failure, including an altered ratio of plasma branched-chain amino acids (BCAAs) to aromatic amino acids (AAAs), also known as Fischer’s ratio (FR), could potentially affect survival. We analyzed associations of FR with mortality in patients with kidney failure. Methods In 328 non-dialyzed kidney failure patients (median age 54 years, 60% men), plasma concentrations of BCAAs (valine, isoleucine, and leucine) and AAAs (phenylalanine, tyrosine) were measured using HPLC. We used Fine-Gray competing-risk regression analysis with renal transplantation as competing risk to compare 5-years survival between high versus low and middle tertiles of FR, and restricted cubic spline analysis to examine associations of BCAA, AAA and FR, as continuous variables, with mortality risk. Results During median 29.4 (range 0.7–60.0) months of follow-up, 82 (25%) patients died. Patients who died had lower FR compared to survivors (2.92 vs. 3.12, p  = 0.034), while BCAAs and AAAs were similarCompared to patients in the high FR tertile, those in the combined middle and low tertiles had higher cumulative incidence of mortality (sHR 2.12, 95% CI 1.23–3.66, p = 0.007). FR was negatively correlated with inflammation markers and protein-energy wasting. Subgroup and interaction analyses showed that the association of FR with mortality was strongest among patients with cardiovascular disease (OR 4.10, 95% CI 1.53–11.00, p  = 0.005; p for interaction = 0.009). Conclusion A low Fischer’s ratio associated with increased mortality risk among individuals with kidney failure and its prognostic strength was most evident in patients with cardiovascular disease. Inflammatory and nutritional alterations contributed to variations of Fischer’s ratio.