Screening, Treatment, and Management of Lupus Nephritis

Publication Date: May 3, 2012
Last Updated: September 2, 2022


Case Definition for Lupus Nephritis (LN)

  • For the purpose of these recommendations, LN is defined as clinical and laboratory manifestations that meet American College of Rheumatology (ACR) criteria (persistent proteinuria >0.5 gm per day or >3+ by dipstick, and/or cellular casts including red blood cells [RBCs], hemoglobin, granular, tubular, or mixed).
  • A spot urine protein/creatinine ratio of >0.5 can be substituted for the 24-hour protein measurement.
  • “Active urinary sediment” (>5 RBCs/high-power field [hpf], >5 white blood cells [WBCs]/hpf in the absence of infection, or cellular casts limited to RBC or WBC casts) can be substituted for cellular casts.
  • An additional, perhaps optimal, criterion is a renal biopsy sample demonstrating immune complex–mediated glomerulonephritis compatible with LN.
  • A diagnosis of LN should also be considered valid if based on the opinion of a rheumatologist or nephrologist.

Renal Biopsy and Histology

The ACR recommends that all patients with clinical evidence of active LN, previously untreated, undergo renal biopsy (unless strongly contraindicated) so that glomerular disease can be classified by current International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification. (C)
The ACR agrees that class I (minimal mesangial immune deposits on immunofluorescence with normal light microscopy) and class II (mesangial hypercellularity or matrix expansion on light microscopy with immune deposits confined to mesangium on immunofluorescence) generally do not require immunosuppressive treatment. (C)

Table 2. Indications For Renal Biopsy In Patients With Systemic Lupus Erythematosus

Increasing serum creatinine without compelling alternative causes (such as sepsis, hypovolemia, or medication) (C)
Confirmed proteinuria of ≥1.0 gm per 24 hours (either 24-hour urine specimens or spot protein/creatinine ratios are acceptable) (C)
Combinations of the following, assuming the findings are confirmed in at least 2 tests done within a short period of time and in the absence of alternative causes: a. proteinuria ≥0.5 gm per 24 hours plus hematuria, defined as ≥5 RBCs per hpf b. proteinuria ≥0.5 gm per 24 hours plus cellular casts (C)


Adjunctive Treatments

The ACR recommends that all SLE patients with nephritis be treated with a background of hydroxychloroquine (HCQ). (C)
All LN patients with proteinuria ≥0.5 gm per 24 hours (or equivalent by protein/creatinine ratios on spot urine samples) should have blockade of the renin–angiotensin system, which drives intraglomerular pressure. (A)
(A for nondiabetic chronic renal disease)
The ACR recommends that careful attention be paid to control of hypertension, with a target of ≤130/80 mm Hg. (A)
(A for nondiabetic chronic renal disease)
The ACR also recommends that statin therapy be introduced in patients with low-density lipoprotein cholesterol >100 mg/dL. (C)
The ACR recommends that women of child-bearing potential with active or prior LN receive counseling regarding pregnancy risks conferred by the disease and its treatments. (C)

Recommendations for Induction of Improvement in Patients With ISN Class III/IV Lupus Glomerulonephritis

The ACR recommends mycophenolate mofetil (MMF) (2–3 gm total daily orally) or intravenous (IV) cyclophosphamide (CYC) along with glucocorticoids. (A)
Asians, as compared to non-Asians, might require lower doses of MMF (maximum dose 2g/day) for similar efficacy. (C)
The ACR recommends that MMF and MPA are likely to be equivalent in inducing improvement of LN, with 1,440–2,160 mg total daily dose of mycophenolic acid (MPA) roughly equivalent to 2,000–3,000 mg total daily dose of MMF. ()
1. low-dose “Euro-Lupus” CYC (500 mg IV once every 2 weeks for a total of 6 doses), followed by maintenance therapy with daily oral azathioprine (AZA) or daily oral MMF, and (B)
2. high-dose CYC (500–1,000 mg/m2 IV once a month for 6 doses), followed by maintenance treatment with MMF or AZA (A)
If CYC is being considered for treatment, the ACR recommends IVCYC at the low “Euro-Lupus” dose for white patients with Western European or Southern European racial/ethnic backgrounds. (B)
Pulse IV glucocorticoids (500–1,000 mg methylprednisolone daily for 3 doses) in combination with immunosuppressive therapy is recommended by the ACR, followed by daily oral glucocorticoids (0.5–1 mg/kg/day), followed by a taper to the minimal amount necessary to control disease. (C)
The ACR recommends that most patients be followed for 6 months after initiation of induction treatment with either CYC or MMF before making major changes in treatment other than alteration of glucocorticoid doses, unless there is clear evidence of worsening at 3 months (50% or more worsening of proteinuria or serum creatinine). (A)
The ACR recommends that MMF was preferable to CYC for patients who express a major concern with fertility preservation, since high-dose CYC can cause permanent infertility in both women and men. (A)
(A evidence of gonadal toxicity)

