The influence of uremia and immunosuppression on an animal model for ischemic colitis

Up to 1 percent of renal transplant recipients have been reported to develop ischemic colitis. Immunosuppressive agents and uremia have been implicated in the development of this complication, but their exact relationship remains unclear. A rat model was developed to determine the effects of uremia alone and in combination with immunosuppression on the development of ischemic colitis. Seventy-six animals were included in the study. Uremia and ischemic colitis were induced surgically. The immunosuppressive agents azathioprine and methylprednisolone were administered for 72 hours after a colonic segment was devascularized in chronically uremic rats. One-way analysis of variance (ANOVA) showed that uremia potentiates colonic ischemia significantly (4.09 cm² vs 1.25 cm²,P<0.03). The addition of parenteral steroids (methylprednisolone) or azathioprine alone and in combination did not potentiate or reduce this ischemic process in uremic animals. Each of these factors alone is commonly present in the renal transplant population and can contribute to the development of potentially fatal ischemic colitis. Supported by Biomedical Research Support Grant RR 05374 from the Division of Research Facilities and Resources, National Institutes of Health, Washington, D.C.     

Can We Predict the Development of Ischemic Colitis Among Patients with Lower Abdominal Pain?

Purpose This study was performed to find clinical risk factors for developing ischemic colitis in patients experiencing lower abdominal discomfort with or without bloody diarrhea. Methods A total of 467 patients who underwent sigmoidoscopy or colonoscopy because of lower abdominal discomforts with or without blood in stool were consecutively enrolled; 147 patients were diagnosed endoscopically and histologically as having ischemic colitis. The control group was composed of the remaining 320 patients with nonspecific endoscopic/histologic findings. Clinical variables were compared between the ischemic colitis group and the control group. Results After excluding 67 patients in the ischemic colitis group, we compared the remaining 80 patients to the control group, using various clinical parameters. According to the logistic regression analysis, six factors were significantly related to ischemic colitis: older than aged 60 years (adjusted odds ratio, 5.7; 95 percent confidence interval: 2.6–11.7), hemodialysis (5; 1.2–21.6), hypertension (4.9; 2.3–10.5), hypoalbuminemia (3.5; 1.8–6.7), diabetes mellitus (3.4; 1.3–8.8), and constipation-inducing medications (2.8; 1.1–7.1). Through our analysis, we were able to predict the development of ischemic colitis for the patients with 0, 1, 2, 3, or 4+ risk factors: 8, 21, 55, 79, and 100 percent, respectively. Conclusions Old age, hemodialysis, hypertension, diabetes mellitus, hypoalbuminemia, and constipation-inducing medications are clinically important risk factors for ischemic colitis in patients experiencing lower abdominal discomfort with or without bloody stool. By considering these factors, we were able to predict with high accuracy the development of ischemic colitis. Poster presentation at the meeting of the American College of Gastroenterology, Honolulu, Hawaii, October 28 to November 2, 2005.     

Mortality from ischemic colitis

Thirty-nine hospital-based cases of ischemic colitis were reviewed. There were 18 males and 21 females. Average age was 68.7 years (range, 18 to 92 years). Associated diseases among 13 patients younger than 65 included renal failure in seven patients and hematologic, vasculitic, or collagen vascular diseases in four. In 26 patients 65 or older, congestive heart failure was seen in 13, vascular disease in eight, and previous aortic surgery in four. Nineteen patients were treated nonsurgically and 8 died (42 percent mortality). Twenty patients (51 percent) underwent surgery: 18 had resection with colostomy or ileostomy and two had resection with reanastomosis; one patient underwent laparotomy followed by second-look exploration without resection. Thirteen of the 20 surgical patients died (65 percent mortality). Both patients who underwent reanastomosis died of sepsis. The data show a close association between ischemic colitis and a number of serious systemic diseases including renal failure, arteriosclerotic heart and vascular disease, and hematologic, vasculitic, and connective-tissue disease. A predilection for the right colon and sigmoid colon and splenic flexure was seen. A formidable mortality rate (53 percent) was found among patients treated both surgically and nonsurgically. Read at the meeting of the American Society of Colon and Rectal Surgeons, Anaheim, California, June 12 to 17 1988.     

