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

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?