bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin allergy: clinical manifestations and management strategies
Authors: Heinzerling L. , Raile K. , Rochlitz H. , Zuberbier T. , Worm M.
Published: August 2010

Insulin allergy in patients with diabetes mellitus on insulin treatment is a rare condition. It is suspected upon noticing immediate symptoms following insulin injections. The immediate vital implications for the patient call for prompt diagnosis and management of insulin allergy.

We review current knowledge and procedures based on four diabetic patients who presented in our clinic. Insulin allergy was suspected as they showed immediate symptoms after insulin injection (urticaria, rash, angioedema, hypotension, dyspnea). A detailed allergologic work‐up was performed and adequate therapy was initiated. In three of the four patients, a specific immunotherapy was started whereas in one patient a switch to oral antidiabetics was possible and consequently initiated. By standard prick testing and measurement of specific IgE antibodies, a type 1 IgE‐mediated allergy was confirmed. After initiation of insulin immunotherapy, the symptoms completely resolved in two out three of patients and significantly improved in the third patient. The fourth patient was successfully switched to oral antidiabetics.

Insulin allergy is a rare but severe condition that calls for immediate allergological work‐up. It can be managed well in close cooperation between the diabetologist and the allergologist. Specific immunotherapy is efficient and should be considered.
Living and deceased donor liver transplantation for unresectable hepatoblastoma at a single center
Authors: Mejia Alejandro , Langnas Alan N , Shaw Byers W , Torres Clarivet , Sudan Debra L
Published: August 2010

Abstract:  Hepatoblastoma (HB) is the most common malignant liver tumor in children. The application of living donor liver transplantation (LDLT) in the management of unresectable HB may add new therapeutic opportunities. We evaluated the outcomes of patients who underwent liver transplantation for treatment of unresectable HB in the period between August 1985 and June 2003. Ten children had a diagnosis of unresectable HB. Mean age at transplantation was 5.8 yr. Eight patients were transplanted with deceased donor grafts. Two patients underwent LDLT. Pre‐transplant chemotherapy was used in 90% of cases. Post‐transplant survival ranges from 3.7 to 18.6 yr. Three patients died of recurrent disease at 4, 14 and 38 months. The two LDLT recipients were able to get pre‐transplant chemotherapy with a rapid decision towards transplantation; both are alive and well at 5.5 and 11 yr post‐transplant. Our experience supports the role of LDLT and deceased donor liver transplantation in the management of unresectable HB when waiting times can be detrimental to the patient's survival.
Systemic strategies for chemoprevention of skin cancers in transplant recipients
Authors: Kovach Bradley T , Sams Hunter H , Stasko Thomas
Published: August 2010

Abstract:  Background:  Solid organ transplant recipients (OTRs) are a growing population at high risk for cutaneous neoplasms, resulting in significant post‐transplant morbidity and mortality. Management of malignant and pre‐malignant cutaneous lesions in transplant recipients is challenging, making prevention of such neoplasms paramount. The objectives of the present study are to review and analyze systemic strategies for chemoprevention of malignant and pre‐malignant cutaneous neoplasms in OTRs.

Methods:  MEDLINE and PubMed searches were performed to identify studies with original data quantifying the effects of systemic agents on the development of malignant cutaneous neoplasms in patients with solid organ transplants.

Results:  We identified nine studies describing 111 transplant recipients that quantified the effects of oral retinoids on cutaneous neoplasms. A majority of the studies found a decrease in the number of malignant and pre‐malignant cutaneous lesions in patients treated with systemic retinoids, with several studies noting increased benefit in those patients with multiple previous skin cancers. Multiple studies described a rebound effect, with increased numbers of neoplasms occurring following discontinuation of retinoids. Side effects often limited dosing, but required discontinuation of retinoids in a minority of patients. No studies were identified that adequately quantified the effects of other systemic agents on skin cancer incidence in this population.

Conclusions:  Although systemic retinoids are frequently used for chemoprevention of cutaneous malignancies in OTRs, the data supporting their use are composed largely of small uncontrolled case reports and case series. However, the available data suggest that retinoids have chemopreventative effects in this population. Although optimal dosing and indications for initiation of systemic retinoid therapy are not conclusive from the data, it suggests that retinoids are most effective in patients with multiple previous non‐melanoma skin cancers. Side effects and beneficial effects were noted across a wide range of doses, suggesting that retinoids should be initiated at a low dose and increased as tolerated to a minimally effective dose. Further investigation through randomized controlled trials is needed to further clarify the tolerability and efficacy of multiple dosing regimens on the incidence of pre‐malignant and malignant lesions in transplant recipients. The therapeutic role of other systemic agents in the transplant population has not been established.
Chronologically different impacts of immunologic and non‐immunologic risk factors on renal allograft function
Authors: Kim Myoung Soo , Kim Dong Kee , Myoung Sung Min , Kim Soon Il , Oh Chang‐Kwon , Kim Yu Seun , Lee Jong Hoon , Kang Shin‐Wook , Park Kiil
Published: August 2010

Abstract:  Introduction:  Upon analysis of the risk factors affecting renal graft survival and function, the time‐dependent effects of each risk factor should be differentiated from their net effects. To evaluate the chronologically different impacts of risk factors on graft renal function, we reviewed 390 recipients who received a kidney from 1‐haplotype‐matched living‐related donors.

