冬虫夏草防治氨基糖甙急性肾衰的分子生物学机理

探讨冬虫夏草对氨基糖甙急性肾衰的防治机理。方法应用斑点杂交和免疫组化等方法，动态观察了冬虫夏草对庆大霉素急性肾衰大鼠肾组织表皮生长因子（ＥＧＦ）前体ｍＲＮＡ、ＥＧＦ、ＥＧＦ受体及尿ＥＧＦ含量的影响。结果冬虫夏草治疗能显著增加损伤早期肾ＥＧＦ前体ｍＲＮＡ表达及肾皮质ＥＧＦ含量，而不影响肾ＥＧＦ受体的数量，同时使尿ＥＧＦ排出量的增加提早出现，肾小管的病变减轻，肾功能恢复加快。结论冬虫夏草可能通过增加肾组织ＥＧＦ前体ｍＲＮＡ表达，促进肾内ＥＧＦ合成，增加肾皮质ＥＧＦ含量，从而加速肾小管再生修复和急性肾衰的恢复     

小儿肾脏疾病血,尿内皮素的变化

目的研究小儿肾脏疾病血、尿内皮素（ＰＥＴ、ＵＥＴ）的水平及其相互关系。方法采用同位素放免方法检测了肾病综合征（ＮＳ），肾小球肾炎（ＧＮ），肾功能衰竭（ＲＦ）共７２例患儿血及尿中ＥＴ，血心钠素（ＡＮＰ）水平。结果ＮＳ，ＧＮ，ＲＦ三组的ＰＥＴ及ＵＥＴ值明显高于对照组，尤其ＲＦ组（Ｐ＜００５，Ｐ＜０．０１）。ＡＮＰ值在ＧＮ组和ＲＦ组明显高于对照组（Ｐ＜００１）。８例ＡＲＦ患儿恢复期血ＥＴ水平下降，６例ＣＲＦ患儿虽经治疗，但血ＥＴ水平不降或上升。结论ＥＴ在小儿肾脏疾病发病机理及病情进展中可能起重要作用，其值高低与病情严重程度及预后有关。     

骨髓间充质干细胞移植对过度运动所致急性肾损伤的研究

目的：探讨外源性骨髓间充质干细胞（MSCs）移植对过度运动导致急性肾损伤的保护作用.方法：建立过度运动致大鼠急性肾损伤模型,随机分为对照组和移植组,于细胞移植后测定血尿素氮（BUN）和血肌酐（Scr）水平,免疫组化观察肾组织切片.结果：移植组大鼠BUN和Scr明显低于对照组（P＜0.05）,免疫组化显示移植组肾损伤病理损伤明显减轻.结论：MSCs移植可促进过度运动所致急性肾损伤的修复,改善肾功能.     

生长因子与肾脏疾病

目前已经清楚，在肾功能受损或肾脏部分切除后，有一系列调节因子能够诱导肾脏的代偿性增生与肥大，这些调节因子统称为生长因子。研究证实，肾脏能产生表皮生长因子（ＥＧＦ）、胰岛素样生长因子（ＩＧＦｓ）、肝细胞生长因子（ＨＧＦ）、血小板源性生长因子（ＰＤＣＦ）等多种类型的生长因子，这些因子在急性肾小管坏死后小管的修复以及肾脏损伤后残余肾小球的代偿增生中发挥着重要作用。用生长因子治疗急性肾小管坏死，以及对慢性肾病持续性肾损害时生长因子的作用进行干预，阻滞肾功能进一步恶化，是目前肾脏病领域研究的重要内容之一。…     

梗阻性黄疸及术后并发肾功能衰竭时血浆内皮素的变化

目的 了解血浆内皮素（ＥＴ）在梗阻性黄疸患者（ＯＪ）及其术后并发肾功能衰竭时（ＲＦ）的变化情况，探讨ＥＴ与ＯＪ及ＲＦ的关系。方法 用特异性放射免疫法检测４５例不同程度ＯＪ患者术前及术后１天、５天血中ＥＴ含量，１８例非黄疸患者作对照。结果 ＥＴ随ＯＪ程度加重是而升高，术后１天各组均比术前升高，非ＲＦ组术后５天ＥＴ量基本恢复术前水平，而ＲＦ组仍持续升高。结论 ＥＴ升高与ＯＪ，ＲＦ有关。     

