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Renal Fibrosis in Lupus Nephritis.

ABSTRACT: Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injury severity, predictors of therapeutic response, and prognostic factors of renal outcome in recent years. This review will discuss the fibrogenesis in LN and known mechanisms of renal fibrosis. The importance of the chronicity index, which was recently added to the histological categorization of LN, and its role in predicting treatment response and renal prognosis for patients with LN, will be explored. A better understanding of cellular and molecular pathways involved in fibrosis in LN could enable the identification of individuals at higher risk of progression to chronic kidney disease and end-stage renal disease, and the development of new therapeutic strategies for lupus patients.

SUBMITTER: Sciascia S

PROVIDER: S-EPMC9699516 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Renal Fibrosis in Lupus Nephritis.

Sciascia Savino S Cozzi Martina M Barinotti Alice A Radin Massimo M Cecchi Irene I Fenoglio Roberta R Mancardi Daniele D Wilson Jones Georgia G Rossi Daniela D Roccatello Dario D

International journal of molecular sciences 20221118 22

Fibrosis can be defined as a pathological process in which deposition of connective tissue replaces normal parenchyma. The kidney, like any organ or tissue, can be impacted by this maladaptive reaction, resulting in persistent inflammation or long-lasting injury. While glomerular injury has traditionally been regarded as the primary focus for classification and prognosis of lupus nephritis (LN), increasing attention has been placed on interstitial fibrosis and tubular atrophy as markers of injur ...[more]

PMID: 36430794

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Project description: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.

Project description:INTRODUCTION: Among various lupus renal vascular changes, thrombotic microangiopathy (TMA) presented with the most severe clinical manifestations and high mortality. The pathogenesis of TMA in systemic lupus erythematosus (SLE) was complicated. The aim of this study was to assess clinical manifestations, laboratory characteristics, pathological features and risk factors for clinical outcomes of lupus nephritis patients co-existing with renal TMA in a large cohort in China. METHODS: Clinical and renal histopathological data of 148 patients with biopsy-proven lupus nephritis were retrospectively analyzed. Serum complement factor H, A Disintegrin and Metalloprotease with Thrombospondin type I repeats 13 (ADAMTS-13) activity, antiphospholipid antibodies and C4d deposition on renal vessels were further detected and analyzed. RESULTS: In the 148 patients with lupus nephritis, 36 patients were diagnosed as co-existing with renal TMA based on pathological diagnosis. Among the 36 TMA patients, their clinical diagnoses of renal TMA were as followings: 2 patients combining with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome, 2 patients combining with anti-phospholipid syndrome, 2 patients with malignant hypertension, 1 patient with scleroderma and the other 29 patients presenting with isolated renal TMA. Compared with the non-renal TMA group, patients with renal TMA had significantly higher urine protein (7.09±4.64 vs. 4.75±3.13 g/24h, P=0.007) and serum creatinine (159, 86 to 215 vs. 81, 68 to 112 ?mol/l, P<0.001), higher scores of total activity indices (AI) (P<0.001), endocapillary hypercellularity (P<0.001), subendothelial hyaline deposits (P=0.003), interstitial inflammation (P=0.005), glomerular leukocyte infiltration (P=0.006), total chronicity indices (CI) (P=0.033), tubular atrophy (P=0.004) and interstitial fibrosis (P=0.018). Patients with renal TMA presented with poorer renal outcome (P=0.005) compared with the non-TMA group. Renal TMA (hazard ratio (HR): 2.772, 95% confidence interval: 1.009 to 7.617, P=0.048) was an independent risk factor for renal outcome in patients with lupus nephritis. The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P=0.007). CONCLUSIONS: There were various causes of renal TMA in lupus nephritis. Complement over-activation via both classical and alternative pathways might play an important role in the pathogenesis of renal TMA in lupus nephritis.

Dataset Information

Renal Fibrosis in Lupus Nephritis.

Publications

Renal Fibrosis in Lupus Nephritis.

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