Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Deonaraine, Kristina K.; Carlucci, Philip M.; Fava, Andrea; Li, Jessica; Wofsy, David; James, Judith A.; Putterman, Chaim; Diamond, Betty; Davidson, Anne; Fine, Derek M.; Monroy‐Trujillo, Jose M.; Atta, Mohamed G.; Haag, Kristin; Rao, Deepak A.; Apruzzese, William; Belmont, H. Michael; Izmirly, Peter; Wu, Ming; Connery, Sean; Payan-Schober, Fernanda; Furie, Richard; Berthier, Céline C.; Dall’Era, Maria; Cho, Kerry; Kamen, Diane L.; Kalunian, Kenneth C.; Anolik, Jennifer H.; Ishimori, Mariko; Weisman, Michael H.; Partnership, Accelerating Medicines; Petri, Michelle; Buyon, Jill P.

doi:10.1136/lupus-2021-000522

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…Twenty biopsy specimens obtained in the first 2 years of follow-up included three showing class II lupus nephritis, three with class III, seven with class IV, three with class V, two with class III/V, and one with class VI lupus nephritis; one biopsy was performed at an outside hospital and was not available (although this patient was started on immunosuppression on the basis of the biopsy result). Progressors who underwent a biopsy were younger compared with progressors who did not undergo a biopsy: median (IQR) age of 25 (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39) and 36 (28-50) years old, respectively (P50.007).…”

Section: Resultsmentioning

confidence: 99%

“…The logical extension in considering the clinical implications of low-grade proteinuria would be to obtain a kidney biopsy at these lower thresholds for these patients at higher risk. Therefore, invoking the safety of kidney biopsy is relevant: recent published data from the Accelerating Medicines Partnership (AMP) showed 34 of 475 (7%) patients with SLE, who were followed prospectively for safety, experienced a related adverse event from a kidney biopsy, with 18 (4%) events deemed serious enough to require hospitalization (26). Comparatively, despite additional research tissue being obtained, patients in AMP had fewer adverse events than reported in the historical cohorts and meta-analyses of patients undergoing clinically indicated biopsies (27,28).…”

Section: Discussionmentioning

confidence: 99%

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Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

Wang

Spielman

Ginsberg

et al. 2022

CJASN

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Background and objectivesLupus nephritis remains a common cause of morbidity and mortality in systemic lupus erythematosus (SLE). Current guidelines recommend performing a kidney biopsy at urine protein-to-creatinine ratio (UPCR) of ≥0.5 g/g. However, cross-sectional studies reported a high prevalence of active histological lupus nephritis lesions, and even chronic irreversible scarring, in patients with low-grade proteinuria. This study was initiated to assess disease progression in SLE patients with low-grade proteinuria to identify risk factors for progression to overt proteinuria suggestive of clinical lupus nephritis. Design, setting, participants, & measurementsSLE patients with incident UPCR ≥ 0.2 and <0.5 g/g without known lupus nephritis were identified from the Einstein Rheumatic Disease Registry. Patients who developed a random UPCR of ≥ 0.5 g/g with or without biopsy during the follow-up period were defined as "progressors". Patients who progressed to UPCR>0.5 g/g within two years from developing UPCR≥ 0.2 &<0.5 g/g were defined as "fast progressors", a subgroup expected to benefit most from early biopsies and therapeutic interventions. ResultsAmong 151 eligible SLE patients with low-grade proteinuria at study entry, 76 (50%) progressed to UPCR≥0.5 g/g of which 44 underwent a clinically indicated biopsy. The median (IQR) time from UPCR≥ 0.2 & <0.5 g/g to progression was 1.2 (0.3, 3.0) years. Of the 20 biopsies performed in the first 2 years, 16 had active, treatable lupus nephritis. Low complement and shorter SLE duration at low-grade proteinuria onset were associated with progression to overt proteinuria across different analyses. Other associated factors included hypertension, diabetes mellitus, younger age and the presence of hematuria. ConclusionsIn this longitudinal cohort of SLE patients with low-grade proteinuria at study entry, over half progressed to UPCR>0.5 g/g in a short time period supporting the role of early biopsy to diagnose and treat lupus nephritis.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

