Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression

Mahajan, Anadi; Amelio, Justyna; Gairy, Kerry; Kaur, Gavneet; Levy, Roger A.; Roth, David A.; Bass, Damon

doi:10.1177/0961203320932219

Cited by 115 publications

(108 citation statements)

References 47 publications

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“…In cSLE populations, decreased creatinine clearance rate and low C3 complement levels with high serum creatinine levels were associated with end-stage renal disease [ 169 ]. A recent study, including 26 previous reports, showed that high serum creatinine (> 1.5 mg/dL) at disease presentation was the major prediction factor for progression to end-stage renal disease [ 170 ]. Furthermore, high titers of anti-dsDNA antibodies have modest accuracy to predict lupus nephritis [ 171 ].…”

Section: Csle Prognosis Factorsmentioning

confidence: 99%

An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus

et al. 2021

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Childhood-onset systemic lupus erythematosus (cSLE) is a prototype of a multisystemic, inflammatory, heterogeneous autoimmune condition. This disease is characterized by simultaneous or sequential organ and system involvement, with unpredictable flare and high levels of morbidity and mortality. Racial/ethnic background, socioeconomic status, cost of medications, difficulty accessing health care, and poor adherence seem to impact lupus outcomes and treatment response. In this article, the management of cSLE patients is updated. Regarding pathogenesis, a number of potential targets for drugs have been studied. However, most treatments in pediatric patients are off-label drugs with recommendations based on inadequately powered studies, therapeutic consensus guidelines, or case series. Management practices for cSLE patients include evaluations of disease activity and cumulative damage scores, routine non-live vaccinations, physical activity, and addressing mental health issues. Antimalarials and glucocorticoids are still the most common drugs used to treat cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients. Disease-modifying antirheumatic drugs (DMARDs) should be standardized for each patient, based on disease flare and cSLE severity. Mycophenolate mofetil or intravenous cyclophosphamide is suggested as induction therapy for lupus nephritis classes III and IV. Calcineurin inhibitors (cyclosporine, tacrolimus, voclosporin) appear to be another good option for cSLE patients with lupus nephritis. Regarding B-cell-targeting biologic agents, rituximab may be used for refractory lupus nephritis patients in combination with another DMARD, and belimumab was recently approved by the US Food and Drug Administration for cSLE treatment in children aged > 5 years. New therapies targeting CD20, such as atacicept and telitacicept, seem to be promising drugs for SLE patients. Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial results in phase II randomized control trials in adult SLE patients, as have some Janus kinase inhibitors, and these could be alternative treatments for pediatric patients with severe interferon-mediated inflammatory disease in the future. In addition, strict control of proteinuria and blood pressure is required in cSLE, especially with angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use.

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Section: Csle Prognosis Factorsmentioning

confidence: 99%

An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus

et al. 2021

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“…Approximately 31-48% of patients with SLE develop lupus nephritis (LN), the most severe organ manifestation of SLE, with 7-31% of patients being diagnosed with LN at SLE diagnosis [4][5][6][7]. Patients with LN have a higher risk of death compared with the general population, a risk that increases further if LN progresses to end-stage kidney disease (ESKD) [8].…”

