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• W4375846655 abstract "See [article type, i.e., Clinical Research] on Page xxx. See [article type, i.e., Clinical Research] on Page xxx. Obesity is a multidimensional risk factor for developing chronic kidney disease (CKD) and CKD progression.1Ejerblad E. Fored C.M. Lindblad P. Fryzek J. McLaughlin J.K. Nyrén O. Obesity and risk for chronic renal failure.J Am Soc Nephrol. 2006; 17: 1695-1702https://doi.org/10.1681/ASN.2005060638Crossref PubMed Scopus (482) Google Scholar Overweight patients living with advanced CKD are incentivized to lose weight to improve their health, mobility, and access to kidney transplantation.2Navaneethan S.D. Yehnert H. Moustarah F. Schreiber M.J. Schauer P.R. Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis.Clin J Am Soc Nephrol. 2009; 4: 1565-1574https://doi.org/10.2215/CJN.02250409Crossref PubMed Scopus (289) Google Scholar However, a phenomenon known as the “obesity paradox” complicates the relationship between obesity and mortality in patients with advanced CKD and end-stage kidney disease. This paradox is defined by findings from observational epidemiologic studies demonstrating an inverse relationship between body mass index (BMI) and mortality.3Doshi M. Streja E. Rhee C.M. et al.Examining the robustness of the obesity paradox in maintenance hemodialysis patients: a marginal structural model analysis.Nephrol Dial Transplant. 2016; 31: 1310-1319https://doi.org/10.1093/ndt/gfv379Crossref PubMed Scopus (43) Google Scholar This has led to a more nuanced understanding of how adipose tissue and fat-free mass (FFM) could mediate obesity’s effect on patients with advanced CKD.4Martin-Taboada M. Vila-Bedmar R. Medina-Gómez G. From obesity to chronic kidney disease: how can adipose tissue affect renal function?.Nephron. 2021; 145: 609-613https://doi.org/10.1159/000515418Crossref PubMed Scopus (15) Google Scholar,5Moorthi R.N. Avin K.G. Clinical relevance of sarcopenia in chronic kidney disease.Curr Opin Nephrol Hypertens. 2017; 26: 219-228https://doi.org/10.1097/MNH.0000000000000318Crossref PubMed Scopus (133) Google Scholar Indeed, prior studies in CKD studies have linked surrogates of muscle mass with worse quality of life, depression, malnutrition, and higher risk of hospitalizations and death in CKD populations.6Martinson M. Ikizler T.A. Morrell G. et al.Associations of body size and body composition with functional ability and quality of life in hemodialysis patients.Clin J Am Soc Nephrol. 2014; 9: 1082-1090https://doi.org/10.2215/CJN.09200913Crossref PubMed Scopus (42) Google Scholar However, it remains unclear to what extent the association of change in BMI or body weight with mortality is influenced by changes in lean mass and other nutritional and clinical characteristics. In this issue of KI reports, Harhay et al.7Harhay M.N. et al.Obesity weight loss phenotypes in chronic kidney disease: findings from the chronic renal insufficiency cohort study (CRIC).KI Rep. Forthcoming 2023; Google Scholar used data from the longitudinal Chronic Renal Insufficiency Cohort Study to identify distinct, multidimensional weight loss phenotypes in CKD and end-stage kidney disease. They identified distinct trajectories of change in BMI, systolic blood pressure, and serum albumin levels among patients with CKD and obesity associated with increased risk of all-cause mortality. This was done using a joint multivariate longitudinal latent class model that considers the probability of belonging to a particular phenotypic class depending on the changes in these 3 variables over time. The second component of this model was to estimate the association between the identified clinical trajectory and mortality after adjusting for covariates using a proportional hazards regression model. Furthermore, they have conducted a secondary analysis to identify BMI and lean body mass trajectories associated with increased mortality risk. The study identified 2831 Chronic Renal Insufficiency Cohort Study participants with obesity (BMI ≥30 kg/m2) with a median age of 61 years, 47% prevalence of females, 50% non-Hispanic Black, and a median BMI of 35.6 kg/m2. The median follow-up period was 6.8 years, with 26% initiating dialysis, 15% being waitlisted for a kidney transplant, and 5% receiving a transplant. At the end of the follow-up, 34% of the cohort had died. The authors characterized 6 latent classes in their model, with class 6 associated with the highest 5-year cumulative incidence of mortality of 6.8%, corresponding to an adjusted hazard ratio of 1.90 (95% confidence interval: 1.45, 2.50). Class 6 was characterized by steep and early BMI loss of >20%, initially stable then rising systolic blood pressure, and early decline in serum albumin followed by increasing levels. The secondary analysis evaluated another 6-class BMI and FFM model associated with mortality. This model revealed that class 1, characterized by early substantial BMI decline followed by BMI gain with a steep FFM decline over time, was associated with the highest level of mortality. The current study underscores the heterogeneity in weight loss phenotypes and their differential association with risk of mortality. It distinguishes high-risk weight loss patterns as a phenotype of rapid weight loss, increasing systolic blood pressure, and declining serum albumin. Direct and indirect measures of FFM are also important for assessment of nutritional status and sarcopenia, or reduced muscle mass and function. Sarcopenia has been linked to poor outcomes independent of BMI across multiple populations, including patients with kidney disease.5Moorthi R.N. Avin K.G. Clinical relevance of sarcopenia in chronic kidney disease.Curr Opin Nephrol Hypertens. 