Interstitial inflammation and interstitial fibrosis and tubular atrophy predict renal survival in lupus nephritis

Abstract

BackgroundThis study examines the effect of interstitial inflammation and interstitial fibrosis and tubular atrophy on renal survival in lupus nephritis.MethodsBaseline characteristics, initial (n = 301) and repeat biopsies (n = 94) and clinical outcomes for patients with biopsy-proven lupus nephritis from 1998 to 2014 were retrospectively collected from the medical record. Clinical and morphologic variables were evaluated using a Cox proportional hazards model and multiple imputation to address missing data. Renal survival was defined as the time from initial biopsy to end-stage renal disease [estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2], dialysis or transplant.ResultsA total of 218 patients had follow-up and Class IV had worse renal survival, especially in patients with active and chronic glomerular lesions {relative to non-IV; Class IV-A: hazard ratio [HR] 0.92 [95% confidence interval (CI) 0.41–2.04], Class IV-AC: HR 5.02 [95% CI 2.70–9.36]}. Interstitial inflammation grade [relative to interstitial inflammation <5%; interstitial inflammation 5–25%: HR 2.36 (95% CI 1.13–4.91), interstitial inflammation 25–50%: HR 3.84 (95% CI 1.53–9.62), interstitial inflammation >50%: HR 7.67 (95% CI 3.75–15.67)] and increased interstitial fibrosis and tubular atrophy (IFTA) category [relative to IFTA <5%; IFTA 5–25%: HR 3.93 (95% CI 1.58–9.75), IFTA 25–50%: HR 4.01 (95% CI 1.37–11.70), IFTA >50%: HR 13.99 (95% CI 4.91–39.83)] predicted worse renal survival among all patients and those with Class IV on initial and repeat biopsy (n = 94) in a dose-dependent manner. Interstitial inflammation grade and IFTA category were significant predictors of renal survival in a multivariable model adjusted for age, gender, race, ethnicity and serum creatinine.ConclusionsInterstitial inflammation and IFTA independently affect renal survival and grading these lesions stratifies risk within the International Society of Nephrology and Renal Pathology Society classification of lupus nephritis.

Ets Family Transcription Factor Fli-1 Promotes Leukocyte Recruitment and Production of IL-17A in the MRL/Lpr Mouse Model of Lupus Nephritis

“…Scores from 0 to 3 (0, none; 1, mild; 2, moderate; and 3, severe) were applied for each of these features and then summed together to yield a final pathology score. Scoring of interstitial inflammation was as follows: score 0, <5% involvement; score 1, 5-25% involvement; score 2, 25-50% involvement; and score 3, >50% involvement [2]. IL-17A was detected in tissues with rabbit polyclonal Cells 2020, 9, 714 3 of 11 anti-IL-17A antibodies (Abcam) and the standard ultra-sensitive avidin-biotin complex (ABC) method (Vector).…”

“…Similarly, FITC-conjugated anti-mouse CD11b (Biolegend) and anti-CCL20 (Abcam) were used to detect immunoreactive CD11b cells and CCL20 (a representative chemoattractant for Th17 cells), respectively [26]. Detection of CD3 + , CD4 + , and CD11b + cells within the kidney infiltrates (mainly interstitial inflammation) was as described previously [2,14]. Briefly, 10 random sites were counted in blinded fashion to determine the number of CD3 + IL-17A + , CD4 + IL-17A + , and CD11b + CCL20 + cells per high-power field (magnification 400×); cells were photographed with a microscope equipped with digital camera (BX63, Olympus, Tokyo, Japan).…”

“…Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology that is associated with chronic inflammation in multiple organs including the kidney [1]. Infiltration of inflammatory cells into the kidney, a condition known as lupus nephritis, can ultimately result in renal failure [2]. Friend leukemia integration 1 (Fli-1) is a member of the Ets family of transcription factors and binds to DNA sequences that include a consensus GGA(A/T) motif.…”

Relationship of CD147 kidney expression with various pathologic lesions, biochemical and demographic data in patients with classes III and IV of lupus nephritis

“…Morphologic lesions of lupus nephritis consisted of mesangial proliferation lonely (class II), endocapillary and extracapillary proliferation; additionally, fibrinoid necrosis, wire loops and hyaline thrombi or podocytopathy may be seen. In glomeruli, involvement may be focal (class III) or diffuse (class IV), global or segmental (3,4). In addition, lesions in tubulointerstitial area are connected with glomerular lesions, however, they have also been detected to be prognostic of kidney outcome in lupus nephritis irrespective of glomerular lesions.…”

Stellenwert der Nierenbiopsie bei Lupusnephritis

“…Bereits eine interstitielle Inflammation von 5-25 % und noch mehr eine interstitielle Fibrose mit tubulärer Atrophie von 5-25 % verschlechtern die Prognose insoweit, daß nach einem Verlauf von 14 Jahren weit mehr als 50 % der Patienten eine terminale Niereninsuffizienz entwickeln[29]. Interessanterweise wurde weniger in-terstitielle Entzündung bei Patienten beobachtet, die Hydroxychloroquin eingenommen hatten [10].…”