Section: Introductionmentioning

confidence: 99%

The Economic Burden of Lupus Nephritis: A Systematic Literature Review

Thompson¹,

Mahajan²,

Scott³

et al. 2021

Rheumatol Ther

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Introduction Few studies have evaluated the economic burden of lupus nephritis (LN). The aim of this systematic literature review (SLR) was to assess the economic burden (direct and indirect costs, and healthcare resource utilization [HCRU]) associated with LN, with particular focus on the burden of renal flares and end-stage kidney disease (ESKD). Methods This SLR (GSK study 213531) was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the MEDLINE and Embase databases were conducted for English language publications reporting cost or HCRU data in patients with LN (regardless of age or LN histological class) until December 10, 2019. Handsearching of conference proceedings and keyword-based searches in PubMed, Google, and Google Scholar were also conducted. Results Twenty-two studies were identified from 28 publications reporting the cost ( n = 19) and HCRU ( n = 13) associated with LN. Most studies were from North America ( n = 13) and many used administrative claims data ( n = 9). LN was associated with substantially higher direct costs (e.g., total annual, hospitalization, and ESKD-related direct costs), total indirect costs, and HCRU (e.g., hospitalization, outpatient services, and medication use) compared with patients without systemic lupus erythematosus (SLE) or non-renal SLE controls. ESKD and dialysis were significant contributors to economic burden. No studies described the cost of renal flares. Conclusions The consensus across the 22 studies was that the economic burden of LN is substantial, particularly in active or severe disease, or if there is progression to ESKD. Total direct cost may be underestimated in claims data given the challenges of identifying patients with LN. Further studies are vital to ascertain the cost of renal flares; a renal flare is likely to result in a period of increased HCRU, which could be mitigated by treatments that extend renal remission. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00368-y.

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“…This condition has now become a global public health problem. IgA nephropathy (IgAN) and lupus nephritis (LN) is the most common primary and secondary glomerular diseases, respectively, and tend to affect young adults, with nearly 20% of patients progressing to ESRD after 10 years because of limited drug treatment options ( Mahajan et al, 2020 ; Natale et al, 2020 ). Although both diseases have complex and varied clinical manifestations, many overlaps have been noted.…”

Section: Introductionmentioning

confidence: 99%

Weighted Gene Co-expression Network Analysis Reveals Different Immunity but Shared Renal Pathology Between IgA Nephropathy and Lupus Nephritis

et al. 2021

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Both IgA nephropathy (IgAN) and lupus nephritis (LN) are immunity-related diseases with a complex, polygenic, and pleiotropic genetic architecture. However, the mechanism by which the genetic variants impart immunity or renal dysfunction remains to be clarified. In this study, using gene expression datasets as a quantitative readout of peripheral blood mononuclear cell (PBMC)- and kidney-based molecular phenotypes, we analyzed the similarities and differences in the patterns of gene expression perturbations associated with the systematic and kidney immunity in IgAN and LN. Original gene expression datasets for PBMC, glomerulus, and tubule from IgAN and systemic lupus erythematosus (SLE) patients as well as corresponding controls were obtained from the Gene Expression Omnibus (GEO) database. The similarities and differences in the expression patterns were detected according to gene differential expression. Weighted gene co-expression network analysis (WGCNA) was used to cluster and screen the co-expressed gene modules. The disease correlations were then identified by cell-specific and functional enrichment analyses. By combining these results with the genotype data, we identified the differentially expressed genes causatively associated with the disease. There was a significant positive correlation with the kidney expression profile, but no significant correlation with PBMC. Three co-expression gene modules were screened by WGCNA and enrichment analysis. Among them, blue module was enriched for glomerulus and podocyte (P < 0.05) and positively correlated with both diseases (P < 0.05), mainly via immune regulatory pathways. Pink module and purple module were enriched for tubular epithelium and correlated with both diseases (P < 0.05) through predominant cell death and extracellular vesicle pathways, respectively. In genome-wide association study (GWAS) enrichment analysis, blue module was identified as the high-risk gene module that distinguishes LN from SLE and contains PSMB8 and PSMB9, the susceptibility genes for IgAN. In conclusion, IgAN and LN showed different systematic immunity but similarly abnormal immunity in kidney. Immunological pathways may be involved in the glomerulopathy and cell death together with the extracellular vesicle pathway, which may be involved in the tubular injury in both diseases. Blue module may cover the causal susceptibility gene for IgAN and LN.

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Systemic lupus erythematosus, lupus nephritis and end-stage renal disease: a pragmatic review mapping disease severity and progression

Cited by 115 publications

References 47 publications

An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus

An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus

The Economic Burden of Lupus Nephritis: A Systematic Literature Review

Weighted Gene Co-expression Network Analysis Reveals Different Immunity but Shared Renal Pathology Between IgA Nephropathy and Lupus Nephritis

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