Higher Weight-Adjusted Waist Index Tied to CKD Mortality, Study Finds

A higher weight-adjusted waist index (WWI) is independently associated with both all-cause and cardiovascular mortality in adults with chronic kidney disease (CKD), according to a cohort study recently published in Medicine.¹ Part of this association appeared to be driven by systemic inflammation, as measured by the neutrophil-to-lymphocyte ratio (NLR).

Why a Better Obesity Marker Is Needed in CKD

In the US, about 14% of adults are affected by CKD, which is projected to reach 29% to 68% by 2030 due to the rising prevalence of obesity and diabetes.^2,3 Obesity, characterized by excessive accumulation of adipose tissue, is defined by a BMI greater than or equal to 30 kg/m².¹ However, BMI comes with limitations in accurately assessing obesity, as individuals with similar BMI values may have different body composition and fat distribution. It also fails to capture abdominal adiposity.

By contrast, WWI offers a more accurate assessment of fat and muscle mass. Compared with BMI, waist circumference, or the visceral adiposity index, WWI reliably reflects abdominal obesity and better measures fat and muscle levels. Prior research found that WWI was independently associated with cardiovascular disease (CVD). Similarly, it showed a positive linear association with mortality among patients with hyperlipidemia. Together, these findings suggest that WWI may be a reliable indicator of obesity-related risk and metabolic health.

However, researchers noted that the relationship between WWI and mortality in CKD remains uncertain, as does whether the neutrophil-to-lymphocyte ratio (NLR) mediates it. To address this gap, they conducted a study assessing the association of WWI with all-cause and cardiovascular mortality in CKD and examined NLR as a potential mediator.

The study drew data from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2018 cycles. The researchers included patients aged 20 years and older who met the Kidney Disease: Improving Global Outcomes criteria for CKD but excluded those lacking anthropometric, mortality, or medical data. The primary analysis was restricted to NHANES 1999 to 2016, but a sensitivity analysis assessing the robustness of the findings included the 1999 to 2018 cycles. The researchers also conducted a mediation analysis to evaluate the indirect effect of NLR on the WWI-mortality relationship.

WWI's Link to All-Cause, CVD Mortality

The study population consisted of 5582 participants, 2235 (40.04%) of whom died over a median follow-up of 8.5 years. The researchers noted that nonsurvivors were significantly older and had higher levels of urinary albumin-to-creatinine ratio and NLR. By contrast, they had lower serum albumin, hemoglobin, and estimated glomerular filtration rate. In addition, non-survivors were more likely to be male, diabetic, dyslipidemic, hypertensive, and to have preexisting CVD.

In the fully adjusted model, each 1-unit increase in WWI corresponded to a 17% higher risk of all-cause mortality (adjusted HR [AHR], 1.17; 95% CI, 1.09-1.26; P < .001) and a 24% higher risk of CVD mortality (AHR, 1.24; 95% CI, 1.09-1.41; P = .001). Patients in the highest WWI quartile faced significantly greater risk than those in the lowest quartile for both all-cause mortality (AHR, 1.28; 95% CI, 1.08-1.52; P = .005) and CVD mortality (AHR, 1.39; 95% CI, 1.03-1.89; P = .033).

Restricted cubic spline modeling found no evidence of nonlinearity (P > .05), meaning mortality risk climbed steadily as WWI increased rather than plateauing at higher values; this pattern was confirmed by Kaplan-Meier curves showing progressively lower survival across ascending WWI quartiles (log-rank P < .001). The association remained after the researchers adjusted for BMI. Similarly, when the researchers compared WWI directly against BMI and waist circumference, WWI showed more consistent associations with mortality. As a result, combining WWI with BMI produced the strongest predictive performance of any model tested, they noted, suggesting the 2 measures may capture complementary risk information.

How NLR Helps Explain the WWI-Mortality Link

Subgroup analyses found the WWI-mortality association to be stronger in men (all-cause mortality: AHR, 1.23; 95% CI, 1.08-1.41) and more pronounced among younger patients. It also remained a strong predictor among patients without hypertension, diabetes, or preexisting CVD, with consistency across BMI categories, racial groups, and baseline kidney function strata, pointing to broad generalizability of the risk signal.

The researchers also tested whether NLR helps explain the relationship. Higher WWI was positively associated with NLR (β = 0.10; 95% CI, 0.03-0.17; P = .004), and NLR itself independently predicted both all-cause (AHR, 1.11; 95% CI, 1.08-1.15; P < .001) and CVD (AHR, 1.09; 95% CI, 1.04-1.15; P < .001) mortality.

Mediation analysis attributed 6.66% of the total WWI effect on all-cause mortality and 4.21% of its effect on CVD mortality to this inflammatory pathway. The researchers pointed to a plausible mechanism: obesity-driven adipose tissue expansion promotes chronic low-grade inflammation, whereas CKD itself is marked by immune dysregulation that may amplify neutrophil activity and lymphocyte depletion.

What the Findings Mean for CKD Care

Still, the authors acknowledged limitations, including the cross-sectional nature of NHANES measurements, which restricts causal inference. Also, data limitations prevented them from adjusting for all potential confounders. Despite these caveats, they emphasized that their findings indicated that elevated WWI was independently associated with higher risks of all-cause and CVD mortality among patients with CKD, with the associations partially mediated by systemic inflammation reflected by NLR.

“Our findings highlight the importance of managing central obesity and inflammatory burden to improve prognosis in CKD populations,” the authors concluded.

References

1. Zhou H, Zhang X, Zhang W, Liu G, Wang H. Weight-adjusted waist index and all-cause and cardiovascular mortality in chronic kidney disease: a cohort study with mediation analysis of systemic inflammation. Medicine. 2026;105(36):e50613. doi:10.1097/MD.0000000000050613
2. Li T, Hu Z, Qiao L, Wu Y, Ye T. Chronic kidney disease and cognitive performance: NHANES 2011-2014. BMC Geriatr. 2024;24(1):351. doi:10.1186/s12877-024-04917-2
3. McCullough KP, Morgenstern H, Saran R, Herman WH, Robinson BM. Projecting ESRD Incidence and Prevalence in the United States through 2030. J Am Soc Nephrol. 2019;30(1):127-135. doi:10.1681/ASN.2018050531