A scanning electron-microscopic study of the peripolar cell of the rat renal glomerulus

Summary The interior of Bowman's capsules of rat kidneys has been examined by scanning electron microscopy, and a distinctive population of cells around the exposed vascular poles of glomerular tufts were identified. The cells were situated in the annular groove at the root of the glomerulus, between the parietal epithelial cells and the podocytes. These peripolar cells were dendritic cells with long processes embracing the glomerular arterioles. Up to three peripolar cells were present at each vascular pole and they were mainly distributed in the glomeruli of the outer third of the renal cortex. This first detailed study of the surface morphology of the glomerular peripolar cell supports the suggestion that changes in the diameter of the polar region of the glomerular tuft may cause variations in stretching of the cuff of peripolar cells, and hence modulation of their secretory activity.     

老年原发性高血压患者血压晨峰与早期肾损害的临床观察

目的:探讨老年原发性高血压患者血压晨峰与早期肾损害的关系。方法:选择我院收治的94例老年原发性高血压患者进行24小时动态血压监测,并根据监测结果,将患者分为晨峰组62例和非晨峰组32例,检测和比较两组的血肌酐和尿素氮、12小时尿微量蛋白、尿β2微球蛋白、空腹血糖、血脂等指标。结果:老年高血压患者晨峰组12小时尿微量蛋白、尿β2微球蛋白均显著高于非晨峰组(P0.05);晨峰血压与12小时尿微量白蛋白(r=0.374)、尿β2微球蛋白(r=0.456)呈显著正相关。结论:老年原发性高血压患者血压晨峰与早期肾损害有关,治疗高血压的同时重视控制晨峰血压有重要意义。     

Effects of light and dark upon photoreceptor synapses in the retina of Xenopus laevis

Summary The adrenergic innervation of the juxtaglomerular complex was studied in kidneys from mice, rats, guinea-pigs, rabbits, cats, dogs, pigs, monkeys, and humans using fluorescence histochemistry of neuronal nor-adrenaline and autoradiography of ³H-noradrenaline. The localization of the nerves was established by phase contrast optics or by perfusing the vascular system with India ink. Adrenergic nerve terminals, exhibiting a formaldehyde-induced fluorescence and having the ability to take up and accumulate ³H-noradrenaline, were easily identified when they enclosed the glomerular afferent arteriole. They continued in between and close to the macula densa and lacis cells to supply the glomerular efferent arteriole. The nerves could be seen to accompany this arteriole for a considerable distance until they branched off to the vasa recta in the juxtamedullary region and to adjacent cortical veins. This innervation pattern was found to be a constant feature except in kidneys from guinea-pigs and cats, in which post-glomerular adrenergic nerves were not found in some of the superficial glomerular units. The fluorescence in all adrenergic fibres supplying the juxtaglomerular complex disappeared after removal of the aortico-renal ganglion, showing that they belong to a common system of renal sympathetic nerves.This work is dedicated to Professor Wolfgang Bargmann in honour of his seventieth birthday, January 26, 1976     

Interleukin-20 targets renal cells and is associated with chronic kidney disease

Interleukin (IL)-10 is an anti-inflammatory factor that suppresses renal fibrosis and improves renal function in CKD rats. IL-20 belongs to the IL-10 family; therefore, we sought to determine whether IL-20 is involved in CKD. CKD patients at stage five expressed significantly higher IL-20 in serum than controls. Immunohistochemical staining demonstrated that more IL-20 protein was expressed in the kidney tubular-epithelial cells, mesangial cells, and immune cells of CKD rats with a 5/6 nephrectomy. The lung, liver, and heart tissue of CKD rats also overexpressed IL-20. Thus, we treated two tubular epithelial cells, TKPTS and M-1 cells, with IL-20 to study its effects on CKD. IL-20 treatment induced apoptosis in these cells via caspase-3 activation. Incubating IL-20 with rat interstitial fibroblasts, NRK-49F cells, upregulated TGF-β1production, one key inducer for renal fibrogenesis. Therefore, IL-20 injured renal epithelial cells and induced fibroblasts to produce TGF-β1 that hastened the progression of CKD.     