Outcome of Patients With Ischemic Colitis: Review of Fifty-Three Cases

PURPOSE: Ischemic colitis is a disease of elderly patients and includes a wide clinical spectrum ranging from mild to severe forms. Some patients may develop complications. Management of this disorder depends on disease severity. Our aim was to review the clinical characteristics of patients diagnosed of ischemic colitis and analyze predictive factors of poor prognosis. METHODS: This study is a retrospective analysis of 53 cases of ischemic colitis (33 men, 20 women), 35 with moderate and 18 with severe forms, respectively. Clinical characteristics, diagnostic procedures, segment of colon involved and long-term evolution after discharge were analyzed. RESULTS: Hypertension (51 percent) was the main risk factor associated with ischemic colitis. Clinical presentation did not differ between groups, except for peritonitis which was present only in the severe group. Colonoscopy and histologic studies were the most used diagnostic procedures (90 percent). Peripheral vasculopathy (P < 0.01) and right colonic involvement (P < 0.001) were risk factors for severe outcome. Five patients died during admission. Among these, the right colon was affected in four (80 percent). No patient in either group developed chronic ischemic colitis during follow-up. CONCLUSION: Ischemic colitis usually runs a benign course after acute colonic insult. Peripheral vasculopathy and right colonic involvement are associated with severe forms of ischemic colitis.     

内科保守联合介入治疗缺血性结肠炎的临床观察

目的观察内科保守联合介入治疗缺血性结肠炎的临床疗效。方法选择25例缺血性结肠炎患者随机分为单纯保守治疗组（A组,13例）和内科保守联合介入治疗组（B组,12例）,比较治疗前后腹痛及便血转归情况、红细胞沉降率（ESR）、血细胞比容（HCT）及纤维蛋白原（FIB）指标。结果单纯保守治疗组较内科保守联合介入治疗组的腹痛持续时间[（91.23±31.17）h、（50.30±20.12）h]和便血持续时间[（64.62±16.64）h、（48.00±13.54）h]更长,差异有统计学意义（P〈0.001）;治疗前后红细胞沉降率,血细胞比容和纤维蛋白原指标变化在各自组内比较有明显改善,差异有统计学意义（P〈0.01）,而在两组间比较则无显著性差异（P〉0.05）。结论与单纯保守治疗组比较,内科保守联合介入治疗组显著改善血液流变学,能更快缓解患者症状,并有可能改善预后。     

Ischemic Colitis Following Colonoscopy in a Systemic Lupus Erythematosus Patient: Report of a Case

BACKGROUND Ischemic colitis is an uncommon complication in patients with systemic lupus erythematosus but may be precipitated by colonoscopy.CASE REPORT A 43-year-old female with systemic lupus erythematosus under treatment with immunosuppressive drugs and prednisone was submitted to colonoscopy because of a change in bowel habit. Apart from the presence of a small metaplastic polyp, colonoscopy showed only a few erythematosus areas in the sigma and left colon. Four hours after colonoscopy, the patient developed lower colic abdominal pain and mucous diarrhea followed by rectal bleeding from ischemic colitis. The patient was successfully treated with fluids, spasmolytic drugs, sodic heparin, antibiotics and enteral feeding.CONCLUSIONS Awareness of the risk of this potential complication, secondary to colonoscopy, in patients with connective tissue disorders may lead to a prompt diagnosis and effective treatment, with a successful outcome.     

