R Emiroğlu

Tgf-β Expression In Renal Allograft Rejection And Cyclosporine Toxicity

Background. To assess short- and long-term influence of the TGF-β1 on renal allografts. Methods. Expression of TGF-β1 and TNF-α, and the proportion of macrophages and eosinophils in interstitium were evaluated in 64 cases including five cases with nonrejected kidneys (NRK), 18 cases with acute rejection (AR), 26 cases with chronic allograft nephropathy (CAN), and 15 cases with acute cyclosporine A (CsA) toxicity. Follow-up biopsies of all cases with AR and CsA toxicity were evaluated for development of interstitial fibrosis (IF) and graft atherosclerosis (GAS). Additionally, influence of tubular-TGF-β1 expression on graft function during 6 months after the diagnostic biopsy was evaluated. Results. A significant differences was seen between rejected kidneys and acute CsA toxicity in regards of tubular TGF-β1 expression that patients with CsA toxicity exhibited significantly higher grade of tubular TGF-β1 expression than patients with AR (P<0.05) and CAN (P<0.05). A significant difference was found between the grades of tubular TGF-β1 expression in regards to graft function of cases with AR and CsA toxicity (P< 0.05). Higher grade tubular TGF-β1 expression showed better graft function during 6 months. Besides the degree of renal TGF-β1 expression was positively correlated with development of diffuse IF and GAS (P<0.05) that the risk of the IF and GAS was higher in cases with grade 2 renal TGF-β1 expression. Conclusions. Despite the short-term posttransplantation tubule-repairing effects of TGF-β1, the overall effects of TGF-β1 in the kidney seem to be negative that increased expression of TGF-β1 promotes IF and vasculopathy associated with CAN.

Vascular Endothelial Growth Factor Expression and Cyclosporine Toxicity in Renal Allograft Rejection

The aim of this study was to evaluate the influence of vascular endothelial growth factor (VEGF) on renal function and on development of interstitial fibrosis (IF) in renal allografts. Tubular and interstitial expressions of VEGF and TNF‐α, and density of macrophages in the interstitium were examined in 92 patients with nonrejected kidneys, acute rejection (AR), chronic allograft nephropathy (CAN), borderline changes (BC) and acute cyclosporin A (CsA) toxicity. Follow‐up biopsy specimens from patients with AR and BC were evaluated for development of IF. A significant difference in tubular and interstitial VEGF expressions was found between patients with AR, BC, CAN and CsA toxicity (p < 0.001). Macrophage infiltration was positively correlated with VEGF and TNF‐α expressions (p < 0.001). VEGF expression increased with increasing expression of TNF‐α (p < 0.001). Renal function in first 6 months after initial biopsy was better in patients with marked tubular VEGF expression (p < 0.01); however, in follow‐up, development of IF and graft loss was found earlier in these patients (p < 0.01 and p < 0.05, respectively). Increased renal VEGF expression has protective properties immediately following renal allograft but allows for increased risk of early IF, and therefore poor graft outcome in the long term.

Effect of Amyloidosis on Long-Term Survival in Kidney Transplantation

Amyloidosis is characterized by the accumulation of an amorphous material in various organs and tissues secondary to a variety of inflammatory, immune, infectious, and hereditary diseases. Since 1975, our transplantation team has performed 1470 renal transplantations. Between 1985 and July 2004, among 1159 kidney transplantations, 953 (82.3%) were from living donors and 206 (17.7%) from cadaveric donors. There were 32 recipients (28 men, 4 women; mean age, 31.4 +/- 1.7 years; range, 21 to 48 years) with amyloidosis, including, 28 (87.5%) who received grafts from living donors and 4 (12.5%) from cadaveric donors. Amyloidosis was secondary to familial Mediterranean fever in 22 (68.7%) patients and rheumatoid arthritis in 1 (3.1%). The remaining 9 (28.1%) patients had primary amyloidosis. The mean follow-up time was 51.2 +/- 5.7 months (range, 2-124 months). Mean HLA mismatch rate was 2.2 +/- 1. Twenty-six (81.2%) patients are alive at this time with functioning grafts, and a mean serum creatinine value of 2.1 +/- 1.5 ng/dL. The 1- and 5-year patient and graft survival rates were 90.6% and 84.3%, and 81.2% and 68.7%, respectively. We conclude that patients with amyloidosis may undergo kidney transplantation safely expecting outcomes similar to those patients who receive transplantations for other reasons.

Multiple-artery anastomosis in kidney transplantation.