肾移植患者骨矿含量的测定及临床意义

测量了６４例肾移植患者移植前后的骨矿含量及骨钙素（ＢＧＰ）、甲状旁腺激素（ＰＴＨ）、血液生化的变化，以探讨它们的相互关系及临床意义。结果术前血肌酐（ＳＣｒ）、尿素氮（ＢＵＮ）、磷（Ｐ）、ＰＴＨ、ＢＧＰ为高水平，血钙（Ｃａ）低，骨矿含量（０．７７７±０．０１５ｇ／ｃｍ２）明显低于对照组（０．８１１±０．０３５ｇ／ｃｍ２）。术后肾功能正常者，ＳＣｒ、ＢＵＮ、Ｃａ、Ｐ及ＰＴＨ、ＢＧＰ均恢复正常，骨矿含量半年后恢复至对照组水平。提示慢性肾功能衰竭及血液透析期间存在明显钙磷代谢异常，严重骨营养不良；肾移植成功后骨矿含量恢复，纠正了肾性骨病；肾移植后骨矿含量低者，往往提示预后不良。     

前列腺素E1对慢性肾功能衰竭患者肾血流和血浆内皮素及降钙素基因相关肽的影响

内皮素（ＥＴ）刺激儿茶酚胺释放,并增强血管平滑肌对儿茶酚胺的反应性,可引起肾脏血管强烈收缩,减少肾血流量。机体微循环障碍及血栓素、转化生长因子β等损伤性物质增加均可刺激血管内皮细胞产生和释放ＥＴ。降钙素基因相关肽（ＣＧＲＰ）的作用与之正相反。我们通过观察慢性肾功能衰竭（ＣＲＦ）患者血浆ＥＴ和ＣＧＲＰ水平及肾血流量的变化并分析其间的相互关系,初步探讨前列腺素Ｅ１（ＰＧＥ１）治疗慢性肾功能衰竭的临床意义。 一、研究对象与方法 １ 对象：ＣＲＦ患者９０例,均为住院患者,其中男性４６例,女性４４例,平均年…     

慢性肾功能衰竭患者血清粒系集落刺激因子水平观察

为了解血清粒系集落刺激因子（Ｇ－ＣＳＦ）的代谢途径，用自行建立ＥＬＩＳＡ法检测了６１例慢性肾功能衰竭（ＣＲＦ）患者及６０例健康对照者Ｇ－ＣＳＦ水平。结果表明８６．９ＣＲＦ患者血清Ｇ－ＣＳＦ水平明显升高，其原因可能是由于Ｇ－ＣＳＦ的排泄障碍，在体内堆积之敌。     

结直肠癌病人手术前后血,尿和唾液中表皮生长因子的含量变化

用放射免疫方法定量检测结直肠癌人手术前后血，尿和唾液中表皮生长因子（ＥＧＦ）含量的变化。结果发现，术后病人血清和唾液中ＥＧＦ含量较术前显著降低，趋近正常对照，但尿ＥＧＦ术前术后比较无显著性差异，因此，可认为ＥＧＦ在结直肠癌的发生发展中起重要作用。     

血浆纤维结合蛋白在肾移植中的监测价值

对４１例透析治疗准备肾移植的患者作移植前、后的血浆纤维结合蛋白（ＰＦｎ）浓度的动态监测发现，移植术前ＰＦｎ低于正常；移植术后肾功能稳定组ＰＦｎ逐渐恢复正常；急性排斥反应组ＰＦｎ浓度下降，随排斥逆转，肾功能恢复，ＰＦｎ又上升到正常，而不可逆急性排斥时，ＰＦｎ始终波动在极低水平；术后并发感染时，感染初期ＰＦｂ一过性增高。结果表明，动态测定ＰＦｎ水平，对了解移植肾功能状态，预测排斥及并发感染的发生和演变     

Influence of kidney or heart transplantation on the urinary excretion of epidermal growth factor

We studied urinary epidermal growth factor (uEGF) in kidney transplant patients with normal and elevated serum creatinine, in cardiac transplant patients with normal serum creatinine, and in patients with chronic renal failure. Patients with chronic renal failure had the lowest uEGF levels. uEGF was reduced in normally functioning kidney transplant patients. If the kidney graft was failing, this reduction was more marked. Cardiac transplant patients had normal uEGF. The type of immunosuppressive therapy did not influence the uEGF excretion. Kidney function and kidney tissue mass appeared to be the most important factors in uEGF excretion.     

Different effects of growth factors on human renal early distal tubular cells in vitro

BACKGROUND: In the kidney, recovery from tubular damage requires regenerative mechanisms leading to re-epithelialization of the injured tubules. Current evidence supports the para- or autocrine role of growth factors in repair and regeneration of ischemic or nephrotoxic experimental acute renal failure. METHODS: We evaluated the effects of EGF, HGF, IGF-1, and bFGF on human renal thick ascending limb and distal convoluted cells (TALDC) in vitro. TALDC were isolated by immunomagnetic separation and cultured. Signal transduction of the growth factors was evaluated by Western blot of ERK1/2 MAP-K phosphorylation. Cell proliferation was measured by MTT assay and a fluorometric assay. RESULTS: A significant, dose- and time-dependent phosphorylation of ERK1/2 could be detected exclusively after stimulation with EGF. No other growth factor induced a significant MAPK phosphorylation. In the same manner, proliferation assays showed a significant growth-promoting effect of EGF. Neither HGF, nor IGF-1 or bFGF showed a stimulative effect on TALDC proliferation. CONCLUSION: The present study highlights the effects of growth factors on cultured TALDC and supports the hypothesis that in vivo EGF plays a para- or autocrine role during renal repair mechanisms.     

Mrna expression of transforming growth factor-alpha and the EGF receptor following nephrotoxic renal injury

We studied gene expression for transforming growth factor (TGF)-alpha, epidermal growth factor (EGF), heparin binding (HB) EGF, and the EGF receptor following acute renal failure induced by mercuric chloride administration to gain insight into potential mechanisms of renal repair. Twenty four hours after HgCl2, 2 mg/kg, creatinine increased from 0.3+/-0.01 mg/dl in controls to 2.2+/-0.26 mg/dl in injured rats (n = 5, p < 0.01). Similar changes were observed after 3 days. Messenger RNA expression for EGF was decreased at 24 hours in HgCl2 treated rats and remained depressed for at least 3 days. On the other hand steady state mRNA for TGF-alpha increased nearly 2 fold at day 3 in HgCl2 treated rats 4 mg/kg. Heparin binding EGF was increased early, by day one in injured kidneys and gene expression for the EGF receptor was increased as well. Immunohistochemistry documented an increase in expression of TGF-alpha in injured kidneys at distal nephron sites. These studies suggest that TGF-alpha along with HB EGF may be important ligands for the EGF receptor during repair from renal injury.     

Biopsy‐Diagnosed Renal Disease in Patients After Transplantation of Other Organs and Tissues

Renal function deteriorates in about half of patients undergoing other transplants. We report the results of 105 renal biopsies from 101 nonrenal transplant recipients (bone marrow 14, liver 41, lung 30, heart 20). Biopsy indications were protracted acute renal failure (9%), creatinine increases (83%), heavy proteinuria (22%), or renal insufficiency before re‐transplantation (9%). Histological findings other than nonspecific chronic changes, hypertension‐related damage, and signs of chronic CNI toxicity included primary glomerular disease (17%), mostly after liver transplantation (21%) or after bone marrow transplantation (29%), and thrombotic microangiopathy (TMA) namely (10%). TMA had the most serious impact on the clinical course. Besides severe hypertension, one TMA patient died of cerebral hemorrhage, 5 had hemolytic‐uremic syndrome, and 6 rapidly developed end‐stage renal failure. TMA patients had the shortest kidney survival post‐biopsy and, together with patients with acute tubular injury, the shortest kidney and patient survival since transplantation. Nine TMA patients had received CNI, 3 of them concomitantly received an mTOR‐inhibitor. CNI toxicity is implicated in most patients with renal failure after transplant of other organs and may play a role in the development of TMA, the most serious complication. However, decreased renal function should not be routinely ascribed to CNI.     