Clinical investigation of 41 patients with ischemic colitis accompanied by ulcer

AIM: To investigate the relationship among the presence of ulcer lesions, underlying disease, and clinical course in patients with ischemic colitis. METHODS: The subjects were 41 patients (10 male and 31 female; mean age 70 years) with ischemic colitis who were admitted to and received treatment in our hospital from 2000 to 2006. We compared their characteristics and analyzed the mean lengths of admission and fast- ing for 9 patients with ulcer lesions (ulcer group) and 32 without (non-ulcer group). RESULTS: The groups with presence and absence of ulcer differed significantly only in white blood cell (WBC) count. Lengths of fasting and admission were 7.9 d and 17.9 d for the ulcer group and 4.4 d and 10.7 d for the non-ulcer group, respectively, and significantly longer in the ulcer group (P = 0.0057 and 0.0001). There was no correlation between presence of ulcer and presence of underlying diseases. CONCLUSION: Lengths of fasting and admission were significantly longer in patients with ischemic colitis with ulcer than for those without ulcer.     

Rebamipide enema therapy for left-sided ischemic colitis patients accompanied by ulcers： Open label study

AIM： TO attempt rectal administration of rebamipide in the treatment of ischemic colitis patients with ulcers, and evaluate its effects.
METHODS： We compared 9 ischemic colitis patients （2 men, 7 women） with ulcers treated by bowel rest only from 2000 to 2005 （conventional therapy group）, with 6 patients （2 men, 4 women） treated by rebamipide enema therapy in 2006 （rebamipide enema therapy group） and analyzed the mean duration of fasting and hospitalization, degree of ulcer healing, and decrease in WBC count for the two groups.
RESULTS： The mean duration of fasting and hospitalization were 2.7±1.8 d and 9.2 ±1.5 d in the rebamipide group and 7.9±4.1 d and 17.9±6.8 d in the control group, respectively, and significantly reduced in the rebamipide group （t = -2.915; P = 0.0121 and t = -3.054; P = 0.0092）. As for the degree of ulcer healing at 7 d after admission, the ulcer score was reduced by 3.5±0.5 （points） in the rebamipide group and 2.8±0.5 （points） in the control group （t = 1.975; P = 0.0797）, while the decrease in WBC count was 120.0±55.8 （×10^2μL） in the rebamipide group and 85.9±56.8 （×10^2μL） in the control group （t = 1.006; P = 0.3360）.
CONCLUSION： In left-sided ischemic colitis patients with ulcers, rebamipide enema therapy significantly reduced the duration of fasting and hospitalization, recommending its use as a new and effective therapeutic alternative.     

Severe recurrent cytomegalovirus disease revealed by a colocutaneous fistula in a kidney transplant recipient

Abstract: Intestinal disorders are classical complications of cytomegalovirus (CMV) infection in kidney transplant recipients (H elderman JH , G oral S. Gastrointestinal complications of transplant immunosuppression. J Am Soc Nephrol 2002: 13: 277–287). Severe ulcerative colitis that is sometimes lethal has been reported (F oucar E , M ukai K , F oucar K , S utherland DE , V an B uren CT. Colon ulceration in lethal cytomegalovirus infection. Am J Clin Pathol 1981: 76: 788–801 and F rankel AH , B arker F , W illiams G , B enjamin IS , L echler R , R ees AJ . Neutropenic enterocolitis in a renal transplant patient. Transplantation 1991: 52: 913–914). The immunosuppressive drugs currently used, and notably mycophenolate mofetil (Cellcept^®), cause significant changes in the incidence, duration, and viral load of CMV infections with severe atypical forms of CMV disease (D e M aar EF , V erschuuren EA , H oman vd H eide JJ, et al. Effects of changing immunosuppressive regimen on the incidence, duration and viral load of cytomegalovirus infection in renal transplantation: a single center report. Transpl Infect Dis 2002: 4: 17–24 and P erez V alentin MA , C ofan F , S ole M, et al. Atypical cytomegalovirus in renal transplantation: a new form of presentation. Nefrologia 2002: 22: 381–385). This report describes a patient who suffered from several episodes of colitis due to an unusual and late‐appearing CMV infection.     

