Background Patients with lupus nephritis (LN) may have improvement or deterioration in renal status over time. To capture bidirectional change we used a reversible multistate Markov model to study transitions in glomerular filtration rate (GFR) and proteinuria (PrU) in a prospective, international, inception cohort of SLE patients receiving standard of care.
Materials and methods Patients were evaluated at enrolment and annually. GFR states were defined: state 1 (eGFR: >60 ml/min); state 2 (eGFR: 30–60 mL/min); and state 3 (eGFR: <30 ml/min). Similarly, PrU states were defined: state 1 (ePrU: <0.25 gr/day); state 2 (ePrU: 0.25–3.0 gr/day); and state 3 (ePrU: >3.0 gr/day). Multistate models provided estimates of relative transition rates and state occupancy probabilities.
Results Of 1,826 SLE patients, 89% were female, 49.2% Caucasian with mean±SD age 35.1 ± 13.3 years. The mean disease duration at enrollment was 0.5 ± 0.3 years and follow-up was 4.6 ± 3.4 years. LN occurred in 700/1,826 (38.3%) patients. The likelihood of improvement in eGFR and ePrU (states 2→1 and 3→2) was greater than deterioration (states 1→2 and 2→3). After 5 years, the estimated transition to ESRD was 62% of patients initially in eGFR state 3 but only 11% from ePrU state 3. The probability of remaining in initial eGFR states 1, 2 and 3 was 85%, 11%, 3% and for ePrU was 62%, 29%, 4%. Male sex (p = 0.04) predicted improvement in eGFR states and older age (p < 0.001), race/ethnicity (p < 0.001), higher ePrU state (p < 0.001), higher renal biopsy chronicity score (p = 0.013) and baseline anticardiolipin antibodies (p = 0.039) predicted deterioration. For ePrU, race/ethnicity (p = 0.009), higher eGFR state (p = 0.011) and higher renal biopsy chronicity score (p = 0.015) predicted deterioration. Positive lupus anticoagulant (p = 0.006) and ISN/RPN class V nephritis (p = 0.013) were associated with lower improvement rates.
Conclusions Multistate modelling in patients with LN generates probability estimates of transitions between disease states that reflect improvement or deterioration in renal outcomes. This approach identifies predictors of change in renal status and can inform clinical trial design by identifying outcomes that new therapeutic interventions for LN should meet or exceed.
Acknowledgements Presented on behalf of the Systemic Lupus International Collaborating Clinics (SLICC)
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