Faculty Bibliography

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 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 and identify correlates of renal parameters. Unbiased analysis identified three immunologically distinct groups of patients 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 showed more active 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 by a high type I interferon signature had a lower likelihood of response to therapy, while a third group appeared immunologically inactive but with chronic renal injuries. The major immunologic axes of variation could be distilled down to five simple cytometric parameters that recapitulate several clinical associations, highlighting the potential for blood immunoprofiling to translate to clinically useful non-invasive metrics to assess immune-mediated disease in LN.

OBJECTIVE:The objective is to provide evidence-based and expert guidance for the screening, treatment, and management of lupus nephritis. METHODS:The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations. The Voting Panel achieved a consensus ≥70% on the direction (for or against) and strength (strong or conditional) of each recommendation. RESULTS:We present 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus-based good practice statements for the screening and management of lupus nephritis. Our recommendations focus on the unifying principle that lupus nephritis therapy is continuous and ongoing, rather than consisting of discrete induction/initial and maintenance/subsequent therapies. Therapy should include pulse glucocorticoids followed by oral glucocorticoid taper and two additional immunosuppressive agents for 3-5 years for those achieving complete renal response. CONCLUSION/CONCLUSIONS:This guideline provides direction for clinicians regarding screening and treatment decisions for management of lupus nephritis. These recommendations should not be used to limit or deny access to therapies, as treatment decisions may vary due to the unique clinical situation and personal preferences of each individual patient.

OBJECTIVES/OBJECTIVE:Glucagon-like peptide-1 receptor agonists (GLP1-RA) are an emerging class of medications with demonstrated promise in improving cardiometabolic outcomes. Whether these drugs may be useful in mitigating the cardiac risk associated with SLE remains unknown, and a recent case of drug induced lupus secondary to GLP1-RA use calls the safety of GLP1-RAs in SLE patients into question. Accordingly, this retrospective analysis was initiated to evaluate outcomes of GLP1-RAs in SLE. METHODS:All patients in the NYU Lupus Cohort who had used a GLP1-RA were eligible for inclusion. Patient characteristics were assessed at baseline (most recent rheumatology visit prior to starting GLP1-RA), 1-4 months, and 6-10 months after GLP1-RA initiation. RESULTS:Of the 1211 patients in the cohort, only 24 had received a GLP1-RA. Six were excluded due to insufficient documentation regarding duration of medication use. Of the remaining 18 (median age 50), 17 (94%) were female and 9 (50%) were white. There was one mild-to-moderate flare at 6-10 months, but no patients accumulated new SLE criteria during the follow up period. Compared with baseline, median BMI was reduced by 3% at 1-4 months (p= 0.002) and 13% at 6-10 months (p= 0.001). Nine (50%) patients were initially denied insurance coverage for a GLP1-RA. CONCLUSION/CONCLUSIONS:While limited by a small sample size, this descriptive study showed that GLP1-RAs did not trigger flares above expected background rates and were associated with significantly decreased BMI. Future studies exploring the potential benefits of GLP1-RAs in patients with SLE are warranted.

OBJECTIVES/UNASSIGNED:Outside of the association of SS-A antibody with congenital heart block, little is known about adverse maternal and neonatal outcomes, in patients with Sjogren's disease (SjD). Our study involved collaboration with maternal-fetal medicine (MFM). METHODS/UNASSIGNED:-test and Fisher's exact test. RESULTS/UNASSIGNED:48 patients were included: 12 SjD patients and 36 controls. APO was significantly increased in SjD with one preterm birth, one fetal growth restriction, and one limb anomaly; non-SjD had one cardiac anomaly. There were no cases of CHB. SjD patients were more likely to be delivered by cesarean delivery. CONCLUSION/UNASSIGNED:There was an increased risk of APO in SjD patients compared with controls. No significant difference in neonatal outcomes was found. We speculate that placental pathology may play a role in pathophysiology and future studies should be performed. KEY POINTS/UNASSIGNED:There was an increased risk of APO in SjD patients compared with controls.No significant difference in neonatal outcomes was found.We speculate that placental pathology may play a role in pathophysiology, prompting future studies.

The accepted version of this article was posted prematurely on March 24, 2025. The final version of record will be made fully available at a later date.

OBJECTIVE:Lupus nephritis (LN) can occur as an isolated component of disease activity or be accompanied by diverse extrarenal manifestations. Whether isolated renal disease is sufficient to decrease health related quality of life (HRQOL) remains unknown. This study compared Patient-Reported Outcomes Measurement Information System 29-Item (PROMIS-29) scores in LN patients with isolated renal disease to those with extrarenal symptoms to evaluate the burden of LN on HRQOL and inform future LN clinical trials incorporating HRQOL outcomes. METHODS:A total of 181 LN patients consecutively enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership completed PROMIS-29 questionnaires at the time of a clinically indicated renal biopsy. Raw PROMIS-29 scores were converted to standardized T scores. RESULTS:Seventy-five (41%) patients had extrarenal disease (mean age 34, 85% female) and 106 (59%) had isolated renal (mean age 36, 82% female). Rash (45%), arthritis (40%) and alopecia (40%) were the most common extrarenal manifestations. Compared with isolated renal, patients with extrarenal disease reported significantly worse pain interference, ability to participate in social roles, physical function, and fatigue. Patients with extrarenal disease had PROMIS-29 scores that significantly differed from the general population by > 0.5 SD of the reference mean in pain interference, physical function, and fatigue. Arthritis was most strongly associated with worse scores in these three domains. CONCLUSION/CONCLUSIONS:Most patients had isolated renal disease and extrarenal manifestations associated with worse HRQOL. These data highlight the importance of comprehensive disease management strategies that address both renal and extrarenal manifestations to improve overall patient outcomes.

