Management of lupus nephritis: KDIGO 2024 Clinical Practice Guidelines

Since the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Glomerular Diseases was updated in 2021,¹ there have been advances in the treatment of lupus nephritis (LN), including the approval of belimumab and voclosporin by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) as add-on immunosuppressives to standard-of-care LN treatment.²

Recently, KDIGO has issued an evidence-based update on recommendations for managing LN, summarized by Rovin et al.² in Kidney International. Here, we provide a summary of the guidelines.

Methods³

An evidence review team updated the systematic evidence review, using their expertise in guideline development methodology, and a work group was established by KDIGO for writing recommendations and practice points. Then, following a public review and incorporating external feedback, the guidelines were finalized and published.

Key findings^2,3

Recommendations

Recommendation statements were formulated for the general management of LN and the initial and maintenance therapy for active Class III/IV LN (Figure 1A). The practice points for all the classes of LN are outlined in Figure 1B.

AZA, azathioprine; BEL, belimumab; BID, twice-daily; BP, blood pressure; CNI; calcineurin inhibitor; CYC, cyclophosphamide; d, day; eGFR, estimated glomerular filtration rate; GC, glucocorticoid; HCQ, hydroxychloroquine; IV, intravenous; IS, immunosuppressive; KDIGO, Kidney Disease: Improving Global Outcomes; LN, lupus nephritis; MMF, mycophenolate mofetil; MP, methylprednisolone; MPAA, mycophenolic acid analog; mo, month; p.o., oral administration; Q2W, every 2 weeks; Q4W, every 4 weeks; RAS, renin-angiotensin system; RTX, rituximab; SCr, serum creatinine; SLE, systemic lupus erythematosus; TAC, tacrolimus; VOC, voclosporin.
*Adapted from Rovin, et al.²; KDIGO Lupus Nephritis Work Group.^3
†The certainty of evidence was graded on a scale of A to D, indicating high to very-low certainty, respectively, and recommendations were graded as Level 1 (“we recommend”) or Level 2 (“we suggest”).

Practice points for management of LN in special situations

Lupus nephritis and thrombotic microangiopathy

• Systemic lupus erythematosus-associated thrombotic thrombocytopenic purpura: plasma exchange + glucocorticoids + rituximab ± caplacizumab.
• Primary or secondary complement-mediated thrombotic microangiopathy: consider eculizumab.
• Antiphospholipid syndrome nephropathy: anticoagulation ± plasma exchange.

Pregnancy in patients with LN

• Patients with active LN should be advised to avoid pregnancy while experiencing active disease or when treatment with potentially teratogenic drugs is ongoing, and for ≥6 months after LN becomes inactive.
• To reduce the risk of pregnancy complications, hydroxychloroquine should be continued during pregnancy, and low-dose aspirin should be started before 16 weeks of gestation.
• Safe immunosuppressive treatments during pregnancy include glucocorticoids, hydroxychloroquine, azathioprine, tacrolimus, and cyclosporine.

Treatment of LN in children

Treat pediatric patients with LN using immunosuppression regimens similar to those used in adults, while accounting for factors such as dose adjustment, growth, fertility, and psychosocial factors when planning therapy.

Management of LN patients with kidney failure

• Patients with LN who develop kidney failure may be treated with hemodialysis, peritoneal dialysis, or kidney transplantation.
• Kidney transplantation is preferred to long-term dialysis.

Key learnings

The key update in the 2024 KDIGO guidelines is the recommendations for the initial treatment of patients with active Class III/IV ± V LN, which involves using glucocorticoids alongside low-dose intravenous cyclophosphamide or mycophenolic acid analogs (dual immunosuppressive therapy). Alternatively, belimumab or voclosporin (or tacrolimus) can be added (triple immunosuppressive therapy).