肾小球毛细血管内皮病合并甲状腺功能减低1例病例报道并文献复习

目的:通过分析我院收治的1例肾小球毛细血管内皮病合并甲状腺功能减退患者的诊治过程,结合相关文献,探讨此病的临床特点和诊疗方法。方法:报告北京军区总医院收治的1例肾小球毛细血管内皮病合并甲状腺功能减退病例的其临床资料及诊疗过程,并复习相关文献,对肾小球毛细血管内皮病合并甲状腺功能减退的病因、临床表现、诊断、治疗及预后进行分析,并总结其诊疗经验。结果:1例肾小球毛细血管内皮病合并甲状腺功能减退患者经综合治疗后病情好转出院,出院后继续接受对症治疗,目前患者恢复良好。结论:肾小球毛细血管内皮病的发病率低,合并甲状腺功能减退更少见,其发病原因不明,部分与药物、毒物或者病毒感染有关,多数病例对症治疗后预后较好。     

In vitro autoradiographic localization of [I]-angiotensin II binding sites in the rat and dog kidney

Light microscopic autoradiographic techniques have been utilized to demonstrate specific regions of the rat and dog kidney where angiotensin II receptors exist. Slide mounted tissue sections were labeled with [¹²⁵I]-angiotensin II using conditions which provided for highly specific binding. These angiotensin II binding sites were localized to several distinct renal structures. In the renal cortex, angiotensin II binding sites were found concentrated in all parts of the glomeruli including the vascular components, the macula densa and the juxtaglomerular apparatus. Angiotensin II binding in the medulla was more diffusely associated with the vasa recta, and to a lesser extent, the thick ascending segment of the loop of Henle. Binding sites specific for angiotensin II were also found in the smooth muscle laminae of the ureter. Scatchard analysis of the binding kinetics allowed the demonstration of two subpopulations of binding sites which differ slightly in their affinities for [¹²⁵I]-angiotensin II. These subpopulations appear to be associated with distinct components of the renal structure.     

The effect of a thermal renal denervation cycle on the mechanical properties of the arterial wall

The aim of this study was to determine the effect that a thermal renal denervation cycle has on the mechanical properties of the arterial wall. Porcine arterial tissue specimens were tested in three groups: native tissue, decellularized tissue, decellularized with collagen digestion (e.g. elastin only). One arterial specimen was used as an unheated control specimen while another paired specimen was subjected to a thermal cycle of 70 °C for 120 s (n=10). The specimens were subjected to tensile loading and a shrinkage analysis. We observed two key results: The mechanical properties associated with the elastin extracellular matrix (ECM) were not affected by the thermal cycle. The effect of the thermal cycle on the collagen (ECM) was significant, in both the native and decellularized groups the thermal cycle caused a statistically significant decrease in stiffness, and failure strength, moreover the native tissue demonstrated a 27% reduction in lumen area post exposure to the thermal cycle. We have demonstrated that a renal denervation thermal cycle can significantly affect the mechanical properties of an arterial wall, and these changes in stiffness and failure strength were associated with alterations to the collagen rather than the elastin extracellular matrix component.     

The effects of cortisol and testosterone on renal function in male Antechinus stuartii (Marsupialia)

Seasonal changes in the physiology of Antechinus stuartii result in complete male mortality after mating. The most important endocrine changes in males are large rises in plasma testosterone and cortisol concentrations. Glomerular filtration rate (GFR) in males declines coincident with high plasma testosterone and cortisol. In the present study GFRs were measured in males captured in May (when endogenous plasma testosterone and cortisol levels are low) and given depot injections of either saline, testosterone-only, cortisol-only or testosterone plus cortisol at doses designed to mimic plasma levels during the mating period. GFR decreased significantly with testosterone injection, independent of cortisol treatment. Urinary concentrations of sodium and chloride, and osmolality decreased significantly with cortisol treatment, although the addition of testosterone reversed the effect. Total urinary excretion of electrolytes was similar between groups. Plasma potassium levels significantly increased in testosterone plus cortisol treated males. Plasma sodium levels significantly increased and plasma chloride significantly decreased in all groups treated with cortisol. Water consumption significantly increased in all cortisol-treated males and food consumption significantly increased in all testosterone-treated males. The seasonal renal functional changes observed in A. stuartii were mimicked by testosterone administration. Accepted: 23 January 1998     

