The guideline authors presented 28 graded recommendations (7 strong, 21 conditional) and 13 ungraded, consensus-based good practice statements (GPS). They include:
Screening
- In people with SLE without known kidney disease, we strongly recommend screening for proteinuria at least every 6–12 months, OR when experiencing extra-renal flares.
Kidney biopsy
GPS: Prompt kidney biopsy should be performed in people with SLE when LN is suspected (unless contraindicated/not feasible).
- In people with SLE who have proteinuria >0.5 g/g and/or impaired kidney function not otherwise explained, we conditionally recommend performing a kidney biopsy.
- For people with treated LN in remission who present with suspected LN flare (increased proteinuria, hematuria and/or worsening kidney function), OR for people with ≥6 months of appropriate treatment and ongoing/worsening proteinuria, hematuria, and/or decreased kidney function, we conditionally recommend repeat kidney biopsy.
Treatment in people with active/new onset/flare of class III/IV or class V
GPS: Prompt glucocorticoid treatment should be administered for suspected LN to suppress acute inflammation while awaiting a kidney biopsy and histopathology results.
GPS: Dosage of LN medications should be adjusted in people with decreased GFR at initiation of therapy and periodically.
GPS: Adjunctive treatment with systemic anticoagulation for people with LN and significant risk factors for thrombosis (e.g., low serum albumin in context of severe proteinuria) should be discussed with nephrology.
- If not on HCQ, we strongly recommend initiation and continuation of HCQ to manage and prevent lupus clinical manifestations, unless contraindicated.
- With any elevation in level of proteinuria, including <0.5g/g, we conditionally recommend the addition of RAAS-I.
- We conditionally recommend pulse intravenous glucocorticoids 250–1,000 mg methylprednisolone daily x 1–3 days, followed by oral glucocorticoid ≤0.5 mg/kg/day (maximum dose 40 mg/day) with taper to a target dose of ≤5 mg/day by 6 months.
- Who have achieved/sustained a complete renal response after treatment with any (triple or dual) immunosuppressive therapy, we conditionally recommend a total duration of therapy of at least 3–5 years.
Treatment in people with active/new onset/flare of class III/IV (with or without class V)
- We conditionally recommend a triple immunosuppressive regimen consisting of pulse intravenous glucocorticoids 250–1,000 mg methylprednisolone daily x 1-3 days, followed by oral glucocorticoid ≤0.5 mg/kg/day (maximum dose 40 mg/day) with taper plus:
- MPAA plus belimumab or
- MPAA plus CNI or
- Euro Lupus Nephritis Trial (ELNT) low-dose CYC plus belimumab (MPAA substituted for CYC after CYC course complete).
- We conditionally recommend an MPAA-based regimen over a CYC-based regimen.
- With proteinuria ≥3g/g, we conditionally recommend a triple immunosuppressive regimen that contains MPAA plus CNI.
- With extra-renal manifestations, we conditionally recommend a triple immunosuppressive regimen that contains belimumab.
- Receiving a CYC regimen, we conditionally recommend ELNT low-dose CYC over a high-dose monthly pulse IV regimen; we also strongly recommend ELNT low-dose CYC over a daily oral CYC regimen.
- Who have undergone triple immunosuppressive therapy and achieved a complete renal response, we conditionally recommend continuing the same immunosuppressive regimen.
- Who have undergone triple immunosuppressive and achieved a partial renal response, we conditionally recommend individualizing therapy depending on clinical factors that include the trajectory of response.
- Who have undergone dual immunosuppressive therapy (glucocorticoids plus either CYC or MPAA) and achieved a complete renal response, we conditionally recommend continuing therapy with MPAA (over AZA).
- Who have undergone dual immunosuppressive therapy (glucocorticoids plus either CYC or MPAA) and achieved a partial renal response, we conditionally recommend escalating therapy to a triple immunosuppressive regimen.
Treatment in people with active/new onset/flare of pure class V
- With proteinuria ≥1 g/g we conditionally recommend treatment with a triple immunosuppressive regimen: pulse intravenous glucocorticoids 250–1,000 mg methylprednisolone daily x 1–3 days, followed by oral glucocorticoid ≤0.5 mg/kg/day (maximum dose 40 mg/day) with taper and MPAA plus CNI.
- With proteinuria <1 g/g, we conditionally recommend treatment with glucocorticoids and/or immunosuppressant therapy (MPAA, AZA, or CNI).
Treatment in people with nonresponsive or refractory LN
GPS: Medication dose and patient adherence should be assessed as an important first step in evaluating inadequate response or refractory LN because insufficient treatment is an important cause of non-response.
- In people with any LN class with an inadequate renal response (i.e., have not achieved at least a partial renal response by 6–12 months) we conditionally recommend escalation of treatment:
- For initial dual therapy, escalate to triple therapy.
- For initial triple therapy, change to an alternative triple therapy or consider addition of an anti-CD20 agent as a second immunosuppressive.
- In people with any LN class with refractory disease (i.e., failed two standard therapy courses), we conditionally recommend treatment escalation to a more intensive regimen, including addition of anti-CD20 agents, or combination therapy with three non-glucocorticoid immunosuppressives (i.e., MPAA, belimumab and CNI), or referral for investigational therapy.
Definitions & Abbreviations
Triple therapy: GC [pulse intravenous glucocorticoids (250–1,000 mg methylprednisolone daily x 1-3 days) followed by oral glucocorticoid (≤0.5 mg/kg/day, maximum dose 40 mg/day) with taper] plus 2 additional immunosuppressive therapies, usually a) MPAA plus belimumab or b) MPAA plus CNI or c) ELNT low-dose CYC plus belimumab (MPAA substituted for CYC after CYC course complete).
Dual therapy: GC [pulse intravenous glucocorticoids (250–1,000 mg methylprednisolone daily x 1–3 days) followed by oral glucocorticoid (≤0.5 mg/kg/day, maximum dose 40 mg/day) with taper] plus one additional immunosuppressive therapy, usually MPAA or ELNT low-dose CYC.
Anti-CD20 therapy: rituximab or obinutuzumab; AZA: azathioprine; BEL: belimumab; CNI: calcineurin inhibitor therapies (cyclosporine, tacrolimus, voclosporin); CYC: cyclophosphamide; ELNT: EuroLupus Nephritis Trial; ESKD: end stage kidney disease; GC: glucocorticoids; HCQ: hydroxychloroquine; MPAA: mycophenolic acid analogs (including mycophenolate mofetil, MMF, and mycophenolic acid, MPA); RAAS-I: renin-angiotensin-aldosterone system inhibitors (including angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, mineralocorticoid receptor antagonists).
Abstracted from the Guideline Summary:
