Risk of End-Stage Renal Disease in Patients With Lupus Nephritis, 1971-2015: A Systematic Review and Bayesian Meta-Analysis

Abstract

Objective: End-stage renal disease (ESRD) is a major consequence of lupus nephritis, but how this risk has changed over time is unknown. We conducted this systematic review to examine changes in ESRD among adults with lupus nephritis from 1971 to 2015 and to estimate risks of ESRD among contemporary patients.

Methods: We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for cohort studies and clinical trials on ESRD in adults with lupus nephritis. We analyzed studies from developed and developing countries separately. The outcome was probability of ESRD at 5, 10, and 15 years of lupus nephritis.

Results: We included 187 articles that reported on 18,309 patients. In developed countries, the 5-year risk of ESRD decreased from 16% (95% confidence interval [95% CI] 14-17%) in 1970-1979 to 11% (95% CI 10-12%) in the mid-1990s and then plateaued. ESRD risks at 10 years and 15 years showed steeper declines in the 1970s and 1980s but also plateaued in 1993-1997, with a notable increase in the late 2000s. The decrease in risk after 1980 coincided with increased use of cyclophosphamide. The 15-year ESRD risk was higher in developing countries than in developed countries. Patients with class IV lupus nephritis had the greatest risk of ESRD, with a 15-year risk of 44% during the 2000s.

Conclusion: Risks of ESRD in lupus nephritis improved between the 1970s and the mid-1990s and then plateaued, with an increase in the late 2000s. This pattern suggests limitations in the effectiveness of, or access to, current treatments.

Figure 1

Flow diagram of the literature search and study inclusion. ESRD = end-stage renal disease; CKD = chronic kidney disease.

Figure 2

Estimated risk (solid lines) of end-stage renal disease (ESRD) at 5 years, 10 years, and 15 years of lupus nephritis in developed countries (105 studies) and developing countries (51 studies), by calendar year of observation, for studies of patients with a clinical diagnosis of lupus nephritis or reporting results for more than one renal histologic class of lupus nephritis. Each individual study contributed to risks starting at the median year of its enrollment period and extending to the end of its observation period. Dashed lines represent 95% confidence limits.

Figure 3

Estimated risk (solid lines) of end-stage renal disease (ESRD) at 5 years, 10 years, and 15 years in developed and developing countries, including data for given studies from the midpoint of enrollment to the end of observation, truncating the study’s contribution at 10 years after the midpoint of enrollment for any study for which follow-up longer than 10 years was reported. Dashed lines represent 95% confidence limits.

Figure 4

Trends in corticosteroid and immunosuppressive treatment among studies of lupus nephritis.

Figure 5

Estimated risk (solid lines) of end-stage renal disease (ESRD) at 5 years, 10 years, and 15 years of class III, class IV, and class V lupus nephritis in developed countries (17, 34, and 19 studies, respectively) and developing countries (11, 22, and 18 studies, respectively), by calendar year of observation. Each individual study contributed to risks starting at the median year of its enrollment period and extending to the end of its observation period. Dashed lines represent 95% confidence limits. Estimates at years in the tails of the data range in studies from developing countries reflect sparse data.