Table 2

Category of evidence and strength of statements*

Statement/itemLevel of evidenceStrength 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)2C
 Clinical, serological or laboratory tests correlate modestly with renal biopsy findings2B
2. Pathological assessment of kidney biopsy
 International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system preferred2C
 Prognostic value of glomerular changes1A
 Prognostic value of activity and chronicity indices1A
 Prognostic value of tubulointerstitial lesions2B
 Prognostic value of vascular lesions associated with anti-phospholipid antibodies3C
3. Indications for immunosuppressive treatment and treatment strategy
 Diagnostic renal biopsy requiredC
 Immunosuppression for class IIIA or IIIA/C (±V) and IVA or IVA/C (±V) nephritis1A
 Immunosuppression for class V nephritis if proteinuria >1 g/24 h4C
 Target: preservation of renal function, prevention of disease flares, avoidance of treatment-related harms and improved quality of life and survivalC
 Prognostic value of complete renal response (UPCR <50 mg/mmol and normal or near-normal GFR)1B
 Prognostic value of partial renal response (≥50% reduction in proteinuria and normal or near-normal GFR)1B
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)1A†
  Low-dose intravenous cyclophosphamide (CY)1B
 If adverse clinical/histological prognostic factors are present: glucocorticoids plus
  Low-dose intravenous CY4C
  High-dose intravenous CY1A
  Oral CY3B
 Use of glucocorticoids
  Three consecutive pulses of intravenous methylprednisolone 500–750 mg3C
  Then, oral prednisolone 0.5 mg/kg/day for 4 weeks with subsequent taperingC
 Pure class V nephritis with nephrotic-range proteinuria: glucocorticoids plus
  High-dose intravenous CY2A
  Ciclosporin (increased rates of relapse of nephrotic syndrome)2A
 Azathioprine (AZA) use in LN
  In selected patients without adverse clinical or histological prognostic factors
   Class III–IV nephritis2B
   Class V nephritis (non-nephrotic-range proteinuria)4C
  When MPA or CY are contraindicated, not tolerated, or unavailableC
  Associated with higher relapse risk2B
 Subsequent immunosuppression in class III–IV or V nephritis
  MPA or AZA, in combination with low-dose glucocorticoids1A
  Successful induction with MPA followed by continuing MPAC
  AZA preferred if pregnancy plannedC
  Duration of immunosuppressive treatment: at least 3 years3C
  Gradual drug withdrawal, glucocorticoids first, can then be attemptedC
  Calcineurin inhibitors can be considered in pure class V nephritis4C
Failure to treatment with MPA or CY
  Switch from MPA to CY4C
  Switch from CY to MPA4C
  Add or switch to rituximab4C
5. Adjunct treatment
 Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for proteinuria or hypertension2B
 Cholesterol lowering with statins for persistent dyslipidaemiaC
 Acetyl-salicylic acid in patients with anti-phospholipid antibodiesC
 Calcium and vitamin D supplementationC
 Immunisations with non-live vaccinesC
 Anticoagulant treatment in nephrotic syndrome with serum albumin <20 g/litreC
Monitoring and prognosis of LN
 Serum creatinine and GFR, proteinuria, and urinary microscopy to define activityC
 Body weight and blood pressure measurement to assess activity and response to treatmentC
 Diagnostic utility of
  Serum C32B
  Serum C42B
  Serum anti-dsDNA2B
  Complete blood cell count3C
  Serum albumin3C
 Prognostic value of
  Anti-phospholipid antibodies2B
  Serum lipids2B
 Prognostic value of serial changes in
  Serum creatinine/GFR1A
  Blood pressure1A
 Frequency of monitoring
  Every 2–4 weeks for the first 2–4 months after diagnosis or flareC
  Lifelong at least 3–6 monthlyC
 Repeat renal biopsy
  Useful in worsening or refractory disease or at relapse3C
  Strong prognostic value of renal biopsy findings2B
7. End-stage renal disease (ESRD) in systemic lupus erythematosus (SLE)
 All methods of renal replacement treatment are safe2B
 Increased risk for infections in patients on peritoneal dialysis2B
 Increased risk for vascular access thrombosis with anti-phospholipid antibodies3C
  Better outcome when lupus activity is absent or at a low level for 3–6 months3C
  Better outcome with living versus cadaveric donor2B
  Better outcome with pre-emptive transplantation3C
  Increased risk for vascular events in patients with anti-phospholipid antibodies2B
8. Treatment of anti-phospholipid syndrome (APS)-associated nephropathy (APSN)
 Antiplatelet/anticoagulation treatmentC
9. LN and pregnancy
 Safe in inactive SLE with UPCR <50 mg/mmol for the preceding 6 months2B
  GFR preferably above 50 ml/minC
 Safety and efficacy of the following medications
  Low-dose prednisone4C
  Calcineurin inhibitors4C
 Intensity of treatment should not be reduced in anticipation of pregnancyC
 Acetylsalicylic acid to reduce the risk of pre-eclampsia3C
 Assessment every 4 weeks, preferably by a specialist physician and obstetricianC
 Flare of nephritis can be treated with same acceptable medications but also with calcineurin inhibitors, intravenous immunoglobulin, immunoadsorption and plasma exchangeC
10. Paediatric LN
 More common at presentation compared to adult-onset SLE1A
 More severe with increased damage accrual compared to adult-onset disease2B
 Similar monitoring with adults3C
 Similar treatment with adults3C
 Importance of coordinated transition programme to adult specialistsC
  • *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.