Acquired cysts of the kidneys in children with chronic renal failure

The study aimed at evaluating an incidence of the acquired cysts of the kidneys in children with chronic renal failure. The study involved 33 children with renal failure treated conservatively with continuous peritoneal dialysis under ambulatory conditions and hemodialyses. CT tomography and sonography were carried out in all patients. The acquired cysts of the kidney were diagnosed in one out of 33 examined patients (3.03%) by ultrasound. This result was confirmed by CT-scanning. It is worth following the development of the cyst in his child waiting for kidney transplantation and further following all dialysed patients with ultrasound performed once per three months and CT-scans in some patients.     

Peripheral distribution of kynurenine metabolites and activity of kynurenine pathway enzymes in renal failure.

We investigated L-kynurenine distribution and metabolism in rats with experimental chronic renal failure of various severity, induced by unilateral nephrectomy and partial removal of contralateral kidney cortex. In animals with renal insufficiency the plasma concentration and the content of L-tryptophan in homogenates of kidney, liver, lung, intestine and spleen were significantly decreased. These changes were accompanied by increase activity of liver tryptophan 2,3-dioxygenase, the rate-limiting enzyme of kynurenine pathway in rats, while indoleamine 2,3-dioxygenase activity was unchanged. Conversely, the plasma concentration and tissue content of L-kynurenine, 3-hydroxykynurenine, and anthranilic, kynurenic, xanthurenic and quinolinic acids in the kidney, liver, lung, intestine, spleen and muscles were increased. The accumulation of L-kynurenine and the products of its degradation was proportional to the severity of renal failure and correlated with the concentration of renal insufficiency marker, creatinine. Kynurenine aminotransferase, kynureninase and 3-hydroxyanthranilate-3,4-dioxygenase activity was diminished or unchanged, while the activity of kynurenine 3-hydroxylase was significantly increased. We conclude that chronic renal failure is associated with the accumulation of L-kynurenine metabolites, which may be involved in the pathogenesis of certain uremic syndromes.     

超声在糖尿病肾病诊断中的应用价值

由于快速变化的生活方式,我国糖尿病的患病率呈逐年上升趋势。糖尿病肾病(diabetic nephropathy,DN)是糖尿病最常见、最严重的微血管病变并发症之一,并且已经成为全球终末期肾病的最常见病因。因此,早期诊断、早期治疗是延缓DN进展的重点。超声是临床评价肾脏形态、功能常用的检查方法,与血、尿实验室检查相比,具有方便、快捷、无创、经济的优势。随着科学技术的发展,越来越多的超声新技术应用于临床,极大的丰富了诊断信息。本文就各项超声检查技术在检测DN患者肾脏体积、实质回声、血流动力学改变中的应用价值作一综述。得出结论:在DN早期血、尿实验室检查正常时超声已经可以发现肾脏体积、血流动力学发生了变化。因此,超声在DN的早期诊断、动态监测病程进展方面所发挥的作用是其他检查方法所不可替代的。三维超声技术和超声弹性成像在DN患者肾脏功能评价方面有着广泛研究空间及临床应用前景。     

Role of interaction of mannan-binding protein with meprins at the initial step of complement activation in ischemia/reperfusion injury to mouse kidney

Ischemia/reperfusion (I/R) is an important cause of acute renal failure. Recent studies have shown that the complement system mediated by the mannan-binding protein (MBP), which is a C-type serum lectin recognizing mannose, fucose and N-acetylglucosamine residues, plays a critical role in the pathogenesis of ischemic acute renal failure. MBP causes complement activation through the MBP lectin pathway and a resulting complement component, C3b, is accumulated on the brush borders of kidney proximal tubules in a renal I/R-operated mouse kidney. However, the initial step of the complement activation has not been studied extensively. We previously identified both meprins α and β, highly glycosylated zinc metalloproteases, localized on kidney proximal tubules as endogenous MBP ligands. In the present study, we demonstrated that serum-type MBP (S-MBP) and C3b were co-localized with meprins on both the cortex and the medulla in the renal I/R-operated mouse kidney. S-MBP was indicated to interact with meprins in vivo in the I/R-operated mouse kidney and was shown to initiate the complement activation through the interaction with meprins in vitro. Taken together, the present study strongly suggested that the binding of S-MBP to meprins triggers the complement activation through the lectin pathway and may cause the acute renal failure due to I/R on kidney transplantation and hemorrhagic shock.     

