Discussion on latest management of lupus nephritis(Part 4)
In the treatment of adult lupus nephritis (LN), in the new guidelines, the treatment recommendations are further defined according to the time since treatment initiation.
In some guidelines, based on post hoc analysis, it is suggested that proteinuria at 12 months, represents the best way to predict long-term renal condition, which may result to end- stage kidney disease (ESKD) where there is an increase in the serum creatine after 10 years.
It is best that the therapy should aim for proteinmuria <0.5-0.7g/24 hours by 12 months (complete clinical response), although up to 50% of patients not reaching this milestone may still have stable longterm kidney function.
There should be evidence of proteinuria improvement. There should be a glomerular filtration rate (GFR) normalisation/stabilisation) should be noted by 3 months, and at least 50% reduction in proteinuria (partial clinical response) by 6 months. For patients with nephrotic-range proteinuria at baseline, the aforementioned time frames may be extended by 6-12 months, due to slower recovery from proteinuria.
In consideration of improving status of proteinuria it may help to avoid premature treatment. As systemic lupus erythemathpsus (SLE) Is a systemic problem, immunosuppresive therapy also targets remission or low disease activity from extra-renal domains.
In class III-IV LN, an updated Cochrane systematic review suggests similar efficacy of mycophenolate mofetil/mycophenolate acid (MMF/MPA) compared with cyclophosphamide (CY), with possible ethnic/racial differences, that is, MMF potentially being more efficacious in African-Americans.
The 10-year Euro-Lupus Nephritis Trial data showed equal efficacy of low-dose CY versus high-dose and the low-dose regimen has been used in non-European populations. Both MMF/MPA and low-dose CY are recommended as firstline options for initial (induction) treatment.
The recommended target dose of MMF is now changed to 2–3 y/day (MPA 1.44-2.16 g/day), based on evidence that therapeutic drug dosage may range between 1 and 3 g/day.
Dose may be adjusted according to tolerance/adverse effects, efficacy and trough MPA bloods levels. High-dose intravenous CY (0.5-0.75 g/m² monthly for 6 months) can be considered in patients with adverse clinical (nephritic urine sediment and impaired renal function with GFR between 25 and 80 mL/min) or histological (crescents or necrosis in >25% of glomeruli) prognostic factors.
There is a need to realize the adverse effects of long-term glucobiscorticoid treatment, together with emerging evidence that following initial pulse intravenous methylprednisolone, lower starting dose of glucocorticoids (≤0.5 mg/kg/day) may be as efficacious as higher dose, led the Task Force to recommend that total intravenous methylprednisolone dose may range from 500 to 2500mg (depending on disease severity), and starting oral prednisone dose may be at the range of 0.3-0.5 mg/kg/day, reducing to ≤7.5 mg/day when the disease reach 3 to 6 months.
The current focus has been placed on the use of calcineurin inhibitors, either as a monotherapy or in combination with MMF/MPA.
In a randomized controlled trial (RCT) in some 362 Chinese patients, it has found that the combination of tacrollmus or TAC plus MMF to be superior to CY in the short-term.
In a phase II RCT, a cyclosporine analogue, voclosporin when combined with MMF was associated with a higher frequency of complete response at 6 months as compared with MMF alone,
There are more side effects and deaths occurrence in the former group.
A number of meta-analyses suggest that CNI (alone or as part of multitarget regimen) may have favour able efficacy/toxicity ratio in LN, and thus, in a new statement (4.4), the combination of MMF with a CNI (especially TAC) is included as therapeutic option, particularly in cases with nephrotic-range proteinuria.
Recommendations for universal first-line treatment can be given only if there are more data for non-Asian populations and more studies with longer follow-up regarding results on renal condition and prevention of kidney failure.
We will continue with the discussion on LN treatment next week.