Pathophysiological analysis of renal fibrosis in SD rats treated with unilateral nephrectomy and fed a high phosphorus die

<p>[Background] Excessive phosphorus intake causes tubular damage with calcification and fibrosis in the tubular interstitium. The changes are known to correlate with decreased renal function, however, the mechanism by which fibrosis occurs is still unknown. In this study, we attempted a histopathological analysis of kidney fibrosis induced by feeding the short-term high-phosphate diet. [Material and Methods] 5-week-old male SD rats were treated with UNx and fed 0.3% or 1.5% KH2PO4-containg diet for 21 days. In the control group, SD rats were sham-operated and fed 0.3% KH2PO4 under the same conditions. Urine was sampled before the day of sacrifice and blood and kidney were sampled at necropsy. [Results] Blood and urine biochemical examinations showed decreased Ccr, increased U-ALB and urinary L-FABP in the UNx+1.5% group. Histopathological findings were observed as follows in the same group: moderate to severe regenerated tubules and inflammatory cell infiltration, slight to severe tubular dilatation and interstitial fibrosis, very slight to moderate calcification. IHC staining revealed CD44 expression in the renal tubular epithelium and increased α-SMA-positive cells in the interstitial area. [Discussion] Severe renal tubular damage with calcification and interstitial fibrosis was induced by UNx and fed 1.5% KH2PO4 in SD rats. Furthermore, CD44 was inferred to be expressed in the regenerating tubular epithelium, indicating that its expression is associated with progression of fibrosis. These results suggested that a high-phosphorus diet may promote the worsening of CKD.</p>