Adult human CD133/1(+) kidney cells isolated from papilla integrate into developing kidney tubules

Approximately 60,000 patients in the United States are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestin(+) and CD133/1(+) cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1(+) cells. Isolated CD133/1(+) papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal-like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1(+) progenitors from the papilla and cortex became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

Protein kinase B, P34cdc2 kinase, and p21 ras GTP-binding in kidneys of aging rats

Renal nephropathy present in male Wistar rats more than 13 months of age was reported as an indication that the rats were in renal failure. In this study, the renal tissue damage at 14 months of age in male Munich Wistar rats was similar to that reported for Wistar rats, indicating that Munich Wistar rats could be another model for study of kidney function in the aging rat. The usual renal response to injury involves increased cell division and/or reparative processes that involve tyrosine kinase activity (TyrK) and/or guanosine triphosphate-binding (G) protein signal trans-duction pathways. This study reveals the presence of renal tissue damage coinciding with significantly reduced activity of Ras, Akt, and p34cdc2 kinase, the signaling proteins that regulate cell division and/or growth, in renal cortical tissues of aging rats compared to young rats (P < 0.005, P < 0.005, and P< 0.001, respectively). These results suggest that proteins involved in signal transduction pathways associated with cell replication are downregulated in the aging kidney cortex at a time when renal cellular damage is also present.     

肝细胞生长因子抗肾纤维化研究进展

慢性肾脏疾病患者的肾功能会随时间的推移而进行性恶化,肾实质细胞进行性丧失及细胞外基质蛋白过度沉积将导致肾纤维化形成,肾纤维化进行性发展将最终走向终末期肾衰竭。肝细胞生长因子(HGF)及其受体c-Met对肾发育和急性肾损伤后的肾脏再生修复具有重要作用,在慢性肾衰竭及肾纤维化时,HGF还具有营养肾脏及抗肾纤维化的作用。简要综述了HGF抑制肾纤维化形成的细胞分子机制的研究进展,提示HGF在治疗肾纤维化方面所具有的前景。     

Adult human CD133/1 kidney cells isolated from papilla integrate into developing kidney tubules

Approximately 60,000 patients in the United States are waiting for a kidney transplant due to genetic, immunologic and environmentally caused kidney failure. Adult human renal stem cells could offer opportunities for autologous transplant and repair of damaged organs. Current data suggest that there are multiple progenitor types in the kidney with distinct localizations. In the present study, we characterize cells derived from human kidney papilla and show their capacity for tubulogenesis. In situ, nestin⁺ and CD133/1⁺ cells were found extensively intercalated between tubular epithelia in the loops of Henle of renal papilla, but not of the cortex. Populations of primary cells from the renal cortex and renal papilla were isolated by enzymatic digestion from human kidneys unsuited for transplant and immuno-enriched for CD133/1⁺ cells. Isolated CD133/1⁺ papillary cells were positive for nestin, as well as several human embryonic stem cell markers (SSEA4, Nanog, SOX2, and OCT4/POU5F1) and could be triggered to adopt tubular epithelial and neuronal-like phenotypes. Isolated papillary cells exhibited morphologic plasticity upon modulation of culture conditions and inhibition of asymmetric cell division. Labeled papillary cells readily associated with cortical tubular epithelia in co-culture and 3-dimensional collagen gel cultures. Heterologous organ culture demonstrated that CD133/1⁺ progenitors from the papilla and cortex became integrated into developing kidney tubules. Tubular epithelia did not participate in tubulogenesis. Human renal papilla harbor cells with the hallmarks of adult kidney stem/progenitor cells that can be amplified and phenotypically modulated in culture while retaining the capacity to form new kidney tubules. This article is part of a Special Issue entitled: Polycystic Kidney Disease.     

