Citrinin nephrotoxicity in rats: A light and electron microscopic study

Citrinin, a myocotoxin produced by Penicillium citrinum, causes hepatic and renal damage. This study describes light and electron microscopic changes in rat kidneys at intervals of 24, 48, 72, and 96 hr following administration of 50 mg/kg citrinin. Twenty-four hours after treatment, the most prominent change was cytoplasmic vacuolization of epithelial cells of proximal convoluted tubules. This vacuolar change involved clusters of proximal convolutions. Such focal changes were distributed throughout the cortex. Other components of the cortex and medulla appeared relatively normal morphologically; distal tubular damage was not observed. At 48 hr following administration of citrinin, multifocal areas of necrotic proximal convoluted tubules were observed. Extensive mineral deposits were present in the necrotic areas. Intact proximal and distal tubules were observed between the necrotic areas, and components of the medulla were not appreciably altered. At 72 hr, various degrees of regeneration of proximal tubular epithelial cells were noted in areas of necrosis in the cortex. Ninety-six hours following citrinin administration, tubular regeneration was still prominent and, in some cases, kidneys appeared completely normal morphologically.     

中华鳖肾组织微细结构的性别差异

目的 探讨雌、雄中华鳖肾组织的微细结构特征及意义。方法 利用甲苯胺蓝半薄切片和透射电镜超薄切片技术,研究20只雌、雄中华鳖肾脏组织结构。结果 雌、雄中华鳖肾脏肾小管的近端小管和中间段上皮细胞结构存在一定差异,表现在雄性的近端小管立方上皮细胞之间含有侧细胞间隙,基底膜与基膜之间存在基底细胞间隙。侧细胞间隙内分布有由质膜形成的指状突起,细胞基底间隙中分布由基底膜形成的基底迷路。雌性近端小管立方上皮细胞间无侧细胞间隙和基底间隙。雌、雄鳖的中间段上皮细胞也表现出与近端小管立方上皮细胞相似的形态差异,即雄性肾小管的中间段立方上皮细胞间存在侧细胞间隙和基底间隙,间隙内分布有细长的指状突起,而在雌性肾小管的中间段上皮中无侧细胞间隙和基底间隙。雄性中华鳖近端小管上皮细胞有3种：主细胞、秃头细胞和基底细胞;与雄性不同,雌性的近端小管上皮仅有亮、暗两种上皮细胞。结论 雌、雄中华鳖肾脏近端小管和中间段的上皮组织结构存在性别差异。侧细胞间隙和基底间隙仅存在于雄性近端小管和中间段上皮细胞之间,上皮组织细胞之间的侧面间隙与细胞基底间隙应与物质运输有关,提示雄性近端小管的尿液重吸收能力和中间段上皮的尿液浓缩能力可能较雌性的强。     

Cubilin, a multifunctional epithelial receptor: an overview

Cubilin is a 460-kDa endocytic receptor coexpressed with megalin, a multiligand receptor of the low-density lipoprotein receptor gene family, at the apical pole of epithelial cells in the renal proximal convoluted tubule, visceral yolk sac, ileum, and placenta. The structure of cubilin is unique: it lacks a transmembrane domain and requires megalin for its internalization. The accumulation of 27 interactive CUB domains provides the potential for multiple, possibly independent interactions and functions. Cubilin is involved in the intestinal absorption of vitamin B12, the catabolism of apolipoprotein A-I by the proximal convoluted tubule and more generally in renal protein reabsorption. The role of cubilin on fetomaternal interfaces is not defined but may be related to its ability to bind and internalize high density lipoproteins.     

