The Prognostic Value of Histopathologic Lesions in Native Kidney Biopsy Specimens: Results from the Boston Kidney Biopsy Cohort Study

Abstract

Background Few studies have evaluated whether histopathologic lesions on kidney biopsy provide prognostic information beyond clinical and laboratory data.Methods We enrolled 676 individuals undergoing native kidney biopsy at three tertiary care hospitals into a prospective, observational cohort study. Biopsy specimens were adjudicated for semiquantitative scores in 13 categories of histopathology by two experienced renal pathologists. Proportional hazards models tested the association between histopathologic lesions and risk of kidney disease progression (≥40% eGFR decline or RRT).Results Mean baseline eGFR was 57.5±36.0 ml/min per 1.73 m² During follow-up (median, 34.3 months), 199 individuals suffered kidney disease progression. After adjustment for demographics, clinicopathologic diagnosis, and laboratory values, the following lesions (hazard ratio; 95% confidence interval) were independently associated with progression: inflammation in nonfibrosed interstitium (0.52; 0.32 to 0.83), moderate and severe versus minimal interstitial fibrosis/tubular atrophy (2.14; 1.24 to 3.69 and 3.42; 1.99 to 5.87, respectively), moderate and severe versus minimal global glomerulosclerosis (2.17; 1.36 to 3.45 and 3.31; 2.04 to 5.38, respectively), moderate and severe versus minimal arterial sclerosis (1.78; 1.15 to 2.74 and 1.64; 1.04 to 2.60, respectively), and moderate and severe versus minimal arteriolar sclerosis (1.63; 1.08 to 2.46 and 2.33; 1.42 to 3.83, respectively). An 11-point chronicity score derived from semiquantitative assessments of chronic lesions independently associated with higher risk of kidney disease progression (hazard ratio per one-point increase, 1.19; 95% confidence interval, 1.12 to 1.27).Conclusions Across a diverse group of kidney diseases, histopathologic lesions on kidney biopsy provide prognostic information, even after adjustment for proteinuria and eGFR.

Keywords: ESRD; chronic kidney disease; histopathology; renal biopsy.

Graphical abstract

Figure 1.

Distribution of semiquantitative severity scores for each of the adjudicated 13 histopathological lesions in the Boston Kidney Biopsy Cohort. The histopathologic categories were graded by percentage of renal cortical volume or affected glomeruli: none, ≤10%; mild, 11%–25%; moderate, 26%–50%; and severe, >50%. ATI, acute tubular injury; IFTA, interstitial fibrosis and tubular atrophy.

Figure 2.

Histopathologic lesions are significantly associated with eGFR and proteinuria. Boxplots show significant differences between grades of adjudicated histopathologic lesions and (A) eGFR or (B) proteinuria.

Figure 3.

Chronic histopathologic lesions are associated with kidney disease progression. (A) Global glomerulosclerosis. (B) Interstitial fibrosis/tubular atrophy. (C) Arterial sclerosis. (D) Arteriolar sclerosis. Generalized log rank P<0.001 for all lesions.