Lethal cytomegalovirus ischemic colitis presenting with fever of unknown origin

We report a fatal case of cytomegalovirus (CMV) ischemic colitis in a renal transplant recipient. The disease was manifested with fever of unknown origin for 27 days followed by progressive right lower abdominal pain. The clinical condition deteriorated rapidly with development of disseminated intravascular coagulopathy and internal bleeding despite right hemicolectomy and antiviral therapy. The patient died 11 days after the onset of abdominal pain. We conclude that the possibility of CMV ischemic colitis should be suspected if a patient presents with fever and abdominal pain in the early months after transplantation, and that early viral detection by CMV polymerase chain reaction can be lifesaving.     

Spectrum of non-inflammatory bowel disease and non-infectious colitis

A variety of inflammatory diseases of the colon, which can be differentiated from inflammatory bowel disease （IBD） and infectious colitis by their clinical, endoscopic and histological characteristics, are reported as non- IBD and non-infectious colitis. These diseases include microscopic colitis, ischemic colitis, segmental colitis associated with diverticula, radiation colitis, diversion colitis, eosinophilic colitis and Behcet＇s colitis. The etiopathogenesis of most of these diseases remains obscure and the epidemiological data are rather limited. These conditions are often troublesome for the patient and are associated with diagnostic difficulties for the physician. In many cases the treatment is empirical and there is a need for future research using randomized controlled trials.     

丹参川芎嗪注射液治疗缺血性结肠炎的疗效观察

目的观察老年患者缺血性结肠炎应用丹参素川芎嗪葡萄糖注射液治疗的疗效。方法对32例老年缺血性结肠炎的患者随机分组，对照组（14例）给予单纯抗生素治疗和其他常规支持对症治疗；治疗组（18例）给予抗生素加丹参素川芎嗪葡萄糖注射液及常规支持治疗，观察治疗前后腹痛、便血的恢复情况、比较红细胞压积、血黏度的变化，检测血清SOD活性值，复查结肠镜比较肠黏膜的愈合情况。结果与对照组比较，治疗组腹痛、便潜血恢复的时间缩短，血红细胞压积降低、血液黏度降低较明显，血清SOD的活性提高，复查结肠镜黏膜恢复率高，治疗结束后黏膜修复状态更好。结论丹参素川芎嗪葡萄糖注射液对缺血性结肠炎症状的恢复、肠黏膜的修复有促进作用，且可以明显改善血液流变学指标、促进血清SOD活性的增加，有利于抑制缺血对肠黏膜的损伤。丹参素川芎嗪葡萄糖注射液可用于缺血性结肠炎的临床治疗。     

Hypertension after Kidney Transplantation: A Pathophysiologic Approach

Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.     

Role of platelet activating factor on severity of ischemic colitis

PURPOSE: Ischemic colitis develops after a sudden decrease in colonic blood supply and has a variety of clinical manifestations. The aim of this study was to assess the role of platelet activating factor in the pathogenesis of ischemic colitis with use of the platelet activating factor antagonist TCV-309. METHODS: Rats were randomly divided into four groups. Rats in Group RV underwent ring attachment around the rectum to induce partial obstruction and ligation of the marginal vessels of the left colon. As control, rats in Group R underwent the ring attachment and rats in Group V underwent the vascular ligation. Rat in Group C underwent sham operation. The effects of TCV-309 on lesion formation in the colon were evaluated. Thiobarbituric acid reactant level was determined in colonic mucosa, and the incidence and severity of ischemic lesions were also determined. RESULTS: Lesions of colitis were frequently observed in Group RV. TCV-309 did not prevent lesion formation, nor did it suppress the increase in thiobarbituric acid reactant level in Group RV. However, TCV-309 mitigated the severity of the lesion. CONCLUSIONS: Partial obstruction of the colon tends to induce ischemic colitis, and additional ischemia completes lesion formation. Platelet activating factor may play a role in the progression of ischemic lesions.Supported in part by Takeda Chemical Industries, Osaka, Japan. Presented in part at the Annual Meeting of the Japan Surgical Society, Chiba, Chiba, Japan, April 10 to 12, 1996.     

