#2832 Lean tissue mass is associated with mortality across different stages of chronic kidney disease: a systematic review and meta-analysis
Authors: Tabinor Matthew , Elphick Emma , Stephens Charlotte , Wall Nadya , Ul Hussain Azm , Shah Rafeea , Peracha Javeria , Anderson Benjamin , Istanbuly Obaida , Solis-Trapala Ivonne , Ferro Charles J , Davies Simon 
Published: May 2024

Abstract

Background and Aims
Loss of lean tissue mass (LLTM) commonly occurs in multiple long-term conditions (LTC), including chronic kidney disease (CKD), and is thought to be associated with adverse outcomes including mortality, frailty surrogates and poor quality of life. It remains unclear whether LLTM is directly associated with mortality in CKD after adjusting for the severity of CKD or the degree of multimorbidity, and whether such associations remain in other LTC with similar levels of multimorbidity, such as heart failure (HF).

Method
A systematic review was conducted in adult CKD [kidney transplant (KT), CKDG3-5 or dialysis treated kidney failure (D-KF)] and HF patients who had whole body bioimpedance defined lean tissue mass (BI-LTM). The primary outcome was mortality, with secondary outcomes including hospitalisation and health related quality of life (HRQoL). The review was registered with PROSPERO (CRD42021240688) and was conducted according to PRISMA guidelines. Electronic database searches of MEDLINE, EMBASE, AMED, CINAHL, PsychInfo, Web of Science, CENTRAL, ICTRP and ISRCTN were searched from inception until June 2023. Data extraction and risk of bias assessments, using the Quality in Prognosis Studies (QUIPS) tool, was performed by two independent reviewers. Random effects meta-analysis was conducted using STATA SE16.2 using restricted maximum likelihood (REML) estimation.

Results
From 10,024 citations, 126 studies were identified (100 D-KF, 12 CKDG3-5, 2 KT, 3 mixed CKD and 9 HF) reporting outcomes on 143,053 D-KF, 15,164 CKDG3-5, 346 KTR and 3716 HF patients respectively. There were 1,227 deaths (over 2-5 years) in the HF studies and 16,471 deaths (over 1-20 years) in the CKD studies. The weighted mean eGFRCreat was 54 and 42 ml/min/1.73 m2 in the KT and CKDG3-5 studies, with only 3 HF studies reporting any measure of renal function (all using categorical cut offs). In 87 studies survival analyses of all-cause mortality (ACM) showed that BI-LTM was associated with mortality in 67%, 100%, 85% and 74% of the HF, KT, CKDG3-5 and D-KF studies respectively after adjusting for age, sex, diabetic status, comorbidity score, CRP / IL-6, albumin and bioimpedance defined fluid measures in 93%, 77%, 64%, 17%, 32%, 59% and 24% of analyses. Meta-analysis within D-KF studies reporting MVA revealed a 1-degree decrease in phase angle (pooled HR 1.82, 95% CI 1.50-2.20: Fig. 1A) and lean tissue index &lt;10th percentile (pooled HR 1.48, 95% CI 1.31-1.66: Fig. 1B) was associated with ACM. Leave one out meta-analysis and sensitivity analyses removing studies at high-risk of statistical analysis and study confounding bias confirmed these pooled estimates were robust. Of the studies reporting secondary outcomes including hospitalisation and HRQoL (including the Short Form-36 and Kidney Disease Quality of Life Instrument), 67% showed associations with BI-LTM.

Conclusion
LLTM is associated with mortality across all stages of CKD and in heart failure. Furthermore, LLTM is associated with adverse outcomes such as hospitalisation and poor quality of life. This study confirms that LLTM potentially has an important role in the explanatory pathway for adverse outcomes in patients with LTCs, including CKD. Using BI-LTM may provide a way to identify early LLTM and target interventions to reduce the risk of adverse outcomes in these multimorbid cohorts.