Materials and methods:  Until 5‐yr post‐transplantation (TX), yearly serum creatinine (Scr), 24‐h urinary excretion of protein, and their yearly changes were compared by the episodes of acute rejection within 1 yr, the kidney weight to recipient body weight (KW/BW) ratio, the donor/recipient (D/R) age ratio, and the D/R gender pairing. The Kaplan–Meier method, Cox proportional hazard model, ANOVA, and repeated measures ANOVA were each applied for different purposes.

Results:  Only the episodes of acute rejection were a significant risk factor affecting graft survival. The episodes of acute rejection, KW/BW ratio, D/R age ratio, and D/R gender pairing consistently and independently had significant influences on Scr. Recipients having the lowest KW/BW ratio (first quartile) or the highest D/R age ratio (fourth quartile) had rapid increments of Scr after 4‐yr post‐TX. After 3‐yr post‐TX, there were significant correlations between the number of non‐immunologic risk factors present and the yearly changes in Scr.

Conclusions:  Non‐immunologic factors had a detrimental effect on renal graft function, especially after 3‐yr post‐TX. If immunologic risks seem to be similar, size matching, age, and gender pairing should be considered for better long‐term graft function in renal TX recipients.
Use of IL‐2 receptor antagonists to reduce delayed graft function following renal transplantation: a review
Authors: Sandrini Silvio
Published: August 2010

Abstract:  Delayed graft function (DGF) occurs in approximately 30% of renal transplant patients, and significantly increases risk of long‐term graft loss. This article reviews the potential for use of interleukin‐2 receptor (IL‐2R) antagonists to reduce the burden of DGF. IL‐2R antagonists decrease incidence of acute rejection without increasing risk of cytomegalovirus infection or malignancy, and show equivalent efficacy to lymphocyte‐depleting antibody agents in standard risk patients with immediate graft function. The nephrotoxicity associated with calcineurin inhibitors (CNIs) has led to use of delayed or low‐dose CNI regimens with induction therapy in patients with DGF. In this setting, use of an IL‐2R antagonist with mycophenolate mofetil and steroids with delayed cyclosporine appears to be associated with a low incidence of biopsy‐proven rejection and comparable renal function to patients with immediate function. Additionally, there is intriguing evidence to suggests that IL‐2R antagonists may reduce risk of DGF occurring. A number of large‐scale and smaller studies have reported a trend to reduced incidence of DGF or improved early renal function using IL‐2R antagonists compared with placebo, although data are not entirely consistent. In conclusion, the ability of IL‐2R antagonists to reduce acute rejection with no additional safety concerns makes them an attractive option for patients with DGF.
C4d as a significant predictor for humoral rejection in renal allografts
Authors: Jianghua Chen , Wenqing Xie , Huiping Wang , Juan Jin , Jianyong Wu , Qiang He
Published: August 2010

Abstract:  Objective:  To determine the diagnostic and clinical significance of C4d accumulation in renal allografts followed by acute rejection.

Methods:  A total of 158 graft biopsies performed from December 1997 to December 2002 were classified, according to the Banff‐97 criteria, into hyperacute rejection (HAR, three cases), acute vascular rejection (AVR, 27), acute cellular rejection (ACR, 24), borderline rejection (BR, 38), acute tubular necrosis (ATN, five), stable graft function (SGF, 30) and baseline kidney (31). Immunohistochemical technique was used to determine the C4d deposition level.

Results:  The percentages of C4d positive in HAR, AVR, ACR, BR, ATN, SGF and baseline kidney groups were 100% (3/3), 77.8% (21/27), 37.5% (9/24), 23.7% (9/38), 0% (0/5), 3.3% (1/30), 0% (0/31), respectively. In acute rejection patients, the peak serum creatinine (sCr) level in C4dptc‐positive group (41 cases) was 334.82 ± 238.37 μmol/L, with that of C4dptc‐negative group (47 cases) being 220.20 ± 176.94 μmol/L (p < 0.01). After treatment, the trough sCr level in C4dptc‐positive group and C4dptc‐negative group were 176.87 ± 111.80 and 121.75 ± 34.59 μmol/L (p < 0.01), respectively. In each AVR, ACR and BR subgroups, the peak sCr level, the trough sCr level, after 3 or 6 months of AR, the sCr level in C4dptc‐positive subgroup was higher than that of C4dptc‐negative subgroup. There were more resistance against steroid therapy [65.9% (27/41) vs. 36.2% (17/47), p = 0.005] and a higher rate of graft loss [29.3% (12/41) vs. 6.4% (3/47), p = 0.001] in C4dptc‐positive group than those of C4dptc‐negative group. In each C4dptc‐positive subgroup of AVR, ACR and BR the complete reversion was 57.1, 56 and 66.7%, respectively, it is almost same.

