The spectrum of renal thrombotic microangiopathy in lupus nephritis

Abstract

IntroductionAmong 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.MethodsClinical 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.ResultsIn 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 μmol/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).ConclusionsThere 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.

Analysis of morphological and functional changes of kidney endothelium in systemic rheumatic diseases

“…Additionally, the co-localization of Ig isotypes IgG, IgA, and IgM with C1q, C4 and C3 (and C5b-9) (the so called "full house" pattern) in the glomeruli is almost exclusively present in glomeruli of patients with lupus nephritis and necrotising vasculitis in MPA [11]. Finally, complement split products such as C3d and C5b-9 can also be detected in the urine of SLE patients [16]. Impaired immune complexes handling plays an important role in the pathogenesis in LGN.…”

“…Only the group of patients with SLE and MPA did not differ in frequency of immune deposits in the kidneys blood vessels that demonstrate fulfilled McNemar-Fischer analysis. Lupus and necrotizing nephritis determines long-term morbidity and mortality in SLE and MPA because renal failure in SRD is associated with a large number of secondary and tertiary complications [12,16].…”

“…Despite some differences in the clinic of primary systemic necrotizing vasculitis -MPA and systemic autoimmune diseases -SLE, they share a number of common pathogenetic mechanisms, which are based on immunological process [15,16]. As expected, IgA deposits in the blood vessels were the most typical to Henoch-Schönlein purpura nephritis, because its a small vessel vasculitis mediated by IgA-immune complex deposition [11], and C1q -for LGN and MPA, C1q deposits are usually found in association with other complement components and immunoglobulins in proliferative glomerulonephritis and may predominate in SLE 9)2017 and MPA [7].…”

An unexpected diagnostic course of systemic lupus erythematosus

“…These immune complexes trigger the complement system and lead to activation of the classical pathway with C4b and C3b deposition which can covalently bind to glomerular endothelial surfaces and basement membranes through the thiol ester site, mounting of the membrane attack complex (C5b-9), release of C3a and C5a anaphylatoxins and commonly causing cellular injury and tissue inflammation. Complement is consumed in active SLE, resulting in hypocomplementemia (typically low C4 and C3) 8,9 .…”

Mycophenolate mofetil in the treatment of lupus vasculopathy

“…In a large series of 36 cases of renal TMA in SLE, Song et al 4 have observed aPL in only two cases, while no other specific cause was noted in 29 cases. Similarly, our case also developed LV and TMA in absence of aPL.…”