GH administration and renal IGF-I system in arthritic rats

Experimental arthritis in rats results in a growth failure and a decrease in circulating and hepatic concentrations of insulin-like growth factor I (IGF-I). Renal damage has also been reported in arthritic rats. The aim of this study was 1) to analyse if alterations in the IGF-I system in the kidney occurs in adjuvant-induced arthritis and 2) to analyse if recombinant human GH (rhGH) administration is able to reverse these effects. Male Wistar rats were injected with complete Freund's adjuvant or vehicle and 22 days later they were killed. Arthritis increased serum creatinine levels, relative kidney weight and IGF-I concentrations in this organ. In a second experiment, arthritic and control rats received rhGH (3 UI/Kg sc) or 250 microl saline from day 14, after adjuvant or vehicle injection, until day 22. IGF-I concentrations were higher in both the renal cortex and medulla of arthritic rats. In contrast, kidney IGF-I mRNA was lower in both areas of arthritic animals. GH treatment significantly decreased serum creatinine levels and IGF-I concentrations in the kidney cortex and medulla of arthritic rats. However, the administration of rhGH to arthritic animals significantly increased the IGF-I gene expression in both the renal cortex and medulla. Serum and kidney concentrations of IGF-I binding proteins (IGFBPs) were increased in arthritic animals and they were reduced by GH administration. CONCLUSION: These data suggest that experimental arthritis causes renal dysfunction and GH treatment can ameliorate this effect.     

Cytotoxic effect of ochratoxin A on the renal corpuscles of rat kidney: could ochratoxin A cause kidney failure?

To demonstrate that Ochratoxin A can cause kidney failure as the kidney is the primary target for OTA cytotoxicity. Ochratoxin A (OTA) is a mycotoxin found in our food. The cytotoxic effect of a low cumulative dose of OTA on the renal corpuscles of the kidney tissue has been investigated in this report. This study was based on two groups in which weaning albino rats were used: (1) control; (2) OTA-treated rats (289 μg/kg/day). After 28 days of treatment, a significant decrease in body weight, kidney weight and relative weight were detected in OTA treated rats. Serum creatinine and urea level were slightly elevated. These results revealed significant histological as well as ultrastructral lesions in the OTA treated group. The lesions included global congestion in the renal tissue and loss of demarcation between the cortex and medulla. The normal architecture of the renal corpuscles was destroyed and most of the corpuscles lost their ordinary look. The most apparent histopathological changes were urinary space disappearance and hypercellularity. In addition, congested, undifferentiated, atrophied, hypertrophied, fragmented, sclerotic, degenerated, and obliterated renal corpuscles were distinct. The ultrastructural lesions observed in the renal corpuscles in OTA on treated rats included; proliferation and swelling of the endothelial cells with occasional loss of fenestrae; narrowing of the capillary lumen; damaged podocytes with deteriorated secondary foot processes, hypertrophied and proliferated mesangial cells with expanded mesangial matrix. The endothelium was clearly defected and vacuolated, and lost its fenestrations in many glomerular capillaries. In addition, the glomerular basement membrane (GBM) became visibly thickened and tortuous. Necrotic glomerular cells were frequently observed. Pre-apoptotic cells were also seen. It was concluded that the exposure to relatively low OTA concentrations induced significant lesions to the renal corpuscles. Moreover, it activated oxidative damage and necrosis which can cause extensive damage to the kidney and ultimately kidney failure.     

Mechanical properties of the dog renal capsule.

The renal capsule is an important determinant of whole kidney volume/pressure relationships. To gain further insights into its possible role we examined the mechanical properties of the dog renal capsule using standard materials testing procedures. From each of four locations on the kidney surface, the following mechanical properties of the renal capsule were determined: elastic modulus (force/unit of cross-sectional area theoretically required to double the length of the specimen), tensile stiffness (force/unit width theoretically required to double the length of the specimen), ultimate strength (stress at time of fracture of the specimen), and maximum strain (percent strain at time of the fracture of the specimen). We found that the elastic modulus of the renal capsule from all capsular sites was substantially greater than values previously reported for dog aorta. The stiffness of the capsule covering the anterior-posterior surface of the kidney was found to be about 50% greater than the stiffness of the capsule covering the lateral and polar surfaces of the kidney. The ultimate strength of the anterior-posterior capsule was significantly greater than that of the lateral or polar capsule. This finding may explain the clinical observation that the spontaneous rupture of the renal capsule and parenchyma associated with the acute swelling of transplant rejection is confined almost exclusively to the lateral and polar portions of the renal capsule and cortex. The mean maximum strain at each capsular site was about 35%. This degree of circumferential expansion corresponds to about a doubling of kidney volume. Thus, this observation suggests that the renal capsule is at risk to undergo spontaneous rupture when renal volume increases of this magnitude are observed.     

