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Kidney Week

Abstract: TH-PO931

Differences in Proximal Tubular Secretion Across Categories of CKD

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

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
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background

Absent a kidney biopsy, the cause of chronic kidney disease (CKD) is determined by clinical assessment, which includes measures of glomerular function (estimated glomerular filtration rate (GFR) and urinary albumin excretion). However, the underlying causes of CKD may also differentially impact non-glomerular tissue, including the proximal tubule. We quantified a set of proximal tubular secretory solutes and compared their clearances among varying causes of CKD.

Methods

We evaluated timed overnight urine specimens from 223 participants in the Seattle Kidney Study, a prospective study of CKD. We used liquid chromatography-mass spectrometry to quantify serum and urine concentrations of ten secretory solutes and calculated clearance of each solute (mL/min). We abstracted CKD causes from review of nephrology clinic notes and categorized these causes as vascular, diabetic, glomerular, and tubulointerstitial kidney diseases. We used one-way analysis of variance to compare differences in solute clearances among the CKD causes and we advanced three solutes for further analyses based on meeting a 5% false discovery threshold. For each significant solute we used linear regression to compare the relative difference in secretory clearance among disease group after adjustment for age, race, gender, body mass index, estimated GFR, and urine albumin to creatinine ratio.

Results

Three secretory solutes met the threshold for significance across the suspected etiologies of CKD: isovalerylglycine, kynurenic acid, and tiglylglycine. Glomerular disease was associated with greater clearances of all three secretory solutes. Diabetic kidney disease was associated with greater isovalerylglycine clearance compared with vascular disease after adjustment (Table).

Conclusion

Secretory solute clearance relative to GFR is higher in CKD patients with glomerular disease compared to vascular disease.

SoluteAdjustment modelVascular disease [n=75](reference)Diabetes [n=72] Fold difference (95% CI)p-valueTubulointerstitial disease [n=26] Fold difference (95% CI)p-valueGlomerular disease [n=50] Fold difference (95% CI)p-value
IsovalerylglycineUnadjusted1.01.12 (0.88, 1.42)0.341.28 (0.92, 1.77)0.141.55 (1.19, 2.02)0.001*
 Adjusted1.01.39 (1.13, 1.72)0.002*1.05 (0.80, 1.37)0.721.48 (1.18, 1.87)0.001*
Kynurenic acidUnadjusted1.01.02 (0.82, 1.27)0.831.12 (0.83, 1.51)0.451.45 (1.14, 1.84)0.003*
 Adjusted1.01.07 (0.88, 1.30)0.480.97 (0.75, 1.24)0.791.28 (1.03, 1.59)0.03*
TiglyglycineUnadjusted1.01.03 (0.81, 1.30)0.791.14 (0.82, 1.59)0.391.52 (1.17, 1.98)0.002*
 Adjusted1.01.10 (0.91, 1.35)0.310.96 (0.75, 1.25)0.791.33 (1.07, 1.67)0.01*

*denotes statistical significance at p-value < 0.05

Funding

  • NIDDK Support