Salim S Hayek1, Douglas P Landsittel2, Changli Wei3, Martin Zeier4, Alan S L Yu5, Vicente E Torres6, Sharin Roth7, Christina S Pao7, Jochen Reiser8. 1. Division of Cardiology, Department of Medicine, University of Michigan, Ann Arbor Michigan; shayek@med.umich.edu Jochen_Reiser@rush.edu. 2. Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania. 3. Department of Medicine, Rush University Medical Center, Chicago, Illinois. 4. Division of Nephrology, University of Heidelberg, Heidelberg, Germany. 5. Kidney Institute, University of Kansas Medical Center, Kansas City, Kansas. 6. Division of Nephrology, Mayo Clinic, Rochester, Minnesota; and. 7. Otsuka Pharmaceutical Development & Commercialization, Inc., Rockville, Maryland. 8. Department of Medicine, Rush University Medical Center, Chicago, Illinois; shayek@med.umich.edu Jochen_Reiser@rush.edu.
Abstract
BACKGROUND: Levels of soluble urokinase plasminogen activator receptor (suPAR), an inflammation marker, are strongly predictive of incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive decline in renal function, but rates of decline and outcomes vary greatly. Whether suPAR levels are predictive of declining kidney function in patients with ADPKD is unknown. METHODS: We assessed suPAR levels in 649 patients with ADPKD who underwent scheduled follow-up for at least 3 years, with repeated measurements of height-adjusted total kidney volume and creatinine-derived eGFR. We used linear mixed models for repeated measures and Cox proportional hazards to characterize associations between baseline suPAR levels and follow-up eGFR or incident ESRD. RESULTS: The median suPAR level was 2.47 ng/ml and median height-adjusted total kidney volume was 778, whereas mean eGFR was 84 ml/min per 1.73 m2. suPAR levels were associated with height-adjusted total kidney volume (β=0.02; 95% confidence interval, 0.01 to 0.03), independent of age, sex, race, hypertension, and eGFR. Patients in the lowest suPAR tertile (<2.18 ng/ml) had a 6.8% decline in eGFR at 3 years and 22% developed CKD stage 3, whereas those in the highest tertile (suPAR>2.83 ng/ml) had a 19.4% decline in eGFR at 3 years and 68% developed CKD stage 3. suPAR levels >2.82 ng/ml had a 3.38-fold increase in the risk of incident ESRD. CONCLUSIONS: suPAR levels were associated with progressive decline in renal function and incident ESRD in patients with ADPKD, and may aid early identification of patients at high risk of disease progression.
BACKGROUND: Levels of soluble urokinase plasminogen activator receptor (suPAR), an inflammation marker, are strongly predictive of incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive decline in renal function, but rates of decline and outcomes vary greatly. Whether suPAR levels are predictive of declining kidney function in patients with ADPKD is unknown. METHODS: We assessed suPAR levels in 649 patients with ADPKD who underwent scheduled follow-up for at least 3 years, with repeated measurements of height-adjusted total kidney volume and creatinine-derived eGFR. We used linear mixed models for repeated measures and Cox proportional hazards to characterize associations between baseline suPAR levels and follow-up eGFR or incident ESRD. RESULTS: The median suPAR level was 2.47 ng/ml and median height-adjusted total kidney volume was 778, whereas mean eGFR was 84 ml/min per 1.73 m2. suPAR levels were associated with height-adjusted total kidney volume (β=0.02; 95% confidence interval, 0.01 to 0.03), independent of age, sex, race, hypertension, and eGFR. Patients in the lowest suPAR tertile (<2.18 ng/ml) had a 6.8% decline in eGFR at 3 years and 22% developed CKD stage 3, whereas those in the highest tertile (suPAR>2.83 ng/ml) had a 19.4% decline in eGFR at 3 years and 68% developed CKD stage 3. suPAR levels >2.82 ng/ml had a 3.38-fold increase in the risk of incident ESRD. CONCLUSIONS:suPAR levels were associated with progressive decline in renal function and incident ESRD in patients with ADPKD, and may aid early identification of patients at high risk of disease progression.
Authors: Qing Huai; Andrew P Mazar; Alice Kuo; Graham C Parry; David E Shaw; Jennifer Callahan; Yongdong Li; Cai Yuan; Chuanbing Bian; Liqing Chen; Bruce Furie; Barbara C Furie; Douglas B Cines; Mingdong Huang Journal: Science Date: 2006-02-03 Impact factor: 47.728
Authors: Vicente E Torres; Jared J Grantham; Arlene B Chapman; Michal Mrug; Kyongtae T Bae; Bernard F King; Louis H Wetzel; Diego Martin; Mark E Lockhart; William M Bennett; Marva Moxey-Mims; Kaleab Z Abebe; Yan Lin; James E Bost Journal: Clin J Am Soc Nephrol Date: 2010-11-18 Impact factor: 8.237
Authors: Jared J Grantham; Vicente E Torres; Arlene B Chapman; Lisa M Guay-Woodford; Kyongtae T Bae; Bernard F King; Louis H Wetzel; Deborah A Baumgarten; Phillip J Kenney; Peter C Harris; Saulo Klahr; William M Bennett; Gladys N Hirschman; Catherine M Meyers; Xiaoling Zhang; Fang Zhu; John P Miller Journal: N Engl J Med Date: 2006-05-18 Impact factor: 91.245
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Changli Wei; Clemens C Möller; Mehmet M Altintas; Jing Li; Karin Schwarz; Serena Zacchigna; Liang Xie; Anna Henger; Holger Schmid; Maria P Rastaldi; Peter Cowan; Matthias Kretzler; Roberto Parrilla; Moïse Bendayan; Vineet Gupta; Boris Nikolic; Raghu Kalluri; Peter Carmeliet; Peter Mundel; Jochen Reiser Journal: Nat Med Date: 2007-12-16 Impact factor: 53.440
Authors: Salim S Hayek; David E Leaf; Ayman Samman Tahhan; Mohamad Raad; Shreyak Sharma; Sushrut S Waikar; Sanja Sever; Alex Camacho; Xuexiang Wang; Ranadheer R Dande; Nasrien E Ibrahim; Rebecca M Baron; Mehmet M Altintas; Changli Wei; David Sheikh-Hamad; Jenny S-C Pan; Michael W Holliday; James L Januzzi; Steven D Weisbord; Arshed A Quyyumi; Jochen Reiser Journal: N Engl J Med Date: 2020-01-30 Impact factor: 91.245
Authors: Wolfgang Winnicki; Gere Sunder-Plassmann; Gürkan Sengölge; Ammon Handisurya; Harald Herkner; Christoph Kornauth; Bernhard Bielesz; Ludwig Wagner; Željko Kikić; Sahra Pajenda; Thomas Reiter; Benjamin Schairer; Alice Schmidt Journal: Sci Rep Date: 2019-09-24 Impact factor: 4.379
Authors: Shosha E I Dekker; Aswin Verhoeven; Darius Soonawala; Dorien J M Peters; Johan W de Fijter; Oleg A Mayboroda Journal: PLoS One Date: 2020-05-22 Impact factor: 3.240