One-third of patients with lupus nephritis classified as complete responders continue to accrue progressive renal damage despite resolution of proteinuria

Abstract

ObjectiveTreatment response in lupus nephritis (LN) is defined based on proteinuria, yet protocol kidney biopsy studies have shown that patients with lupus can have active nephritis in the absence of proteinuria. Using estimated glomerular filtration rate (eGFR) trajectories, we characterised early chronic kidney disease in LN and examined whether certain patients continue to accrue renal damage despite proteinuric response.MethodsWe conducted a single-centre study of patients diagnosed with their first episode of biopsy-proven class III, IV, and/or V LN (n=37). For each patient, eGFR trajectory was graphed over 5 years following renal biopsy. Participants were divided into those with progressive eGFR loss (eGFR slope <−5 mL/min/1.73 m2/year) versus those with stable eGFR. Participant demographics, renal biopsy features and response status at 1 year (urine protein to creatinine ratio <500 mg/g) were compared between eGFR trajectory groups.ResultsOverall, 30% (n=11) of participants accrued progressive eGFR loss despite standard of care therapy over the first 5 years following renal biopsy. There were no significant differences in baseline renal biopsy features, medication regimens or comorbidities between eGFR trajectory groups. Resolution of proteinuria at 1 year did not differentiate between groups: 6 of 18 (33%) of complete responders continued to accrue renal damage compared with 5 of 17 (29%) of non-responders. Response status could not be assigned for two participants in the stable eGFR group due to missing clinical information at 1 year.ConclusionsWe identified an understudied category of patients with LN who accrue progressive renal damage despite apparent response to standard of care therapy. Better definitions and biomarkers of response are needed to improve renal outcomes and trial design.

Urine proteomic insights from the belimumab in lupus nephritis trial

“…Ultimately, long-term studies focused on eGFR preservation are needed to establish the utility of these biomarkers. 19 …”

“…Ultimately, long-term studies focused on eGFR preservation are needed to establish the utility of these biomarkers. 19 Another limitation of this work is that the original outcome assignments in BLISS-LN could not be obtained, though in this case we constructed a definition of complete renal response in line with other clinical trials in LN. Finally, longitudinal renal function dataspecifically, eGFR at baseline and over time-was also not available and could not be obtained.…”

“…Within our group, additional studies are under way exploring these co-correlations and early prediction of treatment response using individual or multidimensional urinary biomarkers. Ultimately, long-term studies focused on eGFR preservation are needed to establish the utility of these biomarkers 19…”

Population‐wide long‐term study of incidence, renal failure, and mortality rates for lupus nephritis

“…LN is heterogenous in terms of clinical and histological presentation and usually requires kidney biopsy to guide initial management 3 . Despite standard‐of‐care immunosuppressive therapy, clinical and histologic responses in LN are frequently discordant with at least a third of patients considered to be in clinical remission continuing to accrue renal damage 4 . This suggests that other, non‐immunological factors also contribute to the risk of developing chronic kidney disease (CKD) that ultimately may require renal replacement therapy 5,6 .…”

“…3 Despite standard-of-care immunosuppressive therapy, clinical and histologic responses in LN are frequently discordant with at least a third of patients considered to be in clinical remission continuing to accrue renal damage. 4 This suggests that other, non-immunological factors also contribute to the risk of developing chronic kidney disease (CKD) that ultimately may require renal replacement therapy. 5,6 Although European data suggest that the clinical course of LN has become less severe in the last decades with better long-term renal outcomes, [7][8][9] the risk of LN-related end-stage renal disease (ESRD) has remained unchanged in the US population since 1990.…”