金雕肾脏的组织学观察

利用生物显微技术观察了金雕Aquila chrysaetos肾脏的组织结构.结果表明,金雕肾实质由许多肾小叶构成,每个肾小叶可分为皮质和髓质两部分.肾单位由一个肾小体和一条与其相连的肾小管构成.肾小体由肾小囊和肾小球组成.肾小管分为近曲小管、髓袢、远曲小管和连接小管.集合管分为小叶周集合小管和髓质集合管两部分.具有发达的极周细胞.     

热休克反应中小鼠肾HSP70和乳酸脱氢酶同工酶表达变化的研究

用免疫组织化学和聚丙烯酰胺凝胶同工酶电泳方法研究了小鼠肾在热休克(46℃,30分钟)恢复期(4h和12h)HSP70的表达和乳酸脱氢酶(LDH)同工酶的变化。结果表明:(1)HSP70主要定位于肾小管上皮细胞胞质中,细胞核内未见表达;(2)HSP70免疫阳性反应在肾髓质较肾皮质强,肾小管较肾小球强;(3)热休克诱导小鼠肾LDH同工酶活性增强。提示:LDH同工酶可能对细胞热耐受性的建立有重要作用。     

PTH-receptors regulate norepinephrine release in human heart and kidney

Recent data suggests that chronic renal failure and hyperparathyroidism are associated with sympathetic overactivity. Since peptide hormones are known to modulate norepinephrine (NE) release by activating prejunctional receptors, this study investigates whether parathyroid hormone fragment (1-34) (hPTH(1-34)) increases neuronal NE release in human heart and kidney. Using specific PTH-receptor agonists and antagonists, this study furthermore highlights functional differences between PTH1 and PTH2 receptors. Human atrial and renal tissues were incubated with [(3)H]-NE and superfused. Three electrical stimulations (5Hz, 1min) induced a stable [(3)H]-NE release which was taken as an index of endogenous NE release. RT-PCR with specific primers for PTH1- and PTH2-receptor was performed in heart and kidney. hPTH(1-34) (0.01-0.1μmol/L) and a stable analog of its second messenger cAMP (8-bromo-cAMP) increased [(3)H]-NE release in human atria. This facilitatory effect of PTH was also observed in human renal cortex. The PTH1-receptor antagonist (D-Trp(12), Tyr(34))-pTH-(7-34) (0.5μmol/L) abolished the effect of hPTH(1-34). This data was verified using isolated perfused mouse kidneys. Tuberoinfundibular peptide of 39 residues (TIP-39) (0.1nmol/L-0.1μmol/L) decreased [(3)H]-NE release in atria. PTH1- and PTH2-receptor expressions were demonstrated in human heart and kidney. Moreover, a splice variant of the PTH2-receptor was detected in human kidney. In conclusion, PTH is able to facilitate NE release in human atria and renal cortex by activation of PTH1-receptors. The highly increased PTH levels that can be observed in chronic renal failure might be one contributor for the elevated sympathetic nerve activity and the associated cardiovascular mortality in patients with end stage renal disease.     

Emerging roles for lymphatics in acute kidney injury: Beneficial or maleficent?

Acute kidney injury, a sudden decline in renal filtration, is a surprisingly common pathology resulting from ischemic events, local or systemic infection, or drug-induced toxicity in the kidney. Unchecked, acute kidney injury can progress to renal failure and even recovered acute kidney injury patients are at an increased risk for developing future chronic kidney disease. The initial extent of inflammation, the specific immune response, and how well inflammation resolves are likely determinants in acute kidney injury-to-chronic kidney disease progression. Lymphatic vessels and their roles in fluid, solute, antigen, and immune cell transport make them likely to have a role in the acute kidney injury response. Lymphatics have proven to be an attractive target in regulating inflammation and immunomodulation in other pathologies: might these strategies be employed in acute kidney injury? Acute kidney injury studies have identified elevated levels of lymphangiogenic ligands following acute kidney injury, with an expansion of the lymphatics in several models post-injury. Manipulating the lymphatics in acute kidney injury, by augmenting or inhibiting their growth or through targeting lymphatic-immune interactions, has met with a range of positive, negative, and sometimes inconclusive results. This minireview briefly summarizes the findings of lymphatic changes and lymphatic roles in the inflammatory response in the kidney following acute kidney injury to discuss whether renal lymphatics are a beneficial, maleficent, or a passive contributor to acute kidney injury recovery.     

