Nierenfunktionsuntersuchungen zur Pathogenese des de Toni-Debré-Fanconi-Syndroms

Zusammenfassung Bei einem 10 4/12 Jahre alten Jungen mit einem idiopathischen de Toni-Debré-Fanconi-Syndrom wurden Nierenfunktionsuntersuchungen durch-geführt. Dabei ergab sich eine leichte Einschränkung der glomerulären Filtrations-rate, eine erhebliche Einschränkung der PAH-Clearance und eine proximal-tubuläre Insuffizienz. Außer der typischen Störung im Resorptionsmechanismus von Phosphat, Glucose und der Aminosäuren, war auch die fraktionelle Resorption von Natrium und Kalium vermindert. Harn-pH und Hypuricämie sprechen außerdem dafür, daß auch die proximal-tubuläre Reabsorption von Bicarbonat und Urat gehemmt ist.

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A study of the renal function in view of the de Toni-Debré-Fanconi syndrome

The de Toni-Debré-Fanconi syndrome was observed in a 10 4/12 years old boy. Storage of cystine could not be detected in either cornea or bone marrow. Studies of the renal function showed a reduction of the glomerular filtration rate and the PAH-clearance, as well as a global proximal tubular insufficiency. Apart from the typical defects in tubular reabsorption of phosphate, glucose, and amino acids, there was a significant reduction in the fractional resorption of sodium and potassium. The pH of the urine and the uric acid concentration in the blood indicate also a defect in the proximal tubular bicarbonate and urate reabsorption mechanism.

Herrn Professor Dr. med. G. de Toni zum 75. Geburtstag gewidmet     

Effects of aging on cadmium and tubular dysfunction markers in urine from adult women in non-polluted areas

Objectives: The objectives of the present analyses were to examine if Cd and tubular dysfunction marker levels in urine show age-dependent changes among women who lived in areas with no known cadmium (Cd) pollution in Japan, and if the trends would be further modified by correction of analyte concentration in terms of urinary creatinine (CR or cr) or urine specific gravity (SG or sg). Methods: The results of urinalysis for Cd, ₁-microglobulin (₁-MG), ₂-microglobulin (₂-MG), and N-acetyl--D-glucosaminidase (NAG) concentrations together with CR and SG were cited from previously established databases. A majority of urine samples were collected in 2000–2002 from adult women (mostly at 40–60 years of age) in various areas in Japan, and the collection was supplemented by cases of 60-year-old women in 2003. In total, 11,090 never-smoking cases were subjected to statistical analysis. The values as observed (e.g., Cd_ob), together with after correction for CR (e.g., Cd_cr) or SG (e.g., Cd_sg), were examined by linear regression analysis after logarithmic conversion. Results: The geometric mean (GM) values for Cd were 1.10 g/l (as observed) or 1.32 g/g cr (after correction for creatinine concentration). No increases were found in the levels of ₁-MG, ₂-MG or NAG on a group basis, in agreement with the conditions that there was no known environmental pollution with Cd in the sampling areas. There were almost linear increases in logarithm of Cd, ₁-MG, ₂-MG and NAG concentrations as age advanced. As CR, and to a lesser extent SG, also decreases steadily throughout life (Ikeda et al. 2005; Moriguchi et al. 2005), the correction of the analyte concentrations for urine density induced substantial increases in the analyte values; i.e., the correction by CR and SG induced amplification of the increases by two- and 1.4-times, respectively, compared with the increase in non-corrected observed values. Conclusions: There were age-related increases in Cd and tubular dysfunction markers in urine among women in areas with no known Cd pollution. The increase was amplified two- or 1.4-times when CR or SG correction was applied, respectively. The observation suggests that care should be practiced in applying CR or SG correction, especially when evaluation of Cd exposure and resulting health effects is made among elderly populations.     

Resolution of medullary nephrocalcinosis in children with metabolic bone disorders

Ultrasonographic resolution of nephrocalcinosis (NC) has been reported in children with furosemide-induced NC, but not in other entities. We report the cases of four children with metabolic bone disease, two with hypophosphatasia and two with X-linked hypophosphatemic rickets, in whom we observed resolution of renal calcifications. At the time of ultrasonographic resolution of NC, 3 of the patients were on anticalciuric diuretics, and all 4 had normal urinalysis, serum creatinine and electrolyte profiles, as well as estimated creatinine clearance. In 3 of the children, evidence of mild tubular dysfunction was found. It thus seems that in some children with bone and mineral disorders who develop NC, ultrasonographic resolution of the renal calcifications can be seen; however, mild tubular dysfunction may remain and require follow-up. Further studies are suggested to explore the possible role of anticalciuric diuretics in promoting the resolution of NC.     

Tubular Na,K-ATPase deficiency,the cause of the congenital renal salt-losing syndrome

In the serum of two infant sisters with a congenital renal salt-losing syndrome, Na was rather low and K considerably increased. Even with Na levels of 126 mval/l, sodium was excreted in the urine. Creatinine and hippurate clearances were normal. Primary disturbances of the steroid metabolism were not detectable; plasma cortisol was normal, aldosterone and renin were compensatorily increased. Treatment with DOCA was unsuccessful. Whereas the first infant died (in another hospital), the second one throve well with high oral substitution of NaCl.There were no pathological findings other than a moderate hyperplasia of the juxtaglomerular apparatus, in a kidney biopsy. Except for minimal activity in the ascending limb of Henle's loop, there was no membrane bound Na, K-ATPase in the microdissected tubules. This finding most probably explains the renal salt loss, as this enzyme is necessary for the transcellular flow of sodium and potassium.Presented in part at the 72nd congress of the Deutsche Gesellschaft für Kinderheilkunde, Munich, September 1975.     