The pattern of distribution of selected ATP-sensitive P2 receptor subtypes in normal rat kidney: an immunohistological study

Using immunohistological techniques and available polyclonal antibodies, we have identified several ATP-sensitive P2 receptor subtypes in specific structures of the normal rat kidney. Of the P2 receptor subtypes examined, P2X1, P2X2 and P2Y1 receptors were found in the smooth muscle layer of intrarenal vessels. The P2Y1 receptor was also found on glomerular mesangial cells, the brush border membrane of the proximal straight tubule and on peritubular fibroblasts. In the cortex, P2Y4 receptors were found on the tubule epithelium of the proximal convoluted tubule, and P2Y2 receptors on glomerular epithelial cells (podocytes). P2X4 and P2X6 receptors were present throughout the renal tubule epithelium from the proximal tubule to the collecting duct. P2X5 receptors were expressed on medullary collecting duct cells and the apical membrane of the S3 segment of the proximal tubule. Possible functions of these receptor subtypes in normal rat kidney are discussed.     

Ultrastructure of medullary tubules in ischemic acute tubular necrosis and acute interstitial nephritis in man

Medullary tubules in renal biopsies from twelve patients suffering from ischemic acute tubular necrosis (ATN) and nine patients with allergic, drug-induced acute interstitial nephritis (AIN) were investigated by electron microscopy using quantitative and semiquantitative methods. For comparison, 12 biopsies from patients without renal disease or with minimal change nephropathy were studied. The mean scores for reduction of brush border and basolateral infoldings of the cell surface were significantly increased in the straight part of the proximal tubule and the thick ascending loop of Henle (straight part of the distal tubule) compared with medullary controls, and these changes were significantly greater than the scores for the corresponding convoluted tubules in the cortex. The numbers of missing tubular epithelial cells (indicating sites of cellular desquamation) were significantly increased in the thick ascending loop of Henle in ATN as well as in AIN and in the straight proximal tubule in ATN. This single cell lesion also occurred in the collecting duct. These findings are discussed in the light of recent experimental data indicating the importance of medullary tubules for the pathogenesis of ATN.     

Animal model: renal lesions in cats with Chediak-Higashi-Steinbrinck syndrome

In this study designed to characterize the renal lesions in cats with the autosomal recessive Chediak-Higashi-Steinbrinck syndrome (CHS), the renal tubular epithelial cells of CHS cats were examined by light microscopy. Numerous cells of proximal convoluted and straight tubules, thin loop of Henle, distal convoluted and straight tubules, and collecting tubules contained enlarged cytoplasmic granules morphologically consistent with lysosomes. In general, the enlarged lysosomes were larger and more numerous in proximal convoluted and straight tubular cells and were generally more massive in older cats. The lesions observed were similar to those in the renal epithelial cells of other species with CHS and were consistent with those reported previously in other tissues of CHS cats. It is concluded that CHS cats are an appropriate model in which to study the effects of the CHS renal lesions on renal function in this syndrome.     

硒酸锌金属自显影技术检测游离锌离子在小鼠肾脏的分布

目的研究游离锌离子在小鼠肾脏的定位分布。方法应用硒酸锌金属自显影技术(ZnSeAMG)检测小鼠肾脏内的游离锌离子分布。结果游离锌离子在肾脏内分布广泛,皮质中有大量AMG反应阳性颗粒,髓质中的AMG阳性颗粒较少。其中,近曲小管、远曲小管、近直小管和远直小管上皮细胞近腔侧均分布有大量的棕黑色AMG阳性颗粒,肾小体、细段和集合管上皮细胞中AMG阳性颗粒较少。结论小鼠肾脏内含有丰富的游离锌离子,锌离子可能参与肾脏的功能。     

Kidney lesion in mice from an antirenal serum]

Intravenous administration of anti-renal serum in a dose 1--1.6 ml to mice line CBA brought about drastic changes in the kidney ranging from severe dystrophy of the tubule cells to necrosis of the epithelium of the proximal and straight tubules. A smaller dose (0.5 ml) produced initially degenerative changes in individual cells of the proximal convoluted and straight tubules, and 2--6 months later degenerative changes were noted almost in all cells of the tubules referred to above. The glomerular apparatus was affected in a lesser degree. The relative weight of the kidneys of the mice treated with anti-renal serum at the end of the 3rd month was less than that in control animals. The urine contained granular and hyaline cylinders and a considerable amount of protein. Concentration of urea in the blood serum of the experimental animals was found to be elevated.     

