Biologic Therapy in Lupus Nephritis

Houssiau, Frédéric

doi:10.1159/000368587

Cited by 15 publications

(14 citation statements)

References 29 publications

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“…Although biologic agents have not yet been successful in patients with LN (146–147) many new approaches remain to be tested (146, 148). Obvious targets include key cytokines expressed in inflamed kidneys such as IL1, IL6, M-CSF, IFNγ, Type I IFN, BAFF, IL17 and IL21, signaling pathways such as tyrosine kinases, costimulatory molecules such as ICOS and TWEAK (149) and effector molecules such as those in the complement pathway (reviewed (150)).…”

Section: Implications For Treatmentmentioning

confidence: 99%

What is damaging the kidney in lupus nephritis?

2015

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Summary Despite marked improvements in the survival of patients with severe lupus nephritis over the last 50 years the rate of complete clinical remission following immune suppression is less than 50% and renal impairment still occurs in 40% of affected patients. An appreciation of factors leading to the development of chronic kidney disease (CKD) following acute or subacute renal injury in lupus patients is beginning to emerge. Processes that contribute to endstage renal injury include continuing inflammation, activation of intrinsic renal cells, cell stress and hypoxia, metabolic abnormalities, aberrant tissue repair and tissue fibrosis. This understanding is leading to the development of novel or adjunctive therapies that may protect from the secondary non-immune consequences of acute injury. Approaches based on a molecular/proteomic/lipidomic classification of disease should yield new information about the functional basis of disease heterogeneity so that the most effective and least toxic treatment regimens can be formulated for individual patients.

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Section: Implications For Treatmentmentioning

confidence: 99%

What is damaging the kidney in lupus nephritis?

2015

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“…that confers substantial morbidity and mortality (1)(2)(3). Current therapies are both toxic and insufficiently effective, with a substantial number of patients progressing to end stage renal disease and death (4,5).…”

Section: Lupus Nephritis (Ln) Is a Frequent Complication Of Systemic mentioning

confidence: 99%

A protocol for single-cell transcriptomics from cryopreserved renal tissue and urine for the Accelerating Medicine Partnership (AMP) RA/SLE network

Rao

Berthier

Arazi

et al. 2018

Preprint

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OBJECTIVEThere is a critical need to define the cells that mediate tissue damage in lupus nephritis. Here we aimed to establish a protocol to preserve lupus nephritis kidney biopsies and urine cell samples obtained at multiple clinical sites for subsequent isolation and transcriptomic analysis of single cells.METHODSFresh and cryopreserved kidney tissue from tumor nephrectomies and lupus nephritis kidney biopsies were disaggregated by enzymatic digestion. Cell yields and cell composition were assessed by flow cytometry. Transcriptomes of leukocytes and epithelial cells were evaluated by low-input and single cell RNA-seq.RESULTSCryopreserved kidney tissue from tumor nephrectomies and lupus nephritis biopsies can be thawed and dissociated to yield intact, viable leukocytes and epithelial cells. Cryopreservation of intact kidney tissue provides higher epithelial cell yields compared to cryopreservation of single cell suspensions from dissociated kidneys. Cell yields and flow cytometric cell phenotypes are comparable between cryopreserved kidney samples and paired kidney samples shipped overnight on wet ice. High-quality single cell and low-input transcriptomic data were generated from leukocytes from both cryopreserved lupus nephritis kidney biopsies and urine, as well as from a subset of kidney epithelial cells.CONCLUSIONThe AMP RA/SLE cryopreserved tissue analysis pipeline provides a method for centralized processing of lupus nephritis kidney biopsies and urine samples to generate robust transcriptomic analyses in multi-center studies.

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“…The introduction of broadly immunosuppressive therapies together with the improved management of hypertension and the wide availability of renal replacement therapy has drastically altered the natural course of diffuse proliferative LN such that it is no longer almost universally lethal. Nevertheless, even in the setting of clinical trials where compliance is monitored, response rates to current immunosuppressive therapies are <50% and up to 40% of patients sustain permanent renal injury with 5–10% requiring dialysis within 10 years (3–5). Poor outcome is more frequent in geographic areas with limited access to high quality medical care (6).…”

Section: Introductionmentioning

confidence: 99%

“…Despite the accelerating pace of discovery in immunology and the development of large numbers of biologic agents that antagonize a multitude of immune pathways, there has not yet been a successful randomized controlled clinical trial of a biologic agent in LN (3, 8). Furthermore, several approaches that have been successful in mouse models have failed in clinical trials in humans (9, 10).…”

Section: Introductionmentioning

confidence: 99%

A systems approach to renal inflammation in SLE

Berthier

Kretzler

Davidson

2017

Clinical Immunology

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Lupus disease and its complications including lupus nephritis (LN) are very disabling and significantly impact the quality of life and longevity of patients. Broadly immunosuppressive treatments do not always provide the expected clinical benefits and have significant side effects that contribute to patient morbidity. In the era of systems biology, new strategies are being deployed integrating diverse sources of information (molecular and clinical) so as to identify individual disease specificities and select less aggressive treatments. In this review, we summarize integrative approaches linking molecular disease profiles (mainly tissue transcriptomics) and clinical phenotypes. The main goals are to better understand the pathogenesis of lupus nephritis, to identify the risk factors for renal flare and to find the predictors of both short and long-term clinical outcome. Identification of common key drivers and additional patient-specific key drivers can open the door to improved and individualized therapy to prevent and treat LN.

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Biologic Therapy in Lupus Nephritis

Cited by 15 publications

References 29 publications

What is damaging the kidney in lupus nephritis?

What is damaging the kidney in lupus nephritis?

A protocol for single-cell transcriptomics from cryopreserved renal tissue and urine for the Accelerating Medicine Partnership (AMP) RA/SLE network

A systems approach to renal inflammation in SLE

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