The document discusses guidelines for diagnosing and treating systemic lupus erythematosus (SLE) and lupus nephritis. It provides details on classifying lupus nephritis based on the ISN/RPS system and describes the patient's biopsy results of class IV diffuse lupus nephritis with active and chronic features. Treatment guidelines and monitoring of SLE and lupus nephritis are also reviewed.

1. DEPARTMENT OF INTERNAL
MEDICINE
GRANDROUNDS
August 2, 2017

3. OBJECTIVES
• By the end of this presentation, we will be able to:
1. Know the approach on how to diagnose SLE
2. Know the 1997 ACR and 2012 SLICC Classification
of SLE
3. Understand the role of Kidney Biopsy
a. Indications/Contraindications
b. Standard Algorithm for Biopsy
c. Risks and Possible Complications
4. Familiar with ISN/RPS (2003)Classification of Lupus
Nephritis
5. Discuss Lupus Nephritis Activity Index/Chronicity
Index

4. OBJECTIVES
• By the end of this presentation, we will be able to:
6. Know the guidelines for the evaluation
and treatment of Lupus Nephritis
7. Treatment for specific Biopsy patterns
8. Familiar with SLE treatment
9. Know how to monitor SLE
10. Know the aims of cure in Lupus
Nephritis

5. 5
R.N.P 24y/F/S
Batan, Aklan
High Urine
Protein
Creatinine Ratio

6. History of Present Illness
• Polyarthralgia –
both hands,
wrists and knees
• Fever
FOUR YEARS PTA
• Anemia: 95 g/L
• Leukocytosis:
31.4 g/l

7. History of Present Illness
• Slightly raised
erythematous
lesions on face
FOUR YEARS PTA
• Hair Loss

8. History of Present Illness
• Chest pain, tolerable and pressing in character
• 2D echo: thickened pericardium with minimal
pericardial effusion
• TB pericarditis
FOUR YEARS PTA
• Bedridden due to severe
polyarthritis
• Quack Doctor
• Alternative medicine

9. History of Present Illness
• Worsening of skin
lesions noted when
exposed to sunlight
• Facial puffiness
THREE YEARS PTA
• Consultation done
• SLE considered

10. History of Present Illness
• Referred to a
Rheumatologist
THREE YEARS PTA
• Meds:
• Hydroxychloroquine 200mg/tab 1 tablet OD
Prednisone 0.5mg/kg/day with tapering
doses

11. Diagnostics
11
ANA (IFA) 1:100 dilution with
speckled pattern
(+)/(-) POSITIVE
Anti-dsDNA 131 IU/ml (-) if <10 IU/ml
Equivocal if 10-
15 IU/ml
(+) if >15 IU/ml
POSITIVE
Complement 3 0.32 g/L 0.9 – 1.8 g/L Low
Complement 4 0.022 0.129 – 0.392 g/L Low
Random Urine Protein 18.60 mg/dl 0.00 -11.90 Elevated
Random Urine
Creatinine
35.4 mg/dl
LPCR 0.525 0.015-0.220 Elevated
NKTI Medical Lab, 2015

12. History of Present Illness
• Had Acute tonsillitis
•  SLE flare
• Admitted at WVSU-
MC
ONE YEAR PTA
• In and Out from the
Hospital due to
Flares

13. History of Present Illness
• More severe, persistent arthralgia
• Accompanied with warm and swollen joints,
symmetrical
• SLE-RA Overlap Syndrome
• Methotrexate 7.5mg/tab/week started
SIX MONTHS PTA

14. History of Present Illness
• Oral ulcers
• Methotrexate stopped
• Urinalysis: Proteinuria:3+ and pyuria: 9-16
hpf
• Urine CS: Enterococcus species
• Repeat Urinalysis: Proteinuria: 2+
• UPCR: >2.5mg/mg
• Diagnostics repeated
ONE MONTH PTA

15. Repeat Diagnostics
15
Labs 6/15 6/17
ANA (IFA) 1:100 dilution with
speckled pattern
1:1280 dilution with
speckled pattern
Anti-dsDNA 131 IU/ml >15,000 IU/ml
Complement 3 0.32 g/L 0.41
Complement 4 0.022 0.07
Random Urine Protein 18.60 mg/dl 145 mg/dl
Random Urine Creatinine 35.4 mg/dl 0.58
LPCR 0.525 2.50 mg/mg
NKTI Medical Lab, 2015 and 2017

