Get Into the Loop - Learn About Lupus
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The document discusses lupus, an autoimmune disease that commonly affects the kidneys and can lead to end-stage renal disease requiring dialysis or transplantation. Kidney involvement from lupus nephritis is a major cause of illness and death, and the document outlines risk factors for progression to end-stage renal disease as well as treatment options and outcomes for lupus patients with kidney failure.
Get Into the Loop - Learn About Lupus
- 1. Get Into the Loop – Learn About Lupus Julie Schwartzman-Morris, MD October 15, 2012
- 2. Agenda Introduction to Lupus Lupus and Your Kidneys Lupus and Pregnancy More about Lupus and the Kidney: Dr. Ansari Question & Answer Session
- 3. Major Concepts SLE is a systemic autoimmune disease Most often affects young women of reproductive age Nearly any and all organ systems can be involved Kidney involvement is common and dangerous Source of major morbidity and mortality
- 4. Major Concepts Treatments for SLE are non-specific Often include high dose steroids and immune suppressive medications Both the disease and treatments can be difficult to manage and potentially toxic to patients SLE can affect physical and mental well being
- 5. What is Lupus? Autoimmune disease: Excessive immune system activation Loss of tolerance of immune system to one’s body Certain genes are more likely to occur in patients with lupus Many of these genes encode components of the immune system. Abnormal estrogen metabolism In animal studies estrogen worsens disease activity and causes early mortality
- 6. Who Gets Lupus? Female:Male ratio of 9:1 during childbearing years Closer to 2:1 during childhood and after menopause, suggesting hormonal influence Disease in males is can be more severe 70% of SLE: females between ages 15-45 10% present age >60
- 7. Who Gets Lupus? Highest occurrence is in Afro-Caribbean females 1:250 African American to Caucasian ratio 3:1 Child of SLE mother - risk of SLE 1:15 (7%) 10-15% of SLE patients have 1st degree relative with SLE
- 8. Mortality Renal disease causes worse prognosis African Americans have more aggressive and treatment resistant disease 2 different causes of death: Early: disease activity and infections Late: cardiovascular disease, disease activity, end stage renal disease, and thromboembolic
- 9. Criteria for the Diagnosis of SLE Malar (Butterfly) Rash Lupus kidney disease Discoid Rash Neurologic Disorders: Stroke, inflammation, Sensitivity rash to the depression, memory sun (Photosensitivity) dysfunction, etc… Ulcers in the nose and Anemia, low platelets mouth and low white blood cell Arthritis count Fluid around the heart, Abnormal blood antibody lungs and in the levels abdomen ANA blood test
- 10. Malar (Butterfly) Rash Fixed red, flat or raised, over the bridge of the nose and cheeks Tends to spare the nasolabial folds
- 11. Discoid Rash Red raised patches with scaling, skin follicle plugging Can be very scarring Singer Seal afflicted with discoid lupus at age 23
- 12. Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation
- 13. Oral and Nasal Ulcers Oral or nasopharyngeal ulcers, usually painless
- 14. Hair Thinning
- 15. Arthritis Non-erosive arthritis involving 2 or more joints, characterized by pain, swelling, or fluid collections 80% of patients have it
- 16. Neuropsychiatric Lupus Seizures Depression Psychosis Cranial neuropathy Headache Peripheral neuropathy Coma Mononeuritis multiplex Dementia Stroke syndrome Aseptic meningitis Transverse myelitis Chorea Ataxia
- 17. Severe or Life Threatening Complications
- 18. Cardiac Disease in SLE Pericarditis Pericardial Effusion Myocarditis CHF, tachycardia, arrhythmias, chest pain, dyspnea 30% by ECHO - most clinically silent Valvular disease Libman Sacks endocarditis Hemodynamically significant valvular disease APLS associated - much more common
- 19. SLE=>Accelerated Atherosclerosis CAD risk is 10-times increased in SLE patients, 50-times increased in SLE pts 35-44 yrs old Increased frequency of traditional risks for CAD 53% of patients have traditional risks Altered lipid metabolism due to treatment with corticosteroid
- 20. NEPHRITIS: Indications for renal biopsy may include UA: Hematuria and proteinuria, abnormal cells; Renal dysfunction Rising dsDNA and Low levels of the complement factor C3 in patient with new or progressive abnl UA; Modifications in therapy: initiation, changes, or discontinuation.
