Kidney Week

Abstract: SU-OR18

Defining the Correlation Between Kidney Function and Histopathological Changes

Session Information

• Emerging Translational Research to Improve CKD Outcomes
  October 25, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: CKD (Non-Dialysis)

• 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

• Quinn, Ghazal Z., University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Ghazal Z. Quinn, MD



Ghazal Z. Quinn, MD is a post-doctoral nephrology research fellow at the University of Pennsylvania. Her research focus is understanding mechanisms of chronic kidney disease progression and manifestation of chronic kidney disease in different demographic populations.

• Abedini, Amin, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Amin Abedini,

• Palmer, Matthew, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Matthew Palmer,

• Havasi, Andrea, Boston Medical Center, Boston, Massachusetts, United States

Andrea Havasi,

• Susztak, Katalin, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States

Katalin Susztak,

Background

Estimated glomerular filtration rate (eGFR) is an imperfect measure of kidney function and does not correlate well with prognosis. Histopathologic analysis of renal biopsy is considered the gold standard to establish disease etiology and prognosis. Kidney biopsy, however, is rarely performed in patients with diabetes due its associated risks. Here we examined whether we could predict the degree of histological damage and kidney function decline based on clinical and demographic information.

Methods

Descriptor based histopathological analysis was performed in 759 human kidney tissue samples obtained from unaffected portion of tumor nephrectomies. Samples were limited to healthy, hypertensive and diabetic kidney disease. Changes in the glomeruli, tubules, interstitium and the vasculature were scored in an unbiased manner. Regression analyses were performed to assess the association between histopathology based on eGFR quantiles. Decline in renal function over time (eGFR slope in ml/min/1.73m² per year) was assessed in subjects with at least 3 months of follow up. Validation analysis was performed on 467 clinically indicated kidney biopsies.

Results

Mean subject age was 61, eGFR was 66 ml/min/1.73m², 70% had hypertension and 37% had diabetes. The association between eGFR and interstitial fibrosis was relatively weak (r²=0.3, p <0.001). There was no association between fibrosis and eGFR greater than 45 ml/min/1.73m2. Samples with eGFR below 45 ml/min/1.73m² showed a reasonably strong association between eGFR and fibrosis (r²=0.51, p <0.001) indicating a non-linear relationship. Hypertension and black race were independently associated with more severe histopathologic changes (p<0.05). Similar non-linear trends and significant associations were observed in our validation cohort. There was an association between severity of histopathologic findings and kidney function decline which did not reach significance in the primary cohort but was significant in the validation cohort.

Conclusion

The eGFR is a poor predictor of fibrosis at values > 45 ml/min/1.73m² but predicts renal structural changes well at lower eGFR. Hypertension and black race were independently associated with renal fibrosis, which may warrant more aggressive therapy in these cohorts. Predictions of kidney function decline are enhanced when eGFR and histopathology are used in combination.

Funding

• NIDDK Support