Involvement of angiotensin-mediated renal vasoconstriction in renal hypertension

Systematic arterial blood pressure and renal vascular resistance were found to be significantly greater in morphine, chloraloseurethane anesthetized renal hypertensive dogs than in similarly treated normotensive dogs. A lower dose infusion of the angiotensin antagonist 1-sar-8-ala-angiotensin II in the concentration of 20 mμg/ml into the renal artery decreased renal vascular resistance in the hypertensive, but not in the normotensive animals. The subsequent administration of a higher dose (approximately 50 mμg/ml) of 1-sar-8-ala-angiotensin II produced a decrease in renal vascular resistance in the normotensives, but a still greater effect in the hypertensives. Systemic blood pressure was significantly decreased with the higher dose in the hypertensive, but not in the normotensive group. The results indicate the participation of angiotensin-mediated renal vasoconstriction in the increased renal resistance in the hypertensive animals.     

Nucleolar organizing regions in renal cell carcinoma, renal oncocytoma and renal adenoma

Nucleolar organizing regions (NORs), as demonstrated by the silver-colloid staining technique, have been counted in 75 renal cell carcinomas (20 grade 1, 22 grade 2, 17 grade 3 and 16 sarcomatoid), eight renal oncocytomas and nine renal adenomas. Mean NOR counts were 3.27, 6.28, 9.24 and 8.12, respectively, for grades 1, 2, 3 and sarcomatoid tumours, 3.09 for renal oncocytomas and 2.63 for renal adenomas. Analysis of data using the unpaired Student's t-test showed significant difference between NOR counts of grade 1, 2 and 3/sarcomatoid renal cell carcinoma, and grades 2, 3 and sarcomatoid renal cell carcinomas when compared to renal oncocytomas and adenomas. The association between type and grade of tumour, NOR value and tumour proliferation is discussed.     

肾盂灌注冲洗对肾脏功能和结构的影响

目的:探讨经皮肾镜碎石术肾盂灌注冲洗压对肾脏结构和功能的影响。方法:建立20头活体猪高压肾盂冲洗模型,建立24F肾造瘘通道,分别在0mmHg(作自身对照,只造瘘不灌注)、150mmHg、200mmHg、250mmHg、300mmHg压力下各冲洗30分钟。术中取肾组织送病理检查,监测肾单位光镜和电镜下的形态学改变;术后5天留取尿标本,应用免疫比浊测定法(ITM)检测尿微量白蛋白(ALB)和β2-微球蛋白(β2-MG);并于术后第5天再次取肾组织行病理检查观察肾单位的形态学改变。结果:所有灌注组术后都出现尿蛋白的增高,术后第1天和术前相比,都有显著差异(P<0.01)。形态学观察:当肾盂灌注冲洗压在150-200mmHg时,光镜下观察见肾小囊腔轻度扩张,压力超过250mmHg,肾小囊腔见红细胞和蛋白渗出物,肾小管扩张。电镜下见肾近曲小管上皮细胞内空泡形成,微绒毛排列杂乱、稀疏、部分微绒毛脱落。结论:肾盂灌注冲洗安全压不应超过200mmHg。     

Proteomic distinction of renal oncocytomas and chromophobe renal cell carcinomas

Background

Renal oncocytomas (ROs) are benign epithelial tumors of the kidney whereas chromophobe renal cell carcinoma (chRCCs) are malignant renal tumors. The latter constitute 5–7% of renal neoplasias. ROs and chRCCs show pronounced molecular and histological similarities, which renders their differentiation demanding. We aimed for the differential proteome profiling of ROs and early-stage chRCCs in order to better understand distinguishing protein patterns.

Methods

We employed formalin-fixed, paraffin-embedded samples (six RO cases, six chRCC cases) together with isotopic triplex dimethylation and a pooled reference standard to enable cohort-wide quantitative comparison. For lysosomal-associated membrane protein 1 (LAMP1) and integrin alpha-V (ITGAV) we performed corroborative immunohistochemistry (IHC) in an extended cohort of 42 RO cases and 31 chRCC cases.

Results

At 1% false discovery rate, we identified?>?3900 proteins, of which?>?2400 proteins were consistently quantified in at least four RO and four chRCC cases. The proteomic expression profiling discriminated ROs and chRCCs and highlighted established features such as accumulation of mitochondrial proteins in ROs together with emphasizing the accumulation of endo-lysosomal proteins in chRCCs. In line with the proteomic data, IHC showed enrichment of LAMP1 in chRCC and of ITGAV in RO.

Conclusion

We present one of the first differential proteome profiling studies on ROs and chRCCs and highlight differential abundance of LAMP1 and ITGAV in these renal tumors.

     

肾盂灌注冲洗对肾脏功能和结构的影响

目的：探讨经皮肾镜碎石术肾盂灌注冲洗压对肾脏结构和功能的影响。方法：建立20头活体猪高压肾盂冲洗模型,建立24F肾造瘘通道,分别在0mmHg（作自身对照,只造瘘不灌注）、150mmHg、200mmHg、250mmHg、300mmHg压力下各冲洗30分钟。术中取肾组织送病理检查,监测肾单位光镜和电镜下的形态学改变;术后5天留取尿标本,应用免疫比浊测定法（ITM）检测尿微量白蛋白（ALB）和β2-微球蛋白（β2-MG）;并于术后第5天再次取肾组织行病理检查观察肾单位的形态学改变。结果：所有灌注组术后都出现尿蛋白的增高,术后第1天和术前相比,都有显著差异（P〈0.01）。形态学观察：当肾盂灌注冲洗压在150-200mmHg时,光镜下观察见肾小囊腔轻度扩张,压力超过250mmHg,肾小囊腔见红细胞和蛋白渗出物,肾小管扩张。电镜下见肾近曲小管上皮细胞内空泡形成,微绒毛排列杂乱、稀疏、部分微绒毛脱落。结论：肾盂灌注冲洗安全压不应超过200mmHg。     

Value of renal biopsy in acute intrinsic renal failure.