Membrane antigens shared by renal proximal tubules and other epithelia associated with absorption and excretion.

The distribution of shared antigens in specialized surface membranes of epithelia associated with absorption and excretion was studied using antisera against isolated epithelial brush borders of renal proximal tubules. Rabbits were immunized with a membrane fraction isolated from rat kidneys and the reactions of the resulting heterologous antisera with different rat organs were studied by immunofluorescence. The antisera reacted with the following structures: epithelial brush border of renal proximal tubules, bile canaliculi and bile duct epithelium of the liver, epithelial brush border of the intestinal villi, luminal parts of some epididymal tubules, allantochorionic epithelium, and apical parts of the exocrine epithelium of the pancreatic, salivary and lacrimal glands. Both quantitative and qualitative differences in antigen contents were suggested by absorption experiments.     

Effect of parathyroid hormone on bicarbonate absorption by proximal tubules in vitro.

The effect of parathyroid hormone on bicarbonate absorption was tested in rabbit proximal renal tubules perfused in vitro. In proximal straight tubules 0.05 U/ml of parathyroid hormone caused a large and reversible increase in the steady-state bicarbonate concentration in tubule fluid. Further, the rates of bicarbonate and fluid absorption (measured at faster flow rates) were inhibited approximately 50% by the hormone. We conclude that parathyroid hormone directly inhibits fluid and bicarbonate absorption by proximal straight tubules, causing an increase in the bicarbonate concentration in the tubule fluid, and we suggest that this action of the hormone contributes to the increase in renal bicarbonate excretion that is generally caused by the hormone. In proximal convoluted tubules, parathyroid hormone was previously demonstrated by other investigators to inhibit fluid and bicarbonate absorption approximately proportionally, so that there was little or no change in the bicarbonate concentration in tubule fluid. In agreement we found in the present studies that 0.05 U/ml of the hormone did not affect the steady-state bicarbonate concentration in proximal convoluted tubule fluid and that 5 U/ml caused only an equivocal increase in tubule fluid bicarbonate concentration.     

Innervation of the kidney in Lacerta muralis (Laur)]

Study of the kidney innervation in the lizard (Lacerta muralis), using the silver impregnation technique, showed nerve terminals with the same contiguous relationship to the proximal and distal convoluted tubules and Bowman's capsule as in Mammals. Innervation of these segments may serve to regulate the contractile activity assigned to the capsule and tubule epithelial cells by various workers. Perimetral fibres were also noted on the so-called "sexual segment". Their target is probably the myoepithelial cells that surround this segment, though the possibility that they regulate its secretory activity cannot be excluded.     

Filamentous actin bundles in the kidney

The distribution of filamentous actin bundles in the rat kidney was studied using a fluorescent phallotoxin label and transmission electron microscopy. The microvillous brush border lining proximal tubules, smooth muscle in renal vessels, and renal corpuscles were the structures most intensely labeled with rhodamine phalloidin. Closer evaluation of renal corpuscles revealed intense labeling of filamentous actin within podocyte foot processes enveloping the glomerular capillary loops. Rhodamine phalloidin also labeled basal bands of filamentous actin in the parietal epithelium and basal bands of actin in proximal and distal tubules. Finally, a band of filamentous actin was evident along the innermost aspect of the kidney capsule, within cells which often joined to form sinus-like compartments.     

