AIM: To assess and correlate the lipid content of various organs in obese subjects and in persons with a normal body weight.

METHODS: Magnetic resonance spectroscopy and a previously validated gradient echo magnetic resonance imaging method with Dixon’s two point technique were used in this study to quantify fat in liver, pancreas as well as kidney.

RESULTS: In 36 volunteers with body mass index (BMI) ranging from 20.0 to 42.9 kg/m2, the median fat content of liver, pancreas and kidney was 2.3% (interquartile range: 0.2%-7.8%), 2.7% (1.0%-6.5%) and 0.7% (0.1%-1.4%), respectively. BMI and subcutaneous fat correlated significantly with liver and pancreas fat content. We show for the first time the significant correlation of liver and pancreas fat content in healthy controls (r = 0.43, P < 0.01). These observations are related to body weight as measured by BMI and the amount of subcutaneous fat. Kidney fat content is very low and correlates with none of the other fat depots.

CONCLUSION: Renal lipid accumulation, unlike the coupled accumulations of fat in liver and pancreas, is not observed in obese subjects. Unlike suggestions made in previous studies, renal lipid accumulation appears not to be involved in the pathogenesis of renal disease in humans.

Background

In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant.

Methods

To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation.

Results

The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Böger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipients-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts.

Conclusions

Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.