- 21. Lupus Nephritis a) Persistent protein in the urine greater than 0.5 grams per day OR b) Cellular casts--may be red cell, hemoglobin, granular, tubular, or mixed
- 22. Lupus Nephritis (WHO Classification) I Normal glomeruli a) Nil by all techniques b) Normal by light but deposits on EM or IF II Mesangial nephritis III Focal glomerulonephritis IV Diffuse proliferative glomerulonephritis V Membranous nephritis VI Advanced sclerosing glomerulonephritis
- 23. US NIH Renal Pathology System for Lupus Renal Disease
- 24. Current Management of Lupus Glomerulonephritis Steroids Pulse solumedrol PO Prednisone Mycophenolate mofetil (Cellcept) Azathioprine (Imuran) Cyclophosphamide* Was for many years main therapy but side effects including hemorrhagic cystitis, bladder ca, and in particular fertility decline in SLE patients led to trials using MMF and Azathioprine Still often used when patients are acutely or severly ill, or if they have many other manifestations at time of presentation such as hemolytic anemia, serositis
- 25. Management of Lupus Glomerulonephritis Combination: pulse solumedrol + cytoxan Sequential: cytoxan then transition to Azathioprine vs MMF ACE inhibitors Disease progression may require dialysis or transplant
- 26. Treatment of SLE Preventative Active treatment Treatment Topical Steroids Sunscreen NSAIDs: At least SPF 30 Advil, Mobic, Naproxen Calcium, Vitamin D, Antimalarials: Folate supplements Plaquenil To help prevent SE from Steroids: other medications Prednisone, Medrol Influenza Vaccine Cytotoxics/Biologics: Pneumococcal Vaccine Cellcept, Cytoxan, Imuran, Benlysta
- 27. Side Effects to Lupus Medications Weight gain Hair loss, or new hair growth in unwanted places Damage to the bones: Osteoporosis and Osteonecrosis High blood pressure High cholesterol Low immune system and infections
- 28. Follow Up Visits How often depends on: Lupus activity, severity, response to treatment, type of treatment, need for monitoring of medication side effects At routine visits, blood and urine tests and should be checked Even in patients with previously normal values Patients with known kidney disease should also have urine checked every 8 weeks.
- 29. Renal disease: major morbidity and mortality Develops in approx 60% pts with SLE 5-22% Progress to ESRD requiring dialysis or transplant (Mojcik) Johns Hopkins Cohort: 15% developed ESRD after 10 yrs of disease (Stone) 10% in NIH experience and 20% pts in NYU/HJD experience progressed to ESRD despite IV Cytoxan (Belmont) Belmont, et al. NYU/HJD experience with IV cyclophosphamide treatment: efficacy in steroid unresponsive lupus nephritis. Lupus (1995) 4, 104-108. Mojcik, CF. End-stage Renal Disease and SLE. Amer Journ Med 1996 (101) 100-107. Stone, et al. End stage renal disease in lupus: Disease activity, dialysis, and the outcome of transplantation. Lupus (1998) 7: 654-659.
- 30. SLE and ESRD US Renal Data Systems 1995 Annual Report: Estimated 1.4% of all ESRD accounted for by SLE nephropathy (Mojcik) ESRD typically defined as GFR < 10% nl Other indications of unfavorable outcomes in LN: Doubling of Serum Cr Persistent nephrotic range proteinuria despite cytotoxic tx (Belmont) Belmont, et al. NYU/HJD experience with IV cyclophosphamide treatment: efficacy in steroid unresponsive lupus nephritis. Lupus (1995) 4, 104-108. Mojcik, CF. End-stage Renal Disease and SLE. Amer Journ Med 1996 (101) 100-107.
- 31. Which LN patients are more likely to progress to ESRD??? High chronicity scores: poor outcomes, lack of response to immunosuppression Pts with severe and active chronic histological changes at increased risk for renal insufficiency and failure
- 32. Risk factors for Progression to ESRD Black Males Presence of aPL Ab Increased Creatinine at time of Dx Anemia Frequent Nephritic Flares HTN Extensive, prolonged proteinuria Moroni, et al Renal replacement therapy in lupus nephritis, Journ Neph 2003; 16: 787-791 Abraham et al, Prognostic factors in DP LN, J Assoc phyisicians India, 1999: 47: 862-5
- 33. ESRD in SLE: Renal Replacement HD PD Renal Transplant
- 34. Initiation of Dialysis- Knowing when to change the plan Although SLE can cause RPGN (loss of renal function in < 3 mo), LN can progress to ESRD over years Risk-Benefit analysis of cumulative effects of treatment over yrs of attempting to save kidneys AVN Opportunistic Infections Risk of malignancy Obesity Inc Susceptibility to CAD Stone, JH. ESRD in lupus: Disease activity, dialysis, and the outcome of transplantation. Lupus (1998) 7: 654-659.