Myosin content and vasoconstrictive ability of the proximal and distal (renin-positive) segments of the preglomerular arteriole

Summary The PAP-technique and antibodies to myosin were used to demonstrate the prerequisites for vasoconstriction in the juxtaglomerular part of the preglomerular arteriole as compared with its proximal segment in rats and mice. In contrast with the myosin-positive/renin-negative proximal part of the afferent arteriole no myosin-like activity could be demonstrated in its distal, renin-positive part. In accordance, no thick myofilaments were found in fully differentiated juxtaglomerular epithelioid cells replete with mature secretory granules. Stimulation of the renin-angiotensin system was followed by an increase of the reninpositive/myosin-negative portions of the preglomerular arteriole. Marked interspecies and internephron variations in the length of this vessel segment under control and stimulated conditions were observed.The juxtaglomerular part of the preglomerular arteriole close to the macula densa seems therefore to have only limited capabilities for vasoconstriction. This finding may be of importance regarding the tubulo-glomerular feedback, a mechanism allegedly triggered by the so-called macula densa-signal. It is suggested that this non-contractile segment of the afferent arteriole may represent the renal vascular receptor responsible for the increase of renin secretion during pressure reduction.Unlike the afferent arterioles, most of the efferent arterioles showed the highest level of their weak but distinct myosin-like immunoreactivity in the juxtaglomerular region, indicating some efferent juxtaglomerular vasoconstrictive ability.These studies were supported by the German Research Foundation within the Forschergruppe Niere/Heidelberg     

免疫学方法作为早期诊断高血压患者肾损害的探讨

为了探讨高血压患者血压与肾脏损害的关系 ,分别以RIA和ELISA共同检测尿视黄醇结合蛋白、尿微量白蛋白、尿 β2 微球蛋白和血中半胱氨酸蛋白酶抑制物C。结果显示高血压组血CystatinC、尿RBP、mALB、β2 MG均显著高于对照组 (p <0 .0 1) ,且随病程的延长而有逐渐升高的趋势。血压昼夜节律异常组的血CystatinC、尿RBP、mALB和 β2 MG也明显高于血压昼夜节律正常组 (p <0 .0 1) ,提示高血压所致的肾损害不仅与血压增高程度有关 ,而且与血压在较高水平持续时间有关。结论 :高血压病引起的肾小球、肾小管损害 ,以检测CystatinC、RBP、mALB、β2 MG可作为早期诊断肾脏损害的敏感指标     

Myoendothelial contacts in glomerular arterioles and in renal interlobular arteries of rat,mouse and Tupaia belangeri

Summary Cell contacts between elements of the tunica media and the intima in the afferent and efferent glomerular arteriole and in the interlobular artery were studied and evaluated semiquantitatively in thin sections of rat and mouse kidney.In the afferent arterioles, including their juxtaglomerular portion, contacts were seen between endothelial and smooth muscle cells, and between endothelial and granulated (renin producing) cells. The form of these musculoendothelial contacts varied from simple appositions of perikarya and cell processes to extensive club-shaped indentations of endothelial cells into media cells (common) or media cells into endothelial cells (rare). Most of these cell contacts seem to contain myoendothelial gap junctions. Fewer, mostly club-shaped myoendothelial contacts were found in the interlobular arteries of rats and mice than in their afferent arterioles. Simple membrane appositions predominated among the numerous myoendothelial contacts of efferent arterioles. Similar results (without quantitative analysis) were obtained in the kidney of Tupaia belangeri. The myoendothelial contacts may allow the detection and propagation of mechanical (autoregulatory) and humoral stimuli.These studies were supported by the German Research Foundation within the SFB 90 Cardiovasculäres System     

Therapeutic potentials of mesenchymal stem cells on the renal cortex of experimentally induced hypertensive albino rats: Relevant role of Nrf2

