Quantitative and qualitative alterations of chondroitin/dermatan sulfates accompanied with development of tubulointerstitial nephritis

Quantitative and qualitative alterations of renal oversulfated chondroitin/dermatan sulfates (C/DSs) accompanied by the development of tubulointerstitial nephritis were examined. The rat model with unilateral ureteral obstruction (UUO) is a suitable model for study of renal interstitial fibrosis, and was utilized in the present study. Cortical regions of serial sections of UUO kidney and sham-operated kidney on glass slides were processed using a small surgical knife under dark field microscopy. Oversulfated C/DSs in tissue sections on a glass slide were degraded to unsaturated disaccharides using chondroitinase ABC and ACII digestion in the presence of bacterial collagenase. The resulting unsaturated disaccharides were subsequently determined by HPLC. These in situ investigations yielded the following results: (1) marked increases in oversulfated C/DSs content and decreases in the oversulfation degree of C/DSs were observed in fibrous lesions, compared to non-fibrous lesions, and (2) iduronic acid content in C/DSs in fibrous lesions was significantly lower than that in non-fibrous lesions. These findings indicate that oversulfated C/DSs with low-iduronic acid content represent a potential marker for tubulointerstitial nephritis.