17. Past Medical History
17
Sept 2014 – Treated with TB pericarditis – failed to
complete 6 months of treatment
June 2015 – SLE
January 2017 – SLE and RA Overlap Syndrome
Previous Hospitalizations:
September 2014 – UTI, Typhoid Fever
October, November 2016– SLE flares
January 2017 – SLE and RA Overlap Syndrome

18. FAMILY
HISTORY
 Hypertension
and Arthritis on
Paternal Side.
 No other
heredo-familial
diseases
OB-GYNE
HISTORY
 G0, single
 LMP: June 20,
2017 Regular
(every month)
 Duration: 3-4
days
PERSONAL-
SOCIAL HISTORY
 Elementary teacher
by profession.
 Presently works as a
Tutor
 Non-alcoholic drinker,
Non-smoker
18

19. PHYSICAL EXAMINATIONS
Temp: 36.3C
RR: 20cpm
CR: 84bpm
BP: 100/60
O2 sat: 100%
BMI: 18.2

20. PHYSICAL EXAMINATIONS
General Survey: Ambulatory,
conscious, coherent, not in CP
distress, well-groomed
Head: sparse, thin hairs
Permitted to post

21. PHYSICAL EXAMINATIONS
HEENT:
Pale conjunctivae
(+) Malar and discoid rash
(-) Oral ulcers
(-) Lymphadenopathies
CARDIAC AND PULMO:
Unremarkable
Permitted to post

22. PHYSICAL EXAMINATIONS
EXTREMITIES:
Grossly normal
(-) Edema
(-) Joint deformities and
tenderness
Permitted to post

24. 24

25. 24/F
Polyarthralgia
Hair Loss
Anemia
Alopecia
Malar Rash
Discoid Rash
Pericarditis
Photosensitivity
Oral ulcers
Labs:
(+) ANA
(+) Anti-dsDNA
(+) Low C3 and C4
High UPCR

26. Symptom complex
suggestive of SLE
Order laboratory tests:
ANA, CBC, platelets,
urinalysis
Harrison’s, 19th ed
All tests normal
symptoms persist
All tests normal
symptoms subside
ANA positive
APPROACH IN DIAGNOSING THIS CASE
Not SLE Repeat ANA, add anti-
dsDNA, anti-Ro

27. Harrison’s, 19th ed
All negative Possible SLE
(<4 criteria
Not SLE
Treatment
Some positive Definite SLE
(≥4 criteria,

30. Definition
 Systemic lupus erythematosus (SLE) is an
autoimmune disease in which organs and cells
undergo damage mediated by tissue-binding
autoantibodies and immune complexes

32. …pathogenesis
 Immune cell activation is accompanied by increased
secretion of multiple cytokines and inflammatory mediators
like:
a) Type 1 and 2 interferons (IFNs),
b) Tumor necrosis factor
c) Interleukin (IL)-17 and IL-10.
d) B cell–maturation/survival cytokines B lymphocyte stimulator
(BLyS/BAFF)
Note: These cytokines produce fever, malaise, myalgia, weight loss etc
(Similar to viral infections)
 Decreased production of other cytokines also contributes
to SLE:
Lupus T and natural killer (NK) cells fail to produce enough IL-2
and transforming growth factor to induce and sustain regulatory
CD4+ and CD8+ T cells.

35. On the day of
admission
A: Lupus Nephritis, SLE in flare
Subjective:
(-) fever
(-) chills
(-) Cough
(-) Urinary/bowel changes
(+) good appetite
(+) good sleep
Orders:
Meds:
1. Hydrochloroquine 200mg/tab 1ab OD
2. Prednisone 20mg/tab 1 tab OD
3. Calcium+Vit.D 1 tab OD
4. Hydrocortisone 100mg single dose prior to
biopsy
Schedule patient for UTZ-guided kidney
biopsy
Objective:
Stable VS
O2sat:98%
Clear breath sounds
Soft abdomen, NABS
No bipedal edema
I:1300 vs O:1000

36. KIDNEY BIOPSY38

37. Indications for Kidney Biopsy39
 Significant proteinuria:
 >1g/day
 protein to creatinine ratio
>100mg/mmol or >1g/g)
 Microscopic hematuria with any
degree of proteinuria
 Unexplained renal impairment (native
or transplanted kidney)
 Renal manifestations of systemic
disease.
PATIENT
 Significant proteinuria:
 >1g/day
 protein to creatinine ratio
>100mg/mmol or >1g/g)
(>2.5g/g UPCR)
Brenner and Rektor’s, 2016

