Role of functional magnetic resonance imaging in evaluating renal hypoxic injury in mice with lupus nephritis / 中华肾脏病杂志

Objective To investigate the utility of diffusion weighted imaging (DWI) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in the assessment of renal hypoxia in an experimental model of mice with lupus nephritis (LN).Methods MRL/lpr mice (n=13) were studied and C57BL/6 mice (n=10) served as controls.Urinary albumin to creatinine ratio (ACR),serum creatinine (Scr),anti-ds-DNA antibody,and complement C3 levels were measured.The mice underwent coronal echo-planar DWI and BOLD MRI of the kidneys when they were 14-16 weeks old.Hypoxyprobe was administered intraperitoneally to the mice 1 hour before they were sacrificed.The distribution of HypoxyprobeTM-1,hypoxia-inducible factor 1 α (HIF-1 o) and heme oxygenase-1 (HO-1) in renal tissues was detected by immunohistochemical analysis and Western blotting.Results Urinary ACR,Scr and anti-ds-DNA antibody levels in MRL/lpr mice were significantly higher than that in C57BL/6 mice.It was found that HypoxyprobeTM-1,HIF-1o and HO-1 distributed widely in the renal tissue of MRL/lpr mice,and closely associated with the renal tubulointerstitial lesion.The mean apparent diffusion coefficient (ADC) value of kidneys in MRL/lpr mice was (1.52±0.27) × 10-3 mm2/s,and the mean R2* values of the renal cortex and medulla were (30.95 ±4.59)/s and (23.43± 3.06)/s respectively,all significantly lower than that in C57BL/6 mice (P=0.037,P=0.030 and P=0.043,respectively).The ADC of medulla was negatively correlated with urinary albumin to creatinine ratio (r=-0.364,P=0.032;r=-0.329,P=0.050),the ADC of cortex was negatively correlated with the level of serum creatinine (r=-0.814,P=0.014;r=-0.755,P=0.031) when b value was 500 s/mm2 and 800 s/mm2,and the mean R2* value was negatively correlated with the degree of tubulointerstitial lesions and the expression of hypoxia parameters (all P ＜ 0.05).Conclusions Renal hypoxia may play an important role in renal tubulointerstitial lesion.Functional MRI may be used to monitor renal function changes,pathological injuries and renal hypoxia in LN.

Correlations of ABCA1 with foam cells formation in renal interstitium, tubulointerstitial lesion and serum cholesterol / 中华肾脏病杂志

Objective To investigate the correlations of ATP-binding cassette transporter A1 (ABCA1) protein expression in renal interstitium with foam cells formation,tubulointerstitial lesion and serum cholesterol in glomerulonephropathy.Methods Five patients with Alport syndrome,28 patients with membranous proliferative glomerular nephritis (MPGN),35 patients with focal segmental glomerulosclerosis (FSGS),36 patients with idiopathic membranous nephropathy (IMN) and 34 patients with IgA nephropathy (IgAN) were enrolled in the study.Expression of ABCA1 protein was detected by immunohistochemical method.The relative area of foam cells in renal interstitium was semi-quantified and the correlations of ABCA1 protein expression in renal interstitium (except for renal tubules) with the relative area of foam cells,integration of tubulointerstitial lesion (TIL) and serum cholesterol were examined using t test and linear correlation analysis.Results In renal interstitium,monocyte-macrophages,foam cells and renal tubular epithelial cells expressed ABCA1 protein.ABCA1 protein expression in renal interstitium with foam cells infiltration was significantly higher as compared to that without foam cells infiltration (P＜ 0.05),but there was no correlation between ABCA1 expression and foam cells area (P＞0.05).In MPGN,FSGS,IMN patients,there was a positive correlation between ABCA1 protein expression in renal interstitium and integration of TIL (P＜0.05).There was a positive correlation between serum cholesterol level and ABCA1 protein expression in renal interstitium (P＜0.05).Conclusions In glomerulonephropathy,cholesterol may promote the ABCA1 expression in renal interstitium.ABCA1 may have double-effects on transportation of cholesterol.ABCA1 may take part in the process of tubulointerstitial lesion.

Effects of Renin-angiotensin System Blockade on Tubulointerstitial Lesions in Adriamycin-induced Nephropathy / 대한신장학회잡지

PURPOSE: Effects of renin-angiotensin system blockade on tubulointerstitial lesions were examined in adriamycin-induced nephropathy. METHODS: Male Sprague-Dawley rats were used. The three experimental groups were intravenously injected with adriamycin (2 mg/kg). After 6 weeks, rats showing heavy proteinuria were orally treated with either cilazapril 1 mg/kg/day (ACEi group, n=7) or losartan 10 mg/kg/day (ARB group, n=7) during the period of additional 6 weeks. The other group was maintained without any drugs (ADR group, n=6). The control group was without adriamycin treatment and maintained during the 12 weeks (Control, n=5). RESULTS: Systolic blood pressure was increased following the adriamycin treatment, which was normalized by treatment with cilazapril or losartan. Accordingly, cilazapril and losartan normalized the 24-h urine protein/creatinine ratio, in association with morphologic improvement of tubulointerstitial lesions. The expression of laminin beta1 was not altered in any experimental groups. CONCLUSION: These results suggest that angiotensin II plays an important role in tubulointerstitial lesions in adriamycin-induced nephropathy.

Interstitial Mononuclear Cell Infiltration and its Phenotypes in IgA Nephropathy

To know the correlation between glomerular and tubulointerstitial lesion and to define the characteristics of interstitial inflammatory cell in IgA nephropathy and classified according to WHO classification and graded tubulointerstitial lesion as mild, moderate and severe. Paraffin-embedded 5u sections were stained with UCHL-l, L26 and CD68 antibodies. More than 20 fields were examined in each case under the high power microscopy and the number of positive cells were counted. There was positive correlation between the severity of glomerular and that of tubulointerstitial lesion. The mostcommoninflammatory cells in the interstitiuin were UCHL-l positive cells followed by CD68 and L26 positive cells. As the WHO grade or tubulointerstitial lesion increased, the numbers of positive cells were increased in all three groups. The proportion of UCHL-1 Positive cells were increased in cases with high WHO grade whereas that of L26 positive cells incases with severe tubulointerstitial lesion Proteinuria was correlated with the degree of inflammatory cell infiltration, especially with that of L26 positive cells.