Conclusion:  The C4d deposition level is of great value in diagnosis of acute rejection caused by humoral immune components. It is a significant predictor of graft survival and will be of great help when treating acute rejection.
Kidney graft survival in patients with hepatitis C: a single center experience
Authors: Arango J , Arbelaez M , Henao J , Mejia G , Arroyave I , Carvajal J , Garcia A , Gutierrez J , Velásquez A , Garcia L , Aguirre C
Published: August 2010

Abstract:  Hepatitis C virus (HCV) infection is highly prevalent in renal transplant candidates; however, its effect on the transplant outcome is still controversial. The aim of the present study was to determine the effect of HCV infection in the outcome of kidney transplantation in a single transplant center. The study population 144 HCV− randomized selected patients and 64 HCV+ patients transplanted from 1973 to 2000, followed for up to 60 months post‐transplantation. This retrospective study included the following variables: type of dialysis, time on renal replacement therapy, number of transfusions before and after transplantation, number of transplants, type of donor, immunosuppression, and rejection episodes. The Kaplan–Meier method was used to estimate graft and patient survival. Log‐rank test was used to assess the difference in survival between HCV+ and HCV−. A multivariate Cox proportional hazards model was used to analyze the relation between graft and patient survival. HCV+ and HCV− patients had similar demographic and clinical characteristics; however, a higher number of HCV+ patients received blood transfusions after transplantation. Patient survival was not significantly different in 39 HCV+ and 96 HCV− patients transplanted with living‐related donors (71% and 77% at five yr, respectively). Similarly, there was not significant difference in 25 HCV+ and 48 HCV− patients transplanted with kidneys from deceased donors, although there was a tendency to better outcome in HCV− patients (55% and 72% at five yr respectively). Regarding graft survival, there was also no differences in HCV+ and HCV− recipients of living‐related grafts (61% and 66% at five yr post‐transplant, respectively) and recipients of kidneys from deceases donors (44% and 41%, respectively). The results show that HCV+ patients can be transplanted with the same success than HCV− patients.
Influence of angiotensin I‐converting enzyme polymorphism on development of post‐transplant erythrocytosis in renal graft recipients
Authors: Kędzierska Karolina , Kabat‐Koperska Joanna , Safranow Krzysztof , Domański Maciej , Gołembiewska Edyta , Bober Joanna , Bohatyrewicz Romuald , Ciechanowski Kazimierz
Published: August 2010

Abstract: Background: Post‐transplant erythrocytosis (PTE) is estimated at 5–20%. Angiotensin II generated by angiotensin I‐converting enzyme (ACE) stimulates erythropoiesis. The highest activity of ACE is observed in DD genotype. The question arises if ACE gene polymorphism influences PTE.

Methods: One‐year prospective study included 89 kidney recipients (28 women and 61 men).

Results: Thirty‐four (38%) recipients proved to be DD genotype, 36 (40%) ID, and 19 (22%) II genotype. Absolute PTE [hematocrit level (HCT) >50% and RBC > 5.5 mln/mm3] was found in 14 (19%) patients. PTE developed 6–12 months after kidney Tx. There were no significant differences in genotype distribution between patients with and without PTE. ANOVA showed that the most significant predictor of PTE development was the time since kidney Tx (p < 0.0001). Analysis of logistic regression showed that male sex was the most important factor in PTE development 12 months after kidney Tx (OR = 13.6: 95% CI 1.2–150.9, p < 0.05). D allele increased the PTE risk (OR = 3.3 for each allele: 95% CI 1.1–10.4, p < 0.05), the use of angiotensin‐converting enzyme inhibitors (ACEI) decreased the PTE risk (OR = 0.15: 95% CI 0.03–0.85, p < 0.05). In patients with DD genotype, there was a correlation between hemoglobin, RBC and HCT concentration, 12 months after Tx and panel of reactive antibody value before Tx (Rs = +0.43, p < 0.05).

Conclusions: Male sex and D allele presence increase the risk of PTE development, especially in highly immunized patients. The use of ACEI decreases the risk of PTE development.
Emergence of drug‐resistant cytomegalovirus in the era of valganciclovir prophylaxis: therapeutic implications and outcomes
Authors: Eid Albert J , Arthurs Supha K , Deziel Paul J , Wilhelm Mark P , Razonable Raymund R
Published: August 2010

Abstract:  Background:  Valganciclovir prophylaxis is reportedly associated with a low incidence of ganciclovir‐resistant cytomegalovirus (CMV). We assessed the incidence, clinical features, and outcome of drug‐resistant CMV among solid organ transplant patients who received valganciclovir prophylaxis.

Methods:  The medical records of all CMV D+/R− kidney, pancreas, liver, and heart recipients were screened for CMV disease, and the clinical course and outcomes of patients with drug‐resistant CMV were reviewed.

Results:  During a four‐yr‐study period, a total of 225 CMV D+/R− transplant patients received valganciclovir prophylaxis for a median of 92 d. Sixty‐five (29%) of the 225 patients developed delayed‐onset primary CMV disease, including nine (14%) suspected to have drug‐resistant virus. Four (6.2%) had confirmed UL97 or UL54 mutations. All except one patient manifested gastrointestinal tissue‐invasive disease. Together with reduction in immunosuppression, intravenous foscarnet with or without CMV hyperimmunoglobulin was the most common treatment. Drug‐associated nephrotoxicity was commonly observed and resulted in allograft loss in two patients. During the mean follow‐up of 2.2 yr, allograft loss and mortality occurred in two of four patients with proven and in three of five patients with clinically suspected drug‐resistant CMV.

