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Kidney Disease Poses Risks in Lupus

Patients with systemic lupus erythematosus (SLE) who had chronic kidney disease were at an increased risk for poor outcomes, including end-stage renal disease and death, a nationwide French study found.

In a multivariate analysis, the hazard ratio for end-stage renal disease among patients who had chronic kidney disease at baseline was 15.9 (95% CI 11.6-21.9, P<0.0001), according to Karim Sacre, MD, and colleagues from Université Paris Diderot.

And the hazard ratio for mortality was almost double, at 1.7 (95% CI 1.3-2.2, P<0.0001), Sacre's group wrote in Autoimmunity Reviews.

“Impaired renal function at lupus nephritis diagnosis and failure to normalize renal function upon aggressive immunosuppressive therapy are associated with a very poor long-term renal outcome,” the team explained.

Approximately half of patients with SLE develop nephritis, which is characterized by glomerular immune complex deposits of immunoglobulin (Ig)M, IgG, and IgA. Progression to end-stage renal disease is generally expected in up to 30% of patients within 15 years of lupus nephritis diagnosis.

However, most reports of lupus nephritis outcomes have been limited by small sample sizes and have come from specialty care centers. Therefore, to provide a more comprehensive picture, Sacre’s group analyzed data from the national administrative database, including 6,439 patients with SLE who enrolled in 2009 and were followed through 2015.

Chronic kidney disease was defined as an estimated glomerular filtration rate below 60 mL/min/1.73 m2.

Patients’ mean age was 46, and the majority were women. A total of 428 (6.7%) had chronic kidney disease at baseline.

From 2009 to 2015, 10.1% of patients without chronic kidney disease at baseline developed the condition, and 33.15% of those who had chronic kidney disease at baseline went on to end-stage renal disease.

The very high risk of developing end-stage renal disease in this cohort requiring kidney transplantation or chronic dialysis, confirms previous studies demonstrating renal failure as an important predictor of morbidity in SLE, Sacre and co-authors said. Moreover, data on other factors that could further increase risk, such as kidney biopsy findings, urinary protein output, and ethnicity were unavailable in the national database.

In a univariate analysis, factors that were associated with chronic kidney disease included the following:

  • Male sex (OR 1.7, 95% CI 1.3-2.1, P=0.0002)
  • Hypertension (OR 3.4, 95% CI 2.7-4.2, P<0.0001)
  • Septic shock (OR 4.1, 95% CI 2.3-7.3)
  • History of cardiovascular disease (OR 3.4, 95% CI 2.7-4.2)

On the multivariate analysis, additional strong and independent associations were seen for cardiovascular events (HR 1.7, 95% CI 1.4-2.2, P<0.0001) as well as septic shock (HR 2.1, 95% CI 1.5-2.8, P<0.0017).

Cardiovascular events associated with atherosclerosis remain the number one cause of death in SLE. Conventional risk-prediction models such as the Framingham score underestimate risks in SLE, the researchers noted. “Our study highlights the strong association of chronic kidney disease and cardiovascular events in SLE and supports a drastic primary prevention of cardiovascular disease in SLE patients with chronic kidney disease,” the team wrote.

The researchers added that another major concern for SLE patients is the development of serious infection, which can lead to both morbidity and mortality. For example, one previous study reported on high rates of pneumococcal infections among SLE patients with nephritis, and another recent study found that approximately one in 10 cases of septic shock were caused by vaccine-preventable organisms. “Hence, our study also points to the need for an optimal vaccination coverage in SLE with chronic kidney disease,” Sacre and colleagues observed.

A limitation of the study, the researchers said, was its reliance on in-hospital data only, so outcomes may have been underestimated.

“Our results illustrate the critical importance of early detection (i.e., before the onset of renal function impairment) and treatment of lupus nephritis,” the investigators concluded.

The authors reported no conflicts of interest.


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