Kidney Week

Abstract: TH-PO1099

Exploring the Lipid Pathway in the Obesity Paradox: LDL as a Nonmediator Between Body Mass Index and Mortality in Patients with CKD

Session Information

• CKD: Therapies, Innovations, and Insights
  November 06, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2302 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

• Takahashi, Rina, The Lundquist Institute, Torrance, California, United States

Rina Takahashi, MD, PhD

• Kovesdy, Csaba P., The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Csaba P. Kovesdy, MD, FASN

• Tran, Diana, The Lundquist Institute, Torrance, California, United States

Diana Tran, MPH

• Simon, Lewis, The Lundquist Institute, Torrance, California, United States

Lewis Simon, PhD, MPH

• Ismail, Adnan M., The Lundquist Institute, Torrance, California, United States

Adnan M. Ismail

• Sumida, Keiichi, The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Keiichi Sumida, MD, PhD, MPH, FASN

• Rhee, Connie, VA Greater Los Angeles Healthcare System, Los Angeles, California, United States

Connie Rhee, MD, MS

• Kalantar-Zadeh, Kamyar, The Lundquist Institute, Torrance, California, United States

Kamyar Kalantar-Zadeh, MD, DrMed, PhD, MPH, FASN

Background

Both obesity and lipid paradoxes have been reported in CKD, but the interaction between BMI, lipid levels, and mortality remains unclear. This study aimed to evaluate the association between BMI and LDL-C, examining the hypothesis that LDL-C mediates the relationship between BMI and all-cause mortality in patients with CKD.

Methods

We analyzed 30,559 U.S. veterans with incident CKD from the national TRI-CKD cohort (2004–2018). Incident CKD was defined by two outpatient eGFR values <60 mL/min/1.73m² at least 90 days apart, both ≥25% below baseline. Patients were categorized into five BMI groups: <20, 20–25 (reference), 25–30, 30–35, and ≥35 kg/m². Baseline BMI and LDL-C were assessed at CKD incidence. Cox proportional hazards models were used to evaluate the association between BMI and all-cause mortality, adjusting for demographics, comorbidities, labs including eGFR, and medications. Mediation analysis was conducted to estimate the mediation effect of LDL-C on the association between BMI and mortality.

Results

Patients with higher BMI were younger (71.5 to 64.3), while mean eGFR remained relatively stable (52.5 to 55.1 mL/min/1.73m²), and the proportion of Black patients peaked at 4.5% in 25–30 kg/m². A reverse U-shaped association was observed between BMI and LDL-C, with LDL-C peaking in 25-30 kg/m². BMI showed a U-shaped association with all-cause mortality, with the lowest risk observed in 30–35 kg/m² in all models. Mediation analysis revealed no significant mediation effect of LDL-C (β = 0.0003 for BMI 30–35).

Conclusion

In patients with CKD, there was no significant mediation effect of LDL-C on the association between BMI and mortality, although the obesity paradox persisted, with the greatest survival among the patients with a BMI of 30–35 kg/m². These findings suggest that LDL does not significantly explain the obesity paradox and highlight the need to explore other underlying mechanisms in CKD.

Funding

• Veterans Affairs Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025v8r5a0s8