Growth differentiation factor 15 as a predictor of adverse renal outcomes in patients with immunoglobulin A nephropathy

Na, Ki Young; Kim, Yoo Hyung; Chung, Hyo Kyun; Yeo, Min‐Kyung; Ham, Young Rok; Jeong, Jin Young; Kim, Koon Soon; Lee, Kang Wook; Choi, Dae Eun

doi:10.1111/imj.13614

Cited by 18 publications

(15 citation statements)

References 36 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Moschovaki-Filippidou

Steiger

Lorenz

et al. 2020

IJMS

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Growth differentiation factor 15 (GDF15) is a member of the transforming growth factor-β (TGF-β) cytokine family and an inflammation-associated protein. Here, we investigated the role of GDF15 in murine anti-glomerular basement membrane (GBM) glomerulonephritis. Glomerulonephritis induction in mice induced systemic expression of GDF15. Moreover, we demonstrate the protective effects for GDF15, as GDF15-deficient mice exhibited increased proteinuria with an aggravated crescent formation and mesangial expansion in anti-GBM nephritis. Herein, GDF15 was required for the regulation of T-cell chemotactic chemokines in the kidney. In addition, we found the upregulation of the CXCR3 receptor in activated T-cells in GDF15-deficient mice. These data indicate that CXCL10/CXCR3-dependent-signaling promotes the infiltration of T cells into the organ during acute inflammation controlled by GDF15. Together, these results reveal a novel mechanism limiting the migration of lymphocytes to the site of inflammation during glomerulonephritis.

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Section: Discussionmentioning

confidence: 99%

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

Moschovaki-Filippidou

Steiger

Lorenz

et al. 2020

IJMS

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Growth differentiation factor 15 (GDF-15) is strongly associated with cardiovascular disease (CVD). The aim of our study was to evaluate plasma and urinary levels of GDF-15 after pediatric renal transplantation (Rtx) and in children with chronic kidney disease (CKD) and its associations to cardiovascular risk factors. In this cross-sectional study, GDF-15 was measured in plasma and urine from 53 children with a renal transplant and 83 children with CKD and related to cardiovascular risk factors (hypertension, obesity, and cholesterol) and kidney function. Forty healthy children served as a control group. Plasma levels of GDF-15 (median and range) for a Tx (transplantation) cohort, CKD cohort, and healthy controls were, respectively, 865 ng/L (463-3039 ng/L), 508 ng/L (183-3279 ng/L), and 390 ng/L (306-657 ng/L). The CKD and Tx cohorts both had significantly higher GDF-15 levels than the control group (p<0.001). Univariate associations between GDF-15 and hyperuricemia (p<0.001), elevated triglycerides (p=0.028), low HDL (p=0.038), and obesity (p=0.028) were found. However, mGFR (p<0.001) and hemoglobin (p<0.001) were the only significant predictors of GDF-15 in an adjusted analysis. Urinary GDF-15/creatinine ratios were 448 ng/mmol (74–5013 ng/mmol) and 540 ng/mmol (5–14960 ng/mmol) in the Tx cohort and CKD cohort, respectively. In the CKD cohort, it was weakly correlated to mGFR (r=−0.343, p=0.002). Plasma levels of GDF-15 are elevated in children with CKD and after Rtx. The levels were not associated with traditional cardiovascular risk factors but strongly associated with renal function.

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“…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].…”

Section: Discussionmentioning

confidence: 99%

“…Recently, GDF-15 has emerged as a biomarker for diagnosis and prediction of disease progression in various diseases, including cardiovascular and chronic inflammatory diseases [7]. Some studies have reported that higher GDF-15 levels are also associated with renal disorders such as diabetic nephropathy, idiopathic membranous nephropathy, and IgA nephropathy [8-11]. Other researchers have demonstrated that GDF-15 levels are correlated with prognosis of chronic kidney disease (CKD) [12, 13].…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Won

et al. 2019

Kidney Blood Press Res

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Background/Aims: Growth differentiation factor-15 (GDF-15) expression has been reported to increase in response to tissue damage and has recently emerged as a useful biomarker for various diseases. Although emerging evidence supports the clinicopathological value of GDF-15 in renal impairment, few studies have analyzed it in the elderly. Thus, we conducted a cross-sectional study to investigate the association of plasma GDF-15 with renal function and the presence of chronic kidney disease (CKD) in community-dwelling elderly. Materials: The present study was based on the baseline data of the Korean Frailty and Aging Cohort Study (KFACS), a nationwide cohort study that began in 2016. Of the 1,559 participants assessed in the first year, 443 with available plasma GDF-15 data were enrolled in this study. We investigated the association of plasma GDF-15 levels with clinical and biochemical parameters. The study population was divided into two groups according to renal function (CKD and non-CKD groups) to investigate whether GDF-15 can determine the presence of renal dysfunction in the elderly. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay (ELISA) kit. Results: In a simple regression analysis, the levels of plasma GDF-15 were negatively correlated with estimated glomerular filtration rate (eGFR; r = –0.383, p < 0.001). In multiple linear regression analysis, GDF-15 levels were still significantly correlated with eGFR, even after adjusting for other parameters (r = –0.259, p < 0.001). Plasma GDF-15 levels were significantly higher in the elderly with CKD than in those without CKD (2,364.025 ± 1,052.23 ng/L and 1,451.23 ± 835.79 ng/L, respectively; p < 0.001). The optimal cut-off value of plasma GDF-15 for detecting the presence of CKD was 1,699.4 ng/L (76.5% sensitivity and 76.0% specificity), as determined by the receiver operating characteristic curve. The area under the curve was 0.793 ± 0.033 (95% CI 0.729–0.857, p < 0.001). Conclusion: Plasma GDF-15 levels were negatively associated with eGFR and were significantly increased in the elderly with CKD. Our results suggested that plasma GDF-15 might be a useful marker for discriminating renal impairment in the elderly. Further large and prospective outcome studies of extended duration are needed.

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Growth differentiation factor 15 as a predictor of adverse renal outcomes in patients with immunoglobulin A nephropathy

Abstract: Initial serum GDF 15 level showed an inverse correlation with serum eGFR and was associated with worse renal outcome. Our results suggested that GDF 15 may play a role as a potential prognosticator in IgAN.

Cited by 18 publications

References 36 publications

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

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

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

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

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