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DISEASE OUTCOME
Acknowledgment: Based on GlomCon’s Glomerular Disease Virtual Fellowship workshop on lupus nephritis by Dr. Tingting Li.
Dr. Diana Mahbod Nephrologist Dallas Renal Group USA
What are predictors of ESRD in Lupus Nephritis?
Lupus nephritis (LN) occurs in up to 60% of adults and 80% of children with SLE1
Renal disease in SLE is clinically variable2
can range from “silent” nephritis to RPGN to nephrotic syndrome, or a combination
can occur in various forms during a patient’s lifetime
10-30% of patients with LN develop ESRD within 15 years
Patients with SLE develop ESRD at a relatively young age3
73% of SLE patients with ESRD are <50 years old
The average age of ESRD onset in LN is 41 years old
Renal damage is a significant predictor of mortality in patients with SLE4
Treatment of LN has changed significantly since the 1960s, resulting in improvement in outcomes3.
identification of histologic subtypes based on biopsy
demonstration of adequate immunosuppression to treat LN
improvement in survival rate from <50% in the 1960s to 80% in the 1990s
Risk factors for progression to ESRD include demographic, clinical, and socioeconomic factors5
Factors that may influence the presentation or prognosis of Lupus Nephritis (adapted from Ntatski & Isenberg, 2015) |
Demographical
|
Environmental
|
Genetic
|
Hormonal |
Immunological
|
Histology
|
Clinical & Laboratory Markers
|
Therapy
|
Some key points:
Age
renal disease is more frequent and severe in childhood than adult-onset SLE
younger age at nephritis onset is a poor prognostic indicator in adults
late-onset SLE (>50 years old) is associated with fewer major organ manifestations
Sex
men with SLE have more frequent and severe LN than females
area for further study: is this biological (such as related to hormones) OR is it due to delay in diagnosis, the difference in healthcare-seeking behavior, and treatment compliance?
Ethnicity
Black and Hispanic patients have been found to have higher rates of renal disease and mortality
area for further study: the role of biology/genetics (such as APOL1, see below) vs. socioeconomic and sociocultural factors (remains controversial)
Environmental/socioeconomic
Socioeconomic status is complex and challenging to measure6
Patients with private insurance were found to have a later onset of ESRD (by eight years!) compared to no insurance OR Medicaid7
Genetic
Genetic associations have been found for the development of SLE
One association for the development of renal disease in SLE: FCGR genes
family of immunoglobulin Fc receptor genes found on many immune response cells
strong association with end-organ damage, including ESRD
PROFILE cohort – multi-center, multi-ethnic, started in 1998
FCGR3A*GG overrepresented in patients who developed ESRD8
APOL1 polymorphisms are associated with risk of LN-ESRD and time to progression to ESRD in African Americans9
Immunologic
immune complexes formed in the circulation can deposit in glomeruli and lead to complement activation and inflammation
anti-dsDNA is linked to proliferative LN, and rising titers may be predictive of proliferative LN occurrence, but studies have not shown an association with interstitial fibrosis and tubular atrophy (IFTA) or progression to ESRD10
area for further study: anti-C1q also strongly correlated with renal involvement, but value as a prognostic marker requires further study
area for further study: does anti-phospholipid antibody cause glomerular and capillary thrombosis, chronic vasculopathy, associated arterial hypertension, and thus negatively impact renal survival?
Histopathology
Worse renal outcomes:
Class 3 or 4 LN2
Chronicity on index biopsy, seen as tubulointerstitial damage (TID), or IFTA11
Moderate-to-severe TID was seen in 13% of SLE patients with eGFR>60 mL/min, 33% of SLE patients with eGFR 30-60 mL/min
area for further study: role of protocol biopsies?
Variables | Scores |
Cellular crescents | 1, 3, or 5 points |
Fibrous crescents | 1-3 points |
Active index >20 | 7 points |
Chronic index >5 | 5 points |
Glomerular sclerosis | 1 or 3 points |
Interstitial fibrosis | 1, 2, or 4 points |
Nephrotic syndrome | 2 points |
eGFR<45 mL/min | 6 points |
Serum complement levels may predict worse outcomes, but C1q and C3 deposits on biopsy did NOT predict ESRD or death in patients with SLE13
This figure adapted from a review article by Maroz and Segal4 summarizes it well:
References