KIDNEY transplantation is a form of renal replacement treatment that offers the patient a more productive and comfortable life. It is no surprise that the demand for this procedure is constantly increasing. Unfortunately, although the need for renal transplantation is growing, organ shortage remains a critical limiting factor. Over the past three decades, graft and patient outcomes have improved significantly as a result of standardization of surgical technique and refinements in immunosuppressive therapy, organ preservation, and antimicrobial therapy. Although kidney grafts with multiple renal arteries have been associated with a higher incidence of vascular and urologic complications, there is increasing pressure to use such kidneys and thus expand the potential donor pool. Multiple renal arteries occur unilaterally and bilaterally in 23% and 10% of the population, respectively, so it would clearly be in the best interests of patients to include these individuals as organ donor candidates. The effect of more than one arterial anastomosis on graft and patient survival has not been clearly defined. Our aim in this study was to measure the prevalence of multipleartery renal transplants, and to calculate the rates of acute tubular necrosis and vascular and urologic complications in recipients of these grafts. We also compared the graft and patient survival rates for patients who underwent singleversus multiple-artery anastomosis.

Fulminant liver failure secondary to mushroom poisoning in children: Importance of early referral to a liver transplantation unit

Abstract:  Patients poisoned with toxic mushrooms have a spectrum of clinical presentations ranging from gastrointestinal symptoms to fulminant liver failure, and outcomes range from complete recovery to the need for liver transplantation. We reviewed the clinical presentation, course, outcome and management of four children poisoned with mushrooms who developed fulminant liver failure. Although one patient survived, two children died and one underwent living related liver transplantation. Early referral to specialized centers for treatment and for liver transplantation is emphasized.

Hepatitis B virus reactivation after renal transplantation: report of two cases

Recovery from acute hepatitis B virus (HBV) infection is associated with the loss of HBV DNA and hepatits B surface antigen (HBsAg) together with the development of antibodies against HBsAg (anti-HBs), HB ‘e’ antigen (anti-HBe) and HBcore antigen (anti-HBc). Individuals with serological markers implying past exposure to HBV are generally believed to have cleared the virus and also to have acquired protective immunity. However, clinical observation has shown that individuals with such a constellation may nevertheless develop the reactivation of HBV infection spontaneously or under immunosuppression. We describe two recipients of a renal transplant who exhibited prior serologic resolution of HBV infection and in whom HBsAg reappeared 10 and 9 months after renal transplantation, respectively. A 35-year-old woman presented with chronic renal failure of unknown etiology requiring dialysis for 2 years. Serologic test results revealed a prior HBV infection that had apparently resolved (HbsAg-negative, anti-HBcIgG and anti-HBs-positive) on admission. The patient’s antiHBs titer was 12 IU/ml, and serum HBV DNA level was not assessed at the time of transplantation. She underwent kidney transplantation from her brother, whose serologic testing was negative for HBV. Ten months after transplantation, she demonstrated the elevated levels of aspartate-aminotransferase (AST) 87 IU/ml and alanineaminotransferase (ALT) 133 IU/ml. Viral markers became positive for HBsAg, HBeAg and HBV DNA (by hybridization) but became negative for anti-HBe and anti-HBs. Liver biopsy revealed a mild degree of active hepatitis without fibrosis and immunohistochemical staining indicated the presence of HBsAg in hepatocytes. Lamivudine treatment was initiated. After 2 months of lamivudine treatment, AST and ALT levels were increased to 105, 193 IU/ml respectively, HBeAg became negative, anti-HBe became positive. Two months later, AST and ALT levels returned to normal and serum HBV DNA became negative with hybridization (Fig. 1). A 24-year-old man exhibited renal failure that had been treated with hemodialysis for 4 years. On admission and also at the time of renal transplantation, the test results for HBsAg were negative and that for anti-HBs, and antiHBcIgG were positive. The patient’s anti-HBs titer was 33 IU/ml at the time of transplantation. Serum HBV DNA levels were not assessed before and at the time of transplantation. He underwent a kidney transplantation from his father, whose serologic results were negative for HBsAg, anti-HBs, and anti-HBcIgG. Early rejection of the transplant (detected by renal biopsy) was treated with pulse steroid treatment. On follow-up 9 months later, liver function and serologic test results were as follows: AST, 54 IU/ml and ALT, 58 IU/ml, HBsAg positive, antiHBs and HBV DNA negative. Thirteen months after transplantation, AST and ALT levels were increased to 60 and 105 IU/ml, respectively and serum HBV DNA level became positive with hybridization (quantitatively > 0.5 pg/ml was accepted as positive). Liver biopsy revealed a mild degree of chronic active hepatitis without fibrosis, and immunohistochemical staining revealed HBsAg in all hepatocytes. Lamivudine treatment was initiated. After 6 months of lamivudine treatment, serum testing for HBV DNA yielded a negative result, and liver function tests returned to normal range (Fig. 2). In our report, both patients had experienced the HBV infection in past silently and they were not treated for HBV infection before the transplantation. For both patients, immunosuppression was not tapered after the diagnosis of hepatitis B reactivation. The possibility of occult HBV infection after complete clinical recovery from acute hepatitis is a known entitity, which suggests possible viral reactivation from occult HBV infection in the presence of anti-HBc and anti-HBs during long-term immunosuppressive therapy after renal transplantation [1,2]. The re-emergence of HBV infection in our cases might have been caused by reactivation of a latent infection or by a new HBV infection. If we had performed HBV DNA measurements at the time of transplantation and if we had got positive HBV DNA levels with low titers, the problem with our cases would be easier with being occult HBV infection. But as we did not perform serum HBV DNA level measurements for both patients at the time of the transplantation, and we were not able to compare the HBV strain identified in each patient’s initial infection with the strain detected after

Effect of immunosuppressive treatment protocol on malignancy development in renal transplant patients.

