Clinical implication of the circumferential crescents lesions in immunoglobulin A nephropathy: a single-center study of Han Chinese population.

A crescentic lesion in renal biopsy could be segmental or circumferential, but the distribution and clinical implication of the circumferential crescents in immunoglobulin A nephropathy (IgAN) remains unknown. A total of 384 crescentic IgAN patients between 2011 and 2019 were included. The subjects were classified as the circumferential crescent who have at least one crescent involving ≥50% circumference of Bowman's capsule, otherwise as to the segmental crescent. Clinical, pathological, and prognostic relationships were analyzed. The primary endpoint was a 30% decline in eGFR, and the secondary endpoint was more than 3.5 g/d proteinuria during follow-up. Of the 384 patients, 72 (18.8%) patients had more than one circumferential crescent. 52 (17.6%) Oxford C1 patients have circumferential crescent. During a mean follow-up of 32.3 months, both the primary and secondary endpoints have occurred more in the circumferential crescent patients. Kaplan-Meier analysis showed the patient with the circumferential crescent had significantly lower renal survival than those without. In multivariable Cox analyses, having the circumferential crescents in at least one-fifth of glomeruli was independently associated with primary endpoint (hazard ratio:3.60, 95% CI:1.46-8.83), after adjusting for Oxford-score, eGFR, systolic blood pressure, and proteinuria. Furthermore, those patients who scored C1 in Oxford and presenting with circumferential crescents, had better renal survival if they received the other immunosuppressants therapy. The circumferential crescents lesion was associated with adverse outcomes in IgAN, and more than one-fifth of glomeruli circumferential crescents is an independent predictor of 30% eGFR decline after adjusting for clinical and histological parameters.

Low-dose paclitaxel ameliorates renal fibrosis in rat UUO model by inhibition of TGF-beta/Smad activity.

Transforming growth factor-beta (TGF-beta) has a pivotal function in the progression of renal fibrosis in a wide variety of renal diseases. Smad proteins have been identified to have an important function in regulating the expression of extracellular matrix (ECM) proteins through TGF-beta signaling pathway. Aberrant TGF-beta/Smad signaling can be modulated by stabilization of microtubules with paclitaxel. In this study, we investigated if paclitaxel can attenuate tubulointerstitial fibrosis in a rat model of unilateral ureteral obstruction (UUO). Rats in groups of six were subjected to UUO and received low-dose intraperitoneal injection of paclitaxel (0.3 mg/kg) twice a week. They were killed at day 7 and 14 after UUO or Sham operation. TGF-beta signaling cascade and status of various ECM proteins were evaluated by RT-PCR, western blotting and immunohistochemical or immunofluorescence staining. The paclitaxel treatment markedly suppressed Smad2 and Smad3 phosphorylation. This was associated with attenuated expression of integrin-linked kinase, collagens I and III, fibronectin (FN) and alpha-smooth muscle actin, and a substantial decrease in renal fibrosis in animals that underwent UUO and received paclitaxel. These data indicate that the low-dose paclitaxel ameliorates renal tubulointerstitial fibrosis by modulating TGF-beta signaling, and thus, the paclitaxel may have some therapeutic value in humans.

[Expression of plasma thrombospondin-1 in renal interstitial fibrosis].

OBJECTIVE: To observe the expression of plasma thrombospondin-1(TSP-1) at different time in protein-overload rats and to analyze the relationship between plasma TSP-1 expression and renal interstitial fibrosis. METHODS: Forty-five male Sprague-Dawley rats were randomly divided into a bovine serum albumin (BSA) group and a control group after uninephrectomization. Rats with protein overload nephropathy induced by intraperitoneally injected BSA were used as a model (control group received saline). At the 1st, 5th, and 9th weekend, the level of 24 h proteinuria and renal function was assessed. Pathological changes were observed by electron and fluorescent microscopy. The expression of plasma TSP-1 was detected by Western blot. The relationship between plasma TSP-1 and tubulointerstitial lesions (TIL) score was analyzed. RESULTS: Twenty-four hour proteinuria and blood urea nitrogen (BUN) significantly increased in protein-overload rats compared with those in the control group. While protein-overload rats developed more severe fibrosis in the tubular and interstitium. Glomerulosclerosis index and TIL score were upregulated compared with those in the control group. The expression of TSP-1 increased significantly at the 5th and 9th weekend. The expression of TSP-1 was positively correlated with TIL score (r=0.836, P<0.01). CONCLUSION: Plasma TSP-1 expression is positively correlated with renal interstitial fibrosis in protein-overload rats. Plasma TSP-1 may be used for an important biomarker of renal interstitial fibrosis.