Mortality Improves in Lupus ESRD Save

The past two decades have seen a significant decline in mortality among patients with lupus nephritis, U.S. registry data indicated.

During the years 1995-1999, mortality from end-stage renal disease (ESRD) associated with lupus nephritis was 11.1 per 100 patient-years (95% CI 10.4-11.8), whereas for the years 2010-2014, the mortality rate was 6.7 per 100 (95% CI 6.2-7.2, P0.001 for trend), according to April Jorge, MD, and colleagues from Harvard Medical School in Boston.

Compared with the earliest 5-year period, the fully adjusted hazard ratio for all-cause mortality in 2010-2014 was 0.68 (95% CI 0.61-0.75), thus representing a 32% decline, the researchers reported online in Arthritis & Rheumatology.

Up to half of patients with systemic lupus erythematosus develop nephritis, and despite recent improvements in treatment, almost one-third of patients with lupus nephritis ultimately develop ESRD.

An earlier study revealed that the premature mortality associated with ESRD in patients with lupus nephritis persisted from 1995 to 2006, but it has not been clear whether there has been a change in more recent years.

To explore this, Jorge and colleagues analyzed data from the United States Renal Data System for the years 1995 to 2014, which includes almost all patients receiving renal replacement therapy.

Incident cases of lupus nephritis ESRD were divided into 5-year cohorts: 1995-1999, 2000-2004, 2005-2009, and 2010-2014. The 1995-1999 cohort was considered the reference group.

The analyses were adjusted for age, gender, body mass index, smoking, geographic region of residence, and comorbidities such as diabetes, hypertension, cerebrovascular accident, and congestive heart failure.

During the entire study period, 20,974 patients with lupus nephritis developed ESRD at a mean age of 40. Most were women, and 48% were African-American.

Mean body mass index increased from a mean of 24.8 in the earliest cohort to 27.3 in the latest group. The incidence of hypertension and diabetes increased, from 69.9% to 85.7% and from 5.9% to 9.7%, respectively, while there was a small decrease in the incidence of congestive heart failure, from 16.3% to 13.7%.

The frequency of kidney transplant declined slightly, being 20.6% in the earliest cohort and 19.8% in the latest group, but mean time to transplant decreased from 1.29 years to 1.07 years (P0.01 for trend).

During the follow-up period, about one-fifth of patients with ESRD associated with lupus nephritis died.

Mortality rates showed similar reductions according to race and ethnicity. Compared with the reference cohort, the fully adjusted hazard ratios in the latest cohort were 0.68 (95% CI 0.58-0.78) for whites, 0.67 (95% CI 0.57-0.78) for African-Americans, and 0.51 (95% CI 0.38-0.69) for Hispanics

The leading causes of death across all cohorts were cardiovascular disease and infections, both of which decreased over time. Cardiovascular deaths included myocardial infarction, atherosclerotic disease, arrhythmias, cardiac arrest, valvular heart disease, pulmonary embolism, and congestive heart failure. Deaths related to infection included septicemia, peritonitis, central nervous system infection, gangrene, endocarditis, and pulmonary, abdominal, and genitourinary infections.

For cardiovascular disease, the likelihood of death decreased by 44% from the earliest to the latest cohorts (HR 0.56, 95% CI 0.48-0.67), while mortality associated with infection decreased by 63% (HR 0.37, 95% CI 0.29-0.47).

"This improved survival among patients with lupus nephritis ESRD may be explained by a combination of improvements in the management of ESRD and of underlying systemic lupus erythematosus," the investigators wrote.

Contributing factors include the use of more intense immunosuppression once ESRD develops, lower cumulative exposure to steroids, better management of comorbidities, and the slight increase in pre-emptive kidney transplantation and modest reduction in time to transplant.

Many studies have found a higher risk of early mortality among African-Americans with lupus nephritis ESRD, but in this analysis the level of mortality reduction was similar for African-Americans and whites, "suggesting that the mortality disparity did not change."

Among potential reasons why the mortality is higher among African-Americans are socioeconomic factors, lower rates of transplantation, and genetic predisposition to worse renal disease. Improved care for African-American patients with lupus nephritis ESRD "is likely still needed," the authors noted.

Nonetheless, they concluded, "collectively, these trends provide an important benchmark of improving care in this high-risk population."

One limitation of the study was lack of access to data on lupus disease activity and treatments before development of ESRD.