Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin as prognostic markers in idiopathic membranous nephropathy

Abstract

Background: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy. Methods: We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function. Excretion of alpha-1-microglobulin and beta-2-microglobulin had been measured previously. Progression was defined as a serum creatinine rise >30%, a rise in serum creatinine to an absolute value of 5135 mmol/L, or a clinical decision to start immunosuppressive therapy. Remission was defined as proteinuria <3.5 g/day and >50% reduction from baseline. Results: Sixty-nine patients were included. Median follow-up was 35 months (interquartile range 18-63 months). Progression occurred in 30 patients (44%), and spontaneous remission in 36 (52%). Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates were significantly correlated with each other, and with alpha-1-microglobulin and beta-2-microglobulin. The areas under the receiver operating characteristic curves for progression were 0.75 (0.62-0.87) for kidney injury molecule-1 and 0.74 (0.62-0.87) for neutrophil gelatinase-associated lipocalin. In multivariate analysis with either alpha-1-microglobulin and beta-2-microglobulin, kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin did not independently predict outcome. Conclusion: Kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion rates correlated with excretion rates of other tubular damage markers and predicted outcome in patients with idiopathic membranous nephropathy. They did not add prognostic value compared to measurement of either alpha-1-microglobulin or beta-2-microglobulin.

Kidney Injury Molecule-1 and Periostin Urinary Excretion and Tissue Expression Levels and Association with Glomerular Disease Outcomes

“…Our findings are consistent with many, demonstrating correlations between uKIM-1/Cr, UACR, and UPCR. Our study also corroborated the finding in a cohort of patients with MN that high uKIM-1/Cr excretion was a good predictor of proteinuria remission [28].…”

“…uKIM-1/Cr predicted decline of renal function in followup better than UACR [27]. In 69 nephrotic patients with MN and normal eGFR followed for a median of 39 months, the urine KIM-1 excretion rate was a good predictor of renal functional outcome and proteinuria remission, but it was not more accurate than other tubular markers including NGAL, α1-macroglobulin, or β 2macroglobulin [28]. Taken together, few studies have addressed the prognostic value of KIM-1 excretion and/or expression on the outcome of proteinuric renal diseases.…”

Urinary neutrophil gelatinase‐associated lipocalin rapidly decreases in the first week after kidney transplantation

“…According to our analysis of changes in renal function‐related indicators within one week after transplantation, we found that both serum and urinary NGAL have the same downward trend as creatinine and β2‐MG, and they have the opposite trend of eGFR, which was consistent with other studies 18‐20 . In the first week after renal transplantation, serum and urinary NGAL, creatinine, and β2‐MG increased, while eGFR decreased.…”

Kidney injury molecule‑1 levels are associated with therapeutic outcomes and renal tubulointerstitial injury severity in idiopathic membranous nephropathy

“…Urinary KIM-1 is a novel biomarker of tubular damage. There is increasing evidence of the prognostic value of KIM-1 in patients with glomerular disease, including diabetic kidney disease and IMN (20,21). However, the influence of the levels of KIM-1 in urine and renal tissue on the therapeutic efficacy for IMN has remained to be determined.…”