The world health community has lost ground in its fight to reduce end-stage renal disease in patients with lupus nephritis, a systematic review and meta-analysis concluded.

The risk of end-stage renal disease (ESRD) at 5 years of lupus nephritis decreased substantially from the 1970s, when it was 16%, to the mid-1990s, when it plateaued at 11%.

ESRD risks at 10 years and 15 years declined more sharply in the 1970s and 1980s but also plateaued in the mid-1990s at 17% and 22%, respectively.

This plateau was followed by a notable increase in risk in the late 2000s, particularly in the 10-year and 15-year estimates, Dr. Maria Tektonidou of the University of Athens and her coauthors reported (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39594).

“Despite extensive use of immunosuppressive medications through the 2000s, we did not find continued improvement in ESRD risks, but instead a slight increase in risks in the late 2000s,” they wrote.

The increase did not appear to be related to greater representation in recent studies of ethnic minorities, who may be more likely to develop ESRD. In the main analysis involving 148 of the 187 studies, “trends suggest this increase may have been temporary, but further follow-up will be needed to determine if this is sustained,” the investigators added.

Notably, patients with class-IV lupus nephritis had the greatest risk of ESRD during the 2000s, with a 15-year risk of 44%.

The 15-year risk of ESRD also was higher by 10 percentage points in developing countries than in developed countries during the 2000s.

The trends are worrisome because ESRD is a costly complication of lupus nephritis, which affects more than half of all patients with systemic lupus erythematosus (SLE). Patients with lupus nephritis have a 26-fold increased risk of death and estimated annual health care costs between $43,000 and $107,000 per patient, the authors noted.

The systematic review and Bayesian meta-analysis included 187 studies reporting on 18,309 adults with lupus nephritis from 1971 to 2015. The main analysis of ESRD risk included 102 studies from developed countries and 46 studies from developing countries.

Across all studies, 86% of patients were women, 32% had elevated serum creatinine levels at study entry, and proteinuria averaged 3.6 g daily. The average age was 31.2 years and mean duration of lupus nephritis was 2.7 years.

The proportion of patients treated with glucocorticoids alone in the studies declined from 54% in 1966 to 9% in 2010, while use of immunosuppressive therapies increased.

The decrease in ESRD risks early on coincided with increased use of immunosuppressives, particularly cyclophosphamide, and better control of hypertension and proteinuria. As for why those gains have stalled, Dr. Tektonidou and her colleagues said it’s possible that the limits of effectiveness of current treatments have been reached and better outcomes will require new therapies. “It is also possible that the plateau primarily reflects lack of progress in the way currently available and effective treatments are deployed,” they added. “This includes health system factors that result in delays in treatment initiation, and patient and health system factors that result in treatment interruptions and reduced adherence.”

In an accompanying editorial, Dr. Candace Feldman and Dr. Karen Costenbader, both of Brigham and Women’s Hospital in Boston, wrote, “While we have made advances over the past 50 years in our understanding of immunosuppressive medications, there have been few meaningful improvements in other domains that contribute to ESRD and to the persistent and disproportionate burden among vulnerable populations” (Ann Rheum Dis. 2016 Jan 27. doi: 10.1002/art.39593).

Despite the clear importance of medication adherence to SLE care, a recent systematic review of adherence interventions in rheumatic diseases (Ann Rheum Dis. 2015 Feb 9. doi: 10.1136/annrheumdis-2014-206593) found few SLE-specific interventions overall and none that significantly improved adherence outcomes, Dr. Feldman and Dr. Costenbader pointed out.

Dr. Tektonidou and her associates acknowledged that the new systematic review and meta-analysis were limited by the inability to estimate risks beyond 15 years and because the findings were similar only when observational studies were considered. Factors associated with ESRD, such as renal flares and uncontrolled hypertension, were not examined, and few studies were judged to be of high-quality.

Still, the results can be used to counsel patients on risks of ESRD and also will provide benchmarks to judge the effectiveness of future treatments, the authors concluded.

Dr. Feldman and Dr. Costenbader disagreed with this conclusion, citing various study limitations and the many nuanced factors that play into a patient’s risk of developing ESRD.

“This study should rather be used to provide a broad overview of our understanding of changes in SLE ESRD over time, rather than data to counsel an individual patient on his/her risks,” they wrote.

The study was supported by the intramural research program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported having no conflicts of interest.