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The spectrum of renal thrombotic microangiopathy in lupus nephritis.

Song D, Wu LH, Wang FM, Yang XW, Zhu D, Chen M, Yu F, Liu G, Zhao MH - Arthritis Res. Ther. (2013)

Bottom Line: 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.The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P=0.007).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

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 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).

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.

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Comparison of renal outcomes between subgroups of patients with renal TMA.
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Figure 2: Comparison of renal outcomes between subgroups of patients with renal TMA.

Mentions: Using the log-rank test for univariate survival analysis of renal prognosis in all the patients with lupus nephritis, we found that renal TMA was a risk factor for renal outcome in lupus nephritis (P = 0.009). Other univariate risk factors included sex (male, P = 0.01), serum creatinine value (P <0.001), proteinuria (P = 0.032), total activity indices score (P = 0.001) and total chronicity indices score (P <0.001) (Details in Table 6). Multivariate analysis revealed that renal TMA (HR: 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) and serum creatinine value (HR: 1.003, 95% confidence interval: 1.002 to 1.005, P <0.001) were independent prognostic factors for renal survival (Additional file 3, Table S1). With further analysis, we found that the patients with both C4d deposition and decreased serum factor H (Group 1) presented with higher pathological AI scores (13.44 ± 3.78 vs. 9.89 ± 3.95, P = 0.024) and poorer renal outcome (P = 0.007, Figure 2) compared with those without the combination in the TMA group (Group 2).


The spectrum of renal thrombotic microangiopathy in lupus nephritis.

Song D, Wu LH, Wang FM, Yang XW, Zhu D, Chen M, Yu F, Liu G, Zhao MH - Arthritis Res. Ther. (2013)

Comparison of renal outcomes between subgroups of patients with renal TMA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672792&req=5

Figure 2: Comparison of renal outcomes between subgroups of patients with renal TMA.
Mentions: Using the log-rank test for univariate survival analysis of renal prognosis in all the patients with lupus nephritis, we found that renal TMA was a risk factor for renal outcome in lupus nephritis (P = 0.009). Other univariate risk factors included sex (male, P = 0.01), serum creatinine value (P <0.001), proteinuria (P = 0.032), total activity indices score (P = 0.001) and total chronicity indices score (P <0.001) (Details in Table 6). Multivariate analysis revealed that renal TMA (HR: 2.772, 95% confidence interval: 1.009 to 7.617, P = 0.048) and serum creatinine value (HR: 1.003, 95% confidence interval: 1.002 to 1.005, P <0.001) were independent prognostic factors for renal survival (Additional file 3, Table S1). With further analysis, we found that the patients with both C4d deposition and decreased serum factor H (Group 1) presented with higher pathological AI scores (13.44 ± 3.78 vs. 9.89 ± 3.95, P = 0.024) and poorer renal outcome (P = 0.007, Figure 2) compared with those without the combination in the TMA group (Group 2).

Bottom Line: 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.The renal outcome was poorer for those with both C4d deposition and decreased serum complement factor H in the TMA group (P=0.007).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

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 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).

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.

Show MeSH
Related in: MedlinePlus