Correlation between tubulointerstitial nephropathy and glomerular lesions induced by adriamycin.

This paper describes a morphometric study of the evolution of tubulointerstitial nephropathy in adriamycin-induced focal and segmental glomerulosclerosis in Wistar rats over 32 weeks old. The earliest changes were located in the glomeruli. In the 10 week of the study, tubulointerstitial nephropathy appeared and, although the interstitial space increased after the 2nd week, this increase only became statistically significant after the 10 week. Proteinuria showed the highest correlation with the interstitial space, however, the interstitial space showed the highest correlation indices with the total number of glomeruli affected and to a lesser extent with adhesions to and thickening of Bowman's capsule.     

Flat electroencephalogram caused by carbon dioxide pneumoperitoneum

Hypercapnia during laparoscopy with CO2 is predicted in the following situations: compromised pulmonary function, retroperitoneal insufflation, and subcutaneous emphysema. We present a case of sudden electroencephalogram (EEG) depression in response to severe hypercapnia during laparoscopic ureteronephrectomy in a 77-yr-old patient with chronic pulmonary emphysema. During intraperitoneal and retroperitoneal insufflation, subcutaneous emphysema and difficult ventilation occurred. Severe hypercapnia ensued, with pH = 6.94, and Paco2 = 137 mm Hg. Subsequent EEG activity was markedly depressed with a minimum Bispectral Index of 4, accompanied by an increase in arterial blood pressure and heart rate. Termination of the laparoscopic procedure improved ventilation, EEG, and hemodynamics. These EEG changes may result from the narcotic properties of CO2 or hypercapnia-induced neurological abnormalities.     

关于椎体成形术的并发症及预防

[目的]探讨椎体成形术治疗痛性椎体病损并发症发生原因和预防措施。[方法]回顾分析14例因椎体成形术治疗所出现的并发症病例,其中因穿刺引起的2例,骨水泥泄漏引起的11例,手术后继发相临椎体骨折1例,本文分别对发生原因、处理方法、预防措施进行了总结。[结果]全部病例经过0.5～4.5年,平均3年的随访,2例病人因为原发病加重死亡,其余现存病例没有遗留与并发症相关的临床症状。[结论]尽管椎体成形术在实施过程中可以出现一些并发症,但是只要合理掌握手术适应证,提高技术水平,掌握手术技巧这些并发症是可以避免的。     

Renal failure caused by long-term use of a germanium preparation as an elixir

Two Japanese women and one Japanese man, who had been taking the same germanium preparation, mainly containing inorganic germanium, as an elixir for health almost every day at 90 mg of germanium per day for 6 to 20 months, suffered from chronic renal failure. Histological examination of the kidney in one patient showed marked interstitial changes with vacuolar degeneration of the renal tubules. High germanium concentrations were found in hair and nails of the three patients, but no germanium was detected in hair or nails of normal persons. These results suggest that long-term use of a germanium preparation at high dosage can cause serious renal tubular damage and renal failure due to germanium toxicity.     

Early referral for 24-h esophageal pH monitoring may prevent unnecessary treatment with acid-reducing medications

Background

Gastroesophageal reflux disease (GERD) affects nearly 25 % of adults; however, an objective diagnosis is rarely established. We hypothesized that patients’ symptoms and response to acid-reducing therapy are poor predictors of the outcome of 24-h esophageal pH monitoring.

Methods

A review of 24-h esophageal pH monitoring studies performed at an ambulatory tertiary care center between 2004 and 2011 was performed. Demographics, type of GERD symptoms, and duration and response to acid-reducing medications before referral for pH monitoring were collected. DeMeester score, symptom sensitivity index (SSI), and symptom index (SI) were tabulated and compared with the patients’ symptoms and response to medical therapy.

Results

One hundred patients were included. Of all reported symptoms, only heartburn was more common in patients with positive DeMeester scores, but there were no correlations between any symptoms and SSI or SI scores. Sixty-nine percent of patients with esophageal symptoms had a positive DeMeester score compared with only 29 % of patients with extraesophageal symptoms (P < 0.01). Esophageal symptoms and endoscopic evidence of GERD significantly increased the likelihood of having a positive DeMeester score, but they had no influence on SSI or SI scores. There was no correlation between response to acid-reducing medications and DeMeester, SSI, or SI scores. A total of 536 person-years of acid-reducing medications were prescribed to the study population, of which 151 (28 %) were prescribed to patients who had a negative pH study.

Conclusions

Extraesophageal symptoms and response to empiric trials of acid-reducing medications are poor predictors of the presence of GERD and the DeMeester score is more likely to identify GERD in patients who met other empiric diagnostic criteria than SSI or SI. Early referral for 24-h esophageal pH monitoring may avoid lengthy periods of unnecessary medical therapy.     

