Urinary Levels of 3 Proteins Are Potential Biomarkers of Lupus Nephritis Progression, Study Suggests

The levels of three specific proteins in the urine may help predict kidney injury and outcomes in patients with lupus nephritis, a study reports.

The study, “Composite urinary biomarkers to predict pathological tubulointerstitial lesions in lupus nephritis,” was published in the journal Lupus.

Kidney dysfunction affects up to half of systemic lupus erythematosus (SLE) patients, a condition known as lupus nephritis, often culminating in end-stage renal disease. These patients need to undergo regular filtering of their body’s waste by a machine (dialysis) or a kidney transplant.

Currently, a renal biopsy is the gold standard in diagnosing lupus nephritis and helping clinicians predict disease progression.

However, “serial and repeat biopsies are impractical in the monitoring of the disease due to their invasive nature,” the researchers wrote.

Tubulointerstitial nephritis is a primary injury that affects the renal tubules and the interstitium (the kidneys’ supporting tissue), and is linked to decreased renal function.

Recent studies suggest that the degree of tubulointerstitial damage may help predict long-term renal outcomes in lupus patients.

Being able to evaluate the presence of biomarkers of tubulointerstitial lesions in lupus nephritis in urine samples, for example, would greatly help clinicians manage and predict a patient’s disease course.

Previous studies suggested that the levels of three proteins — kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte chemoattractant protein-1 (MCP-1) — may highlight the presence of tubulointerstitial injury.

KIM-1 levels were significantly higher in urine samples from patients with renal tubule scarring (fibrosis) and inflammation, and was previously suggested as a biomarker to screen for active lupus nephritis.

In a previous report, researchers suggested that urine NGAL levels were a potential predictor of lupus nephritis disease activity and flares, and that persistent high levels of MCP-1 could indicate ongoing kidney injury.

Now a team of researchers has evaluated the clinical potential of the three biomarkers for detecting renal tubulointerstitial disease using a large, well-defined lupus nephritis group in China.

Their analysis included 109 biopsy-proven lupus nephritis patients, with a mean age of 31 years, of whom 96 were female, and 50 healthy individuals used as controls. They collected urine samples from the healthy controls and lupus patients on the morning of their renal biopsy. Of the lupus patients included in the study, 45 were in remission.

They then measured the levels of KIM-1, NGAL, and MCP-1, which were correlated with patients’ clinical disease activity, measured by the SLE Disease Activity Index (SLEDAI), and renal tissue features.

The levels of all three markers were significantly higher in the lupus nephritis patients than in controls. The levels of the 45 patients in clinical remission were significantly lower than those with active disease. No significant differences were found between the remission group and the normal controls.

The urinary levels of KIM-1 correlated with several disease changes in the renal tubules, including tubule atrophy, or reduction in size. Moreover, KIM-1 levels in the urine increased significantly in the presence of renal injury markers, such as proteinuria (abnormal quantities of protein in the urine), hematuria (presence of red blood cells in the urine), and higher levels of blood creatinine.

Creatinine is a chemical waste product produced by the muscles that is excreted through the kidneys. Higher levels of creatinine in the blood indicate poorer kidney function.

Accordingly, urinary MCP-1 levels were significantly higher in patients with acute renal failure and those with non-infectious leukocyturia, a condition characterized by the presence of white blood cells (a group of immune cells) in the urine without the presence of any infection.

Urinary KIM-1, NGAL, and MCP-1 levels were higher in patients with active tubulointerstitial lesions — characterized by the presence of inflammatory cells — than in those with only chronic lesions.

Researchers identified NGAL as a potential early marker of kidney injury, since an increase in its levels may occur before clinically detectable worsening of lupus nephritis.

While the three biomarkers on their own didn’t show any good predicting power, their triple combination had great diagnostic power for predicting renal outcomes of patients. Moreover, KIM-1 and NGAL together were identified as an independent risk factor for renal outcomes.

Overall, “urinary KIM-1, NGAL, and MCP-1 levels were associated with kidney injury indices in lupus nephritis,” the researchers wrote.

“The combination of the three biomarkers showed increased power in predicting tubulointerstitial lesions and renal outcomes,” the study concluded.