Blood Profiling May Help Identify Lupus Patients at Risk of Kidney Failure

Measuring the level of certain pro-inflammatory cytokines in the blood of patients with systemic lupus erythematosus (SLE) may help to identify those patients with kidney inflammation (nephritis), and so that treatments can begin that might halt the progression to kidney failure.

The study, “Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population,” was published in the journal Mediators of Inflammation.

The kidneys are major organs directly affected in SLE. In fact, up to 50% of patients with SLE exhibit kidney failure (also called end-stage renal disease, ESRD), the last stage of chronic kidney disease. Lupus nephritis-IV is the most common and severe form of nephritis.

Early detection of types IV, V and VI nephritis in lupus patients is crucial, as a recent clinical study suggested that these patients have poorer outcomes, when compared to lupus nephritis-II and -III.

Currently, kidney problems are determined through a renal biopsy, where a doctor uses a needle or another surgical instrument to remove a small piece of kidney tissue for examination. But many patients delay or refuse the procedure, due to its invasive nature.

Researchers investigated if the levels of proinflammatory cytokines IL-18, IL-18/IL-4, and IL-17A/IL-4 (cytokines are small molecules, released by cells of the immune system, that amplify the inflammatory response) contribute to the development of lupus nephritis-IV.

Previous studies suggested that these particular cytokines associate with active forms of lupus nephritis, having strong positive correlations with SLE disease activity index. The researchers here hypothesized that blood cytokine profiling of SLE patients may assist in the early histologic identification of lupus nephritis, reducing the probability of kidney failure in these patients.

They enrolled 49 (45 female and 4 male) patients with newly diagnosed SLE with nephritis, who had not received any immunosuppressive treatment (patients were selected from the Han Chinese cohort of  the Inpatient Department of Nephrology).

Patients were diagnosed by renal biopsy, and divided into three groups according to the disease type — lupus nephritis-III, lupus nephritis-IV and lupus nephritis-V — and a healthy control group was used as controls. All patients were analyzed for their cytokine profile, specifically for cytokines produced by immune T-helper (Th) cells, particularly Th1, Th2 and Th17.

Results showed increased expression of the cytokines IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A (Th1 and Th17) in blood samples from lupus nephritis-IV patients compared to controls. However, only IL-18 and IL-6 were found higher in class IV when compared to class III lupus nephritis patients. The ratio between different cytokines was also found significantly increased in lupus nephritis-IV relative to other forms of the disease (lupus nephritis-III, lupus nephritis-V) and healthy controls.

Researchers also found that lupus nephritis-class IV patients exhibited higher expression of blood cytokines IL-18, IL-17A, and IFN-γ in kidney blood vessels (in a zone of the kidney called the glomerulus). Importantly, these results also suggested that IL-18 is a potential marker for lupus nephritis-IV.

Results suggested that measuring the levels of specific cytokines may help identify and predict the active form of lupus nephritis, especially lupus nephritis-IV, prior to renal biopsy (and, especially, if this procedure cannot be performed). However, researchers noted that renal biopsy remains the gold standard in definitely diagnosing lupus nephritis.