Today we are comparing systemic lupus erythematosus (SLE) guidance from the American College of Rheumatology (ACR), European League Against Rheumatism (EULAR), and Kidney Disease Improving Global Outcomes (KDIGO). The ACR guideline provides recommendations and good practice statements (GPS) for the treatment and management of systemic lupus erythematosus, including organ-specific manifestations. The EULAR guidance statement provides recommendations and overarching principles on the management of SLE with kidney involvement, while the KDIGO guideline provides recommendations, algorithms, and practice points focused specifically on the management of lupus nephritis, or kidney involvement in SLE.
For this side-by-side comparison, we will highlight areas of overlap and distinction between the three guidelines. We encourage you to review the full-text version available at the links below for the most complete look at these publications.
Clinical Guidance for Comparison
| Item | American College of Rheumatology (ACR) | European League Against Rheumatism (EULAR) | Kidney Disease Improving Global Outcomes (KDIGO) |
|---|---|---|---|
| Publication Title | Treatment of Systemic Lupus Erythematosus | Management of Systemic Lupus Erythematosus with Kidney Involvement | Management of Lupus Nephritis |
| Publication Date | November 2025 | October 2025 | January 2024 |
| Links | Summary / Full Text | Summary / Full Text | Summary / Full Text |
Key Takeaways
Organ Specific Recommendations:
- The ACR guideline provides the broadest recommendations for organ-specific manifestations of SLE, including neuropsychiatric, cutaneous, musculoskeletal, cardiopulmonary, and systemic vasculitic disease. The EULAR and KDIGO guidance primarily focus on kidney involvement and lupus nephritis management.
Treatment:
- All three guidance documents recommend treatment with hydroxychloroquine unless contraindicated.
- The ACR guideline provides recommendations for the treatment of SLE and its organ-specific manifestations of SLE. In contrast, EULAR and KDIGO provide more detailed treatment recommendations for lupus nephritis, including combination immunosuppressive regimens, glucocorticoids, and management following initial treatment response.
Lupus Nephritis:
- Both the EULAR and KDIGO guidance documents emphasize early recognition of kidney involvement and close monitoring of treatment response. KDIGO provides the most comprehensive guidance on management of lupus nephritis, covering topics across pharmacologic treatment, relapse considerations, pregnancy, and kidney failure.
Pregnancy:
- EULAR and KDIGO both include recommendations for pregnancy planning and management in patients with lupus nephritis. KDIGO provides additional guidance on pregnancy-related considerations including medication management and care before and during pregnancy.
Side-by-Side Comparison of Clinical Guidance
| Item | ACR | EULAR | KDIGO |
|---|---|---|---|
| Kidney Biopsy | Not addressed. | Kidney biopsy is recommended in every patient with evidence of kidney involvement, especially in those with persistent proteinuria (≥0.5 g/24 h or urine protein-creatinine ratio [UPCR] ≥500 mg/g), glomerular haematuria, and/or unexplained decrease in glomerular filtration rate. Repeat kidney biopsy should be considered, especially in cases of clinical uncertainty, to evaluate (1) response to treatment, (2) worsening of kidney-specific laboratory tests, or (3) contemplated withdrawal of immunosuppressive treatment. | Addressed in Figures 1, 4, 10, and 12 within guidelines. |
| Monitoring | In people with SLE, we conditionally recommend: Assessing disease activity regularly, including when there is a change in clinical status or SLE-directed medications. Assessing disease damage at least annually. | Overarching Principle: In patients with SLE, regular monitoring for signs and symptoms of kidney involvement, input from experts, and timely biopsy are essential to ensure optimal outcomes. Overarching Principle: Management aims to prevent progression of chronic kidney disease and flares, address comorbidities, and improve health-related quality of life; both immunosuppressive therapy and nonimmune therapy, including kidney protection, are essential. | Not addressed. |
| Interdisciplinary Care Teams | GPS: When medications, procedures, and surgeries beyond the scope of rheumatology practice are considered, the decision to proceed with such therapies requires multidisciplinary discussion between the rheumatologist and the relevant specialists/proceduralists/surgeons. | Kidney involvement in SLE carries the risk of progressive chronic kidney disease and is best managed with shared informed patient-physician decisions by rheumatology-nephrology interdisciplinary care teams, with regular assessment of risk factors for chronic kidney disease progression. | Not addressed. |