Conclusions:  Cytomegalovirus disease because of clinically suspected or genotypically confirmed drug‐resistant CMV is not uncommon in CMV D+/R− solid organ transplant patients who received valganciclovir prophylaxis. Because of its significant morbidity and mortality, an optimized strategy of CMV prevention is warranted to reduce the negative impact of drug‐resistant CMV on the successful outcome of organ transplantation.
The outcome of primary liver transplantation from deceased donors in children with body weight ≤10 kg
Authors: Polak Wojciech G. , Peeters Paul M.J.G. , Miyamoto Shungo , Sieders Egbert , De Jong Koert P. , Porte Robert J. , Bijleveld Charles M.A. , Hendriks Herman G. , TenVergert Elisabeth M. , Slooff Maarten J.H.
Published: August 2010

Abstract: Between November 1982 and March 2006, 67 children with body weight ≤10 kg had a primary liver transplantation from deceased donors in our unit. The aim of this study was to analyze the outcome in terms of patient and graft survival and to search for factors affecting this outcome. Overall, one‐, three‐, five‐, and 10‐yr primary patient and graft survival rates were 73%, 71%, 66%, 63% and 59%, 56%, 53%, 48%, respectively. Twenty‐four of 67 (36%) children died and in the remaining 22 (33%), the first grafts failed and they were retransplanted. Cox regression analysis revealed that a need for retransplantation and urgent transplantation were important predictors for patient survival (p = 0.04 and p = 0.001, respectively). To assess whether the need for retransplantation can be influenced, all study variables were compared between surviving grafts and failed grafts. Cox regression analysis showed that only donor/recipient (D/R) weight ratio proved to be independent predictor for graft survival (p = 0.004). After comparison of graft survival with the long rank test according to different D/R weight ratios (3.0–7.0), the cut‐off point for significantly different graft survival approached 4.0. The one‐, three‐, five‐, and 10‐yr graft survival for technical variant grafts with a D/R weight ratio <4.0 was 85%, 68%, 68%, and 68% compared with a D/R weight ratio >4.0 was 44%, 38%, 38%, and 30%, respectively (p = 0.02). In summary, patient survival in children with body weight ≤10 kg is determined by urgent transplantation and the need for retransplantation. Graft loss and retransplantation in small children can be prevented by adequate size matching of donor and recipient whereby a D/R weight ratio <4.0 seems to offer the favorable outcome.
Low incidence of secondary neoplasia after autotransplantation for lymphoproliferative disease: the role of pre‐transplant therapy
Authors: Laurenti Luca , Tarnani Michela , Chiusolo Patrizia , Torre Giuseppe La , Garzia Mariagrazia , Zollino Marcella , Zini Gina , Balducci Mario , Leone Giuseppe , Sica Simona
Published: August 2010

Abstract:  To asses the real contribution of pre‐transplantation treatment in the incidence of secondary neoplasia after autologous transplant for lymphoproliferative disorders, we used stringent inclusion/exclusion criteria. One hundred and forty‐two patients out of 323 that underwent autologous transplantation for lymphoproliferative disorders were studied. The risk factors that were evaluated with univariate and multivariate analysis included: gender, sex, age, diagnosis, radiotherapy, and chemotherapy prior to conditioning regimen, disease status at peripheral blood stem‐cell transplantation (PBSCT) and type of harvest. Three patients developed secondary myelodysplastic syndrome/acute myeloid leukemia (sMDS/AML) and three patients developed solid neoplasia. By univariate analysis diagnosis chronic lymphocytic leukemia and use of fludarabine and monoclonal antibodies were the only variables significantly associated with the development of sMDS/AML. By multivariate analysis, the variables associated with sMDS/AML were the use of fludarabine and disease status at PBSCT. By univariate analysis, we found that radiotherapy and the use of monoclonal antibodies were significantly associated with the development of secondary solid neoplasia. Multivariate analysis confirmed that the only two variables significantly associated with new cancers were radiotherapy and prior treatment with monoclonal antibodies. We report the lowest incidence of sMDS/AML after autologous stem‐cell transplantation for lymphoproliferative malignancies. Major reasons could be ascribed to the stringent inclusion/exclusion criteria used to establish the real incidence of sMDS/AML because of chemo‐radiotherapy used before transplant procedure. The low incidence of secondary solid tumors could be caused by the absence of total body irradiation as part of the conditioning regimen or the short follow‐up.
Impact of pancreatic venous drainage site on long‐term patient and graft outcome in simultaneous pancreas‐kidney transplantation
Authors: Petruzzo Palmina , Lefrancois Nicole , Berthillot Celine , Danjou Fabrice , Contu Paolo , Codas Ricardo , Morelon Emmanuel , Dubernard Jean Michel , Martin Xavier , Badet Lionel
Published: August 2010

Abstract: The impact of portal or systemic venous pancreas graft drainage on patient and graft outcome remains controversial. In the present study, the impact of venous drainage type on long‐term patient and graft survival is assessed. From July 1996 to December 2002 80 simultaneous pancreas‐kidney transplants were enrolled into a prospective study: 44 received a pancreas allograft with portal (P‐SPK group) and 36 with systemic venous drainage (S‐SPK group). Enteric exocrine drainage was performed in all recipients receiving the same immunosuppressive treatment. At one yr, the patient survival rates were 91.7% and 95.5% both for S‐SPK and P‐SPK groups, respectively; no significant difference in survival was shown at any time point of the follow‐up. The one‐, three‐, five‐, and eight‐yr pancreas survival rates were 75%, 60.6%, 56.7%, and 44%, respectively in the S‐SPK group compared to 88.6%, 84.1%, 78.4%, and 31.3% in the P‐SPK group. The one‐, three‐, five‐, and eight‐yr kidney survival rates were 91.7%, 78.15%, 74.1%, and 57.9%, respectively in the S‐SPK group compared to 93.2%, 88.6%, 78.4%, and 38.9% in the P‐SPK group. Comparing the two groups, no significant difference was shown in the total number of surgical complications as well as in the number of each complication. No significant difference in long‐term outcomes between the two groups was shown, even if in S‐SPK group a higher incidence of pancreas graft loss has been reported and it was in part correlated to a higher number of graft thromboses.
Cytomegalovirus viremia in solid organ transplantation: does the initial viral load correlate with risk factors and outcomes?
Authors: Levitsky Josh , Freifeld Alison G. , Puumala Susan , Bargenquast Kim , Hardiman Penny , Gebhart Catherine , Wrenshall Lucy , Langnas Alan , Kalil Andre C.
Published: August 2010