Recommendations for Induction of Improvement in Patients With Class IV Or IV/V Plus Cellular Crescents

The ACR recommends either CYC or MMF for induction of improvement in this type of LN (C), along with IV pulses of high-dose glucocorticoid and initiation of oral glucocorticoids at the higher-range dosage, 1 mg/kg/day orally. (Figure 1) (C)

Recommendations for Induction of Improvement in Patients With Class V “Pure Membranous” LN

The ACR recommends that patients with pure class V LN and with nephrotic range proteinuria be started on prednisone (0.5 mg/kg/day) plus MMF 2–3 gm total daily dose. (Figure 3) (A)

Recommendations for Maintaining Improvement in Patients Who Respond to Induction Therapy

The ACR recommends that either AZA or MMF be used for maintenance therapy. (Figure 1) (A)

Recommendations for Changing Therapies in Patients Who Do Not Respond Adequately to Induction Therapy

In patients who fail to respond after 6 months of treatment (based on the treating physician’s clinical impression) with glucocorticoids plus MMF or CYC, the ACR recommends a switch of the immunosuppressive agent from either CYC to MMF, or from MMF to CYC, with these changes accompanied by IV pulses of glucocorticoids for 3 days. (Figure 1) (C)
The ACR also voted that in some cases rituximab can be used in patients whose nephritis fails to improve or worsens after 6 months of one induction therapy, or after the patient has failed both CYC and MMF treatments. (C)
If nephritis is worsening in patients treated for 3 months with glucocorticoids plus CYC or MMF, the ACR recommends that the clinician can choose any of the alternative treatments discussed. (C)
The ACR recommends that thrombotic microangiopathy be treated primarily with plasma exchange therapy. (C)

Treatment of LN in Patients Who Are Pregnant

In patients with prior LN but no current evidence of systemic or renal disease activity, no nephritis medications are necessary. (C)
Patients with mild systemic activity may be treated with HCQ; this probably reduces activity of SLE during pregnancy. (C)
If clinically active nephritis is present, or there is substantial extrarenal disease activity, the clinician may prescribe glucocorticoids at doses necessary to control disease activity, and if necessary AZA can be added. (C)
For patients with a persistently active nephritis with documented or suspected class III or IV with crescents, consideration of delivery after 28 weeks for a viable fetus is recommended. ()

Monitoring Activity of LN

Recommendations for monitoring LN are shown in Table 3. (C)

Table 3. Recommended Monitoring of Lupus Nephritis (monthly intervals)a

Having trouble viewing table?
Blood pressure Urinalysis Protein/ creatinine ratio Serum creatinine C3/C4 Anti-DNA
Active nephritis at onset of treatment 1 1 1 1 2b 3
Previous active nephritis, none currently 3 3 3 3 3 6
Pregnant with active GN at onset of treatment 1 1 1 1 1 1
Pregnant with previous nephritis, none currently 1 1 3 3 3 3
No prior or current nephritis 3 6 6 6 6 6

a Values are the monthly intervals suggested as the minimum frequency at which the indicated laboratory tests should be measured in the systemic lupus erythematosus scenarios shown in the left-hand column.

b Opinion of authors based on Dall’Era M et al, Arthritis Care Res (Hoboken) 2010:63:351-7, published after the Task Force Panel had voted.

Recommendation Grading



Screening, Treatment, and Management of Lupus Nephritis

Authoring Organization

Publication Month/Year

May 3, 2012

Last Updated Month/Year

April 11, 2024

Supplemental Implementation Tools

Document Type


External Publication Status


Country of Publication


Target Patient Population

Adults, particularly to those receiving care in the US

Target Provider Population

Rheumatologists, nephrologists, and pathologists

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings


Intended Users

Nurse, nurse practitioner, physician, physician assistant


Assessment and screening, Treatment, Management

Diseases/Conditions (MeSH)

D008181 - Lupus Nephritis


lupus, lupus nephritis

Source Citation

Hahn, B.H., McMahon, M.A., Wilkinson, A., Wallace, W.D., Daikh, D.I., FitzGerald, J.D., Karpouzas, G.A., Merrill, J.T., Wallace, D.J., Yazdany, J., Ramsey‐Goldman, R., Singh, K., Khalighi, M., Choi, S.‐I., Gogia, M., Kafaja, S., Kamgar, M., Lau, C., Martin, W.J., Parikh, S., Peng, J., Rastogi, A., Chen, W. and Grossman, J.M. (2012), American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res, 64: 797-808. doi:10.1002/acr.21664

Supplemental Methodology Resources

Evidence Tables, Data Supplement, Data Supplement