Histology of the kidney and urinary bladder of Siphonops annulatus (Amphibia-Gymnophiona)

The histology of the kidney and urinary bladder of Siphonops annulatus was studied by light microscopy in semithin sections of tissue embedded in hydrophilic resin. The kidney's nephron comprises the renal corpuscle, neck segment, proximal tubule, intermediate segment, distal tubule and collecting tubule. Nephrostomes are present. This structure, the neck segment, and intermediate tubules present long cilia, and probably play important roles in the propulsion of the peritoneal fluid and glomerular filtrate. The proximal tubule cells possess loosely packed microvilli and contain abundant polymorphic granules and vesicles that assume the aspect of lysosomes in different stages of intracellular digestion. The distal tubules are characterized by large, vertically disposed mitochondria assuming the aspect of ions transporting cells. The urinary bladder is lined with a transitional epithelium, whose aspect varies according to the quantity of urine.     

The structural organization of the kidney of Typhlonectes compressicaudus (Amphibia, Gymnophiona)

Summary The structural organization of the kidney ofTyphlonectes compressicaudus (Amphibia, Gymnophiona) was studied by light microscopic (LM) examination of serial paraffin and semithin Epon sections. The kidney is slender and quite long and has a mesonephric segmental construction; the excretory duct (Wolffian duct), running along the lateral side of the kidney, segmentally receives the terminal trunks of the collecting duct system. The nephron has the following parts: renal corpuscle, neck segment, proximal tubule, intermediate segment, distal tubule and connecting tubule. The distal tubule is located in a ventromedial (central) zone of the kidney; all other tubular segments lie in a dorsolateral (peripheral) zone. The renal corpuscles are found at the border between these two zones.The renal corpuscle is very large; its urinary pole faces the peripheral zone. A small proportion of neck segments receive either a nephrostomal duct or a blind branch. The proximal tubule is a thick, highly convoluted tubule. The intermediate segment is ciliated and makes a few coils. The distal tubule is composed of three portions: a highly convoluted part in the central zone, subsequently an attachment site with the renal corpuscle and a short postattachment-part. The connecting tubule and the collecting duct have a heterogeneous epithelium consisting of light and dark cells. The collecting duct is distinguished by dilated intercellular spaces. The Wolffian duct has a pseudostratified epithelium.The present study correlates the course and segmentation of the renal tubule ofTyphlonectes. The tubule has three major convolutions. The first occurs in the proximal tubule in the peripheral zone; the second is established by the distal tubule and occurs in the central zone; the third is formed by the connecting tubule and is found in the peripheral zone.Research fellow of the Alexander von Humboldt foundation: home address: Department of Anatomy, Faculty of Medicine, University of Tokyo, Tokyo 113, Japan     

庆大霉素促进小鼠缺血性肾脏损害的体视学分析

应用体视学方法,对庆大霉素促进小鼠缺血性肾脏的近曲小管及远曲小管上皮细胞进行体视学计量研究,结果发现,实验各组的近曲小管、远曲小管上皮细胞的体积密度(Vv)表面积密度(Sv)皆有非常显著性差异,认为近曲小管及远曲小管上皮细胞的体积和数量变化与缺血、庆大霉素毒性呈正相关,其体视学参数,可考虑为肾脏损害的诊断参考之一。     

FGF10及其受体FGFR2 Ⅲb在小鼠肾脏发育中的表达

 摘要：目的 观察FGF10及其受体FGFR2 Ⅲb在小鼠肾脏发生发育中的表达和分布,探讨它们在肾脏发生发育中的作用。方法 选取胚龄12、14、16、18 d和生后1、7、14、21、42 d小鼠肾组织,用免疫组织化学和蛋白印迹技术（Western blot）,检测FGF10和FGFR2 Ⅲb的表达。结果 E12 d FGF10及FGFR2Ⅲb开始在输尿管芽微弱表达;随着肾脏发育成熟,FGF10及FGFR2Ⅲb主要表达于远端小管和集合管;FGF10在近曲小管表达,近直小管无表达;FGFR2Ⅲb在近端小管无阳性表达;生后肾组织及发育各阶段肾小体未见FGF10及FGFR2Ⅲb表达。Western blot显示随着胚（日）龄的增加,FGF10及FGFR2Ⅲb在肾脏的表达量先增后减。结论 FGF10和FGFR2Ⅲb在肾脏发生发育过程中发挥重要作用。     

