Kidney Week

Abstract: FR-PO1132

Discordance Between Cystatin C and Creatinine Provides Insights into Tubular Function and Clinical Outcomes in Sickle Cell Disease

Session Information

• CKD: Screening, Diagnosis, Serum and Urine Biomarkers, and Scoring Indices
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2301 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

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

Kabir O. Olaniran, MD, MPH, FASN

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

Robert D. Toto, MD

Background

The degree of discordance in glomerular filtration rate estimation (eGFR) by cystatin C (eGFR_cys) compared to creatinine (eGFR_creat) provides insights into both tubular secretion and adverse clinical outcomes in the general population. Whether these associations are valid in sickle cell disease (SCD) is unknown. SCD pathophysiology markedly increases proximal tubular secretion of creatinine and promotes chronic inflammation (which can elevate cystatin C [CysC] levels). We investigated the differences between eGFR_cys and eGFR_creat in SCD compared to non-SCD and the association between eGFR discordance and common SCD outcomes.

Methods

We performed a 2-center cross-sectional study of 1060 adult Black race patients over 5 years (2020-2025) across chronic kidney disease (CKD) stages 1-5, excluding dialysis. SCD was confirmed by hemoglobin electrophoresis. Outcomes of interest were eGFR difference (eGFR_diff [eGFR_cys - eGFR_creat]) and eGFR ratio (eGFR_ratio [eGFR_cys/eGFR_creat]). Outcomes were examined in SCD vs non-SCD (linear regression), across CKD stages (trend tests), and in common SCD outcomes (logistic regression): left ventricular hypertrophy (LVH), pulmonary hypertension (pHTN), heart failure (HF) and stroke. Demographics, vital signs, comorbidities and medications were included in multivariable analyses.

Results

We identified 184 SCD and 876 non-SCD patients. The mean age was 58±17 years, 55% were female, the mean eGFR_cys was 50±31 mL/min, and the mean eGFR_creat was 60±33 mL/min. The mean eGFR_diff was -9±17 and the mean eGFR_ratio was 0.85±0.27. Before and after adjusted analyses, eGFR_diff was larger (adjusted β -14.4, p<0.01) and eGFR_ratio was lower (adjusted β -0.16, p<0.01) in SCD compared to non-SCD. The trend test for CKD stages in SCD was significant for narrowing eGFR_diff (Z=3.2, p<0.01) and decreasing eGFR_ratio (Z= -2.1, p=0.04) from stages 1-5. Larger than median SCD eGFR_diff was associated with LVH (adjusted odds ratio [aOR] 2.49, p=0.03), pHTN (aOR 2.62, p<0.01), and HF (aOR 4.28, p<0.01) but not stroke (aOR 1.39; p=0.53). Lower than median SCD eGFR_ratio results were similar.

Conclusion

eGFR_diff and eGFR_ratio in SCD are more discordant than in non-SCD and associated with adverse cardiac outcomes, but not with stroke. CysC may be of unique clinical utility in interrogating renal tubular function and cardiac events in SCD.

Funding

• Other NIH Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025at2hqdag