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
Proteinuria OutcomeLupus Nephritis
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 OutcomeLupus Nephritis
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
Proteinuria OutcomeLupus Nephritis
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
Copyright ©2008 American Society of Nephrology
Figure 2. Renal survival
Chen, Y. E. et al. Clin J Am Soc Nephrol 2008;3:46-53
CR
PR
NR
Copyright ©2008 American Society of Nephrology
Figure 3. Patient survival
Chen, Y. E. et al. Clin J Am Soc Nephrol 2008;3:46-53
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
Copyright ©2005 American Society of Nephrology
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
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