Bone marrow derived-mesenchymal stem cells (BM-MSCs) have brought great attention in regenerative medicine field, various experimental & clinical trials were held to investigate their therapeutic effects in different disorders. We designed a histological & immunohistochemical study to evaluate effectiveness of MSCs therapy in withhold of end-stage renal disease (ESRD) secondary to hypertension which has become a growing & striking public health problem. 30 adult male albino rats were utilized, 20 of them were exposed to experimental induction of hypertension, then divided equally to MSCs treated group (injected with 1 × 10⁶ fluorescent labeled cell i.v./rat), while the second one was left without treatment. Renal specimens were subjected to histopathological, ultrastructural and immunohistochemical examination for Nrf2 in addition to biochemical estimation of serum urea & creatinine. Our results documented that BM-derived MSCs exerts considerable reversing effect of histopathologic and ultrastructural hypertensive nephropathy. Moreover, immunohistochemical results clearly pointed to relevant role of Nrf2 pathway in MSCs related renal therapeutic effects.     

Metabolic syndrome during gestation and lactation: An important renal problem in dams. selenium renal clearance

BackgroundMetabolic syndrome (MS) in lactating dams leads to several cardiometabolic changes related to selenium (Se) status and selenoproteins expression which produce hypertension. However, little is known about the state of these dams’ kidney functions and their Se deposits.MethodsTwo experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65 % and Se: 0.1 ppm). At the end of lactation (21d postpartum) kidney weight and protein content, Se deposits, and the activity of the antioxidant selenoprotein glutathione peroxidase (GPx) were measured in dams. Kidney functional parameters: albuminuria, creatinine clearance, serum aldosterone and uric acid levels and water and electrolyte (Na⁺ and K⁺) balance were also evaluated. Systolic blood pressure (SBP) was measured.ResultsIn MS dams at the end of lactation Se deposits and GPx activity are higher in the kidney; however, lipid renal peroxidation appears, relative Se clearance increases, and the dams have lost Se by urine. MS dams have polyuria and polydipsia, high uric acid serum levels, albuminuria and high creatinine clearance, implying glomerular renal malfunction with protein loss. They also present hypernatremia, hypokalemia and hyperaldosteronemia, leading to high SBP; however, a natriuretic process is taking place.ConclusionSince these alterations appear, at least in part, to be related to oxidative stress in renal cells, Se supplementation could be beneficial to avoiding greater lipid renal oxidation during lactation.     

Interleukin-6 and renal cell cancer: Production,regulation, and growth effects

Summary Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor (TNF) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P <0.05). The combination of interferon IFN and TNF further enhanced the augmented IL-6 mRNA accumulation seen with TNF alone (P <0.05). TNF also significantly stimulated the production of biologically active IL-6 (P <0.01). Furthermore, IFN and TNF were found to enhance IL-6 bioactivity synergistically (P <0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF with synergistic effects seen with IFN at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines.This work was supported in part by National Institutes of Health Grant CA 522 499-01, and the Margaret Early Foundation     

Acute Taxol nephrotoxicity: Histological and ultrastructural studies of mice kidney parenchyma

Taxol is a microtubule inhibitor drug widely used in treatment of many types of cancer. Nephrotoxicity is the most hazardous effect complicating chemotherapy in general and kidney functions must be monitored early during any chemotherapeutic course. The main objective of the present study was to investigate the effect of acute Taxol nephrotoxicity in mice. In the present study Taxol at different doses; MD, ID and MTD (0.6, 1.15 and 1.7 mg/kg), respectively, was given by intra-peritoneal route to 54 adult male mice with an average body weight of 20–25 g. Kidney samples was taken 6, 24, 48 h following administration, fixed in 10% neutral buffered formalin, paraffin sections 5 μm thick were stained by haematoxylin and eosin and PAS and then examined for histological changes. Samples from animals treated by the maximum dose (MTD = 1.7 mg/kg) for 48 h were fixed in 3% gluteraldehyde in phosphate buffer (pH 7.4) and processed for transmission electron microscope. Taxol given for short duration was found to produce marked degenerative changes in kidney parenchyma even in minimum tolerated dose (MD = 0.6 mg/kg). Individual variations were observed regarding the degree of nephrotoxicity. There was marked loss of renal tubules epithelial lining, damage of brush border and formation of hyaline casts within the damaged tubules. The alterations were in the form of both necrotic and apoptotic changes in the kidney tubules. Focal atrophy of glomerular tufts was also observed. Vascular congestion and degenerative changes in renal blood vessels were occasionally evident in some samples. Ultrastructure study revealed damage of glomerular membrane. Proximal tubule showed loss of basal infoldings, damage of brush border, mitochondrial degeneration and nuclear changes. Distal tubules also showed demarked degenerative changes. Increased frequency of micronuclei proved that Taxol had genotoxic effects in mice bone marrow cells. In conclusion Taxol had nephrotoxic effect on mice kidney that must be considered during its use as a chemotherapeutic agent in human.     

