Structural and ultrastructural renal lesions in rats fed high-fat and high-phosphorus diets

Abstract

Background Foods prone to deteriorate renal function are rich in fat and in phosphorus (P), but the interaction between these two factors is not well studied. Method Detailed structural and ultrastructural histopathological studies were performed on the kidneys of rats fed different amounts of fat and P: low (4%) fat (LF) and normal (0.6%) P (NP), LF and high (1.2%) P (HP), high (35%) fat (HF) and NP, HF and HP, and HF with low (0.2%) P (LP) for 28 weeks. Results Glomeruli of the HF groups showed segmental areas of retraction, sclerosis and thickening of the Bowman’s capsule and basal membranes, which were more accentuated in the HF–HP group. Ultrastructural lesions in the glomeruli also were prominent in rats fed HF, particularly in the HF–HP group, and included thickening of the capillary membrane, endothelial damage, mesangial matrix hypercellularity and podocyte effacement. P restriction reduced the severity of endothelial damage, mesangial matrix hypercellularity, thickening of capillary basement membrane and podocyte effacement. The kidneys of rats fed HP showed significant tubular atrophy and dilatation, focal tubular hyperplasia, thickening of the tubular basal membrane, interstitial edema, inflammation and calcification. All groups fed HF also showed tubular lesions that were more prominent in the HF–HP group. P restriction had a beneficial effect on inflammation and calcification. Conclusions Intake of both HF and HP damages the kidneys and their noxious effects are additive. HF intake was preferentially associated with glomerular lesions, while lesions related to HP intake were located mainly in the tubuli and in the interstitium.

High-fructose diet induces earlier and more severe kidney damage than high-fat diet on rats

“…The structural changes in the HFD2 group included glomerular sclerosis with enlarged bowman`s capsule, tubular cloudy swelling, lipid droplets deposition in tubular epithelial cells, and pro-inflammatory mononuclear cells infiltration in the interstitium. Similar histological changes in kidneys were also reported by several other studies following feeding rodents on HFD for ≥ 8w [13,[15][16][17][18][19][20] . Interestingly, Karam, et al [42] only found lipid infiltration in the renal tubules without any other structural changes in kidney of adult male rat fed HFD, similar in composition to that used in our study, for 7w.…”

“…Indeed, Amaral, et al [13] and Tang, et al [12] found that HFT induced very early histological changes (wider Bowman's space, elevated glomerular cell proliferation, and infiltration of mononuclear cells) and functional alterations (glomerular hyperfiltration and sodium retention) in rat kidney. Many other studies reported similar histological and functional disruption following administration of HFD to animals [13,[15][16][17][18][19][20] . Consumption of HFrD also caused similar histological changes and dysfunction in rat kidney [21][22][23][24][25][26][27] .…”

“…For this reason, these three genes were chosen as inflammation and glomerulosclerosis related genes in our study. Moreover, previous studies reported induction of necrosis in both glomeruli and tubular cells following consumption of HFD and HFrD [13,[15][16][17][18][19][20][21][22][23][24][25][26][27] . However, this conclusion based only on the histological examination, and none of these previous studies confirm the occurrence of necrosis at a molecular level.…”

High phosphate‐induced progressive proximal tubular injury is associated with the activation of Stat3/Kim‐1 signaling pathway and macrophage recruitment

“…46 More recent studies showed either no alterations in the kidney but in the bone due to 1.2% HPD in rats over a period of 1 year 42 or glomerular as well as tubular lesions in rats only upon a combination of high fat and high phosphate intake over 28 weeks. 47 Here, we show that chronic oral phosphate loading in healthy mice leads to a systemic phosphate response with hyperphosphatemia, hyperphosphaturia, plasma Fgf23 and levels and impaired kidney function. HPD causes proximal tubular injury with interstitial fibrosis that is associated with the activation of Stat3/Kim-1 signaling pathway, MCP-1 synthesis and a robust innate inflammatory response dominated by macrophages (Figure 8).…”

“…A study already conducted in the early 1980s indicated nephrotoxicity of 2% phosphate in rats after 18 weeks, mainly due to deposition of calcium phosphate in renal tubules 46 . More recent studies showed either no alterations in the kidney but in the bone due to 1.2% HPD in rats over a period of 1 year 42 or glomerular as well as tubular lesions in rats only upon a combination of high fat and high phosphate intake over 28 weeks 47 . Here, we show that chronic oral phosphate loading in healthy mice leads to a systemic phosphate response with hyperphosphatemia, hyperphosphaturia, increased plasma Fgf23 and PTH levels and impaired kidney function.…”