38. Contraindications to Kidney Biopsy
40
ABSOLUTE RELATIVE
Uncontrolled Hypertension Single Kidney
Bleeding diasthesis Antiplatelet/clotting agents
Widespread cystic disease Anatomic abnormalities
Hydronephrosis Small kidneys
Uncooperative patient Active urinary/skin sepsis
Obesity
Brenner and Rektor’s, 2016

39. Indication for Kidney
Biopsy
UTZ excludes obstruction
or significant abnormality
UTI exclude by Negative
midstream urine collection
YES
Brenner and Rektor’s, 2016
YES
NO NO Relieve
Obstruction
Relieve
Obstruction
Anatomy
Normal?
NO
NO Treat
infection
Ultrasound
Unremarkable Kidneys and Urinary Bladder
RK: 10.5 x 5.4 x 6.6 CT: 1.2cm
LK: 12.3 x 5.6 x 4.8 CT:0.9 cm

40. Hgb >11 g/dL
Clotting Normal
Platelet count normal
BP < 150/90
PROCEED TO
BIOPSY
YES
Brenner and Rektor’s, 2016
YES
NO
NO
Transfuse
to achieve
Hgb
>10g/dL
Consider
CT-guided
or open
biopsy
Consider
open or
trans-
jugular
biopsy
YES
Bleeding Parameters
CT and BT : Normal
CBC: Hgb:108
Hct: 0.33
WBC: 2.36
Plt: 285
APTT: 21.3 Dec
Protime: 100% INR:1.0

42. 1st Hospital Day A: Lupus Nephritis, SLE not in flare
S/P UTZ-guided kidney biopsy
Subjective:
(-) fever
(-) chills
(-) Cough
(-) Urinary/bowel changes
(+) good appetite
(+) good sleep
Orders:
UTZ-guided kidney biopsy done
For Urine inspection
For repeat post-biopsy ultrasound
Objective:
Stable VS
O2sat:98%
Clear breath sounds
Soft abdomen, NABS
No bipedal edema
I:2400 vs O:1700

43. Risks of Kidney Biopsy
45
UK Renal Association: http://www.ren.org/information-resources/procedure
Complication Risk
Macroscopic hematuria 1:10
Bleeding that requires a blood transfusion <1:50
Bleeding that may require urgent X-ray or
operation
<1:1500
Severe bleeding necessitating nephrectomy 1:3000
Deaths Extremely rare
Post Biopsy site Ultrasound
(-) Perirenal Hematoma
(-) AV fistula formation

44. On 2nd hospital day46
DISCHARGE

45. Hospital Stay
47
24
Hours
12
Hours
8
Hours
4
Hours

46. DIAGNOSIS (Kidney Biopsy)
• Lupus Nephritis ISN/RPS Class IV Global-Active and
Chronic (Diffuse Proliferative and Sclerosing Lupus
Nephritis) with Activity Index of 10 and Chronicity Index
of 2 with 2% Cellular Crescent (1 of 41 Glomeruli), 2%
Global Glomerulosclerosis (1 of 41 Glomeruli) and 7%
Segmental Glomerulosclerosis (3 of 41 Glomeruli)
• Mild Interstitial Fibrosis and Tubular Atrophy
• Mild Arteriosclerosis
ANO RAW?

47. ISN/RPS (2003) Classification of Lupus Nephritis
49
CLASS DESCRIPTION
I Minimal Mesangial LN
II Mesangial proliferative LN
III Focal LN (<50% of glomeruli)
III (A) Active lesions
III (A/C) Active and chronic lesions
III (C) Chronic lesions
Brenner and Rektor’s, 2016

48. ISN/RPS (2003) Classification of Lupus Nephritis
50
CLASS DESCRIPTION
IV Diffuse LN (≥50% of glomeruli)
Diffuse segmental (IV-S) or global (IV-G) LN
IV (A) Active lesions
IV (A/C) Active and chronic lesions
IV (C) Chronic lesions
V Membranous LN
VI Advanced sclerosing LN
(≥90% globally sclerosed glomeruli without residual activity)
Brenner and Rektor’s, 2016

