Alterations of proximal tubular secretion in autosomal dominant polycystic kidney disease

Abstract

Background and objectives In autosomal dominant polycystic kidney disease (ADPKD), the GFR often remains normal despite significant nephronloss. Proximal tubular secretory clearance may be reduced in ADPKD before detectable changes in GFR. Design, setting, participants, & measurements We used targeted mass spectrometry to quantify secretory solutes from blood and urine samples from 31 patients with ADPKD and preserved GFR (meaneGFR=111611ml/min per1.73m2) and 25 healthy control individuals as well as from 95 patients with ADPKD and reduced GFR (mean eGFR =53621 ml/min per 1.73 m2) and 92 individuals with non-ADPKD CKD. We used linear regression to compare the fractional excretion of each solute between ADPKD and control groups. Among 112 patients with ADPKD, we used linear regression to determine associations of solute fractional excretion with height-adjusted total kidney volume. Results After adjusting for demographics, clinical characteristics, and kidney function measures, the fractional excretions of three secretory solutes were lower in patients with ADPKD and preserved GFR compared with healthy individuals: 52% lower cinnamoylglycine excretion (95% confidence interval, 24% to 70%), 53% lower tiglyl glycine excretion (95%confidenceinterval,23%to71%), and 91% lower xanthosine excretion (95%confidence interval,83%to95%). In addition to lower excretion softiglylglycine and xanthosine, patients with ADPKD and reduced GFR also demonstrated 37% lower dimethyluric acid excretion (95% confidence interval, 21% to 50%), 58% lower hippurate excretion (95%confidenceinterval,48%to66%), 48% lower is ovalerylglycine excretion (95% confidence interval, 37%to56%), and 31% lower pyridoxicacid excretion (95%confidence interval,16%to42%) compared with patients with non-ADPKD CKD and comparable eGFR. Among patients with ADPKD, solute fractional excretions were not associated with differences in kidney volume. Conclusions Patients with ADPKD and preserved and reduced GFR demonstrate lower tubular secretory solute excretion compared with healthy controls and patients with non- ADPKDCKD. Our results suggest that tubular secretion is impaired in ADPKD independent of GFR.