Patients with chronic kidney disease (CKD) and high body mass index (BMI) variability are at elevated risks for death, myocardial infarction, and stroke as well as an increased likelihood for requiring kidney replacement therapy, according to a recent study.

Previous studies have demonstrated that BMI variability or metabolic parameter variability is associated with a higher risk for heart disease in the general population. Investigators in South Korea examined whether BMI variability may affect the prognosis of patients with kidney dysfunction.

The retrospective observational study, published in the Journal of the American Society of Nephrology, included 84,636 patients with CKD who were listed in a national health screening database. Patients had a mean age of 68 years and median BMI of 24.6 kg/m2. At baseline, all the individuals had persistent predialysis CKD (defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m2 or dipstick albuminuria of 1 or higher), and had 3 or more health screenings before the baseline visit. The analysis included factors such as sex, waist circumference, current smoking history, alcohol intake, regular physical activity, diabetes mellitus, income status and other factors.

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After a median follow-up of 4 years, 6% of patients died, 4% needed kidney replacement therapy, 2% had an MI, and 3% had a stroke. Compared with individuals who had the least BMI variability, those with the greatest variability had a 66% higher risk for death, 20% higher risk for kidney replacement therapy, and 19% higher risk for an MI or stroke.

Study investigator Sehoon Park, MD, of the Kidney Research Institute at Seoul National University, said a high BMI is traditionally considered a risk factor for adverse cardiovascular disease (CVD) and mortality in the general population. However, this did not appear to apply to patients with CKD, as baseline BMI was inversely associated with major adverse outcomes.

Unstable Metabolic Status Important

 “The major point which was surprising was that the significance remained both in those with an increasing trend of body mass index and in those with a decreasing trend,” Dr Parks said. “This highlights the importance of unstable metabolic status, which would be more important than obesity or increasing body mass index, even though a higher BMI is one of the most widely acknowledged bad metabolic health statuses in the general population.”

Variabilities in certain metabolic syndrome components were also significantly associated with the prognosis of patients with CKD not on dialysis. Those with a higher number of metabolic syndrome components with higher BMI variability had a worse prognosis. Dr Park and colleagues have previously investigated the long-term effects of BMI variability in the general population.

Clinicians should ask, record, and assess the trends of BMI and metabolic health parameters at regular clinic visits, according to the researchers. “Focusing on a single time point may miss important clinical risk factor associated with the prognosis of CKD patients,” Dr Parks said. “A high variability state of body mass index or metabolic parameters should be carefully assessed. We believe the findings can be generalizable for Western countries, including North America, as unstable metabolic health status also appears to be associated with worse prognosis.”

Underlying Reasons for BMI Changes

Holly Kramer, MD, MPH, a professor of public health sciences and medicine at Loyola University in Maywood, Illinois, said the study findings are not surprising because BMI fluctuations may indicate other serious comorbid conditions. “You have to look at depression and other issues,” Dr Kramer said. “Nutritional parameters are an excellent way to access a patient’s wellbeing.”

Dr Kramer, who is a past president of the National Kidney Foundation, said the study underscores the importance of asking patients about appetite and how they feel mentally. “If you are seeing large fluctuations in their body weight that may mean something is not stable in their life and it could be social problems and not medical problems. Looking at trajectories of body weight can give you information and lead to queries about issues,” Dr Kramer said. Some patients may be using food as an emotional crutch or in some cases they may not have access to food, she said.

She added, “If you don’t look at their weight, you might not find out that the wife died and did all the cooking.”

It is well established that bariatric surgery improves metabolic parameters, but Dr Kramer said it necessary to investigate further the effects that big drops in weight among patients with CKD have on their risk for CVD, the leading cause of mortality in this patient population.

Srinivasan Beddhu, MD, chief of the renal section at Salt Lake VA Healthcare System and professor of internal medicine at the University of Utah School of Medicine in Salt Lake City, said this is a novel observational study for several reasons, but he pointed out that unmeasured confounding factors can be an issue. For example, the reason for weight fluctuation could be due to a recent illness that led to weight loss, which then resolved. “Also, from this study one should not make the inference that trying to lose weight intentionally is harmful as [patients] may gain some weight back and conclude that the effort that leads to transient weight loss is harmful,” Dr Beddhu said.


Sehoon P, Semin C, Soojin L, et al. The prognostic significance of body mass index and metabolic parameter variabilities in predialysis chronic kidney disease: A nationwide observational cohort study. J Am Soc Nephrology. Published online August 12, 2021. doi: 10.1681/ASN.2020121694

Kyoung Kim M, Han K, Park YM, et al. Associations of variability in blood pressure, glucose and cholesterol concentrations, and body mass index with mortality and cardiovascular outcomes in the general population. Circulation. 2018;138:2627-2637.