49. ISN/RPS (2003) Classification of Lupus Nephritis
51
CLASS DESCRIPTION
IV Diffuse LN (≥50% of glomeruli)
Diffuse segmental (IV-S) or global (IV-G) LN
IV (A) Active lesions
IV (A/C) Active and chronic lesions
IV (C) Chronic lesions
V Membranous LN
VI Advanced sclerosing LN
(≥90% globally sclerosed glomeruli without residual activity)
Brenner and Rektor’s, 2016

50. Class I
Delicate mesangial positivity
for IgG.
No structural changes by light
microscopy

51. Mesangial cell proliferation,
mesangial matrix expansion.
Granular mesangial positivity of
all three immunoglobulins and
both complements (C1q and C3)
(“full house” pattern)
Class II

52. Less than 50% of all glomeruli, segmental or global,
swelling and proliferation of endothelial and mesangial
cells associated with leukocyte accumulation, capillary
necrosis, and hyaline thrombi; extracapillary
proliferation, crescents.
Full house pattern as in class II, immune deposits
also identified in tubular basement membranes,
interstitial capillary walls, interstitial collagen,
arterial intima, and media, Fibrinogen positivity
Class III

53. Lesions similar to Class III, but involves >
50% of glomeruli
Class IV

54. Wire loop lesions

55. ISN/RPS class IV
 ISN/RPS class IV or Diffuse proliferative
LN, has qualitatively similar glomerular
endocapillary proliferation as class III, but
the proliferation involves more than 50%
of the glomeruli
 ISN/RPS class IV is subdivided into:
i) Diffuse segmental proliferation (class IV-S)
More than 50% of affected glomeruli have
segmental lesions
ii) Diffuse global proliferation (class IV-G)
More than 50% of affected glomeruli have global
lesions.

56.  The most controversial of these changes in the
ISN/RPS classification system is the subdivision of
class IV into diffuse global and diffuse segmental
LN.
 The Lupus Nephritis Collaborative Study Group
showed the Class IV-S biopsies had more extensive
fibrinoid necrosis and less prominent immune
deposits, and despite similar treatment, Class IV-S
had a worse prognosis than Class IV-G.
 However, several studies have shown that suggest
lupus nephritis Class IV-G has a similar or worse
outcome than lupus nephritis Class IV-S

57.  Class IV patients usually have evidence of active
systemic disease and have the most severe and
active clinical renal presentation.
 Proteinuria is universal, hematuria occurs to variable
degrees in 80% - 90% of patients, and renal
insufficiency is detected in more than 50% of patients.
 These patients have the worst prognosis despite
optimal treatment

58. Diffuse thickening of the capillary walls due to
deposition of subepithelial immune
complexes, increased production of basement
membrane-like material
There are delicate subepithelial
immune deposits staining for IgG with
or without mesangial deposits
Class V

59. Sclerosis of more than 90% of the glomeruli,
end stage renal disease, severe tubular
atrophy, interstitial fibrosis, inflammation.
Class VI

60. Kidney Biopsy: Immunoflourescence
o Immunofluorescence microscopy shows 14 glomeruli
1. Anti-human IgG – 14 glomeruli with diffuse granular mesangial
staining (1-3+); diffuse granular Bowman’s capsular, tubular
basement membrane, peritubular capillary and vascular staining (1+)
2. Anti-human IgA, IgM – 14 glomeruli with diffuse granular mesangial
staining (1-3+)
3. Anti-human C3-14 glomeruli with diffuse granular mesangial staining
(1-2+)
4. Anti-human C1q – 14 glomeruli with diffuse granular mesangial
staining (1-2+); diffuse granular peritubular capillary and vascular
staining (1+)
5. Anti-human fibrinogen – 14 glomeruli with diffuse granular mesangial
staining (trace); (3+) in necrotic segments

61. LUPUS NEPHRITIS ACTIVITY INDEX
ACTIVE LESIONS SCORE
1 Fibrinoid Necrosis 2
2 Endocapillary hypercellularity with or without
leukocyte infiltration and with substantial luminal
reduction
3
3 Crescents, cellular or fibrocellular 1
4 Karyorrhexis 2
5 Subendothelial deposits identifiable by light
microscopy (wire loops)
1
6 Intraluminal immune aggregates (hyaline thrombi) 0
7 Rupture of glomerular basement membrane 1
TOTAL 10

62. LUPUS NEPHRITIS CHRONICITY INDEX
CHRONIC LESIONS SCORE
1 Fibrous crescents 0
2 Glomerular sclerosis (segmental, global) 1
3 Fibrous adhesions 1
TOTAL 2

