Urinary Growth Differentiation Factor-15 (GDF15) levels as a biomarker of adverse outcomes and biopsy findings in chronic kidney disease

Perez-Gomez, María Vanessa; Pizarro-Sánchez, Soledad; Gracia-Iguacel, Carolina; Cano, Santiago; Cannata‐Ortiz, Pablo; Sánchez-Rodríguez, Jinny; Sanz, Ana B.; Sanchez-Niño, María Dolores; Ortíz, Alberto

doi:10.1007/s40620-021-01020-2

Cited by 30 publications

(30 citation statements)

References 42 publications

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“…In our study, mRNA/pro-peptide form of GDF15 and the protein expression of pro-GDF15 form were positively correlated with increased periostin levels and p65 activation, likely associated with the inflammatory response and renal damages in DN. As we have observed in our diabetic mice, GDF15 is expressed mainly in tubular cells in patients with CKD [55] and the urinary GDF15 levels and plasma levels are associated with kidney histology lesions in patients with CKD, including DN [55][56][57]. In GDF15 knock-out mice, it was observed that an increase in renal tissue damage in the STZ and db/db models was associated with an increase in tubular and interstitial injury.…”

Section: Discussionsupporting

confidence: 78%

“…In GDF15 knock-out mice, it was observed that an increase in renal tissue damage in the STZ and db/db models was associated with an increase in tubular and interstitial injury. Moreover, an anti-fibrotic effect has been attributed to GDF15 by the blockage of the TGF-β receptor and the N-Myc signalling pathways in a ureteral obstruction model after GDF15 administration [ 55 ]. All these data suggest an anti-fibrotic effect of GDF15 and therefore the increase in pro-GDF15 observed in our diabetic mice could be considered as a marker and also as a protective reaction to limit the progression of DN.…”

Section: Discussionmentioning

confidence: 99%

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Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy

Abbad

Prakoura

Michon

et al. 2022

Cells

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Diabetic nephropathy (DN) remains the most common reason for end-stage renal disease and a leading cause of kidney replacement therapy. Multifactorial pathophysiological mechanisms underlie the development of DN. Among the signalling pathways involved, nuclear factor-κB (NF-κB) plays a key role in pathogenesis triggering inflammation, oxidative stress and fibrosis. Recent evidence shows that periostin, a matricellular protein, is involved in the development of renal glomerular diseases through interaction with NF-κB signalling. The aim of the present study is to investigate the contribution of periostin and its interaction with NF-κB in DN development. To this end, we used the BTBR ob/ob mice model of diabetes type 2, and we applied transcriptomic analysis, immunostaining and methods quantifying protein and mRNA expressions. We found that increased periostin expression was correlated with decreased renal function, advanced stage renal damage and fibrosis, and NF-κB activation. Subsequently, we identified novel pathways and genes regulated by the NF-κB-periostin interaction which are involved in the mechanisms of progression of DN. Some of these genes, such as FGF1 and GDF15, have the potential to be new biomarkers and/or targets for the therapy of DN.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy

Abbad

Prakoura

Michon

et al. 2022

Cells

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“…Consistent with previous studies, we herein found that the serum GDF15 level is associated with higher WC, HC, HbA1c, and a higher prevalence of T2DM and hypertension. Regarding diabetic complications, several reports have demonstrated the role of serum GDF15 in diabetic nephropathy and have suggested that GDF15 is a predictor of diabetic kidney disease [ 38 , 39 , 40 , 41 , 42 ]. Furthermore, recent studies have described the association between serum GDF15 and diabetic retinopathy both in T2DM [ 22 , 23 ] and T1DM [ 39 ], reporting that the plasma GDF15 level is a significant predictor of diabetic retinopathy, while there is a trend between increased plasma GDF15 level and severity of retinopathy in T2DM.…”

Section: Discussionmentioning

confidence: 99%

Circulating Growth Differentiation Factor 15 Is Associated with Diabetic Neuropathy

