Get Into the Loop - Learn About Lupus

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


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


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

Get Into the Loop - Learn About Lupus

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