63. TREATMENT
Principal goal of therapy in lupus nephritis:
A. normalize renal function
B. prevent the progressive loss of renal function.
Adjunctive Treatments
Primary disease management by immunosuppressive agents
◦ Induction Therapy
◦ Maintenance Therapy
Lifestyle Changes

64. Adjunctive Treatments
Drugs Cause
Hydroxychloroquine
[Max 6–6.5 mg/kg body
weight]
All SLE patients with; unless there is a
contraindication:
• Lower rates of Flare
• Reduced renal damage
• Less clotting events
ACEi/ARBs Patients with proteinuria >0.5 gm/day
• Reduces proteinuria by 30%, and
• Significantly delays doubling of serum
creatinine
• Delays progression to ESRD
Antihypertensive Target of ≤130/80 mmHg
• Significant delay in progression of renal disease
Statin therapy Patients with LDL >100 mg/dl
• As GFR<60ml/min/1.73m2 & SLE itself
accelerated atherosclerosis
Calcium
supplementation
Prevent osteoporosis if the patient is on long-
term corticosteroid therapy

65. Depends upon class of LN diagnosed on kidney biopsy along with
presence of extra-renal manifestations of SLE
Goals of immunosuppressive treatment:
◦ Long-term preservation of renal function,
◦ Prevention of flares,
◦ Avoidance of treatment-related harms, and
◦ Improved quality of life and survival.
IMMUNOSUPPRESSIVE AGENTS

69. MEDICATIONS FOR THE MANAGEMENT OF SLE
MEDICATION DOSE RANGE DRUG INTERACTIONS SERIOUS OR COMMON
ADVERSE EFFECTS
NSAIDs, salicylates Doses toward upper limit
or recommended range
usually required
A2R/ACEi,
glucocorticoids,
fluconazole,
methotrexate, thiazides
Higher incidence of aseptic
meningitis, elevated liver
enzymes, decreased renal
function, vasculitis, Ototoxicity
Topical
glucocorticoids
Mid potency for face; mid
to high potency for other
areas
None Known Atrophy of skin, contact
dermatitis, folliculitis,
hypopigmentation, infection
Topical sunscreens SPF 15 at least; 30+
preferred
None Known Contact dermatitis
Hydroxychloroquine 200-400mg qd (100mg
qd)
None Known Retinal damage,
agranulocytosis, aplastic
anemia, ataxia, myopathy,
seizures
DHEA 200mg qd Unclear Acne, menstrual irregularities,
high serum levels of
testosterone

70. MEDICATIONS FOR THE MANAGEMENT OF SLE
MEDICATION DOSE RANGE DRUG INTERACTIONS SERIOUS OR COMMON
ADVERSE EFFECTS
Methotrexate 10-25mg once a week, PO
or SC, with folic acid,
decrease dose if CrCl <60
ml/min
Acitretin, Leflunomide,
NSAIDs and salicylates,
penicilllins, TMX-SMZ
Anemia, BM suppression,
leukopenia, thrombocytopenia,
hepatotoxicity
Oral Glucocorticoids Prednisone, Prednisolone:
0.5 – 1mg/kg/day for severe
SLE
0.07-0.3mg/kg/day or qod
for milder disease
A2R/ACEi, antiarrhytmics
class III, cyclosporine,
NSAIDs and salicylates,
phenytoins
Infection, VZV infection, HPN,
hyperglycemia, hypokalemia,
acne, allergic reactions, anxiety,
CHF
Methylprednisolone
Na succinate, IV
Severe: 1g IV qd x 3 days As for oral steroids As oral steroids
Cyclophosphamide IV Low dose: 500mg every 2
wks for 6 doses, then
maintenance with MMF or
AZA
High dose: 7-25mg/kg q
month x 6
Allopurinol, doxorubicin,
rituximab
Infection, VZV infection
leukopenia, hemorrhagic cystitis,
bladder CA, alopecia, nausea,
anemia, diarrhea