| Comorbidities and Risk Management | Good practice statements (GPS): All people with SLE should receive screening, monitoring, and management for comorbid conditions associated with SLE and its therapies (including infection, cardiovascular disease, bone and joint damage, malignancy, reproductive health complications, and presence of antiphospholipid antibodies. | Not addressed. | Not addressed. |
| Medication Guidance and Treatment Goals | GPS: The goal of SLE treatment should be optimal control of disease (e.g., remission or a low level of disease activity) to improve long-term clinical outcomes. GPS: Prescribe glucocorticoids promptly to obtain rapid control of acute inflammation using the lowest dose and shortest duration necessary and initiate immunosuppressive therapy early to minimize glucocorticoid-related toxicity. Glucocorticoid therapy:In people with SLE: With organ- or life-threatening SLE flares:We conditionally recommend pulse methylprednisolone treatment (250–1,000 mg for one to three days) followed by oral glucocorticoid taper over high-dose oral glucocorticoid taper without pulse treatment. With stable controlled SLE on prednisone >5 mg/day: We strongly recommend tapering the prednisone to a dose of ≤5 mg daily (and ideally to zero) within six months. With sustained remission on prednisone ≤5 mg/day: We conditionally recommend a slow taper toward zero. Who are unable to taper prednisone to ≤5 mg/day: We conditionally recommend initiating or escalating immunosuppressive therapy. Hydroxychloroquine therapy:In people with SLE, we strongly recommend routine treatment with HCQ unless contraindicated. In people with SLE, we conditionally recommend continuing HCQ therapy indefinitely, even in the setting of sustained remission. In people with SLE receiving HCQ therapy: We conditionally recommend a long-term average daily HCQ dose goal of ≤5 mg/kg over a dose goal of >5 mg/kg to minimize retinal toxicity; use of short courses of higher dose (between 5 and 6.5mg/kg/d) therapy may be necessary at initiation of treatment or to maintain disease control. Immunosuppressive therapy: In people with SLE with sustained clinical remission or low disease activity: We conditionally recommend tapering immunosuppressive therapy after three to five years with the goal of discontinuation | For patients with active lupus nephritis, IV pulse methylprednisolone is recommended, followed by oral glucocorticoids gradually tapered to ≤5 mg/d prednisone-equivalent by four to six months, and slowly withdrawn in patients with sustained complete renal response. For patients with active lupus nephritis, especially those with poor prognostic factors, we recommend combination therapy of (a) mycophenolate or low-dose intravenous cyclophosphamide with belimumab, (b) mycophenolate with a calcineurin inhibitor (voclosporin or tacrolimus), or (c) mycophenolate with obinutuzumab. Alternative regimens include single-agent therapy with either mycophenolate or low-dose intravenous cyclophosphamide. In patients with rapidly progressive glomerulonephritis, a short course (six to seven monthly pulses) of high-dose intravenous cyclophosphamide can also be considered. Following renal response, treatment should continue for at least three years; patients initially treated with mycophenolate alone or in combination with (1) belimumab, (2) a calcineurin inhibitor, or (3) obinutuzumaba should remain on these drugs; mycophenolate or azathioprine should replace cyclophosphamide for those initially treated with cyclophosphamide, alone or in combination with belimumab. Nonimmune treatment with renin-angiotensin-aldosterone blockade (for patients with persistent proteinuria or arterial hypertension), sodium glucose transporter 2 inhibitors (for stable patients with persistent proteinuria or estimated glomerular filtration rate <60 ml/min/m², or other risk factors for progressive chronic kidney disease), statins (based on cardiovascular risk levels), and/or bone protective agents is recommended. In patients with features of thrombotic microangiopathy (antiphospholipid syndrome nephropathy, thrombotic thrombocytopenic purpura-like, or complement-mediated hemolytic uremic syndrome), glucocorticoids (IV pulse methylprednisolone), complement inhibitors, B-cell depleting agents, caplacizumab, plasma exchange, and/or anticoagulation should be