Plasma Soluble Urokinase‐type Plasminogen Activator Receptor (suPAR) as an Early Indicator of Sickle Cell Disease‐Associated Chronic Kidney Disease
Authors: Afangbedji Nowah , Taye Ammanuel , Smith Nathan , Niu Xiomei , Taylor James G. , Nekhai Sergei , Jerebtsova Marina 
Published: June 2021

Background

Chronic kidney disease (CKD) is a major complication of sickle cell anemia (SCA). SCA patients have a three‐fold higher risk of CKD than the general population consequently increasing their risk of cardiovascular disease and death. In clinical practice, methods for screening of kidney disease are limited to the measurement of proteinuria and estimated glomerular filtration rate (eGFR). Because of urine concentration defect among SCA patients, proteinuria is not detected at the early stages of CKD. Also typically increased glomerular filtration in SCA patient complicated early CKD detection. Thus, more sensitive and specific markers are needed for early CKD detection. Elevated soluble urokinase‐type plasminogen activator receptor (suPAR) was recently identified as marker of focal segmental glomerulosclerosis. Also in a recent longitudinal study, elevated plasma suPAR levels were associated with faster progression of CKD. However, suPAR levels have not been measured in SCA patients in relation to the CKD progression.

Objective

Our goal was to measure plasma and urine levels of suPAR and correlate them with CKD progression in SCA patients.

Methods

Urine and plasma samples were collected from 96 SCA patients enrolled in a sickle cell disease registry study at Center for Sickle Cell Disease, Howard University. Levels of creatinine and cystatin C in plasma and albumin and creatinine in urine were measured by ELISA. Estimated GFR (eGFR) was calculated using CKD‐EPI creatinine‐cystatin equation. CKD stages were assigned according to the National Kidney Foundation, Kidney Disease Outcomes Quality Initiatives (K/DOQI) guidelines. We selected a group of 30 patients with CKD stages 1–4 and age‐matched 14 control patients with CKD stage 0. Plasma suPAR concentrations were measured by ELISA.

Results

Our cohort of 44 patients (mean age of 41.1, range 20–67, 47.7% females) comprised 70.5 % HbSS, 18.2% HbSC, 6.8% HbS β+thalassemia and 4.5 % HbS β0 thalassemia. CKD prevalence increased with age but was independent of gender. There was a positive correlation between plasma suPAR levels and progression of CKD (r2=0.31) and a negative correlation between plasma suPAR concentrations and progression of CKD (r2=0.18). As expected, plasma suPAR levels negatively correlated with eGFR (r2=0.4171).

Conclusion

Our study showed a positive correlation between plasma suPAR levels and CKD progression in patients with SCA. Our findings suggest that elevated plasma suPAR levels in SCA patients can serve as a biomarker of SCA‐associated CKD. The limitation of our investigation is the small cohort size and cross‐sectional study. Thus future longitudinal analysis of suPAR levels in patients with SCA is needed.

Support or Funding Information

NIH Research Grants 1P50HL118006, 1R01HL125005 and 5G12MD007597. The content is solely the responsibility of the authors and does not necessarily represent the official view of NHLBI, NIMHD or NIH.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.