Ectopic Adipose Tissue Storage in the Left and the Right Renal Sinus is Asymmetric and Associated With Serum Kidney Injury Molecule-1 and Fibroblast Growth Factor-21 Levels Increase

Abstract

Objective: A potential mechanism by which obesity could promote hypertension and kidney diseases is through accumulation of adipose tissue in the renal sinus (RS). The aim of the study was to quantify RS and abdominal adipose tissue volumes and to evaluate serum kidney injury molecule (sKIM)-1 and fibroblast growth factor (FGF)-21 association with different adipose tissue compartments.

Methods: The cross-sectional study included 280 and follow-up study-40 asymptomatic participants; aged 38.30±4.10. For all study participants computed tomography examination was performed, sKIM-1 and FGF-21 levels were measured.

Results: The results indicated asymmetrical deposition of adipose tissue into the RS even after corresponding kidney volume adjustment. The cross-sectional and the follow-up studies showed that sKIM-1 level was positively associated with RS adipose tissue volume increase for both genders. FGF-21 was positively associated with RS and retroperitoneal adipose tissue amount.

Conclusions: Regardless of gender adipose tissue in RS accumulates asymmetrically-the left RS accumulates a significantly higher amount of adipose tissue. Thus, primarily RS adipose tissue effects should be assessed on the left kidney. Accumulation of adipose tissue in the RS is related with the visceral adipose amount, KIM-1 and FGF-21 concentration increase in the blood serum.

Keywords: Asymmetry; FGF-21; KIM-1; Obesity; Renal sinus; Visceral adipose tissue.

Fig. 1

Design of the cross-sectional and the prospective one-year naturalistic follow-up study.

Fig. 2

Abdominal computed tomography scans demonstrating renal sinus and abdominal adipose tissue compartment measurements. a: The levels of abdominal adipose tissue measurements. A-1 – the level where total abdominal adipose tissue measurements were performed (RP_full, IP_full, SC_full). A-2 – the level where abdominal adipose tissue measurements in three axial slices were performed (RP_{three-slices,} IP_three-slices, SC_three-slices). The red line represents the boundary of RS; b: Example of single abdominal CT slice selected for RS and abdominal adipose tissue compartment measurements; c: Visualization of RS and abdominal adipose tissue compartments as well as kidney using 3D Doctor software; d: Volumetric right and left RS adipose tissue compartment visualization. e: Measure of the kidney length (pole to pole) (1.) in the sagittal plane and sagittal (2.) as well as lateral diameter (3.) in the axial plane; f: 3D reconstruction of RS, IP, RP, SC and kidneys. RS adipose tissue and kidneys were segmented fully; RP, IP and SC adipose tissue at the renal hilum's level. Subcutaneous adipose tissue (SC) (gray); Intraperitoneal (IP) adipose tissue (yellow); RP adipose tissue (purple); Right RS adipose tissue (red); Left RS adipose tissue (green).

Fig. 3

Gender and topography (right and left kidney) effects on the renal sinus adipose tissue accumulation. ***, ^### p < 0.001; ⁺⁺ p = 0.006, °labels potential extremes. Right and left kidney compared by using Wilcoxon rank-sum test; Male and female groups compared by using Mann-Whitney test. Symbols used in the graph: *Right RS ratio vs. Left RS ratio (for male and female group, respectively); ^#Female right RS ratio vs. Male right RS ratio; ⁺ Female left RS ratio vs. Male left RS ratio. RS_Ratio - ratio of RS adipose tissue volume to corresponding total kidney size.

Fig. 4

Bland and Altman plots of the intra-reader (a) and the inter-reader (b) renal sinus adipose tissue volume measurements. The average of the repeated measurements is presented on the x-axis and the difference between two measurements is presented on y-axis. The middle continuous line represents the mean difference between the repeated measures, upper and lower dotted lines represent upper and lower confidence limits for the mean difference, respectively (n = 150 (M/F, 75/75)). The level of significance was set as p < 0.05.

Fig. 5

Serum KIM-1 and FGF-21 levels according to left (a and c) or right (b and d) RS ratio quartiles. Male (M) and female (F) were divided into 3 groups based on left or right RS ratio quartiles: < 25th quartile Q₁ (F/M; 34/38); 25th–75th inter quartile range Q₂ + Q₃ (F/M; 62/60); > 75th quartile Q₄ (F/M; 44/42). *Q₁ vs. Q₄; ^#Q₂ + Q₃ vs. Q₄; ^Q₁ vs. Q₂ + Q₃. *, ^#, ^{^}p < 0.05; ^⁎⁎p < 0.01; Mann-Whitney U test.

Fig. 6

Left (a) and right (b) renal sinus adipose tissue volumes changes (%) in the one year follow-up period, based on the visceral adipose tissue significant (> 5%) increase or decrease. The mean value of the time point “Baseline” was arbitrarily set at 100%. p Value shown above the black, blue and red lines represent difference between “Baseline” and “End” (Wilcoxon rank-sum test). p Value which are indicated under the brace represent difference between control group (Mann Whitney U test). The level of significance was set as p < 0.05.