Recommendations for the management of patients with systemic lupus erythematosus (SLE) with renal involvement
| Statement | Mean (SD) | Median (IQR)* |
|---|---|---|
| 1. Indications for first renal biopsy in SLE | ||
| Any sign of renal involvement—in particular, urinary findings such as reproducible proteinuria ≥0.5 g/24 h especially with glomerular haematuria and/or cellular casts—should be an indication for renal biopsy. Renal biopsy is indispensable since in most cases, clinical, serological or laboratory tests cannot accurately predict renal biopsy findings. | 9.7 (0.5) | 10 (1) |
| 2. Pathological assessment of kidney biopsy | ||
| The use of the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system is recommended with assessment of active and chronic glomerular and tubulointerstitial changes, and of vascular lesions associated with anti-phospholipid antibodies/syndrome | 9.6 (0.7) | 10 (1) |
| 3. Indications and goals of immunosuppressive treatment in lupus nephritis (LN) | ||
| 3.1. Initiation of immunosuppressive treatment should be guided by a diagnostic renal biopsy. Immunosuppressive agents are recommended in class IIIA or IIIA/C (±V) and IVA or IVA/C (±V) nephritis, and also in pure class V nephritis if proteinuria exceeds 1 g/24 h despite the optimal use of renin-angiotensin-aldosterone system blockers | 9.4 (0.7) | 10 (1) |
| 3.2. The ultimate goals of treatment in LN are long-term preservation of renal function, prevention of disease flares, avoidance of treatment-related harms, and improved quality of life and survival. Treatment should aim for complete renal response with UPCR <50 mg/mol and normal or near-normal (within 10% of normal GFR if previously abnormal) renal function. Partial renal response, defined as ≥50% reduction in proteinuria to subnephrotic levels and normal or near-normal renal function, should be achieved preferably by 6 months but no later than 12 months following initiation of treatment | 9.6 (0.8) | 10 (1) |
| 4. Treatment of adult LN | ||
| Initial treatment | ||
| 4.1. For patients with class IIIA or IIIA/C (±V) and class IVA or IVA/C (±V) LN, mycophenolic acid (MPA) (mycophenolate mofetil (MMF) target dose: 3 g/day for 6 months, or MPA sodium at equivalent dose) or low-dose intravenous cyclophosphamide (CY) (total dose 3 g over 3 months) in combination with glucocorticoids, are recommended as initial treatment as they have the best efficacy/toxicity ratio | 9.3 (0.8) | 9 (1) |
| 4.2. In patients with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents and/or fibrinoid necrosis), similar regimens may be used but CY can also be prescribed monthly at higher doses (0.75–1 g/m2) for 6 months or orally (2–2.5 mg/kg/day) for 3 months | 8.8 (1.3) | 9 (2) |
| 4.3. To increase efficacy and reduce cumulative glucocorticoid doses, treatment regimens should be combined initially with three consecutive pulses of intravenous methylprednisolone 500–750 mg, followed by oral prednisone 0.5 mg/kg/day for 4 weeks, reducing to ≤10 mg/day by 4–6 months | 9.0 (1.1) | 9 (2) |
| 4.4. In pure class V nephritis with nephrotic-range proteinuria, MPA (MMF target dose 3 g/day for 6 months) in combination with oral prednisone (0.5 mg/kg/day) may be used as initial treatment based on better efficacy/toxicity ratio. CY or calcineurin inhibitors (ciclosporin, tacrolimus) or rituximab are recommended as alternative options or for non-responders. | 8.9 (1.2) | 9 (2) |
| 4.5. Azathioprine (AZA) (2 mg/kg/day) may be considered as an alternative to MPA or CY in selected patients without adverse prognostic factors (as defined in 4.2), or when these drugs are contraindicated, not tolerated or unavailable. Azathioprine use is associated with a higher flare risk. | 8.6 (1.3) | 9 (2) |
| Subsequent treatment | ||
| 4.6. In patients improving after initial treatment, subsequent immunosuppression is recommended with either MPA at lower doses (initial target MMF dose 2 g/day) or AZA (2 mg/kg/day) for at least 3 years, in combination with low dose prednisone (5–7.5 mg/day). Gradual drug withdrawal, glucocorticoids first, can then be attempted. | 9.4 (0.9) | 10 (1) |
| 4.7. Patients who responded to initial treatment with MPA should remain on MPA unless pregnancy is contemplated, in which case they should switch to AZA at least 3 months prior to conception | 9.4 (0.8) | 10 (1) |
| 4.8. Calcineurin inhibitors can be considered in pure class V nephritis | 9.1 (1.2) | 10 (2) |
| Refractory disease | ||
| 4.9. For patients who fail treatment with MPA or CY either because of lack of effect (as defined in 3.2) or due to adverse events, we recommend that the treatment is switched from MPA to CY, or CY to MPA, or rituximab be given | 9.2 (1.0) | 10 (1) |
