Julie Schwartzman-Morris, MD

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