considered. Overarching Principle: The management of patients with SLE with kidney involvement should align with the general recommendations for SLE, including treatment with hydroxychloroquine. | We recommend that patients with SLE, including those with lupus nephritis (LN), be treated with hydroxychloroquine or an equivalent antimalarial unless contraindicated. We recommend that patients with active Class III or IV LN, with or without a membranous component, be treated initially with glucocorticoids plus any one of the following: mycophenolic acid analogs (MPAA); or low-dose intravenous cyclophosphamide; or belimumab and either MPAA or low-dose intravenous cyclophosphamide; or MPAA and a calcineurin inhibitor (CNI) when kidney function is not severely impaired (i.e., estimated glomerular filtration rate [eGFR] ≤45 ml/min per 1.73m²). Practice Point: A regimen of reduced-dose glucocorticoids following a short course of methylprednisolone pulses may be considered during the initial treatment of active LN when both the kidney and extrarenal disease manifestations show satisfactory improvement Practice Point: Intravenous cyclophosphamide can be used as the initial therapy for active Class III and Class IV LN in patients who may have difficulty adhering to an oral regimen. Practice Point: An MPAA-based regimen is the preferred initial therapy of proliferative LN for patients at high risk of infertility, such as patients who have a moderate-to-high prior cyclophosphamide exposure. Practice Point: Initial therapy with an immunosuppressive regimen that includes a CNI (voclosporin, tacrolimus, or cyclosporine) may be preferred in patients with relatively preserved kidney function and nephroticrange proteinuria likely due to extensive podocyte injury, as well as patients who cannot tolerate standard-dose MPAA or are unfit for or will not use cyclophosphamide-based regimens. Practice Point: A triple immunosuppressive regimen of belimumab with glucocorticoids and either MPAA or reduced-dose cyclophosphamide may be preferred in patients with repeated kidney flares or at high-risk for progression to kidney failure due to severe chronic kidney disease. Practice Point: Other therapies, such as azathioprine or leflunomide combined with glucocorticoids, may be considered in lieu of the recommended initial drugs for proliferative LN in situations of patient intolerance, lack of availability, and/or excessive cost of standard drugs, but these alternatives may be associated with inferior efficacy, including increased rate of disease flares and/or increased incidence of drug toxicities. Practice Point: Newer biologic and non-biologic therapies are under development and may offer future options for the treatment of active LN. Rituximab may be considered for patients with persistent disease activity or inadequate response to initial standard-of-care therapy. We recommend that after completion of initial therapy, patients should be placed on MPAA for maintenance. Practice Point: Azathioprine is an alternative to MPAA after completion of initial therapy in patients who do not tolerate MPAA, who do not have access to MPAA, or who are considering pregnancy. Practice Point: Glucocorticoids should be tapered to the lowest possible dose during maintenance, except when glucocorticoids are required for extrarenal lupus manifestations; discontinuation of glucocorticoids can be considered after patients have maintained a complete clinical renal response for 12 months Practice Point: The dose of mycophenolate mofetil (MMF) in the early maintenance phase is approximately 750–1000 mg twice daily, and for mycophenolic acid (MPA), approximately 540–720 mg twice daily. Practice Point: The total duration of initial immunosuppression plus combination maintenance immunosuppression for proliferative LN should be 36 months. Practice Point: Patients treated with triple immunosuppressive regimens that include belimumab or a CNI in addition to standard immunosuppressive therapy can continue with a triple immunosuppressive regimen as maintenance therapy. Practice Point: If MPAA and azathioprine cannot be used for maintenance, CNIs or mizoribine or leflunomide can be considered. |
