Maria R. Wing

Association between Albuminuria, Kidney Function, and Inflammatory Biomarker Profile in CKD in CRIC

BACKGROUND AND OBJECTIVES Increased risk of mortality in patients with CKD has been attributed to inflammation. However, the association between kidney function, albuminuria, and biomarkers of inflammation has not been examined in a large cohort of CKD patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This study measured the plasma levels of IL-1β, IL-1 receptor antagonist (IL-1RA), IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, and serum albumin in 3939 participants enrolled in the Chronic Renal Insufficiency Cohort study between June 2003 and September 2008. An inflammation score was established based on plasma levels of IL-1β, IL-6, TNF-α, hs-CRP, and fibrinogen. Estimated GFR (eGFR) and serum cystatin C were used as measures of kidney function. Albuminuria was quantitated by urine albumin to creatinine ratio (UACR). RESULTS Plasma levels of IL-1β, IL-1RA, IL-6, TNF-α, hs-CRP, and fibrinogen were higher among participants with lower levels of eGFR. Inflammation score was higher among those with lower eGFR and higher UACR. In regression analysis adjusted for multiple covariates, eGFR, cystatin C, and UACR were strongly associated with fibrinogen, serum albumin, IL-6, and TNF-α. Each unit increase in eGFR, cystatin C, and UACR was associated with a -1.2% (95% confidence interval, -1.4, -1), 64.9% (56.8, 73.3) and 0.6% (0.4, 0.8) change in IL-6, respectively (P<0.001). CONCLUSIONS Biomarkers of inflammation were inversely associated with measures of kidney function and positively with albuminuria.

DNA methylation profile associated with rapid decline in kidney function: findings from the CRIC Study

BACKGROUND Epigenetic mechanisms may be important in the progression of chronic kidney disease (CKD). METHODS We studied the genome-wide DNA methylation pattern associated with rapid loss of kidney function using the Infinium HumanMethylation 450 K BeadChip in 40 Chronic Renal Insufficiency (CRIC) study participants (n = 3939) with the highest and lowest rates of decline in estimated glomerular filtration rate. RESULTS The mean eGFR slope was 2.2 (1.4) and -5.1 (1.2) mL/min/1.73 m(2) in the stable kidney function group and the rapid progression group, respectively. CpG islands in NPHP4, IQSEC1 and TCF3 were hypermethylated to a larger extent in subjects with stable kidney function (P-values of 7.8E-05 to 9.5E-05). These genes are involved in pathways known to promote the epithelial to mesenchymal transition and renal fibrosis. Other CKD-related genes that were differentially methylated are NOS3, NFKBIL2, CLU, NFKBIB, TGFB3 and TGFBI, which are involved in oxidative stress and inflammatory pathways (P-values of 4.5E-03 to 0.046). Pathway analysis using Ingenuity Pathway Analysis showed that gene networks related to cell signaling, carbohydrate metabolism and human behavior are epigenetically regulated in CKD. CONCLUSIONS Epigenetic modifications may be important in determining the rate of loss of kidney function in patients with established CKD.

Circulating and urinary microRNA profile in focal segmental glomerulosclerosis: a pilot study

MicroRNAs (miRNAs) are noncoding RNA molecules that play important roles in the pathogenesis of various kidney diseases. We investigated whether patients with minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) have distinct circulating and urinary miRNA expression profiles that could lead to potential development of noninvasive biomarkers of the disease.

Epigenetics of Progression of Chronic Kidney Disease: Fact or Fantasy?

Epigenetic modifications are important in the normal functioning of the cell, from regulating dynamic expression of essential genes and associated proteins to repressing those that are unneeded. Epigenetic changes are essential for development and functioning of the kidney, and aberrant methylation, histone modifications, and expression of microRNA could lead to chronic kidney disease (CKD). Here, epigenetic modifications modulate transforming growth factor β signaling, inflammation, profibrotic genes, and the epithelial-to-mesenchymal transition, promoting renal fibrosis and progression of CKD. Identification of these epigenetic changes is important because they are potentially reversible and may serve as therapeutic targets in the future to prevent subsequent renal fibrosis and CKD. In this review we discuss the different types of epigenetic control, methods to study epigenetic modifications, and how epigenetics promotes progression of CKD.

Gut microbiome in chronic kidney disease

What is the topic of this review? This review addresses the contribution of the altered gut microbiome to uraemic syndrome, with specific reference to gut microbiome‐derived uraemic toxins. It also discusses the potential treatment options to normalize the disturbed microbiome in chronic kidney disease (CKD). What advances does it highlight? This review highlights the importance of the gut–kidney connection and how the altered microbial landscape in the intestine contributes to dysmetabolism and inflammation in CKD. Recent findings linking gut‐derived uraemic toxins to progression of CKD, cardiovascular disease and mortality are also discussed. Finally, we briefly explain targeted therapies that have been studied to restore intestinal symbiosis in CKD.

Race modifies the association between adiposity and inflammation in patients with chronic kidney disease: Findings from the chronic renal insufficiency cohort study

The race‐specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined.

Race modifies the association between adiposity and inflammation in patients with chronic kidney disease: findings from the CRIC study

The race‐specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined.

A balancing act: protein-energy wasting in chronic kidney disease.

protein energy wasting and its extreme form, cachexia, is common among patients with chronic kidney disease (CKD). This maladaptive metabolic state is fueled by inflammation and is characterized by anorexia, increased energy expenditure, ineffective utilization of nutrients, and augmented protein

Race modifies the association between adiposity and inflammation in patients with chronic kidney disease: Findings from the chronic renal insufficiency cohort study: Adiposity and Inflammation

The race‐specific association of inflammation with adiposity and muscle mass in subjects with chronic kidney disease (CKD) was examined.