Clinical and pathological significance of circadian blood pressure rhythm change in IgA nephropathy patients with hypertension / 中华肾脏病杂志

Objective To investigate whether the clinical and pathological injury of kidney in IgA nephropathy (IgAN) patients with hypertension is associated with circadian blood pressure rhythm change, particularly with elevated nocturnal blood pressure (BP). Methods This study was a retrospective cross-sectional study. Clinic and renal histopathological injury data were obtained from 83 IgAN patients with hypertension. First, 24 h ambulatory BP monitoring (ABPM) data were analyzed. Second, all these IgAN patients were divided into two groups, elevated nocturnal BP group and nocturnal normotensive BP group, and the clinical and pathological differences between this two groups were analyzed. Third, logistic regression analysis was used to analyze the influencing factors of renal tubulointerstitial injury in IgAN patients with hypertension. At last, all these IgAN patients were divided into two groups according to the level of estimated glomerular filtration rate (eGFR), group of patients with eGFR≥60 ml·min-1·(1.73 m2)-1 and the other group with eGFR<60 ml·min-1·(1.73 m2)-1, and the 24 h ABPM data were compared. Results (1) The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension was 79.5％. (2) Compared with nocturnal normotensive BP group, patients in elevated nocturnal BP group had significantly higher levels of 24-hour urinary protein quantity and blood uric acid (both P<0.05), and lower eGFR and urine osmotic pressure clinically (both P<0.05). Index of interstitial fibrosis and tubular atrophy was significantly higher in nocturnal normotensive BP group (P<0.05), while the proportion of glomerular ischemia lesion was not significantly different between two groups. (3) Multivariate logistic regression analysis showed that elevated nocturnal BP was an independent risk factor for severe tubulointerstitial injury of IgAN (OR=1.113, 95％CI 1.038-1.192, P=0.002). (4) Compared with the group of eGFR≥60 ml·min-1·(1.73 m2)-1, 24-hour systolic blood pressure (SBP) and diastolic blood pressure (DBP), daytime SBP and DBP, nocturnal SBP and DBP were significantly higher in group of eGFR<60 ml·min-1·(1.73 m2)-1 (all P<0.05). Conclusion The proportion of non-dipper circadian rhythm of BP in IgAN patients with hypertension is as high as 79.5％. Elevated nocturnal BP is associated with the severity of renal damage, and elevated nocturnal BP is an independent risk factor for severe tubulointerstitial injury in IgAN patients with hypertension. Therefore, 24 h ABPM should be emphasized, and elevated nocturnal BP should be well controlled to slow the progression of IgAN.

The expression and signification of kidney injury molecule-1 on renal ischemia reperfusion injury in rat / 中国小儿急救医学

Objective To observe the expression levels of kidney injury molecule-1(KIM-1) in renal tissues of ischemia-reperfusion rats,and to explore the value in the diagnosis of acute kidney injury.Methods Rats were randomly divided into two groups,control(CON) group (n=64) and acute kidney ischemia reperfusion injury (AIKI) group (n=64).Rats were sacrificed following reperfusion 2h,6h,24h,48h,72h,1 week (w),2 w,and 4 w.The changes of morphology were checked on HE staining sections under light microscope.The extent of tubulointerstitial injury was determined by Sayhan classification.The distribution and expression of KIM-1 in renal tissue were observed by immunohistochemistry and Western blotting.Serum samples were collected and serum creatinine measurement was performed at different reperfusion time points.Results (1) Compared with the CON group,the renal tubulointerstitial injury scores of AIKI group were significantly higher at all times after reperfusion (P<0.01).(2) The expression of KIM-1 was consistent with the tubulointerstitial injury.The positive correlation between KIM-1 and the tubulointerstitial injury scores was significant(r=0.887,P=0.003).(3) Compared with the CON group,serum creatinine in AIKI group was significant higher at 2h,6h,24h,48h,72h after reperfusion (P<0.05).Serum creatinine had no correlation with the damage of renal tubulointerstitial.Conclusion The expression of KIM-1 increases significantly in renal ischemia reperfusion injury,and it is consistent with the tubulointerstitial injury.Compared with serum creatinine,KIM-1 may be a more accurate biomarker of renal damage.

Effect of C peptide on tubulointerstitial oxidative stress in rats with diabetic nephropathy / 实用医学杂志

Objective To investigate the effect of C peptide on tubulointerstitial oxidative stress injury in rats with diabetic nephropathy (DN) induced by streptozotocin (STZ). Methods Wistar rats with DN induced by STZ were randomly divided into control group and C peptide group. All rats were treated via intraperitoneal micro-osmotic pump. Normal Wistar rats at the same age were used as the normal group. Blood glucose and24 h urinary albumin were measured before treatment and every 4 weeks during treatment period. After 12 weeks of treatment, the expression of transforming growth factor - β1 (TGF - β1) in renal tubulointerstitium was detected by immunohistochemical staining. Fresh tubulointerstitial tissue homogenate was harvested and the activity of superoxide dismutase (SOD) was detected in WST-1 method, the content of malondialdehyde (MDA) was detected in TBA method, and the expression of protein kinase A (PKA) mRNA was detected by Real-time PCR. Results Levels of blood glucose, 24 h urinary albumin, MDA content and the expression of TGF-β1 were higher in the control group than those in the normal group, while SOD activity decreased and PKA mRNA was downregulated. C peptide treatment did not change blood glucose level but slowed down the increasing of 24 h urinary albumin, reduced the tubulointerstitial TGF-β1 expression and MDA content, increased the SOD activity and upregulated the PKA mRNA expression. Conclusions C-peptide can decrease the tubulointerstitial oxidative stress in DN rats by activating PKA pathway and then improve tubulointerstitial fibrosis and attenuate proteinuria.