Wang

Spielman

Ginsberg

et al. 2022

CJASN

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“…This work indicates a valuable role for blood cellular biomarkers in evaluating specific dimensions of immune activity of patients with LN to gain insight into the likelihood of response to standard immunosuppressive LN therapies. Phase II study (37,82) if 1) they fulfilled American College of Rheumatology (83) or Systemic Lupus International Collaborating Clinics classification criteria (84) for SLE, 2) had a clinically-indicated renal biopsy for a UPCR > 0.5 (16,17) and 3) had biopsy-confirmed lupus nephritis of class III, IV and/or V, based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) (15). Patients with a history of renal transplantation, with a medical condition considered at risk of participating in this study by the investigator, who was pregnant at the time of study entry, or who had recently been exposed to rituximab (within the past six months) were excluded.…”

Section: Discussionmentioning

confidence: 99%

Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis

Horisberger,

Griffith,

Keegan

et al. 2024

Preprint

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Lupus nephritis (LN) is a frequent manifestation of systemic lupus erythematosus, and fewer than half of patients achieve complete renal response with standard immunosuppressants. Identifying non-invasive, blood-based pathologic immune alterations associated with renal injury could aid therapeutic decisions. Here, we used mass cytometry immunophenotyping of peripheral blood mononuclear cells in 145 patients with biopsy-proven LN and 40 healthy controls to evaluate the heterogeneity of immune activation in patients with LN and to identify correlates of renal parameters and treatment response. Unbiased analysis identified 3 immunologically distinct groups of patients with LN that were associated with different patterns of histopathology, renal cell infiltrates, urine proteomic profiles, and treatment response at one year. Patients with enriched circulating granzyme B+ T cells at baseline showed more severe disease and increased numbers of activated CD8 T cells in the kidney, yet they had the highest likelihood of treatment response. A second group characterized primarily by a high type I interferon signature had a lower likelihood of response to therapy, while a third group appeared immunologically inactive by immunophenotyping at enrollment but with chronic renal injuries. Main immune profiles could be distilled down to 5 simple cytometric parameters that recapitulate several of the associations, highlighting the potential for blood immune profiling to translate to clinically useful non-invasive metrics to assess immune-mediated disease in LN.

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“…Systemic lupus erythematosus (SLE) affects >200,000 Americans, of whom >40% will develop lupus nephritis and 8-10% will develop renal failure over 20 years (1) (2) (3). SLE is caused by the loss of immune tolerance and the production of autoantibodies against nuclear material.…”

Section: Introductionmentioning

confidence: 99%

Intrarenal myeloid subsets associated with kidney injury are comparable in mice and patients with lupus nephritis

Hoover,

Lieb,

Kang

et al. 2023

Preprint

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Resident macrophages and infiltrating monocytes in kidneys of patients with lupus nephritis are altered both in frequency and function relative to their counterparts in healthy kidneys. The extent to which mouse models might be useful in developing approaches to target these cells for treating lupus nephritis is poorly understood. Here, we studied four common lupus mouse models that share clinical, serologic, and histopathologic kidney changes with humans. Using single-cell profiling and multiplex spatial imaging to analyze the intrarenal myeloid compartment with the onset of clinical disease in these models, we identified monocyte and macrophage subsets that expand or contract in kidneys with clinical nephritis. A unique subset of classical monocytes expanded with the onset of disease and expressed genes such as CD9, Spp1, Ctsd, Cd63, Apoe, and Trem2 that were previously shown to be induced by tissue injury and play a role in inflammation, lipid metabolism and tissue repair in other organs. Resident macrophages transitioned from a pro-inflammatory to a similar injury-associated state with onset of disease. To test whether these findings in mouse models were also observed in humans, we re-analyzed monocytes and macrophages in a single-cell RNAseq dataset of kidney biopsies from 155 patients with lupus nephritis and 30 healthy donors, collected by the NIH AMP RA/SLE consortium. Human monocytes and macrophages showed conserved changes in gene expression programs associated with lupus nephritis disease indices, and localized to similar kidney microenvironments as in mice. By identifying myeloid subsets and disease-associated alterations in biological processes that are conserved across species, we provide a strong rationale for functional studies of these cells and pathways in mice to uncover mechanisms and find targets relevant to human lupus nephritis.

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Safety of procuring research tissue during a clinically indicated kidney biopsy from patients with lupus: data from the Accelerating Medicines Partnership RA/SLE Network

Cited by 7 publications

References 28 publications

Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

Short- and Long-Term Progression of Kidney Involvement in Systemic Lupus Erythematosus Patients with Low-Grade Proteinuria

Blood immunophenotyping identifies distinct kidney histopathology and outcomes in patients with lupus nephritis

Intrarenal myeloid subsets associated with kidney injury are comparable in mice and patients with lupus nephritis

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