Outcome of Lupus Nephritis and Impact on Health Related Quality of Life: Results from an International, Prospective, Inception Cohort Study

Abstract

Background/Purpose: Improved immunosuppressive therapies have changed the treatment of lupus nephritis (LN) over the past decade. We examined the outcome of LN with current standard of care in an inception cohort of SLE patients.

Methods: An observational study of new onset SLE was performed by an international network of 32 centers. Patients were evaluated at enrollment and annually. LN was identified as “renal disorder” (ACR classification criterion) and/or biopsy confirmation. Data included medications, estimated glomerular filtration rate (eGFR) and proteinuria (ePrU), end-stage renal disease (ESRD), SLE disease activity index-2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics (SLICC)/ACR damage index (SDI). 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). HRQoL was determined by SF-36 subscale, mental (MCS) and physical (PCS) component summary scores. Statistical analyses included analysis of variance or equivalent t-tests, Chi-squared test, regression and Kaplan-Meier curves.

Results: Of 1,827 SLE patients, 89% were female, 49.2% Caucasian with mean±SD age 35.1±13.3 years. At enrollment, mean SLE duration was 0.5±0.3 years, SLEDAI-2K was 5.4±5.4, SDI was 0.3±0.7. The mean follow-up was 4.6±3.4 years. LN occurred in 700/1,827 (38.3%) patients: 566 (31%) at enrollment and 134 (7.3%) during follow-up. It was more common in Hispanics (49.3%), African ancestry (39.9%) and Asians (36.8%) compared to Caucasians (20.3%) (p<0.001). Renal biopsies from 395 (56.4%) patients revealed ISN classes (%): I: 9 (2.4), II: 36 (9.5), III: 101 (26.8), IV: 163 (43.2), V: 121 (32.1) and VI: 3 (0.8); 21 and 34 biopsies had class III/V and IV/V respectively. At presentation, impaired renal function (eGFR <60 ml/min) occurred in 12.9% and proteinuria (ePrU of >0.25 gr/day) in 55.1% of patients with LN. Medications in LN patients were corticosteroids 651/700 (93%), antimalarials 517/700 (73.9%) and immunosuppressive (cyclophosphamide, azathioprine, mycophenolate mofetil) drugs in 614/700 (87.7%). At final follow-up 113/685 (16.5%) patients with LN had impaired renal function and 417/671 (62.1%) had proteinuria. Following LN the estimated 10 year incidence of ESRD was 10.1% (95%CI: (6.6%, 13.6%)) and there was a higher risk of death (HR=2.98, 95%CI (1.48, 5.99), p=0.002). Patients with eGFR <30 ml/min at diagnosis had lower SF-36 PCS scores (p<0.01) and lower Physical function, Physical role and Bodily pain scores. Over time, patients with abnormal eGFR and ePrU had lower SF-36 MCS (p ≤0.02) scores compared to patients with normal values.

Conclusion: LN occurred in 38.3% of SLE patients, frequently as the initial presentation, in a large multi-ethnic inception cohort. Despite current standard of care, nephritis was associated with ESRD and death, and renal insufficiency was linked to lower HRQoL. New strategies are required to improve outcomes of lupus nephritis.