Are Renal Lipids Increased in Overweight Diabetic Patients? A MR Spectroscopy and Dixon Fat/Water Imaging Study
Gaƫlle Diserens1, Waldo Valenzuela2, Maryam Seif1, Laila Mani3, Daniel Fuster3, Christoph Stettler4, Bruno Vogt3, Mauricio Reyes2, Chris Boesch1, and Peter Vermathen1

1Depts Clinical Research and Radiology, University of Bern, Bern, Switzerland, 2Institute for Surgical Technology and Biomechanics, University of Bern, Bern, Switzerland, 3Dept. of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, Bern, Switzerland, 4Dept. of Endocrinology, Diabetes and Clinical Nutrition, University of Bern, Bern, Switzerland

Synopsis

Renal ectopic lipid accumulation may lead to kidney dysfunction. The study purpose was to determine (1) renal ectopic lipid content in overweight type-2 diabetic patients compared to (a) overweight non-diabetic patients and (b) lean volunteers by 1H-MRS and (2) renal sinus fat content by DIXON-MRI in the same three patient groups. This study demonstrates that renal ectopic lipids appear to be not higher in overweight diabetic patients compared to overweight non-diabetic subjects, while ectopic lipids are higher in both groups compared to healthy subjects. Significantly higher renal sinus bulk lipids were detected for overweight diabetic patients compared to BMI-matched non-diabetics.

Purpose

There is increasing evidence that renal ectopic lipid accumulation leads to kidney dysfunction1,2,3. These ectopic lipids have been associated with type-2 diabetes, obesity-related glomerulopathy and with organ function2,4. However, to our knowledge, no MRI and no MRS study has been performed in humans to non-invasively assess renal ectopic lipids or bulk lipids in the renal sinus in diabetic patients.

The purpose of this study was to use MR techniques to determine (1) the renal ectopic lipid content in overweight patients with type-2 diabetes compared to (a) overweight non-diabetic patients and (b) lean healthy volunteers by optimized 1H-MRS and (2) the fat content of the renal sinus by DIXON fat-water imaging in the same three groups of patients. We hypothesized the renal ectopic lipid content and the fat in renal sinus to be increased in obese diabetic patients.

Subjects and Methods

Study Population

Three groups of 8 patients were measured on a 3T-MR Scanner (Verio,Siemens): (1) overweight (BMI>28) Type-II diabetic, (2) overweight (BMI>28) non-diabetic, (3) lean healthy (BMI=18-25) (Table 1).

MR-Imaging and Spectroscopy

A single voxel PRESS sequence with PACE respiratory-triggering (TR=2000ms, TE=35ms, 16 measurements with 4 acquisitions, 6 saturation bands, voxel size between 10x12x12mm3 and 15x15x15mm3) was placed in visually fat-free renal parenchyma. A standard two-point DIXON sequence was performed in breathold for fat/water imaging of the right kidney in three orthogonal directions, with TR=5.9ms, TE=2.5/3.7ms, FOV=388x400mm2.

Data Processing

MRS: Fat and water peaks from the sum of the 16 SVS spectra of each patient were fitted using jMRUI AMARES5, the lipid ratio was calculated as Fat/(Fat+Water).

MRI: Kidneys from coronal Dixon data were segmented using FISICO6 (Fig.1) and the renal volume as well as the bulk renal sinus fat content determined, after establishing a threshold for supposedly pure lipid content.

Statistical analyses (Student's t-tests, correlations) were performed using Excel and Matlab. Bonferroni corrections for multiple comparisons were applied.

Results

Renal ectopic lipids by SVS

The renal ectopic lipid content in the lean healthy group was only 0.21%±0.08%. One healthy subject had more than 7-times higher content than the average of the other healthy subjects and was thus excluded from the statistical analysis, also because retrospective analysis demonstrated partial voxel-placement outside renal parenchyma.

The average renal ectopic lipid content was significantly higher for the overweight group (0.75%±0.59%) and for the overweight+diabetic group (0.67%±0.46%), compared to the lean healthy group (Table 2, Fig. 2a). No significant difference was found between the overweight group compared to the overweight+diabetic group.