Abstract:  Consistent data for using CMV quantitative PCR (QnPCR) on initial presentation to predict outcomes after solid organ transplantation (SOT) are lacking. Recipients with measurable CMV QnPCR and either CMV‐V (asymptomatic viremia) or CMV‐D (symptomatic CMV infection) were analyzed over 24 months. Risk factors and outcomes were evaluated in relation to initial QnPCR by regression analysis and time‐to‐event curves. Twenty‐eight recipients were identified: five CMV‐V, 23 CMV‐D. Patients with CMV‐D had a higher median initial QnPCR (230 000 copies/mL) compared with CMV‐V (2500 copies/mL; p < 0.05). No patients with CMV‐V had an initial QnPCR > 10 000 copies/mL compared with 83% of the CMV‐D (p = 0.004). The initial QnPCR was higher (250 000 copies/mL) in patients who did not clear CMV PCR than those who cleared (8000 copies/mL) after 14 d of treatment (p = 0.03). Risk factors and indirect CMV effects were not associated with initial QnPCR. Our results highlight the importance of the initial CMV QnPCR in relation to the development of symptomatic CMV and a slower response to therapy. Alternatively, late asymptomatic viremia and recurrent CMV are associated with lower PCR levels and a low likelihood to progress and result in clinical disease.
Pharmacokinetics of mycophenolic acid, tacrolimus and sirolimus after gastric bypass surgery in end‐stage renal disease and transplant patients: a pilot study
Authors: Rogers Christin C , Alloway Rita R , Alexander J. Wesley , Cardi Michael , Trofe Jennifer , Vinks Alexander A
Published: August 2010

Abstract: Background: Promising data regarding the safety and efficacy of gastric bypass surgery (GBS) as an option to address obesity in the transplant population are emerging. The data lack on how GBS may alter the pharmacokinetics (PK) of modern immunosuppression. The objective of this study was to describe the alterations in the PK of modern immunosuppressants and the GBS population.

Methods: Data are presented on six subjects who participated in this trial – four were on dialysis and two were renal transplant recipients. Dialysis‐dependent bypass subjects received a single dose of 6 mg of sirolimus, two 4‐mg doses of tacrolimus and two 1000‐mg doses of mycophenolate mofetil (MMF) over the 24‐h study period. Transplant recipients continued their current regimen. Maximum plasma concentration (Cmax), time to reach the maximum plasma concentration (Tmax) and the area under the plasma concentration vs. time curve (AUC0–12and AUC0–∞where appropriate) were calculated for tacrolimus, sirolimus, mycophenolic acid (MPA) and mycophenolic acid glucuronide (MPAG).

Results: Significant inter‐patient variability in theCmax,Tmaxand AUC of tacrolimus, sirolimus MPA and MPAG was observed. A notable difference in the AUC:dose ratio for tacrolimus was seen when comparing data with published data in the non‐bypass population. Similar differences in PK were seen with sirolimus, MPA and MPAG.

Conclusions: When comparing the PK of sirolimus, tacrolimus, MPA and MPAG to published PK data in the non‐bypass population, significant differences are observed. It is likely that transplant recipients with GBS would need higher doses of tacrolimus, sirolimus and MMF to provide similar exposure to a non‐bypass patient.
De novo autoimmune hepatitis following living‐donor liver transplantation for primary biliary cirrhosis
Authors: Yoshizawa Kaname , Shirakawa Haruaki , Ichijo Tetsuya , Umemura Takeji , Tanaka Eiji , Kiyosawa Kendo , Imagawa Eri , Matsuda Kazuyuki , Hidaka Eiko , Sano Kenji , Nakazawa Yuichi , Ikegami Toshihiko , Hashikura Yasuhiko , Miyagawa Shinichi , Ota Masao , Nakano Masayuki
Published: August 2010

Abstract:  Since first being described in 1998, de novo autoimmune hepatitis (AIH) after liver transplantation has been reported in several cases suffering from non‐autoimmune liver diseases and primary biliary cirrhosis (PBC). Glutathione S‐transferase (GST) T1 genotype mismatches between donor and recipient have also been suggested to constitute a risk factor for de novo AIH. Here, we report a 33‐yr‐old woman who presented complaining of marked fatigue and jaundice four yr after living‐donor liver transplantation for PBC. On examination, transaminase levels were highly elevated and ANA and antimitochondrial antibody M2 were positive. Histological findings showed zonal necrosis with lymphoplasmacytic infiltration closely resembling AIH. She had pretreatment AIH score of 16 and 19 points after relapse of de novo AIH. Two color fluorescence in situ hybridization with X and Y chromosome‐specific probes clearly revealed that the hepatocytes were of donor origin and lymphocytes were of patient origin. The GSTT1 genotype of the patient and the donor were the same null type, suggesting that mechanisms other than GSTT1 mismatches may exist in de novo AIH development. In conclusion, recipient immune cells attacked the allogeneic transplanted liver of the patient via de novo AIH, although the exact participation of autoimmune mechanisms is unclear.
Late acute rejection after liver transplantation impacts patient survival
Authors: Uemura Tadahiro , Ikegami Toru , Sanchez Edmund Q. , Jennings Linda W. , Narasimhan Gomathy , McKenna Greg J. , Randall Henry B. , Chinnakotla Srinath , Levy Marlon F. , Goldstein Robert M. , Klintmalm Goran B.
Published: August 2010

