Soluble ST2 and Galectin-3 and Progression of CKD

Abstract

IntroductionCardiac biomarkers soluble ST2 (sST2) and galectin-3 may reflect cardiac inflammation and fibrosis. It is plausible that these mechanisms may also contribute to the progression of kidney disease. We examined associations of sST2 and galectin-3 with kidney function decline in participants with chronic kidney disease (CKD).MethodsThis was a pooled analysis of 2 longitudinal cohorts of participants with CKD: the Clinical Phenotyping and Resource Biobank (C-PROBE) study and the Seattle Kidney Study (SKS). We measured circulating concentrations of sST2 and galectin-3 at baseline. Our primary outcome was progression to estimated glomerular filtration rate (eGFR) <15 ml/min per 1.73 m2 or end-stage renal disease (ESRD). We used competing risk Cox regression models to study the association of sST2 and galectin-3 with CKD progression, adjusting for demographics, kidney function, and comorbidity.ResultsAmong the 841 participants in the pooled cohort, baseline eGFR was 51 ± 27 ml/min per 1.73 m2 and median urine albumin-to-creatinine ratio (UACR) was 141 (interquartile range = 15−736) mg/g. Participants with higher sST2 and galectin-3 were more likely to be older, to have heart failure and diabetes, and to have lower eGFR. Adjusting for demographics, kidney function, and comorbidity, every doubling of sST2 was not associated with progression to eGFR <15 ml/min per 1.73 m2 or ESRD (adjusted hazard ratio 1.02, 95% confidence interval = 0.76−1.38). Every doubling of galectin-3 was significantly associated with a 38% (adjusted hazard ratio = 1.35, 95% confidence interval = 1.01−1.80) increased risk of progression to eGFR <15 ml/min per 1.73 m2 or ESRD.ConclusionHigher concentrations of the cardiac biomarker galectin-3 may be associated with progression of CKD, highlighting potential novel mechanisms that may contribute to the progression of kidney disease.

Novel Biomarkers in Patients with Chronic Kidney Disease: An Analysis of Patients Enrolled in the GCKD-Study

“…Since some of the most commonly used conventional biomarkers in CVD are chronically elevated in patients with CKD, at least partly because of impaired renal clearance, the finding that sST2 acts independently of renal function might be of significant relevance for clinical practice. Nevertheless, this finding needs to be confirmed in large prospective endpoint trials because it to some extent contradicts the findings of a study by Alam et al In this study, some correlation of sST2 with renal function was observed in a larger, pooled cohort, yet this relationship was very weak [60]. Furthermore, the clinical performance of biomarkers needs to be confirmed in large prospective endpoint trials.…”

IL-33/ST2 pathway regulates neutrophil migration and predicts outcome in patients with severe alcoholic hepatitis

“…Moreover, in patients initially classified as having good prognosis and who respond to therapy, the occurrence of an infection is responsible for a major drop in survival. 8 Circulating sST2 has been proposed as a biomarker in several diseases [34][35][36] and adding this marker to available scoring systems could optimize the prediction of clinical events in SAH. We show here using a large sample size and a robust methodology that sST2 not only predicts mortality but also the probability of getting infected in SAH and in cirrhosis, even though circulating levels of sST2 are different between the 2 conditions.…”

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

“…Recently, Gal-3 has been indicated to be involved in the following broad pathological processes: Inflammation [9], fibrosis, cell-to-cell [10,11] or cell-to-matrix [12] contacts, cell proliferation [13,14], and protection from apoptosis [15,16]. Furthermore, many studies have revealed that Gal-3 expression is detected in many disease conditions, such as heart disease [17][18][19][20][21][22][23], kidney disease [24][25][26][27], diabetes mellitus [24,25,28], viral infection [29][30][31][32], autoimmune disease [33][34][35][36], neurodegenerative disorders [37][38][39][40][41][42], and tumor formation [43][44][45][46][47][48][49][50][51][52].…”

“…Heart disease acute heart failure plasma level combination with natriuretic peptide [62] acute heart failure plasma level promising prognostic marker [63] chronic heart failure plasma level useful in HF patients with preserved LVEF [64] chronic heart failure myocardial and plasma level not associated with histology [65] acute myocardial infarction serum level no definite relationship with ventricular remodeling [66] Nervous system diseases myelin degeneration tissues activation of the phagocytosis of degenerated myelin [42] intracerebral hemorrhage plasma level prognostic predictor [67] subarachnoid hemorrhage plasma level prognostic predictor [68] global brain ischemia cerebrospinal fluid prognostic marker and inflammatory mediator [69] Renal disease CKD plasma level associated with progression of CKD [25] SLE nephritis serum and biopsy specimens associated with SLE patients, particularly in SLE nephritis [70] Liver disease liver fibrosis serum Gal-3 related binding protein assessing liver fibrosis [71] Connective tissue diseases rheumatoid arthritis serum level increased in early rheumatoid arthritis [72] SLE serum anti-Gal-3 antibody a key role in SLE skin lesions [73] systemic sclerosis serum level predictor of mortality [74] Neoplasms colorectal cancer serum and tissues related to tumor progression [52] breast cancer human cell lines important factor for treatment [75] non-small cell lung cancer tumor expression promotion of invasion and metastasis [76] lung and prostate cancers tumor expression therapeutic target of tumor immunity [77] cervical cancer tumor expression targets of multifunctional cancer treatment [78] thyroid cancer tumor expression diagnostic marker [79]…”

“…Higher concentrations of Gal-3 may be associated with progression of CKD, indicating potential novel mechanisms related to Gal-3 expression that may contribute to the progression of CKD [25]. Furthermore, Gal-3 is reported to play a pivotal role in renal interstitial fibrosis and progression of CKD [117].…”