A rare diarrheic parasite in a kidney transplant patient: Cystoisospora belli

Cystoisospora belli colitis is a rare complication of immunosuppression in solid organ transplant recipients. We describe a case of Cystoisospora belli infection with colitis following renal transplantation.     

Endoscopic Findings and Clinicopathologic Characteristics of Ischemic Colitis: A Report of 85 Cases

Ischemic colitis is the most common type of intestinal ischemia and has a clinical spectrum of injury that ranges from mild and transient ischemia to acute fulminant colitis. The aim of this study was to explore endoscopic findings and clinicopathologic characteristics of ischemic colitis and be accurate enough to avoid missed diagnosis or misdiagnosis. A retrospective analysis was undertaken of endoscopy findings and clinicopathologic characteristics of 85 cases of ischemic colitis from March 2005 to April 2008 in the endoscopy center of our hospital. All cases underwent colonoscopy with biopsy within 2 weeks of the onset of symptoms, and all specimens with forceps were stained with hematoxylin–eosin and observed under light microscopy. Of the 85 cases of ischemic colitis (24 men and 61 women, average age 61.36 ± 14.49 years old, range 29–84), 71 were over 50 years of age. These cases were associated with the basal diseases such as hypertension, cardiovascular disorders, diabetes, and hematological diseases as well as a history of abdominal operation. The clinical features usually presented with sudden onset of abdominal pain, diarrhea, and hematochezia. Ischemic lesions were located mainly in the left colon with segmental form (only descending colon affected 16%, only splenic flexure 14%, and only sigmoid colon 23%). The 85 patients consisted of the non-gangrenous type (82), which were composed of reversible IC (76) and chronic IC (6), and the gangrenous type (3). Endoscopic appearance of the transient ischemic colitis consisted of petechial hemorrhages, edematous and fragile mucosa, segmental erythema, scattered erosion, longitudinal ulcerations, and sharply defined segment of involvement. Ischemic colitis of stricture was characterized by full-thickness mucosa, lumens stricture, and diseased haustrations. The mucosa of gangrenous colitis with cyanotic and pseudopolyps was endoscopically observed as well. Clinicopathologic characteristics showed mucosal inflammation accompanied by erosion, granulation tissue hyperplasia and gland atrophy, lamina propria hemorrhage, and macrophages with hemosiderin pigmentation in submucosa in particular. Although endoscopy findings and clinicopathologic characteristics of ischemic colitis are nonspecific, colonoscopy with biopsy plays a vital role in the early diagnosis of ischemic colitis.     

脾切除后暴发性感染并缺血性结肠炎的诊治体会

目的：提高对脾切除术后暴发性感染（OPSI）继发缺血性肠病的认识.方法：报道1例脾切除术后胰漏并暴发性感染,继发缺血性结肠炎患者的临床病历资料,结合文献分析诊治体会.结果：脾切除术后5d发生胰漏、继之肝功能损害、脓毒症,粒细胞缺乏症,反复血便,3次选择性腹腔动脉造影示结肠动脉分支破裂出血,肠镜发现结肠多发溃疡性病变,病理学见黏膜散在坏死,呈缺血性慢性炎症改变,经认真细致的诊断治疗获痊愈.结论：脾切除术后易发生凶险感染,多脏器功能损害,甚至粒细胞缺乏症、缺血性肠病,应早期识别,积极的抗生素治疗.     