The ultrastructural pathology of five lipoprotein lipase-deficient cats

The ultrastructural pathology of cats suffering from familial lipoprotein lipase deficiency is described. There were large numbers of lipid vacuoles within hepatocytes, epithelial cells of the proximal convoluted tubule of kidney and macrophages of the liver, spleen and lymph node. The older cats tended to have larger quantities of ceroid within hepatocytes and macrophages, and all stages of development of ceroid were observed. Chylomicron emboli were seen within the glomerular capillaries and interlobular blood vessels. There was podocyte foot fusion and thickening of basement membranes of glomeruli, Bowman's capsule and some proximal convoluted tubules, similar to that seen in diabetes mellitus. These changes represent a non-specific reaction of the kidney to noxious insults such as hypoxia caused by emboli. Transformation of smooth muscle cells from a contractile to a synthetic state was seen in the splenic trabeculae and, to a lesser extent, in blood vessels. Dilatations of the nuclear membrane of the lymphocytes were noted, the significance of which is unknown.     

Immunohistochemical identification of kidney nephron segments in the dog, rat, mouse, and cynomolgus monkey

Kidney is a major target organ in preclinical studies. In recent years, intense research has been undertaken to characterize novel renal toxicity biomarkers. In this context, we studied nephron segment specific antibodies against aquaporin-1 (AQP-1), α-glutathione-S-transferase (alpha-GST), Tamm-Horsfall protein (TH), calbindin-D(28K) (CalD), and aquaporin-2 (AQP-2), using an immunoperoxidase method on formalin-fixed paraffin-embedded kidney tissues of dogs, rats, mice, and Cynomolgus monkeys. AQP-1 was specific for proximal tubules and thin descending limbs of Henle's loops and AQP-2 for connecting and collecting ducts in dogs, rats, mice, and Cynomolgus monkeys. Alpha-GST stained the straight part of proximal tubules in dogs and proximal convoluted tubule and straight part of proximal tubules in rats. TH was specific for thick ascending limbs of Henle's loops in mice, rats, dogs, and Cynomolgus monkeys and stained additionally scattered cells in cortical connecting/collecting ducts of dogs. CalD was found in distal convoluted tubules and cortical connecting and collecting ducts of dogs, rats, and mice and in distal convoluted tubules, connecting ducts, and cortical and medullary collecting ducts of Cynomolgus monkey. This panel of antibodies may be a helpful tool to identify renal tubules by light microscopy in preclinical studies and to validate new biomarkers of renal toxicity.     

Ultrastructural characteristics of reactive changes in the epithelium of the kidney proximal tubules in massive proteinuria in children

The investigation was designed to analyse the mechanism of the protein transport on the basis of the estimation of ultrastructural organization of the epithelium of proximal convoluted tubules of kidneys of the children, suffering from the nephritic form of glomerulonephritis for a long time. It was established that high tubular proteinuria (from 0.33 to 6.6 g/l) causes many changes in apical, central and basal parts of epithelial cells as well as in intercellular spaces. It was stated that massive proteinuria provoked adaptive processes in epithelial cells of proximal tubules. At the same time signs of exhaustion of adaptive capacities of proximal nephrocytes were demonstrated.     

3～20周人胚和胎儿肾小体的组织发生

应用光、电镜对3～20周22例人胚和胎儿肾小体的组织发生进行了观察.受精后第25天胚肾已有肾小体发生.随着胚龄的增长,肾小体的发生数目增多,肾小体的形成方式是:胚肾内先形成许多厚壁小管,在一部分厚壁小管的诱导下,另一部分厚壁小管的一侧壁呈帽状增厚,分化形成造血干细胞、毛细血管内皮及肾小囊脏层,对侧壁形成肾小囊壁层.即厚壁小管的双侧壁形成肾小体.