The Pathogenesis of Lupus Nephritis

Lech, Maciej; Anders, Hans‐Joachim

doi:10.1681/asn.2013010026

Cited by 394 publications

(331 citation statements)

References 108 publications

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“…Overall, 34% of the patients in this study were found to have AKI, and among them only a small proportion showed mild microscopic hematuria. This finding is distinctly different from AKI occurring in the proliferative LN, which is usually accompanied by massive hematuria and hypertension (1,2). Nevertheless, renal biopsy is still crucially important to differentiate the diagnosis of AKI in SLE patients, as it is essential for deciding the treatment regimen.…”

Section: Discussionmentioning

confidence: 96%

“…Seventeen (34%) cases presented with AKI. Forty-seven (94%) patients achieved remission after immunosuppressive therapy for a median time of 4 weeks (IQR,2,8). Compared with the patients with minimal change and mesangial proliferation, patients with FSGS showed significantly higher incidence of AKI and severe tubule-interstitial injury and a much lower complete remission rate.…”

Section: Introductionmentioning

confidence: 99%

“…NS is particularly characteristic of proliferative LN (class III, class IV) or membranous LN (class V) (1,2). However, it was observed 20 years ago that a subset of SLE patients who presented with NS were found to have normal glomeruli or only mild glomerular mesangial proliferation (3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

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Clinical–Morphological Features and Outcomes of Lupus Podocytopathy

Chen

Wang

et al. 2016

Clinical Journal of the American Society of Nephrology

111

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Background and objectives Lupus podocytopathy, which is characterized by diffuse foot process effacement without peripheral capillary wall immune deposits and glomerular proliferation, has been described in SLE patients with nephrotic syndrome in case reports and small series. This study aimed to better characterize the incidence, clinical-morphologic features, and outcomes of such patients from a large Chinese cohort.Design, setting, participants, & measurements Lupus podocytopathy was identified from 3750 biopsies of SLE patients obtained from 2000 to 2013 that showed mild glomerular histology in patients with a clinical sign of nephrotic syndrome. The biopsy results were divided into three groups: glomerular minimal change, mesangial proliferation, and FSGS.Results Fifty (1.33%) cases were identified as lupus podocytopathy and included minimal change in 13 cases, mesangial proliferation in 28 cases, and FSGS in nine cases. Extensive foot process effacement appeared in all the biopsies and mesangial electron-dense deposits were present in 47 biopsies. All patients demonstrated nephrotic syndrome, and the median proteinuria was 5.72 g/24 h (interquartile range [IQR], 3.82, 6.92). Seventeen (34%) cases presented with AKI. Forty-seven (94%) patients achieved remission after immunosuppressive therapy for a median time of 4 weeks (IQR,2,8). Compared with the patients with minimal change and mesangial proliferation, patients with FSGS showed significantly higher incidence of AKI and severe tubule-interstitial injury and a much lower complete remission rate. During follow-up of a median of 62 (IQR, 36, 84) months, renal relapses occurred in 28 (59.6%) patients. No patient died or developed ESRD. ConclusionsThe findings from this cohort study suggest that lupus podocytopathy may represent a special entity of lupus nephritis with distinct clinical-morphologic features. The differences in AKI incidence, tubular injury severity, and response to treatment between the patients with minimal change/mesangial proliferation and those with FSGS patterns indicate two different subtypes of lupus podocytopathy.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Clinical–Morphological Features and Outcomes of Lupus Podocytopathy

Chen

Wang

et al. 2016

Clinical Journal of the American Society of Nephrology

111

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“…The presentation is highly variable, the disease follows a relapsing and remitting course, and although standardized treatment has improved the short-and medium-term outlook, long-term prognosis remains poor in children with lupus with major organ involvement (1). Lupus has a higher incidence of renal involvement in children than in adults (2)(3)(4). Lupus nephritis is seen in nearly 50% patients with pediatric-onset SLE (pSLE), which may manifest as asymptomatic urinary findings, acute kidney injury, and even chronic renal disease (5).…”

Section: Introductionmentioning

confidence: 99%

Childhood lupus nephritis: 12 years of experience from a developing country’s perspective