| General treatment strategies | GPS: People with active SLE symptoms should be diagnosed and treated promptly, with severity of lupus activity guiding intensity and choice of therapy. GPS: When multiple organ systems are involved at onset or during a flare of SLE, therapy should be directed toward all manifestations but should prioritize areas at greatest risk for irreversible damage. GPS: Organ- or life-threatening SLE should be treated urgently/emergently with aggressive therapy (e.g., pulse/high-dose glucocorticoid and immunosuppressive therapy), including consideration of combination therapies, as time may not permit sequential therapy; the clinical situation and patient’s preference should guide the specific combination therapy. GPS: When clinical or serologic findings suggest an additional diagnosis or overlap with SLE (e.g., aquaporin-4 antibodies in setting of known SLE and new onset transverse myelitis or optic neuritis), therapy should be adjusted if necessary, depending upon which process is predominant and in consultation with the relevant specialist(s). For ongoing SLE disease activity in any organ system(s) refractory to initial therapy, we strongly recommend escalation of therapy. | Treatment should aim for optimisation (preservation or improvement) of kidney function within 3 months, accompanied by a reduction in proteinuria of at least 25% by three months, 50% by six months, and a UPCR target <700 mg/g by 12 months, and as low as possible afterward In patients with sustained complete renal response, gradual withdrawal of immunosuppressive and/or biologic therapy should be considered after three years of therapy following response, taking into consideration the risk for flare. For patients with persistently active or relapsing disease, switching among the aforementioned immunosuppressive and/or biologic drugs and referral to experts is recommended. | Not addressed. |
| Treatment of lupus nephritis relapse | Not addressed. | Not addressed. | Practice Point: After a complete or partial remission has been achieved, LN relapse should be treated with the same initial therapy used to achieve the original response, or an alternative recommended therapy. |
| Neuropsychiatric | Severe neuropsychiatric syndromes: For Active lupus optic neuritis or Lupus acute confusional state or Active lupus mononeuritis multiplex: We conditionally recommend initial therapy with pulse/high-dose glucocorticoid taper plus immunosuppressive therapy with IV CYC, MPAA, or anti-CD20 therapy over pulse/high-dose glucocorticoid monotherapy alone. For active lupus myelitis: We conditionally recommend initial therapy with pulse/high-dose glucocorticoid and IV CYC over pulse/high-dose glucocorticoid combined with other (non-CYC) immunosuppressive agents. For active lupus psychosis: We conditionally recommend anti-psychotic therapy plus glucocorticoid, IV CYC, MPAA, or anti-CD20 therapy over antipsychotic therapy alone. For seizures attributed to active SLE: We conditionally recommend anti-seizure medication plus glucocorticoid, CYC, MPAA, AZA, and/or anti-CD20 over antiseizure medication alone. Cognitive dysfunction: For isolated cognitive dysfunction attributed to SLE and documented by neuropsychological testing: We conditionally recommend against adding immunosuppressive therapy (including glucocorticoid) to cognitive therapy over using cognitive therapy alone. Cutaneous/mucocutaneous GPS: People with SLE should be educated on the use of sunscreen and other sun-protection measures to reduce risk of rash and potential disease flare. GPS: Initial therapy for cutaneous lupus rash—in addition to HCQ—should be topical, including glucocorticoid and/or calcineurin inhibitors (Table 6); initial therapy may also include a course of intralesional glucocorticoid with dermatology and/or a brief, limited course of oral glucocorticoid. Acute, subacute and chronic cutaneous lupus: For mild, ongoing skin-predominant lupus despite treatment with HCQ and/or topical therapies: We conditionally recommend modifying antimalarial therapy (adding quinacrine or switching to chloroquine) over adding an immunosuppressive agent. For ongoing moderate-severe cutaneous lupus refractory to topical and antimalarial therapies, and/or oral glucocorticoidnecessitating escalation of therapy: We conditionally recommend the addition of MTX, MPAA, anifrolumab, and/or belimumab. For ongoing moderate-severe cutaneous lupus refractory to topical therapies, antimalarials, and conventional and/or biologic immunosuppressive agents necessitating escalation of therapy: We conditionally recommend adding or substituting lenalidomide. Bullous lupus erythematosus: For mild ongoing bullous lupus despite treatment with topical therapies and antimalarial therapies: We conditionally recommend the initial addition of dapsone over initiation of glucocorticoid. For moderate-severe bullous lupus refractory to topical therapies, antimalarials, and/or oral glucocorticoid necessitating escalation of therapy: We conditionally recommend adding a conventional