Background/Purpose:

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 our randomized comparative trial of mycophenolate mofetil (MMF) vs tacrolimus (Tac) were studied.  Participants were divided into 3 groups: group 1 (pure membranous lupus Gn: RPS/ISN class V); group 2 (mixed membranous and proliferative Gn: class V+III or IVS/IVG) and group 3 (proliferative lupus Gn: IVS/IVG).  The clinical presentation, treatment response, outcome and complications were compared.

Results:

141 patients were studied (92% women; age 35.2±12.8 years; SLE duration 49.3±62 months at renal biopsy). There were 25 patients (18%), 31 patients (22%) and 85 patients (60%) in group 1, 2 and 3, respectively.  At presentation, group 1/2 patients had significantly higher hemoglobin level (11.3±1.8 vs 9.9±1.7g/dL), creatinine clearance (CrCl) (90.0±31 vs 69.7±27ml/min), complement C3 level (0.62±0.27 vs 0.42±0.16g/L) but lower serum Cr (70.8±25 vs 91.5±33umol/L) and anti-dsDNA titer (166±116 vs 234±89IU/ml;p<0.001) than that of group 3 patients (p<0.001 in all). 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 (46% vs 32%; p=0.08).  Blood pressure and serum albumin level was similar among the 3 groups. 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% vs 42%; p=0.04).  All patients were treated with high-dose prednisolone and either MMF (N=72) or Tac (N=69), followed by low-dose prednisolone and azathioprine for maintenance. 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% vs 62%; p=0.10). After a mean 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 (HR 0.46[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.

Conclusion:

The presence of histological membranous component in lupus nephritis is associated with heavier proteinuria, better renal function but less active lupus serology or extra-renal activity such as arthritis. One-third of patients have either normal complements or anti-dsDNA.  Renal function decline in membranous lupus nephropathy is no different from proliferative lupus nephritis at 5 years, but thrombotic complications are more frequent.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-presentation-treatment-and-outcome-of-membranous-nephropathy-in-sle-a-comparison-with-proliferative-lupus-glomerulonephritis-in-141-patients/