Eighty-four patients presented with acute renal failure and features suggesting a diagnosis of intrinsic renal disease other than "acute reversible renal failure." Renal biopsy proved valuable in establishing the diagnosis, in indicating the reversibility of the lesion, and in helping to decide on treatment.     

Purification and characterization of renal ferredoxin from bovine renal mitochondria

A renal ferredoxin was purified from bovine renal mitochondria to electrophoretic purity. The molecular weight of the renal ferredoxin was estimated by gel filtration and SDS-polyacrylamide gel electrophoresis to be 12,500 and 13,000, respectively. The optical absorption spectrum of renal ferredoxin in the oxidized form showed two peaks at 416 and 457 nm in the visible region, and the EPR absorption spectrum showed peaks at gx = gy =1.94 and gz = 2.02 in the reduced form at 13K. These spectra were typical of the 2S-2Fe type ferredoxins. Dissimilarities were recognized in the amino acid composition and isoelectric point between bovine renal ferredoxin and bovine adrenodoxin, but not in the optical, magnetic, and immunochemical properties. The reconstitution of 25-hydroxyvitamin D3-1 alpha-hydroxylase system was performed with the three components of NADPH-adrenodoxin reductase from bovine adrenal mitochondria, renal ferredoxin, and cytochrome P-450(1) alpha from bovine renal mitochondria. The results showed that the renal ferredoxin was essential for the 1 alpha-hydroxylase activity of 25-hydroxyvitamin D3.     

Regional responsiveness of renal perfusion to activation of the renal nerves

We tested for regional differences in perfusion responses, within the renal medulla and cortex, to renal nerve stimulation in pentobarbital sodium-anesthetized rabbits. Laser-Doppler flux (LDF) was monitored at various depths below the cortical surface (1-15 mm). Basal cortical LDF (1-3 mm, approximately 200-450 U) was greater than medullary LDF (5-15 mm, approximately 70-160 U), but there were no statistically significant differences in basal LDF within these regions. The background LDF signal during aortic occlusion was similar in the cortex (2 mm, 31 U) and outer medulla (7 mm, 31 U), but slightly greater in the inner medulla (12 mm, 44 U). During electrical stimulation of the renal nerves (0.5-8 Hz), cortical LDF and total renal blood flow were similarly progressively reduced with increasing stimulus frequency. Medullary LDF (measured between 5 and 15 mm) was overall less responsive than cortical LDF. For example, 4-Hz stimulation reduced inner medullary LDF (9 mm) by 19 +/- 6% but reduced cortical LDF (1 mm) by 54 +/- 11%. However, medullary LDF responses to nerve stimulation were similar at all depths measured. Our results indicate that while the vascular elements controlling medullary perfusion are less sensitive to the effects of electrical stimulation of the renal nerves than are those controlling cortical perfusion, sensitivity within these vascular territories appears to be relatively homogeneous.     

The renal cortical fibroblast in renal tubulointerstitial fibrosis

Renal cortical fibroblasts have key roles in mediating intercellular communication with neighboring/infiltrating cells and extracellular matrix (ECM) and maintenance of renal tissue architecture. They express a variety of cytokines, chemokines, growth factors and cell adhesion molecules, playing an active role in paracrine and autocrine interactions and regulating both fibrogenesis and the interstitial inflammatory response. They additionally have an endocrine function in the production of epoetin. Tubulointerstitial fibrosis, the common pathological consequence of renal injury, is characterized by the accumulation of extracellular matrix largely due to excessive production in parallel with reduced degradation, and activated fibroblasts characterized by a myofibroblastic phenotype. Fibroblasts in the kidney may derive from resident fibroblasts, from the circulating fibroblast population or from haemopoetic progenitor or stromal cells derived from the bone marrow. Cells exhibiting a myofibroblastic phenotype may derive from these sources and from tubular cells undergoing epithelial to mesenchymal transformation in response to renal injury. The number of interstitial myofibroblasts correlates closely with tubulointerstitial fibrosis and progressive renal failure. Hence inhibiting myofibroblast formation may be an effective strategy in attenuating the development of renal failure in kidney disease of diverse etiology.     

Calcium pump activity of the renal plasma membrane and renal microsomes

ATP-dependent Ca²⁺ uptake distinct from that of the mitochondria is found in both plasma membrane and microsomal membranes of rat kidney. Activity attributed to these fractions is enhanced by ammonium oxalate and is apparently insensitive to NaN₃. In contrast, rat kidney mitochondrial Ca²⁺ uptake is blocked by NaN₃. The pH of optimal activity is significantly higher for the mitochondrial fraction. Microsomal membrane Ca²⁺ uptake differs from that of the plasma membrane. Microsomal membranes are four times as active as the plasma membrane at high (5 mM) ATP levels. Apparent K_m values for Mg²⁺-ATP differ in the two preparations with a higher affinity for Mg²⁺-ATP found in the plasma membrane Ca²⁺ uptake activity of the plasma membrane preparation is readily inhibited by Na⁺. Sucrose gradient density fractionation indicates that the observed microsomal membrane Ca²⁺ pump activity is associated with membrane vesicles derived from the endoplasmic reticulum. Ca²⁺ pump activity of both plasma membrane and microsomal fraction is depressed din the adrenalectomized rat. This activity is not restored by a single natriuretic dose of aldosterone.