Category of evidence and strength of statements*
| Statement/item | Level of evidence | Strength of statement |
|---|---|---|
| 1. Indications for first renal biopsy | ||
| Diagnostic value of urinary findings (proteinuria ≥0.5 g/24 h especially with glomerular haematuria and/or cellular casts) | 2 | C |
| Clinical, serological or laboratory tests correlate modestly with renal biopsy findings | 2 | B |
| 2. Pathological assessment of kidney biopsy | ||
| International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system preferred | 2 | C |
| Prognostic value of glomerular changes | 1 | A |
| Prognostic value of activity and chronicity indices | 1 | A |
| Prognostic value of tubulointerstitial lesions | 2 | B |
| Prognostic value of vascular lesions associated with anti-phospholipid antibodies | 3 | C |
| 3. Indications for immunosuppressive treatment and treatment strategy | ||
| Diagnostic renal biopsy required | – | C |
| Immunosuppression for class IIIA or IIIA/C (±V) and IVA or IVA/C (±V) nephritis | 1 | A |
| Immunosuppression for class V nephritis if proteinuria >1 g/24 h | 4 | C |
| Target: preservation of renal function, prevention of disease flares, avoidance of treatment-related harms and improved quality of life and survival | – | C |
| Prognostic value of complete renal response (UPCR <50 mg/mmol and normal or near-normal GFR) | 1 | B |
| Prognostic value of partial renal response (≥50% reduction in proteinuria and normal or near-normal GFR) | 1 | B |
| 4. Treatment of adult lupus nephritis (LN) | ||
| Class IIIA or A/C (±V) and class IVA or A/C (±V): glucocorticoids plus | ||
| Mycophenolic acid (MPA) | 1 | A† |
| Low-dose intravenous cyclophosphamide (CY) | 1 | B |
| If adverse clinical/histological prognostic factors are present: glucocorticoids plus | ||
| MPA | 2 | B |
| Low-dose intravenous CY | 4 | C |
| High-dose intravenous CY | 1 | A |
| Oral CY | 3 | B |
| Use of glucocorticoids | ||
| Three consecutive pulses of intravenous methylprednisolone 500–750 mg | 3 | C |
| Then, oral prednisolone 0.5 mg/kg/day for 4 weeks with subsequent tapering | – | C |
| Pure class V nephritis with nephrotic-range proteinuria: glucocorticoids plus | ||
| MPA | 2 | B |
| High-dose intravenous CY | 2 | A |
| Ciclosporin (increased rates of relapse of nephrotic syndrome) | 2 | A |
| Tacrolimus | 3 | B |
| Rituximab | 4 | C |
| Azathioprine (AZA) use in LN | ||
| In selected patients without adverse clinical or histological prognostic factors | ||
| Class III–IV nephritis | 2 | B |
| Class V nephritis (non-nephrotic-range proteinuria) | 4 | C |
| When MPA or CY are contraindicated, not tolerated, or unavailable | – | C |
| Associated with higher relapse risk | 2 | B |
| Subsequent immunosuppression in class III–IV or V nephritis | ||
| MPA or AZA, in combination with low-dose glucocorticoids | 1 | A |
| Successful induction with MPA followed by continuing MPA | – | C |
| AZA preferred if pregnancy planned | – | C |
| Duration of immunosuppressive treatment: at least 3 years | 3 | C |
| Gradual drug withdrawal, glucocorticoids first, can then be attempted | – | C |
| Calcineurin inhibitors can be considered in pure class V nephritis | 4 | C |
| Failure to treatment with MPA or CY | ||
| Switch from MPA to CY | 4 | C |
| Switch from CY to MPA | 4 | C |
| Add or switch to rituximab | 4 | C |
| 5. Adjunct treatment | ||
| Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for proteinuria or hypertension | 2 | B |
| Cholesterol lowering with statins for persistent dyslipidaemia | – | C |
| Hydroxychloroquine | 3 | C |
