Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis

Abstract

Background and objectives: The prognostic significance of histopathologic (sub)classes in the current classification of lupus nephritis (LN) is controversial. We analyzed clinical and histopathologic predictors of renal outcome in LN outside the framework of the classification.

Design, setting, participants, & measurements: Variables (50 histopathologic and ten clinical) were tested in mixed, linear, and Cox regression models for their association with renal flare, ESRD, and eGFR during follow-up (1, 5, and 10 years) in 105 patients with LN who underwent biopsy from 1987 to 2011. The Cockcroft-Gault (normalized to a body surface area of 1.73 m²) and Schwartz formulas were used to calculate eGFR for adults and children, respectively.

Results: During median follow-up of 9.9 years (25th-75th percentile, 5.9-13.8), 47 patients experienced a renal flare and 21 progressed to ESRD. Renal flare was predicted by fibrinoid necrosis (hazard ratio [HR], 1.04 per %; 95% confidence interval [95% CI], 1.00 to 1.07) and nonwhite race (HR, 2.23; 95% CI, 1.23 to 4.04). ESRD was predicted by fibrinoid necrosis (HR, 1.08 per %; 95% CI, 1.02 to 1.13), fibrous crescents (HR, 1.09 per %; 95% CI, 1.02 to 1.17), interstitial fibrosis/tubular atrophy (IF/TA) ≥25% (HR, 3.89; 95% CI, 1.25 to 12.14), eGFR at baseline (HR, 0.98 per ml/min per 1.73 m²; 95% CI, 0.97 to 1.00), and nonwhite race (HR, 7.16; 95% CI, 2.34 to 21.91). A higher mean eGFR during follow-up was associated with normal glomeruli (+0.2 ml/min per 1.73 m² per %; 95% CI, 0.1 to 0.4). Like ESRD, a lower eGFR during follow-up was associated with fibrous crescents, IF/TA≥25%, and nonwhite race, as well as with cellular/fibrocellular crescents (-0.4 ml/min per 1.73 m² per %; 95% CI, -0.6 to -0.2) and age (-0.8 ml/min per 1.73 m² per year; 95% CI, -1.2 to -0.4).

Conclusion: The LN classification should include an index of evidence-based prognosticators. Awaiting validation of a formal index, we suggest that at least fibrinoid necrosis, fibrous crescents, and IF/TA warrant explicit independent scoring to assess the risk of progressive renal dysfunction in conjunction with clinical findings.

Keywords: atrophy; clinical pathology; evidence-based medicine; fibrosis; follow-up studies; glomerular filtration rate; humans; kidney; kidney failure, chronic; kidney glomerulus; lupus nephritis; prognosis; renal insufficiency, chronic.

Figure 1.

Histopathologic variables that were assessed. For definitions of histopathologic lesions, see Supplemental Material 1. Percentages represent the proportion of involved scorable glomeruli. Crescent score: a multiplication factor of 1 was used for segmental crescents, and 2 for circumferential crescents. *Excluded from analyses because of low prevalence (≤5 patients). ^†Excluded from analyses because the variable was strongly correlated with another variable (r/rho>0.8). ^‡Interstitial fibrosis and tubular atrophy were combined to form the composite variable “IF/TA” (interstitial fibrosis/tubular atrophy; whichever was the higher value). +/−, scored as either present or absent.

Figure 2.

Probabilities of renal survival and renal flare among patients in the cohort. Time to ESRD (A, n=105) and time to first renal flare (B, n=99) are depicted according to the Kaplan–Meier method. (A) During follow-up, 21 patients progressed to ESRD. The probability of renal survival was 93% at 1 year, 90% at 5 years, 85% at 10 years, and 71% at 20 years of follow-up. (B) Patients were only considered who achieved (partial) remission after renal biopsy and were not censored because they already reached ESRD. During follow-up, 47 patients experienced a renal flare. The probability of renal flare was 8% at 1 year, 35% at 5 years, and 48% at 10 years.