Chronic rejection in renal transplantation

With renal transplantation, chronic rejection is currently the most prevalent cause of late transplant failure. Clinically, chronic rejection presents as chronic transplant dysfunction, characterized by a slow loss of function, often in combination with hypertension and proteinuria. Transplant glomerulopathy and multilayering of the peritubular capillaries are highly characteristic for chronic rejection. Risk factors have been identified and include young recipient age, black race, presensitization, histoincompatibility, and acute rejection episodes, especially vascular rejection episodes and rejections that occur late after transplantation. Chronic rejection develops in grafts that undergo intermittent or persistent damage from cellular and humoral immune responses resulting from indirect recognition of alloantigens. Progression factors such as advanced donor age, renal dysfunction, hypertension, proteinuria, hyperlipidemia, and smoking play an important role. At the tissue level, senescence conditioned by ischemia/reperfusion may contribute to the development of chronic rejection. The most effective option to prevent renal failure from chronic rejection is to avoid graft injury from both immune and nonimmune mechanism together with nonnephrotoxic maintenance immunosuppression.     

Urinary epidermal growth factor in different renal conditions in children

Several studies have demonstrated the important role of growth factors, particularly epidermal growth factor (EGF) and transforming growth factor alpha (TGFalpha), in cellular growth after renal damage. EGF is mainly synthesized by the kidney. Many studies indicate that urinary EGF concentration significantly decreases in patients with acute and chronic renal failure. In this study we determined urinary EGF concentrations in children with renal and/or urological pathologies. We investigated 38 patients, 17 males and 21 females, of 3.34+/-2.96 years (mean +/- standard deviation), who were followed in the Nephrologic Unit of the Pediatric Department of the University of Verona for recurrent urinary tract infections: seven of these had vesicoureteric reflux and 4 had hypodysplasia. The results were compared with those from a healthy age-matched group of 44 children. In all patients, we assessed renal function including an examination of the urine with a microbiological evaluation. Moreover, a renal ultrasound and a voiding cystourethrogram were performed.     

Relation of distal nephron changes to proximal tubular damage in uranyl acetate-induced acute renal failure in rats

AIMS: To elucidate the pathophysiological roles of the changes of distal nephron in uranyl acetate (UA)-induced acute renal failure (ARF), we investigated the relation of changes of constituent molecules in distal nephron to proximal tubular damage and repair in UA-treated rats. METHODS: ARF was induced in rats by intravenous injection of UA, and all rats received bromodeoxyuridine (BrdU) intraperitoneally 1 h before sacrifice. RESULTS: Proximal tubular damage with necrosis appeared as early as day 2, mainly in the outer stripe of outer medulla and reached a peak level at day 5. Slight cellular damage was evident in the distal nephron as early as day 3, reaching a peak level around day 9. Immunoreactive BrdU- or vimentin-positive regenerating proximal tubules (PT) appeared at day 2 and regenerating PT relining was almost completed by day 7. Immunostaining for EGF, which was constitutively expressed in the thick ascending limb (TAL) and distal convoluted tubule (DCT), diminished significantly as early as day 2, when PT regeneration became evident, and remained below normal levels until day 21. In contrast, slight immunoreactivity for EGF was observed in regenerated PT accompanying brush-border formation mainly after day 9, suggesting newly expressed EGF might contribute to PT maturation. Lectin staining or immunostaining for representative constituent molecules of the thin descending limb, TAL, DCT and collecting duct demonstrated marked and transient reduction after day 5. CONCLUSIONS: EGF was not associated with regenerating PT, but may be involved in the maturation of PT. Transient reduction in expression of constituent molecules of the distal nephron following the reduction in EGF could reflect dedifferentiation or phenotypic simplification during regenerative repair of PT in UA-induced ARF in rats.     