Samanta¹,

Nandi²,

Mondal³

et al. 2017

Eur J Rheumatol

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Objective: To assess the long-term outcome of lupus nephritis in children with systemic lupus erythematosus followed up over 12 years at a tertiary care teaching hospital in Eastern India. Material and Methods:This is a retrospective observational study of the clinicopathological presentation, management, and outcome in 46 children with lupus nephritis over a period of 12 years at a tertiary teaching hospital in Eastern India. Mortality was compared between different lupus classes and therapy groups with Kaplan-Meier analysis and log-rank testResults: The incidence of lupus nephritis was 58.97% [95% confidence interval (CI) 48.06%-59.89%] with the mean age at presentation being 10.2±2.43 years (range 5.5-14.5) years. Majority belonged to class IV (30.43%), followed by class II (26.91%), class III (23.91), and class V (8.70%). Outcome analysis of children with lupus nephritis over 12 years revealed that 24 (52.17%) achieved complete remission of disease activity, 5 attained partial remission, 4 continued to have active disease, 5 developed end-stage renal disease (ESRD), and 8 died. Overall mortality thus observed was 17.39% with septicemia in the background of ESRD being the commonest cause. No significant difference in mortality was observed between different lupus nephritis classes or therapy arm groups. Conclusion:The study throws light on various aspects of lupus nephritis and their long-term outcome patterns in children from developing countries such as India.

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“…9 Interestingly, the corresponding autoantigens are exactly those that we identified as ligands for FH on the apoptotic cell surface, suggesting a possibility of disturbance of FH function in SLE. Glomerulonephritis is one typical manifestation of human SLE 10 and mutations in FH and another complement inhibitor CD46 are associated with earlier onset of nephritis in SLE patients. 11 FH-deficient (CFH − / − ) mice spontaneously develop membranoproliferative glomerulonephritis, which is dependent on C3 activation.…”

mentioning

confidence: 99%

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

et al. 2016

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Factor H (FH) binds apoptotic cells to limit the inflammatory potential of complement. Here we report that FH is actively internalized by apoptotic cells to enhance cathepsin L-mediated cleavage of endogenously expressed C3, which results in increased surface opsonization with iC3b. In addition, internalized FH forms complexes with nucleosomes, facilitates their phagocytosis by monocytes and induces an anti-inflammatory biased cytokine profile. A similar cytokine response was noted for apoptotic cells coated with FH, confirming that FH diminishes the immunogenic and inflammatory potential of autoantigens. These findings were supported by in vivo observations from CFH − / − MRL-lpr mice, which exhibited higher levels of circulating nucleosomes and necrotic cells than their CFH +/+ littermates. This unconventional function of FH broadens the established view of apoptotic cell clearance and appears particularly important considering the strong associations with genetic FH alterations and diseases such as systemic lupus erythematosus and age-related macular degeneration. Factor H (FH), one of the most abundant plasma proteins, is the major soluble inhibitor of the alternative complement pathway. Apoptotic cells bind FH while triggering complement activation by binding of C1 complex, which ensures efficient opsonization and removal of apoptotic debris but prevents excessive complement activation and inflammation. 1,2 Dysregulation of complement contributes significantly to the pathology of many diseases. 3 Recently, novel roles and intracellular location for complement have been identified suggesting that its functions exceed our current understanding. 4 After previously identifying the ligands for FH on the apoptotic cell surface as dsDNA, histones and annexin A2, 5 we sought to explore the functional consequences of the FH-apoptotic cell interaction in the context of the chronic autoimmune disorder systemic lupus erythematosus (SLE) and age-related macular degeneration (AMD). Aberrant apoptosis and impaired clearance of apoptotic cells are of central importance in the pathogenesis of SLE and lead to formation of autoantibodies. 6-8 Anti-chromatin autoantibodies are a hallmark of SLE and anti-annexin A2 autoantibodies are also frequently observed in SLE patients. 9 Interestingly, the corresponding autoantigens are exactly those that we identified as ligands for FH on the apoptotic cell surface, suggesting a possibility of disturbance of FH function in SLE. Glomerulonephritis is one typical manifestation of human SLE 10 and mutations in FH and another complement inhibitor CD46 are associated with earlier onset of nephritis in SLE patients. 11 FH-deficient (CFH − / − ) mice spontaneously develop membranoproliferative glomerulonephritis, which is dependent on C3 activation. 12 When crossed with the MRL-lpr mouse strain, a model of lupus, the originated CFH − / − MRLlpr mice exhibit accelerated lupus nephritis and die at younger age than their CFH +/+ MRL-lpr littermates. 13,14 AMD is the leading cause of visual impairm...

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The Pathogenesis of Lupus Nephritis

Cited by 394 publications

References 108 publications

Clinical–Morphological Features and Outcomes of Lupus Podocytopathy

Clinical–Morphological Features and Outcomes of Lupus Podocytopathy

Childhood lupus nephritis: 12 years of experience from a developing country’s perspective

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

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