85例缺血性结肠炎患者内镜表现及病理特点分析

目的 探讨缺血性结肠炎(IC)的内镜表现和病理特征,以引起临床医师对该病的重视,减少漏诊和误诊.方法 对南京大学医学院附属鼓楼医院内镜中心2005年5月至2008年3月85例IC患者进行回顾性分析.所有患者均在发病2周内行结肠镜检查和病理活检.结果 85例IC患者临床主要表现为腹痛、腹泻和便血、可伴有低热等.结肠镜下所见病变主要在左半结肠(80%,68/85).85例IC患者中非坏疽型82例和坏疽型3例.非坏疽型中一过性IC内镜表现为点状出血,黏膜水肿、发脆.节段性红斑,散在糜烂和纵行溃疡,病变与正常黏膜分界清楚.非可逆性IC内镜表现为黏膜发紫或发黑、伪性、假息肉及假性肿瘤,其中狭窄性IC内镜表现为全壁增厚、肠腔狭窄及结肠袋消失.坏疽型IC内镜表现为黏膜发紫和假息肉形成.IC病理特征为黏膜组织炎症伴糜烂和肉芽组织增生、腺体萎缩、固有层出血,特别是黏膜下层见含铁血黄素沉着的巨噬细胞.结论 尽管IC内镜及病理改变缺乏特异性,但早期行结肠镜检是诊断IC的重要方法,有助于临床医师提高对IC的诊治,减少误诊.     

Immunosuppression and metabolic syndrome in renal transplant recipients

Cardiovascular disease is the major cause of death in renal transplant recipients. Renal transplant recipients share the same cardiovascular risk factors as the general population, including hypertension, hyperlipidemia, diabetes mellitus, smoking, and positive family history. However, renal transplant recipients are also exposed to transplant-specific risk factors such as chronic immunosuppression. Most renal transplant recipients receive combinations or permutations of immunosuppressive drugs including a calcineurin inhibitor (cyclosporine or tacrolimus), a mammalian target of rapamycin (mTOR) inhibitor (sirolimus), an antiproliferative drug (mycophenolate mofetil and azathioprine), and corticosteroids. Cyclosporine and tacrolimus can induce glucose intolerance, hypertension, and hyperlipidemia. Sirolimus can induce hyperlipidemia. Corticosteroids can induce glucose intolerance, hypertension, hyperlipidemia, and weight gain. Central to the development of metabolic complications in renal transplant recipients is insulin resistance induced by immunosuppressive drugs. Insulin resistance is considered to be the central pathophysiological feature of metabolic syndrome, which is linked to increased risk of cardiovascular disease and to chronic renal failure. Therefore, metabolic syndrome likely contributes to cardiovascular disease and chronic renal allograft dysfunction in renal transplant recipients. Treatment of metabolic complications in renal transplant recipients is difficult, as conversion to an alternate immunosuppressive drug may lead to introduction of new metabolic complications, and as discontinuation of immunosuppressive therapy may lead to rejection. Future research should focus on designing immunosuppressive regimens that have minimal effects on insulin resistance and metabolic complications but that are effective in preventing acute rejection and in prolonging both allograft and patient survival.     

Hypoxia-inducible factor 1 alpha and vascular endothelial growth factor overexpression in ischemic colitis

AIM: To examine the etiology and pathophysiology in human ischemic colitis from the viewpoint of ischemic factors such as hypoxia-inducible factor 1 alpha (HIF-1 alpha and vascular endothelial growth factor (VEGF). METHODS: Thirteen patients with ischemic colitis and 21 normal controls underwent colonoscopy. The follow-up colonoscopy was performed in 8 patients at 7 to 10 d after the occurrence of ischemic colitis. Biopsy samples were subjected to real-time RT-PCR and immunohistochemistry to detect the expression of HIF-1 alpha and VEGF. RESULTS: HIF-1 alpha and VEGF expression were found in the normal colon tissues by RT-PCR and immunohistochemistry. HIF-1 alpha and VEGF were overexpressed in the lesions of ischemic colitis. Overexpressed HIF-1 alpha and VEGF RNA quickly decreased to the normal level in the scar regions at 7 to 10 d after the occurrence of ischemic colitis. CONCLUSION: Constant expression of HIF-1 alpha and VEGF in normal human colon tissue suggested that HIF-1 alpha and VEGF play an important role in maintaining tissue integrity. We confirmed the ischemic crisis in ischemic colitis at the molecular level, demonstrating overexpression of HIF-1 alpha and VEGF in ischemic lesions. These ischemic factors may play an important role in the pathophysiology of ischemic colitis.