Prediction of the outcome of antenatal hydronephrosis: significance of urinary EGF

Background

Down-regulation of epidermal growth factor (EGF) in the renal parenchyma has been demonstrated in children who underwent pyeloplasty due to ureteropelvic junction obstruction (UPJO). Urine levels of EGF were confirmed to parallel this finding before and after surgery. The aim of our study was to evaluate the relationship between urinary EGF (uEGF) concentrations and Society of Fetal Urology (SFU) high-grade hydronephrosis in infants presenting unilateral antenatal hydronephrosis (ANH).

Methods

This was a prospective study involving 45 infants (33 in the observational group, 12 in the surgical group) who presented with unilateral ANH. Postnatal evaluation included a clinical examination, renal ultrasonography, and voiding cystourethrography. Diuretic renal scans were performed in infants with an initial SFU grade 3 or 4 hydronephrosis or increasing hydronephrosis during follow-up. Pyeloplasty was performed when a well-tempered renogram showed an obstructive drainage curve with a half-life of >20 min and/or an obstructive washout curve pattern during the diuretic phase. We studied the longitudinal changes in SFU hydronephrosis grade and uEGF in each group and compared concentration levels at three time points in both groups. The enzyme-linked immunosorbent assay (ELISA) method was used to measure EGF concentrations in the urine. The results were normalized with urinary creatinine (Cr).

Results

During the first 6?months, from 6 to 12?months, and in the second year of life, median SFU hydronephrosis grade and uEGF levels were 2, 2 (p?=?0.015), and 1 (p?<?0.01), and 50, 59 (p =?0.015), and 69.5?ng/mg Cr (p?<?0.01), respectively, in the observational group. In the first 6?months, preoperatively and at 3–12?months postoperatively, the median SFU hydronephrosis grade and uEGF levels were 4, 4, and 3 (p?>?0.05), and 38, 46, (p >?0.05), and 55?ng/mg Cr (p?<?0.01), respectively, in the surgical group. uEGF levels in the first 6?months of life were significantly lower in the surgical group than in the observational group (p?<?0.01). Patients in the observational group with SFU grade 3–4 hydronephrosis showed higher uEGF levels than those in the surgical group with SFU grade 3–4 in (p?=?0.048).

Conclusions

Urinary EGF changes over time are associated with inverse changes in SFU hydronephrosis grade, which suggests a role for uEGF as a predictive marker of worsening hydronephrosis grades in infants with ANH. uEGF in the first 6?months of life may predict the need for surgery in infants with ANH.     

Thrombotic microangiopathy developing in early stage after renal transplantation with a high trough level of tacrolimus

Thrombotic microangiopathy (TMA) is characterized clinically by hemolytic anemia, thrombocytopenia, and renal failure. Cyclosporine (CyA)-associated TMA is a well-documented complication, but tacrolimus (TAC)-associated TMA is rare. We report the case of a renal transplant recipient who developed TMA in the early stage after renal transplantation with a high trough level of TAC. A 56-year-old female suffering from end-stage renal disease received a living renal graft from a blood-type-identical donor. She had developed hemolytic anemia, thrombocytopenia and acute renal failure 4 days after transplantation (6 days after TAC administration). She was diagnosed as having TMA without rejection by the clinical course and pathological findings. Renal function and hemolytic parameters improved by solely a decrease of the TAC trough level. When TAC-associated TMA develops in renal transplant recipients, we recommend a decrease of the TAC trough level before changing to CyA.     

群体反应性抗体在肾移植中的意义

目的 研究群体反应性抗体（ＰＲＡ０在肾移植中的意义。方法 对１７８例肾移植患者进行了术前、术后ＰＲＡ检测。结果 肾移植术前ＰＲＡ阳性患者有２３例,肾移植术后发生急性排斥反应的为２０例。术后ＰＲＡ阳性受者５８例,发生排斥反应的有３４例。移植前后ＰＲＡ阴性患者有１０８例,有８例发生排斥。在肾移植患者中所产生的抗ＨＬＡ抗体的频率和ＨＬＡ抗原的分布不同。结论 ＰＲＡ检测对预测移植肾排斥有重要意义。