Abstract: SA-PO513
Exploring KIM-1 as a Marker for Kidney Disease in ADPKD: Analysis from the HALT-PKD Studies
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
- Noureddine, Lama A., Universty of Iowa Carver College of Medicine, Iowa City, Iowa, United States
- Gitomer, Berenice Y., Div. Renal Diseases and Hypertension,, Aurora, Colorado, United States
- You, Zhiying, UC Denver, Aurora, Colorado, United States
- Wang, Wei, University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
- Chonchol, Michel, University of Colorado, Aurora, Colorado, United States
- Jalal, Diana I., University of Iowa, Iowa City, Iowa, United States
Group or Team Name
- HALT Investigators
Background
Cyst compression of renal tubules and intrarenal microvasculature play a vital role in progression of autosomal dominant polycystic kidney disease (ADPKD) and may induce kidney injury molecule-1 (KIM-1). We hypothesized that urinary KIM-1 is a marker of disease progression in ADPKD.
Methods
We measured baseline and 48-month urinary KIM-1/urinary creatinine (UKIM-1/Cr) of participants in the HALT-PKD studies. We evaluated whether UKIM-1/Cr predicted decline in eGFR in studies A and B (n=738) or increase in height-adjusted TKV (TKV) in study A (n=283) and whether intensive, compared to standard, blood pressure (BP) control lowered UKIM-1/Cr over 48 months in study A (n=101).
Results
Higher baseline UKIM-1/Cr was associated with decline in eGFR in unadjusted analysis (β-estimate for eGFR slope=-0.04, 95% C.I. -0.06- -0.01, P=0.0006). After adjusting for demographics, PKD1 genotype, SBP, DBP, BMI, baseline eGFR, urinary albumin/Cr ratio (UACR), and TKV, baseline UKIM-1/Cr was associated with slightly greater kidney function decline (β-estimate = -0.03, 95% C.I. -0.05- -0.003, P= 0.03). In linear mixed model regression analysis, baseline UKIM-1/Cr was associated with increased TKV over time in the multivariate model (β-estimate= 0.10, 95% C.I. 0.002-0.20, P=0.05). Intensive, compared to standard, BP control was not associated with lower UKIM-1/Cr levels. However, after adjusting for interaction with baseline UACR, intensive BP control was associated with lower KIM-1 in the multivariate model (β-estimate= -0.27, 95% C.I. -0.52- -0.011, P= 0.04). This persisted after adjustment for renal blood flow and inflammatory markers (Table).
Conclusion
UKIM-1/Cr was associated with slightly greater decline in kidney function in ADPKD and intensive BP control was associated with lower UKIM-1/Cr over 48 months. Further studies are needed to determine what role KIM-1 plays in ADPKD progression.
Effect of intensive vs standard BP control on UKIM-1/Cr in study A:
| Odds ratio (CI) | P value |
| -0.32 (-0.58 to -0.06) * | 0.02 |
| -0.33 (-0.59 to -0.06) # | 0.02 |
*adjusted for demographics age, male gender, PKD1 genotype, SBP, DBP, BMI, baseline eGFR, baseline UACR, baseline TKV, and baseline renal blood flow #: Variables in * + high sensitivity CRP (hs-CRP), interleukin-6 (IL-6)