CANCER is more common in transplant recipients than in the general population. The reported incidence of malignant tumors after renal transplantation is 14 to 500 times higher than the rate in the general population. The prevalence of malignant tumors in different series of renal recipients ranges from 1 to 16% (mean 4%) and varies with type of organ transplant, age of the recipient, individual transplant center, and type of immunosuppression (IS). Other possible contributing factors are chronic antigenic stimulation, oncogenic virus activation, genetic susceptibility, and uremia. In this article, we describe 50 cases of malignant tumor development in renal transplant recipients who were treated with different immunosuppressive protocols in the Transplantation Center at Baskent University Faculty of Medicine.

Treatment results in renal transplant recipients with non-Hodgkin’s lymphoma

The purpose of this study was to investigate the incidence of non-Hodgkins lymphoma (NHL), response to treatment, and survival time in renal transplant recipients at our center who developed this form of neoplasia. Between October 1985 and August 2002, 1077 renal transplantations were carried out at our center. The incidence of NHL after transplantation was 1.1% (12/1077). All patients had their immunosuppressive doses reduced after they were diagnosed with NHL. Complete remission was achieved in eight cases, and five of these individuals were still alive at the time of writing. The circumstances for each of the three deaths in this group were as follows: (1) progressive gastric adenocarcinoma 9 years after being diagnosed with NHL, (2) stage III NHL cured with chemotherapy, but died of infection 2 years after NHL diagnosis, and (3) recurrent intestinal lymphoma, with death during second line chemotherapy. Of the five survivors in the remission group, one had to return to hemodialysis. The four patients who did not enter remission all died. The median time from transplantation to diagnosis of NHL was 66 months. At the time of writing, the median survival time for the eight patients who achieved complete remission was 41.5 months. The study showed that treatment of localized disease (skin or intestinal NHL) with surgery and/or radiotherapy/chemotherapy leads to complete remission and long survival times; however, patients in remission are at risk for other causes of death.

The comparison of angiotensin-converting enzyme inhibitors with calcium antagonists in renal transplant patients under cyclosporin treatment

ARTERIAL hypertension is a multifactorial common complication of renal transplantation. The prevalance of hypertension after renal transplantation has been reported to be as high as 80%. 1,2 The triggering factors for hypertension have been shown as steroid treatment, acute and chronic rejection, etiology of primer renal disease, presence of primary disease, and stenosis of renal artery. Immunsuppressive drugs such as corticosteroids and cyclosporin have hypertensive effects. Cyclosporin has a vasoconstructive effect especially in renal vasculature and decreases the intracellular calcium influx during renal ischemia and reperfusion period. This results in an increase in intracellular free oxygen radicals. For the patients with excellent graft function, cyclosporine may be the main factor responsible for posttransplant hypertension. Calcium canal blockers have vasodilator effect and are used commonly in hypertensive renal transplant patients. But, calcium canal blockers may increase blood cyclosporin levels through competetive inhibition of cyclosporin metabolism at the level of cyctochrome P-450 thereby increasing the risk of renal toxicity. Calcium canal blockers have adverse effects such as worsening of gout, leg oedema, postural dizzines, and leg cramps. Other antihypertensive medications such as angiotensin converting enzyme inhibitors are used in renal transplant patients. In this study, we compared the antihypertensive effect of calcium canal blockers and angiotensin converting enzyme inhibitors.

Heterotopic liver transplantation during adolescence

EVERE shortage of donor organs has led medical experts to search for new ways to expand the world’s transplant sources. Cadavers are currently the main source of donor livers, but most end-stage hepatic failure patients die before they ever receive a transplant. In the field of liver transplantation today, our primary goal is to boost the currently low rate of procedures performed, and thus extend the lives of increasingly more chronic liver failure patients for whom liver transplantation is the only hope of survival. Improved technique and understanding of liver anatomy have given surgeons the tools to develop and perform more complicated procedures. Cadaveric split-liver transplantation (CSLT) and living-donor liver transplantation (LDLT) are attracting increased attention, and are being promoted as solutions for liver failure patients who would otherwise die on a cadaver-donor waiting list. Since 1992, a number of groups have reported good results with LDLT in pediatric recipients. 1,3 We have been doing LDLT since 1990, and CSLT since 1998, performing both procedures in patients of all age groups. To date, we have carried out 27 living-donor partial hepatectomies and 6 split-liver procedures using cadaveric grafts. The pediatric patient group included eight teenage patients who were .16 years of age. Our results in teens ,16 years of age have already been published. 1 In this report, we present a retrospective study of the results of liver transplantation in our eight pediatric patients who were .16 years of age.