Progress of vascular endothelial growth factor and the tubulointerstitial injury / 国际儿科学杂志

Vascular endothelial growth factors (VEGF) are cytokines that leading to endothelial cell differentiation,proliferation,migration,and increase vascular permeability,which take part in the pathological process of microvascular.Recent studies have found that VEGF have close relationship with tubulointerstitial pathological changes.VEGF take part in the renal interstitial extracellular matrix synthesis and degradation.Therefore,we take more attention to the important role of VEGF in renal tubular damage.The present review will outline the current understanding of VEGF in the tubulointerstitial injury.

Urinary N-Acetyl-beta-D-Glucosaminidase and beta 2-Microglobulin in Children with Various Renal Diseases

PURPOSE: Urinary N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-microglobulin(B2M) is considered to be a marker of tubulointerstitial injury. The aim of this study was to examine the urinary levels of NAG and B2M in children with various renal diseases. METHODS: We studied 21 children(8.9+/-4.5 years, Male:Female=14:7) and they were divided into three groups: group I(steroid-sensitive nephrotic syndrome-4 patients), group II(various kinds of glomerulonephritis-4 patients), and group III(normal urinalysis or non-glomerular renal diseases-13 patients). RESULTS: Urinary NAG levels in groups I and II were significantly higher than those in group III(19.4+/-11.5 and 30.0+/-30.1 vs. 4.7+/-3.9, P=0.01), while urinary B2M levels did not differ among the 3 groups, although urinary NAG levels were positively correlated with urinary B2M levels(r=0.49, P=0.03). Urinary NAG and B2M levels were all correlated with proteinuria(r=0.79, P<0.001 and r=0.68, respectively, P=0.001) serum albumin(r=-0.72, P<0.001 and r=-0.57, respectively, P=0.01) and cholesterol(r=0.58, P=0.006 and r=0.56, respectively, P=0.013) levels. Conclusions: Urinary excretions of NAG and B2M are increased in children with steroid-sensitive nephrotic syndrome and various kinds of glomerulonephritis, suggesting tubular dysfunction might be present in these diseases.

Protective Effect of N-Acetylcysteine on Progression of Adriamycin-induced Nephropathy

Effects of antioxidants on the established nephropathy were investigated. The experimental nephropathy was induced in rats by intravenous injection of adriamycin (2 mg/kg). Six weeks later, when proteinuria was apparent, the rats were supplemented with N-acetylcysteine (NAC, 1 g/kg/day) in drinking water for additional 6 weeks. Glomerulosclerosis score and tubulointerstitial injury index were determined by light microscopy. Expression of transforming growth factor (TGF) beta1 and laminin beta1 was determined in the renal cortex by reverse transcription-polymerase chain reaction, Western blotting, immunohistochemistry, and immunogold electron microscopy. The adriamycin-induced proteinuria as well as the glomerulosclerosis and tubulointerstitial injury was ameliorated by the treatment with NAC. Adriamycin increased the expression of TGF beta1 mRNA and protein, which was ameliorated by NAC. Although the expression of laminin beta1 mRNA was increased, adriamycin did not significantly alter that of its protein. These results indicate that antioxidants ameliorate the established nephropathy in association with normalization of overexpressed TGF beta1.

Comparison between Osteopontin Expression and Renal Function in Spontaneous Renal Failure Model / 대한신장학회잡지

Tubuolointerstitial inflammation and tubular injury account for most types of glomerulonephritis. The injury is characterized by an infiltration of mononuclear cells with atrophy and dilation of tubules and increased deposition of collagen in the interstitium. Despite the fact that the degree of tubulointerstitial injury in glomerular diseases may be the best predictor of overall outcome, the pathogenic mechanism by which the tubular injury develops remains unknown. Osteopontin, a highly acidic, phosphorylated, secreted glycoprotein, is up-regulated in renal cortex in many experimental models of tubulointerstitial fibrosis. In this study, we examined the expression of osteopontin in tubulointerstitium in experimental renal failure mouse, FGS/KIST. Mice were assigned three groups and sacrificed at 1 month, 2 months, and 3 months, in each. Proteinuria, GFR, the degree of tubulointerstitial inflammation, tubular atrophy, glomerulosclerosis and osteopontin expression were measured. Three-month-old group showed severely decreased GFR and marked tubulointerstitial inflammation and glomerulosclerosis compared with other groups. The expression of osteopontin increased with the severity of tubulointerstitial injury. These data suggest that osteopontin may act as a chemotactic or adhesive factor in the recruitment of the monocyte/macrophages and have a role in the pathogenesis of the tubulointerstitial injury.