Abstract
Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.
Highlights
The prevalence of obesity among adults in the European Union ranges from 8% in Romania to 24% in the United Kingdom [1], exceeds 35% in the United States [2], and is approximately 11% worldwide [3]
Body mass index (BMI) is not an ideal measure of body adiposity and associated health risk [4], multiple studies have shown that increased body mass index (BMI) is an independent risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD), even after adjustment for obesityrelated conditions such as hypertension and type 2 diabetes [5,6,7]
Body mass index (BMI) increased across tertiles of increasing kidney cortex triglyceride, and there was a significant positive correlation between triglycerides and BMI analyzed as continuous variables (Figure 1)
Summary
The prevalence of obesity (body mass index $30) among adults in the European Union ranges from 8% in Romania to 24% in the United Kingdom [1], exceeds 35% in the United States [2], and is approximately 11% worldwide [3]. Body mass index (BMI) is not an ideal measure of body adiposity and associated health risk [4], multiple studies have shown that increased BMI is an independent risk factor for chronic kidney disease (CKD) and end-stage renal disease (ESRD), even after adjustment for obesityrelated conditions such as hypertension and type 2 diabetes [5,6,7]. The mechanisms by which obesity can directly contribute to increased CKD and ESRD risk, independent of its association with hypertension and type 2 diabetes, are incompletely understood. While the pathophysiology of uric acid nephrolithiasis is likely multifactorial [16], animal and cell culture experiments have shown that lipid accumulation in proximal tubule cells may contribute to the urinary biochemical abnormalities that underpin uric acid stone risk [17,18,19]
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