proteinuria outcome lupus nephritis classes of lupus nephritis i.minimal ii.mesangial iii.focal...

Proteinuria OutcomeLupus Nephritis

Classes of Lupus NephritisI. MinimalII. MesangialIII. Focal proliferative*IV. Diffuse proliferative*V. Membranous**VI. SclerosingMixed membranous and proliferative*

* Focus of clinical trials


Lupus membranous nephropathy Proteinuria is the practical outcome Doubling Cr is very late outcome Proteinuria associated with increased

Thromboembolic diathesis* Cardiovascular events*

* Because of effects on survival, multiple interventions are brought to bear, aside from ISD


Proteinuria Substantive issue in most, but not all,

proliferative LN: eg, IV > III or II Level of baseline proteinuria predicts

prognosis in some, but not all, studies Duration has impact, but is

confounded by early interventions Regression of proteinuria appears to

be stronger predictor of prognosis -- appears to be a graded effect


In SLE, more than 10 GN, proteinuria is a component of composite outcomes

Proteinuria reduction Cr stable or improved Improved urinary sediment Clinical remission of extrarenal

disease activity Stable or improved lupus serologies

Proteinuria OutcomeRange of Definitions

Complete Remission (CR) < 1 g/d or U Pr/Cr < 1 < 0.5< 0.5 < 0.3< 0.3 < 0.2

Proteinuria OutcomeRange of Definitions

Partial Remission (PR) > 50% reduction > 50% reduction and < 3.5 > 50% reduction and < 3.0 > 50% reduction and < 2.0> 50% reduction and < 2.0 > 50% reduction and < 1.5 > 50% reduction and < 1.0

Value of CR or PR in SevereLupus Nephritis

LTFU of 86 pts from PE trial 1981-88 CR: Cr <1.4; proteinuria <0.33 g/d

(within 5 yr) PR: Cr < 25% over baseline;

proteinuria >50% reduction to <1.5 g/d (within 5 yr)

ESRD Death

Chen YE. Clin J Am Soc Nephrol 2008;3:46-53

Copyright ©2008 American Society of Nephrology

Figure 1. Renal remission

Chen, Y. E. et al. Clin J Am Soc Nephrol 2008;3:46-53

CR

PR


Figure 2. Renal survival


CR

PR

NR


Figure 3. Patient survival


CR

PR

NR

Achievement of CR or PRLupus Nephritis

Dutch Trial 87 pts with PLN: AZ/MP vs CY

Grootscholten. Kidney Int 2006; 70:732

CR: Cr <130%; proteinuria <0.5 g/d; RBC <10

PR: Cr stable or improved; proteinuria >50% reduction to <3 g/d

Grootscholten. Kidney Int 2006

AZ/MP vs IV-CY study

Renal RemissionLupus Nephritis

Italian cohort 93 pts with proliferative LN

Moroni. NDT 2007; 22:2531

Complete Remission: Cr improved or not > 125% of baseline Proteinuria <0.2 g/d

Copyright restrictions may apply.

Probability of not doubling serum creatinine in patients who achieved or not complete remission

Predictors of Favorable OutcomeLupus Nephritis

ELNT: 90 pts PLN (hi vs lo dose IV-CY)Houssiau. A&R 2004; 50:3934

LTFU: sustained normal renal function PPV: proteinuria <1 g/d @6 mo: 87% PPV: proteinuria 75% @6 mo: 90% Multivariate analysis of nl renal fcn:

Cr decreased @6 mo Proteinuria <1 g/d @6 mo Baseline variables did not contribute

Change ProteinuriaLupus Nephritis

MMF vs IV-CY induction trial Inclusion: proteinuria >0.5 (44% NS) Proteinuria at 6 mo:

Not significantly different MMF: 2.0 g/d (~50% decrease) IV-CY: 1.5 g/d (~65% decrease)

Ginzler. NEJM 2005; 353:2219


Chan TM. J Am Soc Nephrol 2005;16:1076-1084

CKD outcome Cr >3

MMF: 4/32

IV-CY: 0/30

~80%

Asian population

Aspreva (ALMS) Trial

MMF superiority trial: class III, IV, and V

MMF vs IV-CY induction (6 mo) MMF vs AZ maintenance 370 patients randomized

Caucasian 40% Hispanic 35%Asian 33% Non-Hispanic 65%Other 27%

(Black 12%, mixed 10%)

Appel, Ginzler et al (abstracts ASN, ACR 2007)

Aspreva (ALMS) Trial

MMF IV-CYPR 56% 53%

Deaths 9 5

(Superiority achieved in “Other race” cohort)

Appel, Ginzler et al (abstracts ASN, ACR 2007)

Boumpas. Lancet Boumpas. Lancet 19921992

CR, PR and NR and Doubling CrLupus Nephritis

Treatment severe lupus nephritis --Within 5 years:

Doubling Cr NR: > 2 g/d 14/19 74%CR: < 0.5 g/d 1/22 5%PR: 50%, < 2 g/d 4/9 44%PR + CR 5/31 16%

Unpublished: LUPULSE cohort

ConclusionsLupus Nephritis

Baseline proteinuria controversial – generally poor predictor of CKD

No racial differences in baseline proteinuria or severity of LN

PR proteinuria ~75% at 1 yr CR proteinuria ~50% at 1 yr

Blacks ~30% at 1 yr

ConclusionsLupus Nephritis

CR: predicts very low rate CKD PR: intermediate predictor NR: predicts high rate CKD Current practice of combining CR and

PR improves number of outcome events and may contribute to statistical significance but its weakness as a stand-alone outcome raises question about this practice

proteinuria outcome lupus nephritis classes of lupus nephritis i.minimal ii.mesangial iii.focal...

Documents