Abstract
Case 1: 52-year-old female with SLE, LN and recurrent flare A 52-year-old female was diagnosed with systemic lupus erythematosus (SLE) in 1983. She had positive antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA) >666 IU/mL, C3 0.35 g/L, C4 0.07 g/L, CH50 20 IU/mL AI hemolytic anemia, lymphopenia, arthritis, probable lupus nephritis (LN) due to the presence of microhematuria, non-nephrotic proteinuria with preserved renal function, no renal biopsy was performed. She was treated with steroids, cyclophosphamide 6 x 500 mg, hydroxychloroquine 200 mg/d and subsequent maintenance with azathioprine 100 mg/d, prednisone 7.5 mg/d + calcium and vitamin D prophylaxis. Complete renal response was achieved after 18 months but with persistence of anti-dsDNA >600 and low levels of C3-C4. In 2006, she had clinical remission of SLE. GFR > 90 ml/min, inactive sediment and proteinuria 500 mg/d, persistently high anti-dsDNA titer and low C3-4 levels. The first renal biopsy revealed LN Class IIIC (IA 0/24, IC 2/12) and Grade 1 interstitial fibrosis and tubular atrophy. In 2012, she experienced a new flare. A renal biopsy revealed Class III (AC) (IA 6/24, CI 3/12. Complete renal remission was achieved after 1 year of treatment with steroids plus sodium mycophenolate, but persistent immunological activity. On March 2021 she experienced a new flare, with proteinuria up to 2.5 g/d, microhematuria, AKI 1, arthritis, malar rash and positive AAF. Renal biopsy showed LN Class IV (AC) AI: 10/24 CI: 4/12. Triple therapy with steroids, mycophenolate mofetil and belimumab was started. The response to triple therapy in this grumbling disease is discussed, from a renal and immunological point of view.
Case 2: 22-year-old woman with progressive worsening of proteinuria A 22-year-old woman, diagnosed with SLE at 18 years, presented with deep vein thrombosis, a study was carried out, revealing positive ANA, anti-dsDNA >666 IU/mL, positive IgG anti-β2-Glycoprotein-I and lupus anticoagulant, and low C3, C4 and CH50, microhematuria and proteinuria of 2 g/d, with normal renal function. Renal biopsy showed LN Class III, AI 4/24, IC 0/12. Steroids, mycophenolate mofetil and hydroxychloroquine, as well as anticoagulation with Vitamin K antagonists were initiated. Despite treatment, the patient presented progressive worsening of proteinuria up to 6 g/d. A new biopsy was performed 6 months later. The light micrograph showed LN Class IV-G (AC) IA 11/24 and IC 2/12 with immune deposits (IF and EM) compatible with associated membranous nephropathy. A sequential regimen of steroids plus cyclophosphamide 3 g (total dose) was started and later triple therapy with MMF-tacrolimus-steroids was continued due to persistent proteinuria in nephrotic range.
A third renal biopsy was performed for control of proteinuria stagnant in 3.5 g, revealing LN III + V with AI 4/24 and CI 3/12, IFTA ≥15%. Treatment with rituximab 1 g x 2 and nephroprotective treatment with losartan 50 mg/12 h were initiated. Under this treatment, a progressive decrease in anti-dsDNA titers up to 125 IU/mL and partial improvement in C3-C4 levels was confirmed, but there was an increase in proteinuria up to 4.5 g/d. In view of these findings and the high burden of immunosuppression administered, nephroprotective treatment was prioritized by sequentially adding dapagliflozin 10 mg/d and spironolactone 50 mg/d, achieving resolution of the nephrotic syndrome, with stable renal function and residual proteinuria of 1 g/d.
Currently, effective antiproteinuric treatments are available and they act by multiple mechanisms. The importance of establishing an adequate clinical correlation between the trajectory of immunological activity and proteinuria will be discussed in order to obtain better clinical results in LN.
Learning Objectives
Describe clinical and histological findings that identify challenging cases of proliferative LN
Explain the current role of therapy with anti-BAFF biologics in LN
Discuss principles and strategies in the management and prevention of organ damage and preservation of kidney function in the long term