| Acetyl-salicylic acid in patients with anti-phospholipid antibodies | – | C |
| Calcium and vitamin D supplementation | – | C |
| Immunisations with non-live vaccines | – | C |
| Anticoagulant treatment in nephrotic syndrome with serum albumin <20 g/litre | – | C |
| Monitoring and prognosis of LN | ||
| Serum creatinine and GFR, proteinuria, and urinary microscopy to define activity | – | C |
| Body weight and blood pressure measurement to assess activity and response to treatment | – | C |
| Diagnostic utility of | ||
| Serum C3 | 2 | B |
| Serum C4 | 2 | B |
| Serum anti-dsDNA | 2 | B |
| Complete blood cell count | 3 | C |
| Serum albumin | 3 | C |
| Prognostic value of | ||
| Anti-phospholipid antibodies | 2 | B |
| Serum lipids | 2 | B |
| Prognostic value of serial changes in | ||
| Serum creatinine/GFR | 1 | A |
| Proteinuria | 1 | A |
| Haemoglobin | 2 | B |
| Blood pressure | 1 | A |
| Frequency of monitoring | ||
| Every 2–4 weeks for the first 2–4 months after diagnosis or flare | – | C |
| Lifelong at least 3–6 monthly | – | C |
| Repeat renal biopsy | ||
| Useful in worsening or refractory disease or at relapse | 3 | C |
| Strong prognostic value of renal biopsy findings | 2 | B |
| 7. End-stage renal disease (ESRD) in systemic lupus erythematosus (SLE) | ||
| All methods of renal replacement treatment are safe | 2 | B |
| Increased risk for infections in patients on peritoneal dialysis | 2 | B |
| Increased risk for vascular access thrombosis with anti-phospholipid antibodies | 3 | C |
| Transplantation. | ||
| Better outcome when lupus activity is absent or at a low level for 3–6 months | 3 | C |
| Better outcome with living versus cadaveric donor | 2 | B |
| Better outcome with pre-emptive transplantation | 3 | C |
| Increased risk for vascular events in patients with anti-phospholipid antibodies | 2 | B |
| 8. Treatment of anti-phospholipid syndrome (APS)-associated nephropathy (APSN) | ||
| Hydroxychloroquine | – | C |
| Antiplatelet/anticoagulation treatment | – | C |
| 9. LN and pregnancy | ||
| Safe in inactive SLE with UPCR <50 mg/mmol for the preceding 6 months | 2 | B |
| GFR preferably above 50 ml/min | – | C |
| Safety and efficacy of the following medications | ||
| Hydroxychloroquine | 3 | B |
| Low-dose prednisone | 4 | C |
| Azathioprine | 4 | C |
| Calcineurin inhibitors | 4 | C |
| Intensity of treatment should not be reduced in anticipation of pregnancy | – | C |
| Acetylsalicylic acid to reduce the risk of pre-eclampsia | 3 | C |
| Assessment every 4 weeks, preferably by a specialist physician and obstetrician | – | C |
| Flare of nephritis can be treated with same acceptable medications but also with calcineurin inhibitors, intravenous immunoglobulin, immunoadsorption and plasma exchange | – | C |
| 10. Paediatric LN | ||
| More common at presentation compared to adult-onset SLE | 1 | A |
| More severe with increased damage accrual compared to adult-onset disease | 2 | B |
| Similar monitoring with adults | 3 | C |
| Similar treatment with adults | 3 | C |
| Importance of coordinated transition programme to adult specialists | – | C |
*Quality of evidence was graded 1–4 and the strength of statements was graded A–C (refer to web-only appendix table 1 for details).
†MPA refers to either mycophenolate mofetil (MMF) or enteric-coated MPA sodium at equivalent dose based on evidence for comparable efficacy of the two regimens. MMF has been used in most controlled trials in LN.
dsDNA, double-stranded DNA; GFR, glomerular filtration rate; UPCR, urine protein:creatinine ratio.