OBJECTIVE:Traditional initial treatment regimens for lupus nephritis (LN) used oral glucocorticoids (GC) in starting doses up to 1.0 mg/kg/day prednisone equivalent with or without a preceding intravenous methylprednisolone pulse. More recent management guidelines recommend lower starting oral GC doses following intravenous pulse therapy. As there have been no large studies directly comparing patients receiving low versus high initial oral GC doses, this pooled analysis of high-quality randomised controlled trials (RCTs) aims to evaluate differences in efficacy and safety. METHODS:Published data were analysed from RCTs that assessed variable GC doses in the standard of care (SOC) treatment arms. Patients receiving starting prednisone doses up to 0.5 mg/kg/day (low dose) were compared with 1.0 mg/kg/day (high dose). Complete renal response requiring urine protein-creatinine ratio <0.5 mg/mg (CRR 0.5), CRR or partial renal response (PRR), serious adverse events (SAE) and SAE due to infections at 12 months of treatment were compared between groups. RESULTS:417 patients from SOC arms of five studies were exposed to low-dose initial GC after intravenous pulse, while 521 patients from four studies were treated with high-dose oral GC. In patients with low-dose oral GC, 25.2% achieved CRR 0.5 at 12 months compared with 27.2% in high-dose groups, p=0.54. CRR or PRR was attained in 48.7% low-dose vs 43.6% high-dose patients, p=0.14. SAEs and infection SAEs were less common in the low-dose GC group (19.4% vs 31.6%, p<0.001 and 9.8% vs 16.5%, p=0.012, respectively). CONCLUSIONS:Based on pooled RCT data, there was no significant difference in 12-month renal responses between patients receiving low-dose prednisone following intravenous GC compared with those receiving initial high doses. SAEs were less frequent in patients receiving low-dose initial GC. These findings support the use of lower oral GC doses in LN treatment.

INTRODUCTION/BACKGROUND:Lupus nephritis (LN) is a frequent complication of SLE, occurring in up to 60% of adult patients and ultimately progressing from acute inflammation to chronicity with fibrosis and end-stage kidney failure in 10%-30% of patients. Racial/ethnic minority patients with lupus have worse long-term outcomes, including progression to end-stage renal disease and overall mortality. A major challenge in the management of patients with SLE is delayed identification of early kidney disease, which ultimately leads to a greater burden on both patients and the health system. METHODS AND ANALYSIS/METHODS:Using a mixed methods approach, this study will develop, adapt and evaluate a home urine sampling protocol with a text-messaging reminder and data capture system for patients at elevated risk of de novo LN or relapse. First, a feasibility pilot using a single-group trial design (n=18) will be implemented, with a feasibility assessment and qualitative, debriefing interviews with patients to further refine the intervention. The second phase is a comparative effectiveness trial of the intervention (n=160) with the primary outcome of biopsy eligibility, that is, the participant has a clinical indication for a kidney biopsy (urine protein-creatinine ratio≥0.5), whether or not the patient actually undergoes the biopsy procedure. The randomised trial includes an economic evaluation of the adapted home urinalysis protocol. DISCUSSION AND DISSEMINATION/CONCLUSIONS:It is unknown whether weekly home-based urine sampling can identify proteinuria sooner than standard care; if found sooner, kidney problems could be diagnosed earlier, hopefully leading to earlier care for less-involved disease and subsequent reduced morbidity. The data collected in this trial will inform future feasibility and effectiveness of text-messaging-based home urine sampling interventions. TRIAL REGISTRATION NUMBER/BACKGROUND:The randomised trial will be registered with ClincialTrials.gov prior to enrolment start.

OBJECTIVE:Autoantibodies are a hallmark of lupus nephritis (LN), but their association with LN classes and treatment response are not adequately known. In this study, we quantified circulating autoantibodies in the Accelerating Medicines Partnership LN longitudinal cohort to identify serological biomarkers of LN histologic classification and treatment response and how these biomarkers change over time based on treatment response. METHODS:Peripheral blood samples were collected from 279 patients with systemic lupus erythematosus undergoing diagnostic kidney biopsy based on proteinuria. Of these, 268 were diagnosed with LN. Thirteen autoantibody specificities were measured by bead-based assays (Bio-Rad Bioplex 2200) and anti-C1q by enzyme-linked immunosorbent assay at the time of biopsy (baseline) and at 3, 6, and 12 months after biopsy. Clinical response was determined at 12 months. RESULTS:Proliferative LN (International Society of Nephrology/Renal Pathology Society class III/IV±V, n = 160) was associated with higher concentrations of anti-C1q, anti-chromatin, anti-double-stranded DNA (dsDNA), and anti-ribosomal P autoantibodies compared to nonproliferative LN (classes I/II/V/VI, n = 108). Anti-C1q and-dsDNA were independently associated with proliferative LN. In proliferative LN, higher baseline anti-C1q levels predicted complete response (area under the curve [AUC] 0.72; P = 0.002) better than baseline proteinuria (AUC 0.59; P = 0.21). Furthermore, all autoantibody levels except for anti-La/SSB decreased over 12 months in patients with proliferative, but not membranous, LN with a complete response. CONCLUSION/CONCLUSIONS:Baseline levels of anti-C1q and anti-dsDNA may serve as noninvasive biomarkers of proliferative LN, and anti-C1q may predict complete response at the time of kidney biopsy. In addition, tracking autoantibodies over time may provide further insights into treatment response and pathogenic mechanisms in patients with proliferative LN.