71. MEDICATIONS FOR THE MANAGEMENT OF SLE
MEDICATION DOSE RANGE DRUG INTERACTIONS SERIOUS OR COMMON
ADVERSE EFFECTS
Mycophenolate
Mofetil (MMF) or
mycophenolic acid
(MPA)
1.5-3mg/kg/day; decrease
dose for CrCl<25mL/min
MMF: 2-3g/d PO for
induction therapy, 1-2g/d for
maintenance therapy; max
1g BID if CrCL<25mL/min
MPA: 360-1080 mg BID
Acyclovir, antacids, AZA,
iron, salts, oral
contraceptives
Infection, leukopenia, anemia,
thrombocytopenia, lymphoma,
malignancy, laopeci, peripheral
edema, tremors, rash
AZA 2-3mg/kg/day PO for
induction;
1-2 mg/kg/day for
maintenance; dec frequency
of dose if CrCl <50mL/min
ACEi, allopurinol, bone
marrow suppressants,
interferons, MMF, warfarin
Infection, VZV infection,
leukopenia, pancreatitis, anemia,
flulike illness, GI symptoms
Belimumab 10mg/kg IV wks, 0,2,4 then
monthly
IVIg Infusion reactions, allergy,
infections probable
Rituximab 375 mg/m2 q wk x 4 or 1g
q2ks x 2
IIVIg Infections, infusion reactions,
headaches, arrhythmias, allergic
reactions

73. Clinical Guidelines for the Evaluation and Treatment
of Lupus Nephritis (ACR 2012)
1) All patients with lupus who develop glomerulonephritis
should have a renal biopsy
2) Evaluating renal activity should include the following:
urine sediment appearance, serum creatinine, blood
pressure, serum albumin, C3-complement determination,
anti-dsDNA antibody level, proteinuria (often estimated by
protein-to-creatinine ratio), and creatinine clearance.

74. Clinical Guidelines for the Evaluation and Treatment
of Lupus Nephritis (ACR 2012)
3) Patients with APLAs and lupus nephritis have a poorer renal outcome,
more histologic thrombotic microangiopathy, and increased complications
with dialysis and transplantation
4) Hypertension must be aggressively treated. With lupus nephritis, the goal
should be age-appropriate blood pressure (especially important in young
patients)
5) The following parameters are essential to monitor toxicity associated with
corticosteroids, diuretics, and cytotoxic agents : blood pressure, complete
blood count, platelet count, potassium, glucose, cholesterol, liver function
tests, weight, muscle strength, gonadal function, and bone density

75. Clinical Guidelines for the Evaluation and Treatment
of Lupus Nephritis (ACR 2012)
6) Patients are instructed to avoid therapeutic doses of salicylates and
NSAIDs because they may impair renal function, exacerbate edema and
hypertension, and increase the risk of gastrointestinal toxicity, particularly in
combination with corticosteroids and immunosuppressive agents.
7) Pregnancy should be discouraged in patients with nephritis; the risks for
maternal and fetal morbidity and mortality, active including renal failure, are
increased
8) Antimalarial medications may be given or continued for active skin
disease or to reduce risks of APLA syndrome

76. Therapies are advised for specific biopsy patterns
(ACR)
1 ISN class I or class II (WHO class I and class II):
Many mesangial lesions do not need specific therapy. In
patients with ISN class I or class II, hydroxychloroquine
and prednisone are usually administered in accordance
with the degree of extrarenal clinical activity

77. Therapies are advised for specific biopsy patterns
(ACR)
2 ISN class III or class IV (WHO class III and class IV):
These classifications are treated similarly because they
have similar prognoses. Because the risk of ESRD in 10
years may exceed 50%, unless a complete remission is
attained, aggressive management is advised. The
following recommendations are offered

78. Class III LN (focal) and class IV LN (diffuse)
At high risk of progressing to ESRD
Require aggressive therapy.
Therapy for class III and IV LN has 2 phases:
◦ Initial/Induction phase: to rapidly decrease kidney
inflammation
◦ Maintenance phase: to consolidate treatment over a
longer time.

