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Kidney Week

Abstract: TH-PO430

Associations of Plasma YKL-40 with Kidney Disease Progression, Mortality, and Histopathologic Lesions in Native Kidney Biopsies

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Schmidt, Insa Marie, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • Srivastava, Anand, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Palsson, Ragnar, Harvard, Belmont, Massachusetts, United States
  • Sabbisetti, Venkata, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Stillman, Isaac Ely, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Rennke, Helmut G., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Weins, Astrid, Brigham & Women's Hospital, Boston, Massachusetts, United States
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
Background

YKL-40 is a chitinase-like protein and important regulator of renal tissue injury and apoptosis. We evaluated the association of plasma YKL-40 with progression to ESRD and all-cause mortality among patients with diverse kidney diseases. Furthermore, we tested whether YKL-40 is associated with specific clinicopathologic diagnoses and histopathologic lesions in human kidney biopsies.

Methods

We measured plasma YKL-40 levels in 490 participants of the Boston Kidney Biopsy Cohort—a prospective cohort study of patients undergoing native kidney biopsies. Biopsies were reviewed by renal pathologists and adjudicated for histopathologic findings. Cox proportional hazard models tested the association between YKL-40 and the risks of progression to ESRD and all-cause mortality. Multivariable linear regression models were used to assess the relationship between YKL-40, histopathologic lesions, and clinicopathologic diagnoses. Models were adjusted for age, race, sex, diagnosis, proteinuria, and eGFR.

Results

YKL-40 correlated positively with proteinuria and inversely with eGFR (r=0.27, r=-0.51; p<0.0001, respectively). During a median follow-up time of 25 months, higher YKL-40 levels were independently associated with an increased risk for progression to ESRD (adjusted HR per 1-SD increase of natural log-transformed YKL-40=1.59, 95%CI (1.10-2.31)) and all-cause mortality (adjusted HR=2.28, 95%CI (1.44-3.62)). YKL-40 levels were significantly higher in non-proliferative glomerulopathies (adjusted β=0.48 [ref=normal or thin basement membrane], 95%CI (0.16-0.79), p=0.003) and significantly associated with more severe arterial sclerosis (adjusted β=0.16 [ref=no sclerosis], 95%CI (0.005,0.32), p=0.043).

Conclusion

YKL-40 is independently associated with increased risks of all-cause mortality and progression to ESRD in patients with a diverse spectrum of kidney diseases. Higher levels of YKL-40 were seen in non-proliferative glomerulopathies and biopsies with more severe arterial sclerosis.

Funding

  • Other NIH Support