Expression and regulation of adrenomedullin in renal glomerular podocytes

Adrenomedullin (AM) is postulated to exert organ-protective effects. It is expressed in the renal glomeruli, but its roles in the glomerular podocytes have been poorly elucidated. In the present study, we investigated the expression and regulation of AM in recently established conditionally immortalized mouse podocyte cell line in vitro and podocyte injury model in vivo. The cultured differentiated podocytes expressed AM mRNA and secreted measurable amount of AM. AM secretion from the podocytes was increased by H(2)O(2), hypoxia, puromycin aminonucleoside (PAN), albumin overload, and TNF-alpha. Real-time RT-PCR analysis revealed that AM mRNA expression in the podocytes was enhanced by PAN and TNF-alpha, both of which were suppressed by mitochondrial antioxidants. Furthermore, AM expression was upregulated in the glomerular podocytes of PAN nephrosis rats. These results indicated that AM expression in the podocytes was upregulated by stimuli or condition relevant to podocyte injury, suggesting its potential role in podocyte pathophysiology.     

Structure of cells and nerve endings in abdominal vagal paraganglia of the rat

Summary The abdominal vagal paraganglia of the rat consist of small groups of cells, interspersed by blood vessels and nerve bundles and lying close to, or within, the vagus nerve or its branches. Each cell group consists of 2–10 Type I cells incompletely invested by 1–3 satellite cells. Type I cells are characterised by the presence of numerous dense-cored vesicles in their cytoplasm and may exhibit synaptic-like contact with each other.Small efferent nerve endings make synaptic contacts with Type I cells. Larger cup-shaped afferent nerve endings also make synaptic contacts of two kinds with Type I cells. Nerve-nerve synapses are often seen within or close to paraganglia.Attention is drawn to the close similarity of fine structure of abdominal vagal paraganglia, carotid body and small intensely fluorescent cells of the superior cervical ganglion in rats. Possible functional implications of this morphological similarity are discussed.     

Zinc deficiency during growth: influence on renal function and morphology

This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.     

Polycystic kidney disease: The complexity of planar cell polarity and signaling during tissue regeneration and cyst formation

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is an inherited systemic disease with intrarenal cystogenesis as its primary characteristic. A variety of mouse models provided information on the requirement of loss of balanced polycystin levels for initiation of cyst formation, the role of proliferation in cystogenesis and the signaling pathways involved in cyst growth and expansion. Here we will review the involvement of different signaling pathways during renal development, renal epithelial regeneration and cyst formation in ADPKD, focusing on planar cell polarity (PCP) and oriented cell division (OCD). This will be discussed in context of the hypothesis that aberrant PCP signaling causes cyst formation. In addition, the role of the Hippo pathway, which was recently found to be involved in cyst growth and tissue regeneration, and well-known for regulating organ size control, will be reviewed. The fact that Hippo signaling is linked to PCP signaling makes the Hippo pathway a novel cascade in cystogenesis. The newly gained understanding of the complex signaling network involved in cystogenesis and disease progression, not only necessitates refining of the current hypothesis regarding initiation of cystogenesis, but also has implications for therapeutic intervention strategies. This article is part of a Special Issue entitled: Polycystic Kidney Disease.