Abstract:  Hepatic allograft rejection still remains an important problem following liver transplantation. Early acute rejection, occurring within three months of transplant, is a common event and usually of lesser significance with respect to prognosis than other non‐immune‐related post‐transplant morbidities. However, little is known about late acute rejection (LAR) including factors affecting its occurrence and long‐term outcome. In this study, we analyzed LAR including the incidence, clinical risk factors, patient survival, and graft survival. LAR was defined as acute cellular rejection later than six months after liver transplant. Adult patients who had a minimum of 24 months of graft survival were included in this study. A total of 1604 case records of consecutive adult patients (over age 18 yr) who underwent liver transplant between 1985 and 2003 were reviewed. Of the 1604 patients, 305 (19.0%) developed LAR. Patients with primary diagnoses of autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis had higher incidences of LAR, while patients with metabolic disease and retransplant had lower incidence of LAR (p = 0.0024). The LAR group had more female and younger recipients than the no LAR group (p = 0.0026, p = 0.0131, respectively). Patient survival as well as graft survival were significantly lower in the LAR group (p = 0.0083, p = 0.0075, respectively). PTLD was the only significant independent predictor of late rejection. The careful management and treatment of PTLD, especially immunosuppressive management, is important to prevent LAR, which is related to poorer patient survival.
Protein levels of heme oxygenase‐1 during reperfusion in human kidney transplants with delayed graft function
Authors: Öllinger Robert , Kogler Pamela , Biebl Matthias , Sieb Michael , Sucher Robert , Bösmüller Claudia , Troppmair Jakob , Mark Walter , Weiss Helmut , Margreiter Raimund
Published: August 2010

Abstract: Introduction:  Delayed graft function (DGF) as a consequence of ischemia reperfusion injury (IRI) is associated with a decrease in long‐term allograft survival. Heme oxygenase‐1 (HO‐1) is a stress responsive gene that is highly expressed in multiple pathological processes. The aim of our study was to analyze whether HO‐1 protein levels in human kidney transplants during IRI correlate with the incidence of DGF.

Methods:  Kidney biopsies were obtained from 27 kidney allografts at two time points: at the end of cold storage and shortly after reperfusion. Samples were analyzed for HO‐1 protein levels by Western blot.

Results:  Heme oxygenase‐1 protein levels were significantly higher in post‐reperfusion biopsies (39.4 vs. 13.7 arbitrary units, p = 0.001). In pre‐reperfusion biopsies no association was observed between HO‐1 protein levels and DGF. In post‐reperfusion biopsies, higher levels of HO‐1 protein were measured in kidneys with DGF (53.7 vs. 36.2 arbitrary units, p = 0.064). DGF kidneys showed a significantly higher increase from pre‐ to post‐reperfusion in HO‐1 protein (42.0 vs. 18.7 arbitrary units, p = 0.025).

Conclusion:  Heme oxygenase‐1 protein levels shortly after allograft reperfusion are closely related with initial graft function. Assessment thereof may be considered a valuable tool to predict DGF.
Aspergillus flavus myositis in a patient after liver transplantation
Authors: Li Dong Ming , Xiu Dian Rong , Li Ruo Yu , Samson R.A. , De Hoog G.S. , Wang Duan Li
Published: August 2010

Abstract:  We describe the first case of Aspergillus myositis caused by Aspergillus flavus in a liver transplant patient. The patient was a 43‐year‐old man who underwent liver transplantation because of end‐stage hepatic cirrhosis. He experienced pain in his left calf two months after the operation. Nodules with weakness, swelling, and flaring were found in the calf two wk later. Color ultrasonic examination showed uneven resonance in the left gastrocnemius. Needle aspiration and biopsy of the muscle revealed septate hyphae consistent with Aspergillus species and focal necrosis of the muscle cells with inflammatory cell infiltration. A culture subsequently yielded A. flavus, confirming histopathologic diagnosis. Sequencing of the internal transcribed spacer region confirmed the morphologic identification. The patient was first given itraconazole 0.2 g twice daily for one wk and was then switched to terbinafine 0.25 g once a day. A three‐month regimen of terbinafine therapy cured the infection, though the cultured fungus showed resistance to a number of antifungal agents. Aspergillus, a genus of ubiquitous molds, may cause invasive and even fatal disease in immunosuppressed patients.
Determinants and patterns of renin–angiotensin system inhibitors’ prescription in the first year following kidney transplantation
Authors: Thilly Nathalie , Bayat Sahar , Alla François , Kessler Michèle , Briançon Serge , Frimat Luc
Published: August 2010

