TY - JOUR
T1 - Soluble urokinase-type plasminogen activator receptor in Black Americans with CKD
AU - Luo, Shengyuan
AU - Coresh, Josef
AU - Tin, Adrienne
AU - Rebholz, Casey M.
AU - Chen, Teresa K.
AU - Hayek, Salim S.
AU - Tracy, Melissa
AU - Lipkowitz, Michael S.
AU - Appel, Lawrence J.
AU - Levey, Andrew S.
AU - Inker, Lesley A.
AU - Reiser, Jochen
AU - Grams, Morgan Erika
N1 - Funding Information:
The authors thank the staff and participants of the African-American Study of Kidney Disease and Hypertension for their important contributions. J.C., A.T., L.J.A., and M.E.G. are supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK108803-02. J.C. and M.E.G. are supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant U01-DK085689-07. C.M.R. is supported by a mentored research scientist development award from the National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK107782). T.K.C. is supported by the Norman S. Coplon Extramural Grant Program by Satellite Healthcare, a not-for-profit kidney care provider. Part of this work was presented as a moderated poster on March 20, 2018 at the American Heart Association EPI/Lifestyle 2018 Scientific Sessions in New Orleans, Louisiana.
Funding Information:
J.C., A.T., L.J.A., and M.E.G. are supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant R01-DK108803-02. J.C. and M.E.G. are supported by the National Institute of Diabetes and Digestive and Kidney Diseases grant U01-DK085689-07. C.M.R. is supported by a mentored research scientist development award from the National Institute of Diabetes and Digestive and Kidney Diseases (K01 DK107782). T.K.C. is supported by the Norman S. Coplon Extramural Grant Program by Satellite Healthcare, a not-for-profit kidney care provider.
Publisher Copyright:
© 2018 by the American Society of Nephrology.
PY - 2018/7/6
Y1 - 2018/7/6
N2 - Background and objectives Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria. Design, setting, participants, & measurements Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5–10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death. Results At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02). Conclusions Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.
AB - Background and objectives Black Americans with and without APOL1 kidney disease risk variants face high risk of ESKD. Soluble urokinase-type plasminogen activator receptor (suPAR), a circulating signaling protein and marker of immune activation, constitutes a promising biomarker of CKD-associated risks. We aimed to quantify the associations between serum suPAR concentration and adverse outcomes in Black Americans with and without APOL1 kidney disease risk variants, over and above iodine-125 iothalamate measured GFR and proteinuria. Design, setting, participants, & measurements Using data from the African-American Study of Kidney Disease and Hypertension, a multicenter clinical trial followed by a cohort phase with a median total follow-up of 9.7 years (interquartile range, 6.5–10.9 years), we examined the associations of suPAR with CKD progression (defined as doubling of serum creatinine or ESKD), ESKD, worsening proteinuria (defined as pre-ESKD doubling of 24-hour urine protein-to-creatinine ratio to ≥220 mg/g), and all-cause death. Results At baseline, the median suPAR was 4462 pg/ml, mean measured GFR was 46 ml/min per 1.73 m2, and median 24-hour urine protein-to-creatinine ratio was 80 mg/g. After controlling for baseline demographics, randomization arm, GFR, proteinuria, APOL1 risk status, and clinical risk factors, there was a 1.26-times higher risk for CKD progression per SD higher baseline log-transformed suPAR (hazard ratio [HR], 1.26; 95% confidence interval [95% CI], 1.11 to 1.43; P<0.001). Higher suPAR was also independently associated with risk of ESKD (HR, 1.36; 95% CI, 1.17 to 1.58; P<0.001) and death (HR, 1.25; 95% CI, 1.08 to 1.45; P=0.003). suPAR was only associated with worsening proteinuria in patients with two APOLI risk alleles (HR, 1.46; 95% CI, 1.08 to 1.99; P=0.02). Conclusions Higher suPAR was associated with various adverse outcomes in Black Americans with CKD, with and without APOL1 kidney disease risk variants, independently of proteinuria and GFR.
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U2 - 10.2215/CJN.13631217
DO - 10.2215/CJN.13631217
M3 - Article
C2 - 29903900
AN - SCOPUS:85049776327
SN - 1555-9041
VL - 13
SP - 1013
EP - 1021
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
IS - 7
ER -