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Julie Schwartzman-Morris, MD
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Get Into the Loop – Learn About Lupus
Julie Schwartzman-Morris, MD
October 15, 2012
Agenda
Introduction to Lupus
Lupus and Your Kidneys
Lupus and Pregnancy
More about Lupus and the Kidney: Dr. Ansari
Question & Answer Session
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
Major Concepts
Treatments for SLE are non-specificOften 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
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
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
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
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
Criteria for the Diagnosis of SLE
Malar (Butterfly) Rash
Discoid Rash
Sensitivity rash to the sun (Photosensitivity)
Ulcers in the nose and mouth
Arthritis
Fluid around the heart, lungs and in the abdomen
Lupus kidney disease
Neurologic Disorders:
Stroke, inflammation, depression, memory dysfunction, etc…
Anemia, low platelets and low white blood cell count
Abnormal blood antibody levels
ANA blood test
Malar (Butterfly) Rash
Fixed red, flat or raised, over the bridge of the nose and cheeks
Tends to spare the nasolabial folds
Discoid Rash
Red raised patches with scaling, skin follicle plugging
Can be very scarring
Singer Seal afflicted with discoid lupus at age 23
Photosensitivity
Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation
Oral and Nasal Ulcers
Oral or nasopharyngeal ulcers, usually painless
Hair Thinning
Arthritis
Non-erosive arthritis involving 2 or more joints, characterized by pain, swelling, or fluid collections
80% of patients have it
Neuropsychiatric Lupus
Seizures
Psychosis
Headache
Coma
Dementia
Aseptic meningitis
Chorea
Ataxia
Depression
Cranial neuropathy
Peripheral neuropathy
Mononeuritis multiplex
Stroke syndrome
Transverse myelitis
Severe or Life Threatening Complications
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
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
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.
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
Lupus Nephritis (WHO Classification)
I Normal glomerulia) Nil by all techniques
b) Normal by light but deposits on EM or IF
II Mesangial nephritisIII Focal glomerulonephritisIV Diffuse proliferative glomerulonephritisV Membranous nephritisVI Advanced sclerosing
glomerulonephritis
US NIH Renal Pathology System for Lupus Renal Disease
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
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
Treatment of SLE
Active treatment
Topical Steroids NSAIDs:
Advil, Mobic, Naproxen
Antimalarials: Plaquenil
Steroids: Prednisone, Medrol
Cytotoxics/Biologics: Cellcept, Cytoxan,
Imuran, Benlysta
Preventative Treatment
Sunscreen
At least SPF 30
Calcium, Vitamin D, Folate supplements
To help prevent SE from other medications
Influenza Vaccine
Pneumococcal Vaccine
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
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.
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.
SLE and ESRDUS 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.
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
Risk factors for Progression to ESRD
BlackMalesPresence of aPL AbIncreased Creatinine at time of DxAnemiaFrequent Nephritic FlaresHTNExtensive, 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
ESRD in SLE: Renal Replacement
HD
PD
Renal Transplant
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.
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.
Survival of SLE pts on Dialysis5 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.
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 8]: 2-9.
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.
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
Specific risk factors for Transplanted pts with SLE Nephritis
Disease activity and recurrent nephritis
Antiphospholipid ab Syndrome
Atherosclerosis
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
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.
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
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