79. Therapies are advised for specific biopsy patterns
(ACR)
2A One mg/kg/day of prednisone equivalent is
administered for at least 4 weeks, depending on clinical
response. The age of the patient will affect steroidal therapy;
children and young adults into their early 20s may require higher
doses of prednisone than older patients

80. Therapies are advised for specific biopsy patterns
(ACR)
2B Unless contraindicated by infection or other compelling
clinical circumstances, cytotoxic drugs should be added at the
onset of therapy. The results of the ALMS trial have supported the
use of either MMF or IVC therapy for 6 months as an induction
therapy.
 IVC is administered monthly for 6 months, per the NIH regimen
beginning with 0.5 to 0.75 gr/m2 up to 1 g/m2 while maintaining the
patient's white blood cell count above 3000/mm3 for 7 to 10 days;
therapy is not currently administered consecutively for more than 6
months

81. Therapies are advised for specific biopsy patterns
(ACR)
2C The dosing of MMF may be started at 250 to 500 mg twice daily,
advancing by 500 mg every few days to 1 week (between 2 and 3 g/day).
 Based on the Contreras study, which demonstrated improved 5-year
outcomes with 6 months of IVC therapy, followed by one of two agents for
up to 5 years—MMF (2 g/day) or AZA (2 mg/kg/day), we follow induction
with one of these agents. The ALMS maintenance trial demonstrated the
superiority of MMF to AZA in this global trial. The length of maintenance is
not clear, but at least 2 to 5 years is supported by the NIH and ALMS trials

82. Therapies are advised for specific biopsy patterns
(ACR)
3 Acute flares with renal deterioration can
be managed with pulse MP and consideration of a
new immunosuppressive regimen

83. Therapies are advised for specific biopsy patterns
(ACR)
4 Somewhere between 20% and 40% of cases
especially in patients of minority descent (e.g., African
American, Hispanic) and those with nephritic urinary
sediment, will be refractory to prednisone plus IVC or
MMF.
 Among this subset, the following options are
available:

84. Therapies are advised for specific biopsy patterns
(ACR)
4A Switch the patient to the alternative induction agent
(IVC or MMF)
4B Change to oral immunosuppressive with MMF,
cyclosporine A, or tacrolimus, or to a combination of these
drugs
5C Consideration of experimental therapies including B-
cell depletion with rituximab (anti-CD20), intravenous gamma
globulin, addition of CTLA4-Ig to CyX therapy, or bone marrow
transplantation

85. Therapies are advised for specific biopsy patterns
(ACR)
5 Class V: Patients may be treated with 1
mg/kg/day of prednisone equivalent for 6 to 12 weeks,
followed by its discontinuation if no response occurs
or tapering to a maintenance level of 10 mg/day
prednisone equivalent for 1 to 2 years if a response
occurs

86. Therapies are advised for specific biopsy patterns
(ACR)
5A Aggressive immunosuppressant management is
usually not advised unless a high activity index is also present or
extrarenal disease is evident, which would warrant cytotoxic
therapy.
5B Patients may be maintained on 5 to 10 mg/day of
prednisone equivalent if needed to control extrarenal lupus,
bearing in mind the increased risk of infection if the patient
requires a peritoneal or hemodialysis catheter rather than a shunt
or graft for dialysis access

90. How do we monitor SLE?

94. Future Directions in SLE Nephritis
Despite the disappointing results of a number of clinical trials
in SLE nephritis that were directed at controlling systemic
autoimmunity, many therapeutic targets have now been
identified that provide a rich source of ideas for both
prevention and treatment of this devastating SLE
manifestation.

95. Examples of Systems Biology Analyses of Lupus
Nephritis
1. Identify genetic variations to define genetic risk and protective alleles of the individual.
2. Analysis of epigenetic modulation in leukocytes and tissue to capture the effect of earlier live events
on genetic information.
3. Transcriptional analysis of tissue and leukocytes to define currently activated disease processes.
4. Protein expression and function in plasma, tissue, and urine to capture the cellular machinery
currently at work.
5. Metabolite levels in plasma, tissue, and urine to measure the metabolic status of the disease.
6. Histologic examination of tissue obtained by biopsy to define the net effect of the preceding
regulatory cascade on structural composition of the diseased end organ.
7. Demographic and clinical characteristics to capture environmental exposures and mitigating factors,
including treatment effect

101.  Female sex is permissive for SLE with evidence for
hormone effects, genes on the X chromosome and
epigenetic differences.

102.  Flares in 70% SLE
 Increasing apoptosis in skin cells or by altering DNA
and intracellular proteins to make them antigenic

103. SAVE THE DATE
Rheumatology Educational Trust Foundation Inc. (RETFI) &
Iloilo Mission Hospital - Department Of Medicine
• 17 November 2017
1:00 – 5:00 PM– Applies Rheumatology Made Simple (ARMS)
• 18 November 2017
8 :00 – 5:00 PM – LUPUS ROADSHOW
ILOILO MEDICAL ARTS BUILDING CONFERENCE ROOM