Evaluation of water and electrolyte transport of tubular epithelial cells under osmotic and hydraulic pressure for development of bioartificial tubules

Our aim was to develop bioartificial tubules using tubular epithelial cells and artificial membranes and evaluate the function of water and electrolyte transport by various tubular epithelial cells. The cells were cultivated onto extracellular matrix (ProNectin F) coating polycarbonate membrane. Water transport from the apical to the basolateral site of cells was examined using a modified Ussing chamber module. Water transport under colloidal osmotic pressure on the apical site and hydraulic pressure on the basolateral site were higher in JTC-12, LLC-PK1 cells than in MDCK cells. Water transport under osmotic plus hydraulic pressure was highest in LLC-PK1 cells. We made bioartificial tubules using LLC-PK1 cells and polysulfone hollow fiber cartridges. Water and Na ion transport function was high, and BUN and creatinine passage was recognized in these bioartificial tubules. BUN and creatinine concentrations of reabsorption fluid in these bioartificial tubules were significantly lower than those concentrations of control media and of noncell attached polysulfone hollow fiber cartridges. Though LLC-PK1 cells were more preferable cells for the use of bioartificial tubules in terms of water and electrolyte transport, the passage of BUN and creatinine was not appropriate for clinical use. To select more preferable cells for bioartificial tubules which transport water and electrolytes and do not induce passage of uremic toxins is necessary.     

Contrast-enhanced MR imaging of experimental acute tubular necrosis

Purpose: To demonstrate the involvement of the various renal structures in acute tubular necrosis (ATN).Material and Methods: In 15 rats, using a T1-/T2-weighted sequence, either gadodiamide alone, or gadodiamide in combination with sprodiamide (a susceptibility agent) were used to enhance the various anatomical substrates of the kidney. The results were compared to those of pathological verification.Results: Experimentally induced ATN of the rat kidney causes profound changes in the medulla, leaving the cortex largely intact. The difference between the normal cortex and the partially necrotic outer medulla, on the one hand, and the papillary region, was significantly enhanced with the combination, whereas a larger region composed of the inner and outer medulla was enhanced after the gadolinium chelate alone.Conclusion: The results varied considerably between the two procedures; the double contrast demonstrated a clear difference between the inner and outer medulla, and the gadolinium chelate alone demonstrated a clear difference between the medulla and the cortex. These results demonstrated a clear difference in the compartmentalization between the inner and outer medullary regions, providing complementary information about the pathological condition of the kidney.     

Sinonasal epithelial-Myoepithelial carcinoma-A rare entity

Epithelial-myoepithelial carcinoma is a rare salivary gland tumor. It comprises less than 1% of all salivary gland tumors. It generally arises from the parotid gland. Unusual sites of occurrence include sinonasal tract, lung, trachea, lacrimal gland and breast. Histopathologically epithelial-myoepithelial carcinoma comprises a dual population of ductal and myoepithelial cells. We report an extremely rare case of epithelial-myoepithelial carcinoma occurring in the sinonasal tract of young man.     

管状吻合器及缝合器在Roux-en-Y上消化道重建术中的临床应用

目的：探讨使用管状吻合器及缝合器在Roux-en-Y上消化道重建术中的临床应用价值。方法：回顾性分析本院2000年1月~2010年1月329例应用管状吻合器及缝合器行Roux-en-Y近端胃切除和全胃切除手术患者的临床资料与并发症的发生率。结果：全组均获手术成功,无手术死亡病例,手术时间1.6～4.0h,平均2.8h,无吻合口瘘、出血及狭窄等严重并发症。术后随访0.5～2年,发生吻合口狭窄3例,经放置支架后恢复正常饮食,其余患者胃镜或钡餐示吻合口愈合良好,进食状态良好。结论：Roux-en-Y上消化道重建术中应用管状吻合器及缝合器具有操作简单、安全有效,手术时间短、并发症少等优点,有较高的临床应用价值。     

黄芪通过c-met调控TGF-β1诱导的肾小管上皮细胞转分化

AB 目的：探讨黄芪对TGF-β1诱导的肾小管上皮细胞转分化及细胞外基质分泌的作用及机制。方法：体外培养正常大鼠肾小管上皮细胞（NRK52E）,应用倒置相差显微镜观察NRK52E细胞形态学变化;免疫组织化学染色法及实时荧光定量PCR法检测α-平滑肌肌动蛋白（α-SMA）,肝细胞生长因子HGF受体（c-met）的表达;ELISA法定量检测细胞上清液中胶原Ⅰ（Col-Ⅰ）,胶原Ⅲ（Col-Ⅲ）和纤维黏连蛋白（FN）的水平。结果：TGF-β1可诱导肾小管上皮细胞肌成纤维细胞转分化（TEMT）,TGF-β1诱导组细胞肥大、拉长,呈长梭形,α-SMA表达明显增强,Col-Ⅰ、Col-Ⅲ和FN分泌增加（P〈0.05）。加入不同浓度黄芪后,细胞形态接近正常肾小管上皮细胞形态,α-SMA表达、Col-Ⅰ、Col-Ⅲ和FN分泌均较TGF-β1诱导组明显抑制（P〈0.05）,c-met表达较TGF-β1诱导组增加（P〈0.05）且呈剂量依赖性。结论：TGF-β1可以诱导肾小管上皮细胞肌成纤维细胞转分化,增加细胞外基质成分Col-Ⅰ、Col-Ⅲ和FN的分泌;黄芪能够抑制TGF-β1诱导的NRK52E细胞转分化以及细胞外基质的分泌;黄芪抑制细胞转分化的机制可能与其增强c-met的表达有关。