The artificial kidney and related procedures; a report on clinical experience

The Skeggs-Leonards artificial kidney and related methods were applied by the author in about thirty instances in patients with various kinds of renal disease. The treatment brought about clinical improvement of varying degree and appeared to be life-saving in four of five patients with acute renal failure. Treatment with the artificial kidney is indicated for patients with acute renal failure who develop clinical signs of uremia. The artificial kidney should be applied before the patient's condition has become irreversible. Removal of edema fluid is possible with modern artificial kidney equipment and appears to extend the therapeutic possibilities of the procedure. The artificial kidney may be of help in barbiturate and other intoxications. It affords temporary palliation in certain patients with chronic uremia; it may be used to overcome acute exacerbations of chronic renal disease; it may make it possible to operate on uremic patients who otherwise could not withstand operation.     

Localization of fucosyl moieties in the mouse renal cortex by lectin histochemistry using the fucose binding lectins LTA and UEA I and by autoradiography using 3H-labelled fucose

The binding patterns of the two fucose binding lectins, Lotus tetragonolobus (LTA) and Ulex europeus I (UEA I) were investigated using fluorescence lectin histochemistry on the unfixed renal cortex of the mouse (NMRI) embedded in LR-Gold. The fluorescence staining results were compared with the autoradiographic localization of the incorporation of radioactive fucose into the renal cortex. For this study the turnover of incorporated 3H-fucose in the renal cortex was investigated 30 min, 2 h and 8 h after application. The localization of the radioactive fucose within the renal cortex corresponded well to the labelling pattern observed for lecting histochemistry using LTA. In contrast, with UEA I, no binding sites for this lectin could be observed. The results of our investigation clearly showed that fucosyl moieties in the renal cortex of the NMRI mouse are recognized by the fucose binding lecting LTA, but not by UEA I and that postembedding fluorescence histochemistry with LTA on the LR-Gold embedded kidney is a suitable technique for the localization of fucosyl moieties at the light microscopical level.     

The Expression of EPOR in Renal Cortex during Postnatal Development

Erythropoietin (EPO), known for its role in erythroid differentiation, has been shown to be an important growth factor for brain and heart. EPO is synthesized by fibroblast-like cells in the renal cortex. Prompted by this anatomical relationship and its significant impact on the maturation process of brain and heart, we asked whether EPO could play a role during the development of renal cortex. The relationship between the development of renal cortex and the change of EPO receptor (EPOR), through which EPO could act as a renotropic cytokine, became interesting to us. In this study, the day of birth was recorded as postnatal day 0(P0). P7, P14, P21, P28, P35, P42 and mature mice (postnatal days>56) were used as the animal model of different developmental stages. Immunohistochemistry and Western blotting were used to detect the expression of EPOR in mouse renal cortex. Results showed that expression of EPOR decreased with the development of renal cortex and became stable when kidney became mature. The expression of EPOR was detected at the renal tubule of all developmental stages and a relatively higher expression was observed at P14. However, at the renal corpuscle the expression was only observed at P7 and quickly became undetectable after that. All these suggested that a translocation of EPOR from renal corpuscle to renal tubule may take place during the developmental process of renal cortex. Also, EPO may be an essential element for the maturation of renal cortex, and the requirement for EPO was changed during postnatal development process.     

N-demethylation activity of renal and hepatic subcellular fractions: an interspecies comparison.

The enzymatic activity of the mixed-function oxidase system in the kidney and liver was evaluated by means of an in vitro N-demethylation activity assay with aminopyrine as the substrate. Renal and hepatic demethylation activity of 9000 x g supernatant fraction was determined in the rat, rabbit, and guinea-pig. In terms of interspecies comparison, the renal tissue demethylation activities were on a similar level with a slight increase in the order guinea-pig, rabbit and rat. In relation to hepatic activity, these relative demethylation activities of renal tissue had the same values in the rat and rabbit, whereas that in the guinea pig was significantly lower. The distribution of demethylation activity in the kidney was determined by comparing the cortex and medullary activity in relation to the total kidney tissue activity in the rabbit and guinea-pig. Although the higher demethylation activities were obtained in rabbit renal preparations and low demethylation activity was detected in the guinea-pig renal medulla only, no significant interspecies differences were found by the statistical evaluation. It may be concluded that the mixed-function oxidase system responsible for renal demethylation activity seems to be concentrated in the renal cortex and its distribution coincides in the rabbit and guinea-pig kidney.