- 35. When to Initiate Dialysis Renal Bx demonstrating sclerotic glomeruli and high chronicity index may signal ESRD GFR < 10% Doubling of Serum Cr Persistent nephrotic range proteinuria despite cytotoxic tx Failure to respond to immunosuppressives Dialysis vs. Transplant? In SLE pts with numerous comorbidities or aPL Ab syndrome, HD or PD may be most appropriate choice of renal replacement 1994 NEJM: Waiting period for cadaveric allograft in USA> 2yrs, longer for AA Stone, JH. ESRD in lupus: Disease activity, dialysis, and the outcome of transplantation. Lupus (1998) 7: 654-659.
- 36. Survival of SLE pts on Dialysis 5 year survival rates approach 90% No substantial differences observed b/t HD and PD, though increase risk of peritonitis in PD Early studies showed greatest mortality in first 3 mo of dialysis– usually result of infections After first 3 mo, infection and CV disease are largest threats Stone, JH. ESRD in lupus: Disease activity, dialysis, and the outcome of transplantation. Lupus (1998) 7: 654-659. Coplon, et al. Hemodialysis in end-stage lupus nephritis. Trans Am Soc Artif Int Org (1973) 19: 302-304.
- 37. Should SLE pts on Dialysis continue to receive immunosuppressive therapy? Risk-benefit analysis of continued therapy after dialysis starts Infection risks Tx for flares usually same as in non-dialysis pts Alteri, et al. Immunosuppressive treatment in dialysis patients. Neph Dial Transpt. (2002) 17 [Suppl
- 38. Renal Transplantation Some pts with living related donors proceed successfully straight to transplant 3 months of dialysis done first in many cases to ensure that spontaneous renal recovery will not occur Barnes, et al. Renal transplantation in congenital and metabolic diseases. JAMA 1975: 232: 148-153.
- 39. Transplant Issues Most, but not all studies found overall survival rates at 5 and 10 years similar to non-SLE pts. Ward, et al used data from US Renal Data System to compare SLE and non-SLE transplant recipients adjusting for confounding factors: Recipient age, sex, race Donor age, sex, race Year of transplantation # of HLA mismatches # of Pre-op blood transfusions Cadaveric transplants Length of cold ischemia time
- 40. Specific risk factors for Transplanted pts with SLE Nephritis Disease activity and recurrent nephritis Antiphospholipid ab Syndrome Atherosclerosis
- 41. Recurrent Nephritis Reported incidence is 1-3%- comparable to non-SLE May be underestimated because of absence of routine biopsies or insufficient follow up period Stone, et al. Frequency of recurrent LN among 97 renal transplant pts during the cyclosporine era. Arth Rheum: 1998 Apr; 41 (4): 678-86
- 42. Thrombotic Complications After transplant, renal artery or renal vein thrombosis has been reported in SLE pts Pts with APL-Ab and history of recurrent thrombosis should be treated with anticoagulation, during and after transplant Radhakrishan, et al. Renal transplant in anticardiolipin Ab+ SLE pts. Am J Kidney Ds 1994; 23: 286-289.
- 43. Atherosclerosis Accelerated atherosclerosis is observed in all renal transplant recipients, independent of primary renal disease Aggressive treatment of HTN and dyslipidemias is warrented in renal transplant recipients with SLE given their potential risk for CVD Reducing cardiovascular risk can only be accomplished by reducing the impact of these defined risk factors early after the onset of chronic kidney disease and effectively after renal transplantation
- 44. Conclusions: ESRD in SLE Histopathology can be used to prognosticate There are known risk factors for progression to ESRD The majority of studies support the tendency toward reduced clinical and serological activity following ESRD and an immune basis may be responsible Outcomes of SLE pts on dialysis not significantly different from non-SLE pts Renal Transplantation is a viable option for renal replacement SLE pts
Editor's Notes
- #33: Abraham et al identified HTN and extensive, prolonged proteinuria as risk factors for dev of ESRD in 29 pts w/ DPGN (Abraham et al, Prognostic factors in DP LN, J Assoc phyisicians India, 1999: 47: 862-5
- #40: These factors comprise many of the main determinants of graft survival
- #42: Histo on recurrent bx: dpgn, fpgn, membranous, and mesangial 3 of pts w/ recurrence had serologic evidence of sle activity but only 1 had arthritis