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Both malnutrition and inflammation affect patient outcome after kidney transplantation. The Metabolic Vulnerability Index (MVX) is a novel multi-marker risk score encompassing 6 metabolic malnutrition biomarkers, i.e. the glycoprotein inflammation biomarker, GlycA, small HDL, branched chain amino acids (valine, leucine and isoleucine), and the mitochondrial dysfunction biomarker, citrate. The utility of this biomarker risk score has not been determined in solid organ transplantation cohorts. We aimed to evaluate the prognostic value of MVX in kidney transplant recipients (KTRs).
MVX was measured in fasting EDTA plasma samples using nuclear magnetic resonance (NMR) spectroscopy. Data and samples were derived from two non-overlapping cohorts (initiated in 2008 and 2015, respectively) within the TransplantLines Biobank and Cohort Programme (Groningen, The Netherlands).
In the first cohort, MVX was evaluated in 690 KTRs (57% male, age 53 ± 13 years, estimated glomerular filtration rate (eGFR) 45 ± 19 mL/min/1.73m2) at a median of 5.4 (interquartile range 1.9 - 12.0) years after transplantation. During follow-up, 147 deaths and 84 graft failure events were observed. Mean MVX score was 51.1 ± 10.5 arbitrary units. MVX was positively associated with age, history of cardiovascular disease, serum creatinine, leukocytes, high-sensitivity CRP and use of calcineurin inhibitors. MVX was inversely associated with serum albumin, total cholesterol and 24-hour urinary urea excretion.
Cox regression analyses revealed an association of MVX with all-cause mortality (hazard ratio per standard deviation (HR per SD), 1.48; 95% confidence interval (CI) 1.23 to 1.78; p < 0.001), adjusted for age, sex, eGFR and 24-hour urinary protein excretion. Addition of MVX to the previous model yielded an improvement in c-index from 0.731 ± 0.020 to 0.754 ± 0.012. MVX was not associated with graft failure.
Regarding the two main MVX components, both the Inflammation Vulnerability Index (IVX; comprised of GlycA and small HDL) and the Metabolic Malnutrition Index (MMX; comprised of valine, leucine, isoleucine and citrate) were each independently associated with mortality: HR per SD, 1.45; 95% CI 1.22 to 1.73; p < 0.001 and HR per SD, 1.22; 95% CI 1.04 to 1.44; p = 0.016, respectively.
These results were independently replicated in a second, non-overlapping cohort of 943 KTRs (61% male, age 55 ± 14 years, eGFR 49 ± 18) which showed similarly strong and independent associations of MVX with mortality (HR per SD 1.80; 95% CI 1.45 to 2.23; p < 0.001; C-index increase from 0.750 ± 0.023 to 0.794 ± 0.020).
Both MVX and its main components are independently associated with mortality in two large independent cohorts of KTRs. These results highlight the potential value of MVX to identify individuals at risk of premature mortality after kidney transplantation.