immunosuppressive agent (MPAA, MTX, AZA) and/or anti-CD-20 therapy. Chilblain lupus: For chilblain lupus despite symptomatic, topical, and antimalarial therapies (including quinacrine): We conditionally recommend the addition of pentoxifylline, PDE5 inhibitors (e.g., sildenafil, tadalafil) and/or calcium channel blockers (e.g., nifedipine) over initiation of immunosuppressive therapies. Leukocytoclastic vasculitis: For ongoing mild cutaneous vasculitis despite topical and antimalarial therapies: We conditionally recommend addition of dapsone or colchicine over immunosuppressive therapies including oral glucocorticoid. For lupus pleuropericarditis: We conditionally recommend initial treatment with NSAID, colchicine, or their combination, with a low threshold for escalation to glucocorticoid therapy over initiating glucocorticoid therapy alone. For ongoing/recurrent episodes of lupus pleuropericarditis despite treatment with HCQ, NSAIDs, colchicine, and/or glucocorticoids necessitating escalation of therapy: We conditionally recommend conventional (MPAA, AZA) or biologic immunosuppressive therapies. | Not addressed. | Not addressed. |
| Musculoskeletal | GPS: Initial therapy for acute or recurrent episodes of inflammatory arthritis in people with SLE may include a course of NSAID or a limited course of oral glucocorticoid while waiting for recommended long-term therapies to take effect. Arthritis: For persistent or recurrent active SLE arthritis on HCQ, regardless of prior/current NSAIDs or short-term glucocorticoid therapy: We conditionally recommend initial therapy with MTX, MPAA, or AZA, with a low threshold to add or substitute with belimumab or anifrolumab for inadequate response over initial biologic therapy. Systemic Vasculitis: For vasculitis attributed to active SLE: We conditionally recommend initial therapy with pulse/high-dose glucocorticoid taper and conventional (IV CYC, MPAA, AZA) orbiologic (anti-CD20 therapy, belimumab, anifrolumab) immunosuppressive therapy over glucocorticoid monotherapy alone. For severe vasculitis attributed to SLE: We conditionally recommend IV CYC or anti-CD20 therapy as initial therapy over other immunosuppressive therapies. For life-threatening vasculitis attributed to active SLE (e.g., diffuse alveolar hemorrhage or mesenteric vasculitis): We conditionally recommend the addition of PLEX and/or IVIG to pulse/high-dose glucocorticoid taper and immunosuppressive therapy over glucocorticoid and immunosuppressive therapy alone. | Not addressed. | Not addressed. |
| Cardiopulmonary | For lupus myocarditis that is acute and/or worsening: We conditionally recommend treatment with glucocorticoid and IV CYC, MPAA, anti-CD20 therapy, and/or IVIG over glucocorticoid monotherapy. For non-bacterial (Libman-Sacks) endocarditis: We conditionally recommend immunosuppressive therapy and/or anticoagulation. | Not addressed. | Not addressed. |
| Pregnancy | Not addressed. | In patients with inactive nephritis and adequately controlled extrarenal manifestations, pregnancy may be planned after preconception counselling, initiation of pregnancy-compatible medications, and regular multidisciplinary assessments. | Pregnancy in patients with lupus nephritis Practice Point: Patients with active LN should be counseled to avoid pregnancy while the disease is active or when treatment with potentially teratogenic drugs is ongoing, and for 6 months after LN becomes inactive. Practice Point: 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. Practice Point: Glucocorticoids, hydroxychloroquine, azathioprine, tacrolimus, and cyclosporine are considered safe immunosuppressive treatments during pregnancy. |
| Kidney Transplant | Not addressed. | All methods of kidney replacement therapy can be used in patients with SLE; in those with clinically inactive extrarenal disease for at least six months, transplantation (including living donor and pre-emptive transplantation) should be considered. | Not addressed. |
| Lupus in Children | Not addressed. | Not addressed. | Practice Point: Treat pediatric patients with LN using immunosuppression regimens similar to those used in adults, but consider issues relevant to this population, such as dose adjustment, growth, fertility, and psychosocial factors, when devising the therapy plan. |
| Kidney Failure | Not addressed. | Not addressed. | Practice Point: Patients with LN who develop kidney failure may be treated with hemodialysis, peritoneal dialysis, or kidney transplantation; and kidney transplantation is preferred to long-term dialysis. |
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