| 5. Adjunct treatment in patients with LN | ||
| 5.1. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers are indicated for patients with proteinuria (UPCR >50 mg/mmol) or hypertension | 9.7 (0.8) | 10 (0) |
| 5.2. Cholesterol lowering with statins is indicated for persistent dyslipidaemia (target low-density lipoprotein (LDL)-cholesterol 2.58 mmol/litre (100 mg/dl)) | 9.2 (1.3) | 10 (1) |
| 5.3. Hydroxychloroquine is recommended to improve outcomes by reducing renal flares and limiting the accrual of renal and cardiovascular damage | 9.3 (1.7) | 10 (1) |
| 5.4. Acetyl-salicylic acid in patients with anti-phospholipid antibodies, calcium and vitamin D supplementation, and immunisations with non-live vaccines may reduce treatment or disease-related comorbidities and should be considered | 9.3 (1.3) | 10 (1) |
| 5.5. Consider anticoagulant treatment in nephrotic syndrome with serum albumin <20 g/litre, especially if persistent or in the presence of anti-phospholipid antibodies | 9.2 (1.1) | 10 (1) |
| 6. Monitoring and prognosis of LN | ||
| 6.1. Active LN should be regularly monitored by determining at each visit body weight, blood pressure, serum creatinine and eGFR, serum albumin, proteinuria, urinary sediment (microscopic evaluation), serum C3 and C4, serum anti-dsDNA antibody levels and complete blood cell count. Anti-phospholipid antibodies and lipid profile should be measured at baseline and monitored intermittently. | 9.3 (0.9) | 10 (1) |
| 6.2. Changes in serum creatinine (eGFR), proteinuria, haemoglobin levels and blood pressure are predictors of long-term outcome in LN | 9.2 (1.2) | 10 (1) |
| 6.3. Visits should be scheduled every 2–4 weeks for the first 2–4 months after diagnosis or flare, and then according to the response to treatment. Monitoring for renal and extra-renal disease activity should be lifelong at least every 3–6 months. | 9.1 (1.4) | 10 (1) |
| 6.4. Repeat renal biopsy may be used in selected cases, such as worsening or refractoriness to immunosuppressive or biological treatment (failure to decrease proteinuria by ≥50%, persistent proteinuria beyond 1 year and/or worsening of GFR), or at relapse, to demonstrate change or progression in histological class, change in biopsy chronicity and activity indices, to provide prognostic information, and detect other pathologies | 9.2 (1.4) | 10 (1) |
| 7. Management of end-stage renal disease (ESRD) in LN | ||
| 7.1. All methods of renal replacement treatment can be used in patients with lupus, but there may be increased risk of infections in patients on peritoneal dialysis still on immunosuppressive agents and vascular access thrombosis in patients with anti-phospholipid antibodies | 9.5 (0.8) | 10 (1) |
| 7.2. Transplantation should be performed when lupus activity has been absent, or at a low level, for at least 3– 6 months, with superior results obtained with living donor and pre-emptive transplantation. Anti-phospholipid antibodies should be sought during transplant preparation because they are associated with an increased risk of vascular events in the transplanted kidney. | 9.4 (0.9) | 10 (1) |
| 8. Anti-phospholipid syndrome-associated nephropathy in SLE | ||
| In patients with lupus and anti-phospholipid syndrome (APS)-associated nephropathy (APSN), hydroxychloroquine and/or antiplatelet/anticoagulant treatment should be considered | 9.0 (1.4) | 9 (2) |
| 9. LN and pregnancy | ||
| 9.1. Pregnancy may be planned in stable patients with inactive lupus and UPCR <50 mg/mmol, for the preceding 6 months, with GFR that should preferably be >50 ml/min. Acceptable medications include hydroxychloroquine, and where needed, low dose prednisone, azathioprine and/or calcineurin inhibitors. The intensity of treatment should not be reduced in anticipation of pregnancy. During pregnancy, acetylsalicylic acid should be considered to reduce the risk of pre-eclampsia. Patients should be assessed at least every 4 weeks, preferably by a specialist physician and obstetrician. | 9.3 (1.0) | 10 (1) |
| 9.2. Flare of LN during pregnancy can be treated with acceptable medications stated above depending on severity of flare | 9.0 (1.5) | 10 (2) |
| 10. Management of paediatric LN | ||
| Compared to adult-onset disease, LN in children is more severe with increased damage accrual and more common at presentation but the diagnosis, management and monitoring is similar to that of adults. A coordinated transition programme to adult specialists is important in assessing concordance to treatments and optimising long-term outcomes. | 9.6 (0.7) | 10 (1) |
*Numbers are mean (SD) and median (IQR) agreement level among experts. A score of 10 represents the highest level of agreement.
GFR, glomerular filtration rate; UPCR, urine protein:creatinine ratio.