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lupus nephritis

Classification: of renal disease 1) class 1: normal 2) class 2: a) mild mesangial change b) no clinical findings of renal disease in 50% of patients c) mild proteinuria d) microscopic hematuria 3) class 3: a) focal & segmental proliferative glomerulonephritis b) 20% nephritic with or without nephrotic syndrome - < 50% of glomeruli involved [2] c) hypertension may be present d) progresses to class 4 in 20% of patients 4) class 4: a) diffuse proliferative glomerulonephritis b) 70% nephritic with or without nephrotic syndrome - > 50% of glomeruli involved [2] c) necrotizing lesions with large amounts of subendothelial deposits d) active SLE serology e) active urine sediment f) treatable with glucocorticoids with or without cytotoxic agents 5) class 5: a) membranous glomerulonephritis b) nephrotic syndrome without active sediment c) usually not treatable with immunosupressive agents 6) class 6 a) advanced sclerosing glomerulonephritis b) > 90% glomerulosclerosis c) no treatment prevents renal failure Etiology: 1) systemic lupus erythematosus (SLE) 2) drug induced lupus seldom involves the kidney 3) common in women with active SLE during pregnancy [14] Epidemiology: 1) 50% of lupus patients present with renal disease 2) 90% of lupus patients have renal disease at some time during their disease 3) poor outcomes in African Americans & Hispanics compared to Caucasians [4] Pathology: 1) acute & chronic tubulointerstitial nephritis 2) vasculitis 3) chronic changes (not responsive to therapy) a) glomerular scarring b) tubular atrophy c) interstitial fibrosis 4) thrombotic microangiopathy (hypercoagulable states due to antiphospholipid antibodies & anticardiolipin antibodies) 5) renal vein thrombosis Clinical manifestations: - new onset hypertension or edema - often begins concurrently with or shortly after the onset of SLE - features of SLE generally present - polyarthritis, oral ulcers ... Laboratory: - anti-nuclear antibody in serum present - dsDNA antibodies in serum present with high titer - CH50: hypocomplementemia - low complement C3 in serum & complement C4 in serum [2] - urinalysis: - proteinuria (> 500 mg/24 hours) - hematuria - erythrocyte casts, granular casts - laboratory features of SLE may be present Special laboratory: - renal biopsy for suspected lupus nephritis - required for diagnosis [2] - defines histologic subtype, degree of disease activity & chronicity for treatment planning [2] - begin high dose glucocorticoid prior to biopsy Management: 1) ACE inhibitor or ARB for class 1 or 2 lupus nephritis [2] 2) therapy for proliferative glomerulonephritis (class 3 or 4) a) high-dose glucocorticoids for 6-8 weeks b) cyclophosphamide 1] 0.5-1.0 g/m2 IV every 4-6 weeks 2] may be given in combination with azathioprine 3] 6 monthly doses may be most effective regimen [2] 4] continue every 3 months for up to 2 years [2] c) mycophenolate may be better than cyclophosphamide or azathioprine for induction & for maintenance of remission [2,5] (up to 48 months) d) combination prednisone/mycophenolate recommended for flare of lupus nephritis (class IV) [2] 3) class 5 membranous lupus nephritis - glucocorticoids + cyclophosphamide similar to class 4 - cyclosporine, tacrolimus* or mycophenolate less toxic than cyclophosphamide [2] 4) supportive therapy for membranous glomerulonephritis 5) anticoagulation for thrombotic events 6) hydroxychloroquine for all patients with lupus nephritis, unless contraindicated [3]; not mentioned in [2] (MKSAP) 7) lupus 'burns out' with end-stage renal disease & generally does not recur in renal transplant recipients 7) renal transplantation lowers ESRD-associated mortality ~50% [13] * or other calcineurin inhibitor

Related

nephrotic syndrome

General

glomerulonephritis (GN, nephritic syndrome) systemic lupus erythematosus

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 609-610
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  3. Hahn BH et al American College of Rheumatology Guidelines for Screening, Treatment, and Management of Lupus Nephritis Arthritis Care & Research 2012, 64(6):797-808 PMID: 22556106 http://onlinelibrary.wiley.com/doi/10.1002/acr.21664/abstract (corresponding NGC guideline withdrawn Dec 2017)
  4. Contreras G, Lenz O, Pardo V, Borja E et al Outcomes in African Americans and Hispanics with lupus nephritis. Kidney Int. 2006 May;69(10):1846-51 PMID: 16598205
  5. Dooley MA, Jayne D, Ginzler EM et al Mycophenolate versus azathioprine as maintenance therapy for lupus nephritis. N Engl J Med. 2011 Nov 17;365(20):1886-95. PMID: 22087680
  6. Seshan SV, Jennette JC. Renal disease in systemic lupus erythematosus with emphasis on classification of lupus glomerulonephritis: advances and implications. Arch Pathol Lab Med. 2009 Feb;133(2):233-48 PMID: 19195967
  7. Kamanamool N, McEvoy M, Attia J et al Efficacy and adverse events of mycophenolate mofetil versus cyclophosphamide for induction therapy of lupus nephritis: systematic review and meta-analysis. Medicine (Baltimore). 2010 Jul;89(4):227-35. PMID: 20616662
  8. Lee SJ, Silverman E, Bargman JM. The role of antimalarial agents in the treatment of SLE and lupus nephritis. Nat Rev Nephrol. 2011 Oct 18;7(12):718-29. PMID: 22009248
  9. Appel GB, Contreras G, Dooley MA et al Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis. J Am Soc Nephrol. 2009 May;20(5):1103-12. PMID: 19369404 Free PMC Article
  10. Weening JJ, D'Agati VD, Schwartz MM et al The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004 Feb;65(2):521-30. Review. PMID: 14717922 Free Article
  11. Bertsias GK, Tektonidou M, Amoura Z et al Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012 Nov;71(11):1771-82. PMID: 22851469 Free PMC Article
  12. Almaani S, Meara A, Rovin BH. Update on Lupus Nephritis. Clin J Am Soc Nephrol. 2017 May 8;12(5):825-835. Review. PMID: 27821390 Free PMC Article
  13. Jorge A, Wallace ZS, Lu N, Zhang Y, Choi HK. Renal transplantation and survival among patients with lupus nephritis: A cohort study. Ann Intern Med 2019 Jan 22; PMID: 30665236 - Goyal N, Weiner DE, Levey AS. Kidney transplantation in lupus nephritis: Can we do even better? Ann Intern Med 2019 Jan 22; PMID: 30665233
  14. NEJM Knowledge+ Nephrology/Urology
  15. Lupus Nephritis http://kidney.niddk.nih.gov/kudiseases/pubs/lupusnephritis/index.htm