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Kidney Week

Abstract: SA-PO503

Alteration of Tubular Secretion in 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

  • Wang, Ke, University of Washington, Seattle, Washington, United States
  • Zelnick, Leila R., Kidney Research Institute, Seattle, Washington, United States
  • Chen, Yan, University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Watnick, Terry J., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Seliger, Stephen L., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of kidney disease. Glomerular filtration rate (GFR) typically remains normal during early stages of disease; however the impact of ADPKD on other kidney functions is less certain. We compared proximal tubular solute clearance in 124 ADPKD patients from the Baltimore PKD Center to that of healthy controls and individuals with non-ADPKD chronic kidney disease (CKD).

Methods

We used liquid chromatography-mass spectrometry to quantify serum and urine concentrations of ten secretory solutes and calculated solute fractional excretions relative to creatinine. For 31 ADPKD patients with normal estimated GFR (eGFR), we compared fractional excretions with 25 healthy individuals. For 93 ADPKD patients with impaired eGFR, we compared fractional excretions with 91 general CKD patients from the Seattle Kidney Study matched by age, race, gender, and eGFR stage. We used linear regression to compare relative differences in fractional excretions adjusted for eGFR, age, gender, and body mass index. Among ADPKD patients we used linear regression to assess associations of fractional excretion with height adjusted kidney volume, determined by magnetic resonance imaging.

Results

The fractional excretions of most secretory solutes were lower in PKD patients compared with healthy controls and general CKD patients. Associations for six solutes were significant after accounting for multiple comparisons (Table). None of the secretory solutes were associated with kidney volume.

Conclusion

Secretory solute excretion is lower in ADPKD patients compared with healthy controls and general CKD patients independent of eGFR.

Secretory soluteFold-difference ADPKD (eGFR ≥90 ml/min/1.73m2) versus healthy** [95% CI]p-valueFold-difference ADPKD (eGFR<90 ml/min/1.73m2) versus CKD**[95% CI]p-valueDifference in height-adjusted kidney volume (cm3/m)** [95% CI]p-value
Cinnamoylglycine0.57 (0.41, 0.78)0.0006*0.63 (0.46, 0.86)0.003*200 (-227, 627)0.36
Hippurate0.66 (0.51, 0.86)0.002*0.40 (0.32, 0.51)<0.0001*59 (-362, 480)0.78
Indoxyl sulfate0.84 (0.67, 1.05)0.130.96 (0.81, 1.15)0.68-110 (-494, 275)0.58
Isovalerylglycine0.57 (0.42, 0.76)0.0001*0.51 (0.42, 0.60)<0.0001*-28 (-491, 434)0.91
Kynurenic acid1.46 (1.09, 1.97)0.011.11 (0.95, 1.29)0.18-34 (-379, 311)0.85
Pantothenic acid1.04 (0.72, 1.51)0.821.20 (0.96, 1.49)0.11-109 (-513, 296)0.6
P-cresol sulfate0.63 (0.49, 0.80)0.0003*0.87 (0.73, 1.04)0.13-355 (-721, 12)0.06
Pyridoxic acid0.81 (0.64, 1.02)0.080.73 (0.60, 0.89)0.001*-355 (-721, 12)0.82
Tiglylglycine0.59 (0.43, 0.79)0.0005*0.57 (0.48, 0.67)<0.0001*57 (-405, 520)0.81
Xanthosine0.08 (0.06, 0.13)<0.0001*0.27 (0.21, 0.35)<0.0001*506 (-6, 1018)0.05

*denotes statistical significance at Bonferroni p-value threshold <0.005 **Adjusted for age, gender, body mass index, eGFR

Funding

  • NIDDK Support