细胞增殖与凋亡在单侧输尿管梗阻大鼠肾间质纤维化发病中的意义

目的 了解细胞增殖与凋亡在肾小管间质纤维化中的意义。方法 动态观察单侧输尿管梗阻（ＵＵＯ）大鼠模型中梗阻侧肾脏及假手术组肾脏肾小管细胞及间质细胞的增殖细胞核抗原（ＰＣＮＡ）表达及细胞凋亡情况,以及间质α平滑肌肌动蛋白（α－ＳＭＡ）表达水平。结果 ＵＵＯ大鼠梗阻肾从第３天至第１１天,均可见较大量的细胞凋亡,以肾小管上皮细胞居多,其中亦有间质细胞。无论肾小管或间质细胞,ＰＣＮＡ的表达在第３天已达高峰,     

Retransplantation in patients with graft loss caused by polyoma virus nephropathy

The characteristics and outcome in 10 patients who underwent retransplantation after losing their renal grafts to BK virus-associated nephropathy (BKAN) are described. The patients underwent retransplantation at a mean of 13.3 months after failure of the first graft. Nephroureterectomy of the first graft was performed in seven patients. Maintenance immunosuppression regimens after the first and second grafts were similar, consisting of a combination of a calcineurin inhibitor, mycophenolate mofetil, and prednisone. BKAN recurred in one patient 8 months after retransplantation, but stabilization of graft function was achieved with a decrease in immunosuppression and treatment with low-dose cidofovir. After a mean follow-up of 34.6 months, all patients were found to have good graft function with a mean creatinine of 1.5 mg/dL. From this collective experience from five transplant centers (although the follow-up after retransplantation was not extensive), it can be concluded that patients with graft loss caused by BKAN can safely undergo retransplantation. The risk of recurrence does not seem to be increased in comparison with the first graft.     

Reduction in connective tissue growth factor by antisense treatment ameliorates renal tubulointerstitial fibrosis

Connective tissue growth factor (CTGF/CCN2) is one of the candidate factors mediating fibrogenic activity of TGF-beta. It was shown previously that the blockade of CTGF by antisense oligonucleotide (ODN) inhibits TGF-beta-induced production of fibronectin and type I collagen in cultured renal fibroblasts. The in vivo contribution of CTGF in renal interstitial fibrosis, however, remains to be clarified. With the use of a hydrodynamics-based gene transfer technique, the effects of CTGF antisense ODN are investigated in rat kidneys with unilateral ureteral obstruction (UUO). FITC-labeled ODN injection via the renal vein showed that the ODN was specifically introduced into the interstitium. At day 7 after UUO, the gene expression of CTGF, fibronectin, fibronectin ED-A, and alpha1(I) collagen in untreated or control ODN-treated obstructed kidneys was prominently upregulated. CTGF antisense ODN treatment, by contrast, markedly attenuated the induction of CTGF, fibronectin, fibronectin ED-A, and alpha1(I) collagen genes, whereas TGF-beta gene upregulation was not affected. The antisense treatment also reduced interstitial deposition of CTGF, fibronectin ED-A, and type I collagen and the interstitial fibrotic areas. The number of myofibroblasts determined by the expression of alpha-smooth muscle actin was significantly decreased as well. Proliferation of tubular and interstitial cells was not altered with the treatment. These findings indicate that CTGF expression in the interstitium plays a crucial role in the progression of interstitial fibrosis but not in the proliferation of tubular and interstitial cells during UUO. CTGF may become a potential therapeutic target against tubulointerstitial fibrosis.     

蛋白尿致肾小管间质纤维化的机制及防治

肾间质纤维化是各种不同病因的慢性肾脏病进展到终末期肾病（ESRD）的共同病变过程。动物实验和临床试验表明，各种肾脏疾病进行性肾功能恶化主要取决于肾间质损伤的严重程度。蛋白尿是肾小球疾病的共同临床表现，长期蛋白尿不仅引起肾小球硬化，而且可以直接导致肾小管间质损伤，后者与肾小球疾病进展的关系更为密切。我们的研究发现，在血压、肾功能均正常且其他各项临床指标相近的条件下，显著蛋白尿IgA肾病患者的肾小球及肾小管间质损害程度更为严重，蛋白尿可作为独立的致病因子，直接造成IgA肾病患者肾小管间质损害。因此，研究肾间质纤维化的分子机制，探索有效的防治措施，对延缓ESRD的进程意义重大。本文重点阐述蛋白尿致肾小管间质损伤的机制及防治现况。     

Chronic tubulointerstitial changes induced by germanium dioxide in comparison with carboxyethylgermanium sesquioxide.

Chronic nephrotoxicity was investigated in rats orally administered germanium dioxide (GeO2) and carboxyethylgermanium sesquioxide (Ge-132) for 24 weeks. Increased BUN and serum phosphate as well as decreased creatinine clearance, weight loss, anemia and liver dysfunction were apparent at week 24 only in the GeO2 treated group. Vacuolar degeneration and granular depositions were observed by light microscope in the degenerated renal distal tubules in the rats of this group, with the semiquantitative scores of tubular degeneration being 95 +/- 9% in the GeO2 group, 3 +/- 1% in the Ge-132 group and 1 +/- 1% in the control group, respectively. Electron microscopy revealed electron-dense inclusions in the swollen mitochondrial matrix of the distal tubular epithelium in the GeO2 group. Although systemic toxicities were reduced after GeO2 was discontinued at week 24, renal tubulointerstitial fibrosis became prominent even at week 40 (16 weeks after discontinuation). A Ge.K alpha X-ray spectrum was clearly demonstrated in the mitochondrial matrix of the distal tubular epithelium in the GeO2 group with the help of electron probe X-ray microanalysis. On the other hand, neither toxic effects nor renal histological abnormalities were manifested in either the Ge-132 or the control group. The renal tissue content of germanium was high at weeks 24 and 40 in the GeO2 group. From these results, it is concluded that GeO2 causes characteristic nephropathy while Ge-132 does not. In addition, it appears that residual GeO2 remains for a considerably long time even after the cessation of GeO2 intake.