Lupus Nephritis Guidelines

Updated: Feb 25, 2021
  • Author: Lawrence H Brent, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Guidelines Summary

Guidelines for managing lupus nephritis have been issued by the American College of Rheumatology. [81]  Key points of the guidelines are as follows:

  • Patients with clinical evidence of active, previously untreated lupus nephritis should have a renal biopsy to classify the disease according to International Society of Nephrology/Renal Pathology Society criteria

  • All patients with lupus nephritis should receive background therapy with hydroxychloroquine, unless contraindicated; this recommendation was based on a prospective controlled trial showing lower flare rates in those who continued hydroxychloroquine, compared with those who switched to placebo [82]

  • Glucocorticoids plus either cyclophosphamide intravenously (IV) or mycophenolate mofetil orally for induction in patients with ISN class III and IV disease; patients with ISN/RPS class I and II nephritis do not require immunosuppressive therapy

  • Administer ACEIs or ARBs if proteinuria is 0.5 g/24 h or more

  • Maintain blood pressure at or below 130/80 mm Hg

In 2019, the joint guidelines for the management of adult and pediatric lupus nephritis were updated by the European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA). The EULAR/ERA-EDTA revised recommendations include the following [64] :

  • Goals of treatment include patient survival, long-term preservation of kidney function, prevention of disease flares, prevention of organ damage, management of comorbidities and improvement in disease-related quality of life
  • Kidney biopsy should be considered when there is evidence of kidney involvement, especially in the presence of persistent proteinuria ≥ 0.5 g/24 hours (or UPCR ≥ 500mg/g in morning first void urine), and/or an unexplained decrease in glomerular filtration rate (GFR)
  • Initial treatment for class III–IV disease: Mycophenolate mofetil or or low-dose IV cyclophosphamide plus glucocorticoids 
  • Alternate option for class III–IV disease: Combination therapy of mycophenolate mofetil with a calcineurin inhibitor, especially tacrolimus, particularly in patients with nephrotic-range proteinuria
  • To reduce cumulative glucocorticoid dose: Intravenous pulses methylprednisolone (total dose 500–2500 mg, depending on disease severity), followed by oral prednisone (0.3–0.5 mg/kg/day) for up to 4 weeks, tapered to ≤7.5 mg/day by 3 to 6 months
  • Initial treatment for pure class V disease with nephrotic-range proteinuria: Mycophenolate mofetil in combination with methylprednisolone followed by oral prednisone 
  • Alternate options for pure class V:  IV cyclophosphamide or calcineurin inhibitors, especially tacrolimus, as monotherapy or in combination with mycophenolate mofetil/mycophenolic acid
  • In all LN patients: Hydroxychloroquine (HCQ) should be coadministered at a dose not to exceed 5 mg/kg/day and adjusted for the GFR, in the absence of contraindications
  • Patients who improve after initial treatment should receive mycophenolate mofetil/mycophenolic acid (especially if it was the initial treatment) or azathioprine (preferred in women who may become pregnant) in combination with low-dose prednisone when needed to control disease activity
  • Gradual withdrawal of treatment (glucocorticoids first, then immunosuppressive drugs) can be attempted after at least 3 to 5 years therapy in patients with complete clinical response. HCQ should be continued long-term.
  • Continuation, switching to or addition of calcineurin inhibitors, especially tacrolimus, can be considered in pure class V nephritis at the lowest effective dose and after considering nephrotoxicity risks
  • Patients in whom initial therapy fails should be switched to one of the alternative initial therapies or to rituximab

A European initiative, the Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) project, has published guidelines on the diagnosis and treatment of childhood-onset lupus nephritis. [83, 84]

Diagnostic recommendations from SHARE include the following [84] :

  • Although pediatric patients with lupus nephritis may present with renal dysfunction, hypertension, and macro- or microscopic hematuria and proteinuria, percutaneous renal biopsy is required because symptoms alone do not reflect disease severity
  • For patients with proteinuria and/or a low glomerular filtration rate, consult with a pediatric nephrologist to discuss the need for biopsy
  • Consult with an experienced renal pathologist to evaluate renal biopsies
  • Exclude orthostatic proteinuria, which is the leading cause of proteinuria in teenagers, by collecting a first-morning urine sample; in girls, avoid collecting samples during menstruation

SHARE recommends complete renal response as the treatment goal in lupus nephritis, with an early-morning urinary protein/creatinine ratio of less than 50 mg/mmol and normal renal function. Patients should achieve a partial response within 6 to 12 months after starting treatment. [84]  Treatment recommendations include the following:

  • Immunosuppressive treatment should be guided by renal biopsy results; when biopsy is not possible, patients with nephrotic syndrome, hypertension, and impaired renal function should be treated as for lupus nephritis class IV.
  • In patients with proteinuria, consider adding angiotensin-converting enzyme inhibitors or angiotensin receptor blockers.

Recommendations for management based on the International Society of Nephrology/Renal Pathology Society 2003 classification system include the following [84] :

  • Class I: Treatment should be guided by symptoms
  • Class II: Low-dose prednisone, followed by a disease-modifying antirheumatic drug in patients who have 3 months of persistent proteinuria or develop prednisone dependency.
  • Class III/IV: Induction with mycophenolate mofetil (MMF) or intravenous cyclophosphamide plus steroids; maintenance treatment for at least 3 years with MMF, azathioprine, or both
  • Class V: MMF with low-dose prednisone for induction; maintenance treatment with MMF