Weng

Chen

Shen

et al. 2022

JCM

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Background: Growth differentiation factor (GDF15) is a superfamily of transforming growth factor-beta which has been suggested to be correlated with various pathological conditions. The current study aimed to investigate the predicted role of circulating GDF15 in diabetic metabolism characteristics and diabetic neuropathy. Methods: 241 diabetic patients and 42 non-diabetic subjects were included to participate in the study. The plasma GDF15 levels were measured using ELISA. Chronic kidney disease and albuminuria were defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guideline. The nerve conductive study (NCS) was performed with measurement of distal latency, amplitude, nerve conduction velocity (NCV), H-reflex, and F-wave studies. Results: The diabetic group had a significantly higher prevalence of chronic kidney disease and higher plasma GDF15 level. After adjusting for age and BMI, GDF15 was significantly positively correlated with waist circumference (r = 0.332, p = <0.001), hip circumference (r = 0.339, p < 0.001), HbA1c (r = 0.302, p < 0.001), serum creatine (r = 0.146, p = 0.017), urine albumin/creatinine ratio (r = 0.126, p = 0.040), and HOMA-IR (r = 0.166, p = 0.007). As to NCS, GDF15 was significantly correlated with all latency and amplitude of sensory and motor nerves, as well as F-wave and H-reflex latencies. The area under the curve (AUC) in predicting tibial motor nerve neuropathy (MNCV) in all subjects and in the diabetic group for GDF15 was 0.646 (p = 0.001) and 0.610 (p = 0.012), respectively; for HbA1c was 0.639 (p = 0.001) and 0.604 (p = 0.018), respectively. Predicting ulnar sensory nerve neuropathy for GDF15 was 0.639 (p = 0.001) and 0.658 (p = 0.001), respectively; for HbA1c was 0.545 (p = 0.307) and 0.545 (p = 0.335), respectively. Predicting median sensory nerve neuropathy for GDF15 was 0.633 (p = 0.007) and 0.611 (p = 0.032), respectively; for HbA1c was 0.631 (p = 0.008) and 0.607 (p = 0.038), respectively. Predicting CKD for GDF15 was 0.709 (95% CI, 0.648–0.771), p < 0.001) and 0.676 (95% CI, 0.605–0.746), p < 0.001), respectively; for HbA1c was 0.560 (95% CI, 0.493–0.627); p = 0.080) and 0.515 (95% CI, 0.441–0.588); p = 0.697), respectively. Conclusions: We suggest that there is a significant association between the increased serum GDF-15 level and metabolic parameters and diabetic neuropathy. Plasma GDF15 may be an independent predictor of diabetic neuropathy.

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“…Finally, Growth Differentiation Factor 15 (GDF15), a stress-inducible cytokine, also has important implications in the context of ccRCC. It plays key roles in prenatal development, inflammation, regulation of cellular responses to stress signals, and tissue repair [ 41 , 42 ]. GDF-15 has been reported as a biomarker in several kinds of pathologies, including kidney disease [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

et al. 2021

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Due its ability to provide a global snapshot of kidney physiology, urine has emerged as a highly promising, non-invasive source in the search for new molecular indicators of disease diagnosis, prognosis, and surveillance. In particular, proteomics represents an ideal strategy for the identification of urinary protein markers; thus, a urinomic approach could also represent a powerful tool in the investigation of the most common kidney cancer, which is clear cell Renal Cell Carcinoma (ccRCC). Currently, these tumors are classified after surgical removal using the TNM and nuclear grading systems and prognosis is usually predicted based upon staging. However, the aggressiveness and clinical outcomes of ccRCC remain heterogeneous within each stratified group, highlighting the need for novel molecular indicators that can predict the progression of these tumors. In our study, we explored the association between the urinary proteome and the ccRCC staging and grading classification. The urine proteome of 44 ccRCC patients with lesions of varying severity was analyzed via label-free proteomics. MS data revealed several proteins with altered abundance according to clinicopathological stratification. Specifically, we determined a panel of dysregulated proteins strictly related to stage and grade, suggesting the potential utility of MS-based urinomics as a complementary tool in the staging process of ccRCC.

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Urinary Growth Differentiation Factor-15 (GDF15) levels as a biomarker of adverse outcomes and biopsy findings in chronic kidney disease

Cited by 30 publications

References 42 publications

Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy

Role of Periostin and Nuclear Factor-κB Interplay in the Development of Diabetic Nephropathy

Circulating Growth Differentiation Factor 15 Is Associated with Diabetic Neuropathy

Does the Urinary Proteome Reflect ccRCC Stage and Grade Progression?

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