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LUPUS

NEPHRITIS

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CLASSIFICATION

History

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CLASS IV S versus IV G

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THE FIRST RULE:BIOPSY

Is it for diagnosis versus prognosis

Why dont we treat empirically and follow clinically

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CLASS I and II

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INDUCTION IV Methylpred

CYCLOPO!P"MI#$

MM%

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Cytotoxic TherapyProlongs Renal Survival

Steinberg at el 1992

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Induction therapy &I

$uro'lupus &ephritis (riaL

"ML! ()I"L

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NIH

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TheNIH Protocol Improved )$&"L not

overall survival

"ll classes of renal

histology included

*++, Caucasian

Long duration -**months. of nephritis

prior to entry

$/cluded patients withrenal insu0ciency

1uarterlycyclophosphamidetherapy employed

Comor2idities overtime not reported

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Maintenance MM%

"3athioprine

Cyclosporine

Prednisolone

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19 19 15 10 9 4 2 AZA20 19 12 6 3 2 1 IVCY20 20 14 11 6 2 2 MMF

Time (months)

C

umulativepr

obability

Patient survival

p= 0.11, MMF vs IVCYp= 0.02, AZA vs IVCYp= 0.33, MMF vs AZA

0.00

0.25

0.50

0.75

1.00

0 12 24 36 48 60 72

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Free of relapsep= 0.021, MMF vs IVCYp= 0.124, AZA vs IVCYp= 0.222, MMF vs AZA

C

umulativeprobability

19 15 10 6 4 3 1 AZA17 10 4 2 2 1 1 IVCY19 17 12 8 3 2 1 MMF

0.00

0.25

0.50

0.75

1.00

0 12 24 36 48 60 72

Time (months)

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Cyclosporine

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RITUXIMAB

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ManyPatientsDoNotAchieve

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Many Patients Do Not Achieve

Complete Remission Following InductionPrevalence of Complete Remission in Lupus Nephritis

Following Induction Therapy (24 weeks)

Complete remission defined as return to within 10% of normal values of serum creatinine, proteinuria, and urinesediment. Source: Ginzler et al. NEJM. 2005; 353(21)

N =140

(Intent-to-treatanalysis)

Percentage ofPatients

ImportanceofMaintaining

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Importance of Maintaining

Complete Remission in Lupus Nephritis

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/dlSource: Chen et al. Clin J Am Soc Neph. 2008; 3(1)

N = 86

Results of a long-term prospective study in patients with diffuse lupus nephritis

Patient survival withoutESRD less than 50% at 10

years with partial remissionPercentage ofPatientsSurviving

Without ESRD

Patient Survival Without ESRD at 10 Years

P

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UKM regime Induction > IV methylpred ;?+mg @/

Cyclophosphamide A++ '?++ mg every ; wee9s for ;months

If responding4 monthly CYCLO *+'*;mg