Growth Differentiation Factor-15 as a Predictor of Idiopathic Membranous Nephropathy Progression: A Retrospective Study

Abstract

Idiopathic membranous nephropathy (IMN) is a major cause of nephrotic syndrome. No biomarker to predict the long-term prognosis of IMN is currently available. Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor-β superfamily and has been associated with chronic inflammatory disease. It has the potential to be a useful prognostic marker in patients with renal diseases, such as diabetic nephropathy and IgA nephropathy. This study examined whether GDF-15 is associated with the clinical parameters in IMN and showed that GDF-15 can predict IMN disease progression. A total of 35 patients with biopsy-proven IMN, treated at Chungnam National University Hospital from January 2010 to December 2015, were included. Patients younger than 18 years, those with secondary membranous nephropathy, and those lost to follow-up before 12 months were excluded. Levels of GDF-15 at the time of biopsy were measured using enzyme-linked immunosorbent assays. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate (eGFR) or the development of end-stage renal disease. The mean follow-up was 44.1 months (range: 16–72 months). Using receiver operating curve analysis, the best serum GDF-15 cut-off value for predicting disease progression was 2.15 ng/ml (sensitivity: 75.0%, specificity: 82.1%, p = 0.007). GDF-15 was significantly related to age and initial renal function. In the Kaplan-Meier analysis, the risk of disease progression increased in patients with GDF-15 ≥ 2.15 ng/ml when compared with those with GDF-15 < 2.15 ng/ml (50.0% versus 9.7%) (p = 0.012). In the multivariate Cox regression analysis adjusted for potential confounders, only GDF-15 was significantly associated with disease progression in IMN (p = 0.032). In conclusion, the GDF-15 level at the time of diagnosis has a significant negative correlation with initial renal function and is associated with a poor prognosis in IMN. Our results suggest that GDF-15 provides useful prognostic information in patients with IMN.

Growth Differentiation Factor 15 Ameliorates Anti-Glomerular Basement Membrane Glomerulonephritis in Mice

“…Moreover, in DN patients, high levels of GDF15 are associated with a decline in estimated glomerular filtration rate and faster progression to kidney failure [ 57 ]. Surely, the enhanced levels of GDF15 can deliver information about the deterioration of kidney function [ 60 , 61 , 62 ]. However, the suitability of GDF15 as a precise marker for kidney disease needs further investigation.…”

Growth Differentiation Factor 15 in Children with Chronic Kidney Disease and after Renal Transplantation

“…GDF-15 has also been associated with fibrosis in diseases of other organ systems such as dilated cardiomyopathy [28], systemic sclerosis [29], and chronic liver disease [30]. Two recent studies have shown GDF-15 to be associated with biopsy-proven fibrosis in the kidneys, the first in patients with IgA nephropathy [31] and the other in idiopathic membranous nephropathy [32]. GDF-15 might therefore also be a marker or a causative factor of kidney fibrosis that is responsible for decreased renal function in our pediatric cohorts.…”

Association between Plasma Levels of Growth Differentiation Factor-15 and Renal Function in the Elderly: Korean Frailty and Aging Cohort Study

“…Na et al [11] demonstrated that plasma GDF-15 has an inverse correlation with eGFR and is associated with poor renal outcomes in patients with IgA nephropathy, and Ham et al [10] reported similar trends in patients with idiopathic membranous nephropathy. Higher levels of GDF-15 predicted faster decline of renal function in patients with type 1 DM who have nephropathy [8] and starting dialysis in light chain amyloidosis patients [23].…”