Kidney Week

Abstract: FR-PO0251

Urine Symmetric Dimethylarginine and Methylmalonic Acid Identify Sickle Cell Disease-Associated CKD Across Three Definitions and Associate with Continuous Glomerular Filtration Rate

Session Information

• CKD: Omics, Systemic Stressors, and Targeted Pharmacotherapy
  October 23, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2201 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Olaniran, Kabir O., The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States

Kabir O. Olaniran, MD, MPH, FASN

• Shalaby, Ahmed, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Ahmed Shalaby

• Peters, Jessica Lucas, The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Jessica Lucas Peters, MS

• Zacharias, Lauren G., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Lauren G. Zacharias, MS

• Mathews, Thomas P., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Thomas P. Mathews, PhD

• Ataga, Kenneth I., The University of Tennessee Health Science Center, Memphis, Tennessee, United States

Kenneth I. Ataga, MBBS

• Deberardinis, Ralph J., The University of Texas Southwestern Medical Center, Dallas, Texas, United States

Ralph J. Deberardinis, MD, PhD

• Moe, Orson W., The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States

Orson W. Moe, MD

• Toto, Robert D., The University of Texas Southwestern Medical Center Department of Internal Medicine, Dallas, Texas, United States

Robert D. Toto, MD

Background

Sickle cell chronic kidney disease (SCKD) affects 30% of adults with sickle cell disease (SCD) and is associated with early mortality. SCKD remains difficult to detect and biologically phenotype using conventional kidney measures. We performed paired plasma and urine metabolomics to identify metabolites reproducibly associated with SCKD and to evaluate their association with estimated glomerular filtration rates (eGFR).

Methods

Sixty SCD adults (outpatient, not in crisis) in the prospective Sickle Cell Kidney Study (NCT07064174; Dallas, TX) underwent paired spot urine and plasma metabolomics. SCKD was defined in 3 overlapping strata: persistent albuminuria [≥30 mg/g, n=35], eGFR by creatinine (eGFRcr<90 (n=13), and cystatin C (eGFRcys)<60 mL/min/1.73m² (n=13). Untargeted mass spectrometry yielded 268 annotated features. Urine metabolites were normalized to urine creatinine. Regression models adjusted for age, sex, and genotype (HbSS/Sβ⁰ vs other) were first screened using a relaxed threshold, then bootstrap-validated (1,000 iterations). Metabolites were then tested against continuous eGFRcr and eGFRcys.

Results

Mean age was 40±10 years, 60% were female, 70% had HbSS/Sβ⁰, with mean eGFRcr 106 ± 24 mL/min/1.73m². Seven endogenous metabolites (1 plasma, 6 urine) demonstrated bootstrap-validated associations across all 3 SCKD definitions, with concordant effect estimates. Urine symmetric dimethylarginine (SDMA, N3,N4-Dimethyl-L-arginine) was most robust (albuminuria β = -0.52, 95% CI -0.91 to -0.17). Urine methylmalonic acid (MMA) was the only positively associated metabolite (albuminuria β = +0.29, 95% CI 0.05 to 0.63). Other validated metabolites were plasma glycine and urine glucuronic acid, methylhistamine, methylhistidine, and acetylcytidine. Histidine metabolism was the sole significant pathway (p = 0.018). In the filtration analysis, all 7 metabolites associated with eGFRcr and eGFRcys (all p<0.05). SDMA (β= −0.53, p=0.004) and glucuronic acid (β= −0.91, p=0.018) showed the strongest associations with eGFRcys.

Conclusion

Seven metabolites demonstrated consistent SCKD associations across 3 definitions and associated with eGFRcr and eGFRcys, supporting their potential as filtration-associated biomarkers. The signal was urine predominant. Standardization and prospective validation are indicated and ongoing.

Acknowledgment

Research reported in this abstract was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1 TR003163 and under the CTSA KL2 Program award number 5KL2TR003981-05. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Funding

• Other NIH Support