Intra-renal and urinary RNA expression of podcyte-associated molecules in patients with IgA nephropathy

Background Podocyte injury probably plays important roles in the pathogenesis of IgA nephropathy (IgAN). We studied intra-renal and urinary messenger RNA (mRNA) expression of podocyte-associated molecules in patients with IgAN. Methods We studied 43 consecutive patients with biopsy-proven IgAN. Intra-renal and urinary expression of mRNAs was determined and compared to that of 20 patients with nephrectomy for kidney cancer and 12 normal subjects. Results Intra-renal mRNA expression levels of nephrin, podocin and synaptopodin were significantly lower in patients with IgAN than that of controls. In contrast, their urinary mRNA expression levels were similar. Intra-renal gene expression of nephrin inversely correlated with proteinuria (r = –0.620, P 【0.001), GFR (r = 0.538, P 【0.001), and the degree of tubulointerstitial scarring (r = –0.423, P = 0.013). After followed for an average of 33.4 ? 12.6 months, intra-renal nephrin expression significantly correlated with the rate of GFR decline (r = 0.324, P = 0.041). Conclusions Intra-renal mRNA expression of podocyte associated molecules was down-regulated in patients with IgAN, and the degree of down- regulation of nephrin correlated with disease severity and the rate of progression. Our result supports the hypothesis that podocyte injury is an important component in the pathophysiology of IgAN.

The gene expression of NGAL and TLR9 in glomerulus and tubulo-interstitium of patients with lupus nephritis

Background The role of neutrophil gelatinase associated lipocalin (NGAL) and Toll-like receptor 9 (TLR9) in the pathogenesis of lupus nephritis remain elusive. Methods We quantified the glomerular and tubulointerstitial mRNA expression of NGAL and TLR9 in 42 patients with lupus nephritis (LN group) and 10 controls. Results As compared to controls, LN group had higher glomerular expression of TLR9, and higher tubulointerstitial expression of NGAL and TLR9. Tubulointerstitial NGAL expression significantly correlated with proteinuria (r = 0.492;p = 0.003), renal function (r = -0.386;p = 0.022) and histological chronicity index (r = 0.540;p = 0.004). Proteinuria had significant correlation with glomerular (r = 0.554;p = 0.001) and tubulointerstitial (r = 0.379;p = 0.043) TLR9 expression. Furthermore, there was a significant difference in tubulointerstitial expression of NGAL between treatment response groups. Conclusion There is an increase in intra-renal mRNA expression of NGAL and TLR9 in LN. Although tubulointerstitial expression of NGAL does not correlate with systemic disease activity, it correlates with proteinuria, renal function, and therapeutic response. The role of NGAL in the pathogensis in LN, as well as its application as biomarker for lupus nephritis, requires further study.