Abstract
In chronic kidney disease it is hypothesised that the association between loss of lean tissue mass (LLTM) and mortality is purely a function of multimorbidity. We conducted a systematic review in CKD patients to quantify the strength of association between LLTM and mortality or frailty surrogates, including hospitalisation and quality of life (QoL). Muscle mass was estimated using different whole-body bioimpedance methods (BI-MM). Searches of electronic databases identified 132 studies for inclusion (147542 dialysis patients; 15378 CKD(G3−5) patients; 356 kidney transplant recipients [KTR], with 14429 deaths). From 67 studies reporting unadjusted analyses, 52 (78%) demonstrated associations between LLTM and mortality. In 80 studies reporting analyses adjusting for age, sex, and multimorbidity, 59 (74% overall: 74, 67 and 100% in dialysis, CKD, and KTR studies respectively) reported an association. Meta-analysis of dialysis studies reporting adjusted survival analyses found each degree decrease in phase angle or a lean tissue index < 10th percentile was associated with a 92 and 49% higher hazard of mortality respectively. In studies reporting hospitalisation and QoL measures, 63 and 76% reported associations with BI-MM respectively. In conclusion, having accounted for multimorbidity, LLTM remained associated with mortality and frailty surrogates in CKD, irrespective of the BI-MM method used. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-34111-2.