Abstract:  The benefit of prescribing angiotensin‐converting enzyme inhibitors (ACEi) and angiotensin‐II receptor antagonists (ARB) to kidney transplant recipients remains controversial. We investigated determinants and prescribing patterns of ACEi/ARB during the first year following kidney transplantation. All recipients of a first kidney transplant performed at the university hospital of Nancy (France) between January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription were identified by Cox models among various recipient characteristics (at transplantation and during follow‐up), donor characteristics and transplant parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after transplantation, and 26.9% were taking them at one yr. Recipient determinants of ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre‐transplant hypertension (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post‐transplant proteinuria (HR: 1.62, p < 0.0001) and anemia (HR: 4.08, p < 0.0001). Glomerular filtration rate level was not associated with ACEi/ARB use. Post‐transplant hypercholesterolemia (HR: 0.42, p = 0.013) and higher donor age (HR: 0.98, p = 0.015) were associated with a lower likelihood of ACEi/ARB use. Fewer HLA mismatches (HR: 1.16, p = 0.029) and shorter cold ischemia duration (HR: 1.02, p = 0.045) were also independent predictors of ACEi/ARB use. Regardless of recipient characteristics, nephrologists were more likely to prescribe ACEi/ARB after kidney transplantation when the transplant parameters were favorable.
Pharmacodynamic immune monitoring of NFAT‐regulated genes predicts skin cancer in elderly long‐term renal transplant recipients
Authors: Sommerer Claudia , Hartschuh Wolfgang , Enk Alexander , Meuer Stefan , Zeier Martin , Giese Thomas
Published: August 2010

Abstract:  Introduction:  Among elderly allograft recipients non‐melanoma skin cancer (NMSC) is the most common malignancy. We have previously shown that malignancies are associated with a higher intensity of ciclosporin A (CsA)‐induced immunosuppression.

Method:  Fifty‐five long‐term elderly renal transplant patients with a stable transplant function had regular skin examinations. The expression of the nuclear factor of activated T cells (NFAT)‐regulated genes (interleukin‐2, granulocyte‐macrophage colony stimulating‐factor, interferon‐γ) was determined by real‐time PCR at CsA trough levels and two h after oral intake.

Results:  The CsA dose was 2.0 mg/kg (0.95–3.50), with CsA trough level (C0) level 97 μg/L (33–157) and CsA two‐h level (C2) 538 μg/L (350–1228). NMSC was diagnosed in 14/55 patients (25.4%). A total of 85.7% of allograft recipients with NMSC were male (p < 0.005). Age, time after transplantation, CsA dose, CsA C0 and C2 level were comparable in both groups. NFAT‐regulated gene expression was signficantly lower in patients with skin cancer compared with patients without skin cancer [4.94% (0.91–13.4) vs. 11.6% (3.3–40.8), p < 0.001).

Conclusion:  The unproportional high incidence of NMSC in elderly long‐term kidney‐transplanted patients correlates with a lower NFAT‐regulated gene expression which is a surrogate biomarker for a higher degree of functional immunosuppression. Further studies are required to determine whether the reduction of CsA with an increased NFAT‐regulated gene expression is associated with a lower NMSC incidence.
Excellent outcome using “impaired” standard criteria donors with elevated serum creatinine
Authors: Greenstein Stuart M , Moore Norman , McDonough Patricia , Schechner Richard , Tellis Vivian
Published: August 2010

Abstract:  Introduction:  To maximize organ utilization, the United Network for Organ Sharing (UNOS) encourages use of Expanded Criteria Donors (ECD). However, Standard Criteria Donors (SCD) may also be under‐utilized, some centers discarding kidneys with serum creatinine (S.Cr) >2.0 at nephrectomy. Our experience with the use of such ``impaired’’ kidneys was reviewed retrospectively.

Results:  From January 1, 2003 to October 1, 2006, of 130 DD kidneys transplanted at our center, 26 were ECD. Also, 22 kidneys were from Impaired SCD (ISCD), with mean S.Cr 3.2 (2.1–4.4) at nephrectomy; eight of these had S.Cr >4.0. For these 22 ISCD, mean age was 22 yrs (11–42), sex: 16 Males; race:12 Caucasians/10 African‐Americans; All had evidence of rhabdomyolysis (Mean peak CPK 11,924 u/l). Thirty‐seven percent came from outside OPOs. Recipient demographics: age 45 years; sex 50% male, 45% African‐American. Mean HLA match was 1; dialysis was required in 28% within the first week. Mean length of stay was 10.7 days. Average discharge S.Cr was 4.2. All kidneys are currently functioning (S.Cr at 3 months, 6 months and 1 year 1.6, 1.7 and 1.7 respectively).

Conclusion:  An elevated creatinine should not be the only cause for discarding deceased donor kidneys.
Practical tests for clinical diagnosis of kidney allograft dysfunction
Authors: Miura Masayoshi , Harada Hiroshi , Morooka Kanako , Tanabe Tatsu , Takada Norikata , Seki Toshimori , Togashi Masaki , Hirano Tetsuo
Published: August 2010

Abstract:  Graft dysfunction after renal transplant occurs due to a variety of causes. Graft biopsy is a mainstay in the diagnosis of graft dysfunction, including rejection, infection, glomerulonephritis and drug toxicity. Clinical tests including regular laboratory tests, antibody tests and imaging studies, however, are also important in the process of diagnosis. The possible causes of graft dysfunction are different depending on the period after transplantation. Pre‐transplant donor factors may also affect the early graft function. Perioperative graft dysfunction is mainly related to hemodynamic factors and surgical complications. Early acute rejection may occur in immunologically high‐risk cases. Later graft dysfunction may be related to infection, acute and chronic rejection or drug toxicity. Clinical tests to differentiate these factors are discussed in this paper.
Utility of protocol biopsy for the early diagnosis of transplanted kidney dysfunction
Authors: Ushigome Hidetaka , Sakai Kazuki , Suzuki Tomoyuki , Nobori Syuji , Yoshizawa Atsushi , Kaihara Satoshi , Okamoto Masahiko , Urasaki Koji , Yoshimura Norio
Published: August 2010

