Growth Differentiation Factor–15 and Risk of CKD Progression

Abstract

Growth differentiation factor-15 (GDF-15) is a member of the TGF- cytokine superfamily that is widely expressed and may be induced in response to tissue injury. Elevations in GDF-15 may identify a novel pathway involved in loss of kidney function among patients with CKD. Among participants in the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS), we tested whether kidney tissue expression of mRNA correlates with circulating levels of GDF-15 and whether elevations in circulating GDF-15 are associated with decline in kidney function. In matching samples of 24 patients with CKD from the C-PROBE study, circulating GDF-15 levels significantly correlated with intrarenal transcript levels (=0.54, =0.01). Among the 224 C-PROBE and 297 SKS participants, 72 (32.1%) and 94 (32.0%) patients, respectively, reached a composite end point of 30% decline in eGFR or progression to ESRD over a median of 1.8 and 2.0 years of follow up, respectively. In multivariable models, after adjusting for potential confounders, every doubling of GDF-15 level associated with a 72% higher (95% confidence interval, 1.21 to 4.45;=0.003) and 65% higher (95% confidence interval, 1.08 to 2.50; =0.02) risk of progression of kidney disease in C-PROBE and SKS participants, respectively. These results show that circulating GDF-15 levels strongly correlated with intrarenal expression of and significantly associated with increased risk of CKD progression in two independent cohorts. Circulating GDF-15 may be a marker for intrarenal -related signaling pathways associated with CKD and CKD progression.

Plasma FGF‐21 and GDF‐15 are elevated in different inherited metabolic diseases and are not diagnostic for mitochondrial disorders

“…Another patient with infantile fatal renal tubulopathy and RRM2B gene mutations had the highest values of FGF‐21 and GDF‐15 (35 777 and 326 320 pg/mL). Both cytokines are known to be highly expressed in kidney and recent publication showed that level of circulating GDF‐15 strongly correlates with an intrarenal expression of GDF15 and is strongly associated with increased risk of chronic kidney disease progression . Three patients with infantile encephalopathy and hypertrophic cardiomyopathy due to SCO2 and COX10 genes mutations had elevated plasma GDF‐15 with normal FGF‐21.…”

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

“…Although several kidney biomarkers such as cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) have been introduced, identification of a new marker is needed to assess accurate renal function and to understand the complex pathophysiology of renal disorders [12, 24]. Our findings suggest that GDF-15 may be a useful kidney biomarker, especially in the elderly.…”

“…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]. Viji et al [12] demonstrated that the level of plasma GDF-15 strongly correlates with intrarenal expression of GDF-15 mRNA, and that elevated GDF-15 was significantly associated with increased risk of renal function deterioration in patients with CKD.…”

“…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]. However, only a few studies have analyzed the association between GDF-15 and renal function in the elderly [14].…”

Czynnik różnicowania wzrostu 15 jako biomarker w niewydolności serca

“…Okazało się podwyższone przy obniżonym przesączaniu kłębuszkowym (eGFR, estimated glomerular filtration rate), a wewnątrznerkowe nasilenie ekspresji GDF-15 mRNA u pacjentów z przewlekłą chorobą nerek było skorelowane ze stężeniem krążącego we krwi GDF-15 [43]. Każde podwojenie stężenia tego markera wiązało się z 72-procentowym wzrostem ryzyka progresji przewlekłej choroby nerek (zmniejszeniem eGFR o 30%) w ciągu trwają-cej blisko 2 lata obserwacji.…”