Objectives To study the presentation and outcome of membranous nephropathy in SLE in comparison with proliferative lupus glomerulonephritis.
Methods Patients with biopsy firmed active lupus nephritis who were recruited in a randomized trial of mycophenolate mofetil (MMF) and tacrolimus (Tac) from 2005 to 2011 were studied. Participants were divided into 3 groups according to renal histology: group I (pure membranous lupus Gn:RPS/ISN class V); group 2 (mixed membranous/proliferative Gn: V+III or IVS/IVG) and group 3 (proliferative lupus Gn:IVS/IVG). The clinical presentation, treatment response, outcome were compared.
Results 141 patients were studied (92%women; age 35.2±12.8 years, SLE duration 49.3±62 months). There were 25 (18%), 31 (22%) and 85 (60%) patients in group 1, 2 and 3, respectively. At presentation, group 1/2 patients had significantly higher hemoglobin (11.3±1.8vs9.9±1.7g/dL), creatinine clearance (CrCl) (90.0±31vs69.7±27ml/min), complement C3 level (0.62±0.27vs0.42±0.16g/L) but lower serum Cr (70.8±25vs91.5±33umol/L) and anti-dsDNA titer (166±116vs234±89IU/ml) than group 3 patients (p<0.001). 18 (32%) patients in group 1/2 had normal range C3 or anti-dsDNA, compared to 3 (4%) patients in group 3 (p<0.001). Nephrotic syndrome was more common in group 1/2 than group 3 patients (46% vs 32%; p=0.08) but the difference was no significant. Blood pressure and serum albumin level was similar among the 3 groups of patients. The SLE disease activity index (SLEDAI) score was significantly lower in group 1/2 than group 3 patients (13.5±4.9 vs 18.0±5.3 points;p<0.001). Extra-renal activity was less common in group 1/2 than group 3 patients, but the difference was only statistically significant for arthritis (25%vs42%;p=0.04). All patients were treated with high-dose prednisolone and either MMF (N=72) or Tac (N=69) assigned by random for induction, followed by low-dose prednisolone and azathioprine for maintenance (mean dose: 84.1±23mg/day). Complete response to induction treatment at 6 months, defined as urine P/Cr of <1.0, resolution of active urine sediments, improvement in lupus serology and stabilization of CrCl, was less common with group 1/2 than group 3 patients (45%vs62%;p=0.10). After an observation of 48.5±21 months, the cumulative risk of loss in 30% of CrCl compared to baseline was 4.6% at year 1, 6.3% at year 3 and 18% at year 5. Group 1/2 patients did not differ significantly from group 3 patients in terms of decline in CrCl (HR0.46[0.15-1.46];p=0.19, adjusted for age, sex, SLE duration, initial CrCl and treatment arms). There were 4 arterial events (2 acute coronary syndrome; 2 cerebrovascular accidents) and 1 venous event (deep vein thrombosis)- all occurred in group 1/2 patients (compared with group 3;p=0.01). Infections (major and minor) were numerically more common in group 1/2 than group 3 patients but the difference was insignificant.
Conclusions The presence of histological membranous component in lupus nephritis is associated more proteinuria, better renal function but less active lupus serology or extra-renal activity at presentation. One-third of patients have either normal complements or anti-dsDNA, and complete response to induction therapy is less likely. Renal function decline in membranous lupus nephropathy is no different from proliferative lupus nephritis at 5 years, but thrombotic complications are more frequent.
Disclosure of Interest None Declared