2017; 26: 219-228https://doi.org/10.1097/MNH.0000000000000318Crossref PubMed Scopus (133) Google Scholar,8Carrero J.J. Johansen K.L. Lindholm B. Stenvinkel P. Cuppari L. Avesani C.M. Screening for muscle wasting and dysfunction in patients with chronic kidney disease.Kidney Int. 2016; 90: 53-66https://doi.org/10.1016/j.kint.2016.02.025Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar The study also emphasizes the clinical relevance of measured FFM in interpreting risks associated with weight and BMI trajectories. Specifically, it demonstrates that patients with obesity and CKD experiencing a greater increase in BMI relative to their increase in FFM have a higher risk of death compared to those with a proportional gain of both values. The strength of the current investigation by Harhay et al.7Harhay M.N. et al.Obesity weight loss phenotypes in chronic kidney disease: findings from the chronic renal insufficiency cohort study (CRIC).KI Rep. Forthcoming 2023; Google Scholar included the use of a sophisticated multivariate latent trajectory modeling strategy in a racially representative group of participants with CKD and obesity, with adjustments of important confounders including whether the weight loss was unintended. Limitations included an inability to distinguish specific weight loss strategies used by the participants in the Chronic Renal Insufficiency Cohort Study cohort. Second, it is unclear if the mortality risk associated with these weight loss phenotypes applies to populations with end-stage kidney disease treated with dialysis where higher muscle mass has been associated with greater survival.9Delgado C. Chiang J.M. Kittiskulnam P. et al.Longitudinal assessment of body composition and its association with survival among participants of the ACTIVE/ADIPOSE study.J Ren Nutr. 2022; 32: 396-404https://doi.org/10.1053/j.jrn.2021.09.001Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Third, it is unclear how changes in tissue hydration status may influence the accuracy of FFM measures from bioelectrical impedance analysis in CKD.8Carrero J.J. Johansen K.L. Lindholm B. Stenvinkel P. Cuppari L. Avesani C.M. Screening for muscle wasting and dysfunction in patients with chronic kidney disease.Kidney Int. 2016; 90: 53-66https://doi.org/10.1016/j.kint.2016.02.025Abstract Full Text Full Text PDF PubMed Scopus (170) Google Scholar Furthermore, reliance on bioelectrical impedance analysis may not be feasible in clinical practice, and more practical bedside measures of assessing muscle function such as physical performance testing should be evaluated. Future studies should investigate if longitudinal change in physical performance measures assessing functional muscle mass further distinguishes the risk associated with these trajectories independent of BMI, weight loss, and FFM. Weight loss strategies preserving or improving muscle mass and function through healthy diet and exercise training are foundational to improving health in overweight and obese patients living with CKD. Indeed, previous randomized controlled trials had demonstrated that a low-intensity, home-based walking program has been shown to improve patients’ functional capacity and cognitive function,S1 and adding endurance training to a strengthening or balancing training regimen has been shown to improve muscle mass and physical performance in patients with advanced CKD.S2 More research is needed to determine the optimal interventions for achieving a healthy weight loss pattern in patients with CKD while preserving or improving their muscle mass, strength, and endurance. These interventions have implications for reducing the burden of frailty and improving the quality of life in patients living with CKD. All the authors declared no competing interests. Download .pdf (.12 MB) Help with pdf files Supplemental File (PDF) Supplemental References. Obesity Weight Loss Phenotypes in CKD: Findings From the Chronic Renal Insufficiency Cohort StudyKidney International ReportsPreviewAlthough people with chronic kidney disease (CKD) and obesity have important motivations to lose weight, weight loss is also associated with health risks. We examined whether patterns of change in systolic blood pressure (SBP), serum albumin level, and fat-free mass (FFM) can help to differentiate between healthy and high-risk weight loss in this population. Full-Text PDF Open Access" @default.
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• W4375846655 title "Dissecting the Obesity Paradox in Patients With Obesity and CKD" @default.
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