Augmented transcripts of kidney injury markers and renin angiotensin system in urine samples of overweight young adults

Abstract

Obesity has been firmly established as a major risk factor for common disease states including hypertension, type 2 diabetes mellitus, and chronic kidney disease. Increased body mass index (BMI) contributes to the activation of both the systemic and intra-tubular renin angiotensin systems (RAS), which are in turn associated with increased blood pressure (BP) and kidney damage. In this cross-sectional study, 43 subjects of normal or increased body weight were examined in order to determine the correlation of BMI or body fat mass (BFM) with blood pressure, fasting blood glucose (FBG), and urinary kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 (KIM-1). Our results showed that: (1) subjects with increased body weight showed significantly higher BP, BFM, total body water and metabolic age; (2) BMI was positively correlated to both systolic (R2 = 0.1384, P = 0.01) and diastolic BP (R2 = 0.2437, P = 0.0008); (3) BFM was positively correlated to DBP (R2 = 0.1232, P = 0.02) and partially correlated to urine protein (R2 = 0.047, P = 0.12) and FBG (R2 = 0.07, P = 0.06); (4) overweight young adults had higher urinary mRNA levels of renin, angiotensinogen, IL-18 and CTGF. These suggest that BMI directly affects BP, kidney injury markers, and the activation of the intra-tubular RAS even in normotensive young adults. Given that BMI measurements and urine analyses are non-invasive, our findings may pave the way to developing a new and simple method of screening for the risk of chronic kidney disease in adults.

Poor Glycemic Control Can Increase the Plasma Kidney Injury Molecule-1 Concentration in Normoalbuminuric Children and Adolescents with Diabetes Mellitus

“…This study aimed to evaluate the plasma and urinary NGAL and KIM-1 levels in diabetic children and determine their roles in predicting renal injury. Despite a lack of evidence and age-dependent changes in the reference interval for plasma and urinary NGAL and KIM-1, many publications have highlighted them as promising biomarkers reflecting early renal tubular injury in patients with CKD including DN [18,26,27]. The results of the present study were consistent with those of such previous studies.…”

Urinary Angiotensinogen Displays Sexual Dimorphism in Non-Diabetic Humans and Mice with Overweight

“…Also, CTGF excretion was related to the severity of diabetic nephropathy, suggesting that urinary CTGF may provide a marker of renal injury [ 40 ]. In a cross-sectional study, we reported that the mRNA levels of urinary kidney injury markers such as interleukin-18 (IL-18) and CTGF were augmented in individuals with a high BMI [ 12 ]. However, we did not find any changes in the neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) mRNA levels [ 12 ].…”

“…In a cross-sectional study, we reported that the mRNA levels of urinary kidney injury markers such as interleukin-18 (IL-18) and CTGF were augmented in individuals with a high BMI [ 12 ]. However, we did not find any changes in the neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) mRNA levels [ 12 ]. Terami et al showed that uAGT positively correlated with the albumin/creatinine ratio and urinary α1-microglobuline and pointed out that uAGT–α1-microglobulin correlation more accurately reflected the tubular injury associated with the intrarenal RAS activation in patients with T2DM [ 41 ].…”

“…Urinary mRNA levels of AGT and kidney injury markers such as interleukin-18 (IL-18), connective tissue growth factor (CTGF), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) correlated with increased body mass index (BMI) in young human adults. In these subjects, systolic blood pressure (SBP), fasting blood glucose levels (FBG), and urinary protein also correlated with BMI [ 12 ], suggesting that injury and inflammatory kidney markers are augmented in obesity and are associated with increased oxidative stress [ 13 , 14 ].…”