Renal sinus fat by Dixon imaging

The amounts of renal sinus fat were significantly different between all three groups (p<0.02 for all), with highest content for the overweight+diabetic group (39.2 cm3± 12.0cm3), intermediate for the overweight group (24.9cm3±7.2cm3) and lowest for the healthy group (12.3cm3±6.8cm3) (Table 2, Fig.2b).

Kidney Volume without sinus lipid volume

The renal volume of the lean healthy group after subtraction of the sinus lipid volume (107cm3±18cm3) was significantly lower than the volume of the overweight group (155cm3±29cm3) and also significantly below that of the overweight+diabetic group (181cm3±57cm3) (Table 2, Fig.2c). Renal volumes of the overweight group and overweight+diabetic group were not significantly different.

Correlations between the lipid contents and the BMI

No significant correlation was found between the renal ectopic lipid measured by SVS and the renal sinus fat (R=0.15, p=0.49) and between ectopic lipid and BMI (R=0.38, p=0.07). The renal sinus fat amount of all subjects correlated strongly with BMI (R=0.70, p<0.001, Fig.3a). Kidney volumes after removal of the sinus lipid volume were significantly correlated with BMI (R=0.69, p<0.001, Fig.3b).

Discussion and Conclusion

This study demonstrates that renal ectopic lipids appear to be not higher in overweight diabetic patients compared to overweight non-diabetic subjects, while the ectopic lipids are higher in both groups compared to healthy subjects. This result suggests no increase of renal ectopic lipid content in relation with diabetes.

In contrast, significantly higher bulk lipids in the renal sinus were detected for overweight diabetic patients compared to BMI-matched non-diabetics. In addition, our data suggests that fat infiltration into the renal sinus occurs– though at lower extend – with increased BMI, as also shown previously7. The kidney volume without the renal sinus fat content shows a significant correlation with BMI, suggesting that a complex reorganisation process seems to take place inside the kidney itself7. While the renal sinus fat content seems to be strongly affected by the diabetes status, the renal volume is mainly related to the BMI and not to diabetes, as the kidney volume was not significantly different between the two overweight groups.

Acknowledgements

This work was supported by the Swiss National Science Foundation SNF grant #320030-138150.

References

1. Bobulescu IA. et al., Triglycerides in the Human Kidney Cortex: Relationship with Body Size. Plos One 2014; 9(8):e101285.

2. de Vries AP. et al., Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol. 2014; 2:417.

3. Herman-Edelstein M. et al., Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res. 2014; 55(3).

4. Sieber J. et al., Free fatty acids and their metabolism affect function and survival of podocytes. Front Endocrinol. 2014; 5:186.

5. Vanhamme L. et al., Improved method for accurate and efficient quantification of MRS data with use of prior knowledge. Journal of Magnetic Resonance 1997, 129: 35-43.

6. Valenzuela W. et al., Correction Tool for Active Shape Model Based Lumbar Muscle Segmentation. In IEEE Engineering in Medicine and Biology Society (pp. 1–4), 2015.

7. Foster MC. et al., Fatty Kidney, Hypertension, and Chronic Kidney Disease, The Framingham Heart Study. Hypertension 2011; 58:784.

Figures

Table 1: Patient demographic summary

Figure 1: Kidney segmentation examples based on fat Dixon images. a) Slim subject-coronal projection of the kidney segmentation; b) Kidney 3D-segmentation of a slim subject; c-d) Same as a-b) but for an overweight+diabetic subject

Figure 2: Box plots: a) SVS renal ectopic lipid content; b) Renal sinus lipid volume; c) Renal volume without sinus lipid volume; before the removal of the outlier (x).

Table 2: Ectopic lipid content detected in the lean healthy (LH), overweight (O) and overweight+diabetic(OD) group detected by SVS, sinus lipid content and kidney volume in those three groups, with p-values comparing the three groups (with Bonferroni corrections for multiple comparisons).

Figure 3: a) Correlation between sinus lipid volume and BMI; b) Correlation between kidney volume after removal of sinus lipid volume and BMI.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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