LUPUS

NEPHRITIS

CLASSIFICATION
History

CLASS IV S versus IV G

THE FIRST RULE:

BIOPSY
Is it for diagnosis versus prognosis
Why dont we treat empirically and follow clinically

CLASS I and II

INDUCTION
IV Methylpred
CYCLOPHOSPHAMIDE
MMF

Cytotoxic Therapy
Prolongs Renal Survival

Steinberg at el 1992

Induction therapy
NIH
Euro-lupus Nephritis TriaL
AMLS TRIAL

NIH

The NIH Protocol

Improved RENAL not
overall survival
All classes of renal
histology included
100% Caucasian
Long duration (11
months) of nephritis
prior to entry

Excluded patients with

renal insufficiency
Quarterly
cyclophosphamide
therapy employed
Comorbidities over
time not reported

Euro Lupus

Maintenance

MMF
Azathioprine
Cyclosporine
Prednisolone

University of Miami Study Methods:

Study design & patient population
Open label, randomized clinical trial
Inclusion criteria
o Adults > 18 years of age, World Health Organization (WHO)
classes III, IV, V with proliferation

Exclusion criteria
o
o
o
o

Have received IVCY > 7 doses or AZA > 8 weeks

Creatinine clearance < 20 mL/min
Pregnancy
Any clinically significant infection within 2 weeks of
enrollment

Patient survival
Cumulative probability

1.00

0.75

0.50

p = 0.11, MMF vs IVCY

p = 0.02, AZA vs IVCY
p = 0.33, MMF vs AZA

0.25

0.00

19
20
20

19
19
20

12

15
12
14

24

10
6
11

9
3
6

36

4
2
2

48

Time (months)

2 AZA
1 IVCY
2 MMF

60

72

Free of relapse
p = 0.021, MMF vs IVCY
p = 0.124, AZA vs IVCY
p = 0.222, MMF vs AZA

Cumulative probability

1.00
0.75
0.50
0.25
0.00

19
17
19

15
10
17

12

10
4
12

24

6
2
8

4
2
3

36

3
1
2

48

Time (months)

1 AZA
1 IVCY
1 MMF

60

72

Cyclosporine

CLASS V
LUPUS NEPHRITIS

RITUXIMAB

Many Patients Do Not Achieve

Complete Remission Following Induction
Prevalence of Complete Remission in Lupus Nephritis
Following Induction Therapy (24 weeks)

Percentage of
Patients

N=
140
(Intentto-treat
analysi
s)
Complete remission defined as return to within 10% of normal values of serum creatinine, proteinuria, and urine
sediment. Source: Ginzler et al. NEJM. 2005; 353(21)

Importance of Maintaining
Complete Remission in Lupus Nephritis
Results of a long-term prospective study in patients with diffuse lupus nephritis
Patient Survival Without ESRD at 10 Years

Percentage of
Patients
Surviving
Without ESRD

Patient survival without

ESRD less than 50% at 10
years with partial remission

P<0.0001 (CR vs PR)

N = 86

Partial Remission: 50% reduction in baseline proteinuria to < 1.5 g/d with not more than 25% increase in baseline sCr.
Complete Remission: Proteinuria < 0.33 g/d and serum creatinine < 1.4 mg/dl
Source: Chen et al. Clin J Am Soc Neph. 2008; 3(1)

UKM regime
Induction : IV methylpred 250mg 3x
Cyclophosphamide 400 -500 mg every 2 weeks for 2
months
If responding, monthly CYCLO 10-12mg/kg for 4
months
If not responding, continue 400-500mg 2 weekly for 4
months and than monthly for 2 months

Maintenance :
Prednisolone 30mg x 1 mth. Monthly taper
MMF 500-1000mg bd 6-12 months
Cyclosporine 4-5mg/kg