Abstract: SA-OR038
The Association of sTNFR-1 and sTNFR-2 with Histopathologic Lesions and Progression to ESRD: The Boston Kidney Biopsy Cohort Study
Session Information
- Biomarkers in CKD
November 09, 2019 | Location: 152, Walter E. Washington Convention Center
Abstract Time: 04:30 PM - 04:42 PM
Category: CKD (Non-Dialysis)
- 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Srivastava, Anand, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
- Palsson, Ragnar, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Sabbisetti, Venkata, Brigham and Women's Hospital, Boston, Massachusetts, United States
- Schmidt, Insa Marie, 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
- Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
Background
The relationship of soluble tumor necrosis factor-1 (sTNFR-1) and sTNFR-2 with histopathologic lesions and progression to ESRD in individuals with biopsy-confirmed kidney disease is unknown.
Methods
We measured plasma sTNFR-1 and sTNFR-2 levels in 523 individuals enrolled into a prospective, observational cohort study of patients undergoing native kidney biopsy at three tertiary care hospitals. Two experienced renal pathologists adjudicated biopsy specimens for semiquantitative scores of histopathology. Linear regression models tested the association between biomarkers and histopathologic lesions. Proportional hazards models tested the association between biomarkers and risk of progression to ESRD.
Results
Mean age was 53±17 years and mean baseline eGFR was 56±36 ml/min/1.73m2. sTNFR-1 and sTNFR-2 correlated with eGFR (Rs = -0.70 and -0.62, P<0.001, respectively). After adjustment for age, sex, race, and eGFR, sTNR-1 and sTNFR-2 levels were highest among individuals with glomerulopathies and diabetic nephropathy (Figure). sTNFR-1 and sTNFR-2 followed slightly different patterns of injury after multivariable adjustment (Figure). Both biomarkers were associated with more severe interstitial fibrosis/tubular atrophy and mesangial expansion. Only sTNFR-1 associated with more severe acute tubular injury and presence of inflammation in the nonfibrosed interstitium. Only sTNFR-2 associated with presence of endocapillary glomerular inflammation and segmental sclerosis. During a median follow-up time of 25 months, 78 individuals progressed to ESRD. sTNFR-1 and sTNFR-2 were each independently associated with greater than 2-fold increased risk of progression to ESRD (Figure).
Conclusion
Higher levels of sTNFR-1 and sTNFR-2 are independently associated with increased risk of progression to ESRD across a diverse set of biopsy-confirmed kidney diseases.
Funding
- NIDDK Support