Abstract: SA-PO517
Soluble Urokinase Plasminogen Activator Receptor Levels Predict Renal Function Decline in Autosomal Dominant Polycystic Kidney Disease
Session Information
- ADPKD: Clinical Studies
October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidney
- 1001 Genetic Diseases of the Kidney: Cystic
Authors
- Hayek, Salim, Emory University School of Medicine, Atlanta, Georgia, United States
- Roth, Sharin, Otsuka Pharmaceutical Development and Commercialization, Princeton, New Jersey, United States
- Pao, Christina, Otsuka Pharmaceutical Development and Commercialization, Princeton, New Jersey, United States
- Zeier, Martin G., Heidelberg University , Heidelberg, Germany
- Wei, David Changli, Rush University Medical Center, Chicago, Illinois, United States
- Reiser, Jochen, Rush University Medical Center, Chicago, Illinois, United States
Background
Levels of soluble urokinase-type plasminogen activator receptor (suPAR), a signaling molecule and marker of immune activation, have been shown to predict incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive but highly variables rates of decline in renal function, with highly heterogenous outcomes. Whether suPAR levels are predictive of decreasing kidney function in patients with ADPKD independently of known prognostic factors such as proteinuria and kidney volume, is unknown.
Methods
SuPAR levels were measured in a subset of 479 patients with ADPKD (mean age 39, 52% male, 80% Caucasians) enrolled in the TEMPO 3:4 trial and randomized to the placebo arm. All subjects randomized into the placebo arm with plasma samples that were available were included. Patients underwent scheduled follow-up for 3 years, with repeated measurements of height-adjusted kidney volume (htTKV), urine albumin-creatinine ratio (UACR), and Cockcroft-Gault calculated estimated glomerular filtration rate (eGFR). Linear mixed models for repeated measures were used adjusting for age, gender, baseline eGFR, UACR and htTKV to examine the association between baseline suPAR levels stratified by tertiles and follow-up eGFR measures.
Results
At baseline, the median suPAR level was 2544 pg/mL [IQR 2125-3221], with 32% of subjects having suPAR levels≥3000 pg/mL, while median eGFR was 78 [IQR 62;96] and htTKV 853 mL/m [IQR 623-1151]. Baseline suPAR levels were weakly associated with htTKV (β 0.15 95%CI[0.00;0.29] independently of eGFR, UACR, gender, age and hypertension. Patients in the first, second and third tertiles of suPAR had a 10%, 15% and 23% decrease in eGFR (P<0.001), and a 18%, 18% and 17% increase in htTKV at 3-years follow-up (P=0.6). The associations did not differ according to gender and was independent of age, baseline UACR and eGFR.
Conclusion
SuPAR levels were associated with decline in renal function in patients with ADPKD. Whether suPAR can be used as a prognostic marker to identify patients at high risk of decline in renal function that would benefit from early therapeutic intervention remains to be determined.
Funding
- NIDDK Support