Abstract:  We performed protocol kidney biopsies for the early diagnosis of asymptomatic histopathological acute rejection (AR), commonly defined as subclinical rejection and drug nephrotoxicity. Forty‐seven kidney recipients that had asymptomatic and stable kidney function underwent protocol biopsies both one month and one yr after kidney transplantation. The protocol biopsies one month after transplantation revealed borderline change in 13 of 47 cases (27.6%). AR 1a was observed in eight cases (17.2%) and AR 1b was observed in three cases (6.4%). The AR 1a and AR 1b groups were treated with methyl prednisolone pulse and deoxyspergualin. Toxic tubulopathy was found in four cases (8.5%). In the cases of nephrotoxicity, cyclosporine or tacrolimus was reduced. The borderline change group was observed without any additional treatment. Every case diagnosed with acute rejection one month after transplantation improved histopathologically one yr after transplantation, and the borderline change group partially remained borderline change and partially improved histopathologically one yr after transplantation. The nephrotoxicity group improved histopathologically one yr after transplantation. In our institution, protocol biopsies one month and one yr after kidney transplantation proved useful in screening for subclinical rejection and toxic tubulopathy and subsequently effective in improving long‐term graft survival.
Successful treatment of de novo thrombotic microangiopathy after minor ABO‐mismatched living donor kidney transplantation
Authors: Ushigome Hidetaka , Sakai Kazuki , Suzuki Tomoyuki , Nobori Syuji , Yoshizawa Atsushi , Kaihara Satoshi , Okamoto Masahiko , Urasaki Koji , Yoshimura Norio
Published: August 2010

Abstract:  We report a case of thrombotic microangiopathy developing after minor ABO‐mismatched living donor kidney transplantation. The patient was a 57‐yr‐old woman whose blood group was B‐positive. She received a kidney transplant from her husband whose blood group was O‐positive. The recipient human leukocyte antigen haplotype was entirely different from that of the donor and the direct lymphocyte cross‐match test was negative. The patient’s hemoglobin and platelet (Plt) count fell rapidly from 11.0 g/dL and 34 × 104/μL to 6.0 g/dL and 0.4 × 104/μL between days 10 and 15 after kidney transplantation, with no evidence of bleeding. On day 8, anti‐group B IgG and IgM antibodies were found in her serum. This anti‐B antibody was thought to be produced from passenger B lymphocytes in the donor’s kidney. Although in the case of hemolytic anemia after minor mismatched transplantation, the kidney function usually remains stable, the serum creatinine (s‐Cr) rose from 0.8 to 5.2 mg/dL. On day 16, the helmet cells appeared in the serum and a total of 20 units of group O packed red blood cells and 30 units of group O Plts were transfused. Biopsy of the transplanted kidney was performed, which revealed thrombotic microangio‐pathy, and appropriate therapy for DIC was administered, including anticoagulants, and cyclosporine A and mizoribine were replaced with tacrolimus and mycophenolate mofetil. Frequent plasma exchanges (PEX) with fresh frozen plasma were carried out. Furthermore, the anti‐CD20 antibody rituximab was administered, because PEX had no effect. Following the adoption of these measures, the anti‐donor antibodies disappeared to reduce the reaction on flow cytometric cross‐match test; an anti‐groupB antibody did not completely disappear but decreased in titer, and all the symptoms resolved immediately. The graft function recovered to a s‐Cr level of 1.6 mg/dL by 34 d after the transplantation and she was discharged by 36 d after the transplantation. At present, she is entirely healthy and the graft function remains good with a s‐Cr level of 1.1 mg/dL.
Persistent subclinical rejection associated with nodular B‐cell infiltrates in a renal transplant recipient
Authors: Toki Daisuke , Ishida Hideki , Horita Shigeru , Tokumoto Tadahiko , Shimizu Tomokazu , Iizuka Jyunpei , Tunoyama Kuniko , Masumoto Kentaro , Shirakawa Hiroki , Setoguchi Kiyoshi , Iida Shoichi , Tanabe Kazunari , Yamaguchi Yutaka
Published: August 2010

Abstract:  Recently, B‐cell infiltrates in acute rejection grafts have attracted interest as an indicator of refractory rejection. Here, we report a case of deceased donor renal transplantation in a Japanese recipient operated overseas in which the recipient suffered from persistent tubulointerstitial rejection episodes associated with B‐cell infiltrates. A 59‐yr‐old man with end‐stage renal disease caused by immunoglobulin A nephropathy underwent deceased donor renal transplantation overseas in December 2005. The initial post‐operative course was uneventful. The patient was referred to our hospital one month after transplantation. He maintained stable renal function throughout the follow‐up period. The maintenance immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil and methylprednisolone. His serum creatinine concentration remained around 1.0 mg/dL, with no evidence of proteinuria. However, a discrepancy was detected between the renal function and the pathological findings. The pathology showed subclinical tubulointerstitial rejection with nodular B‐cell infiltrates refractory to aggressive antirejection therapy. A steroid pulse and 15‐deoxyspergualin were ineffective and the patient developed interstitial fibrosis and tubular atrophy by one yr after the transplantation, with persistent tubulitis and B‐cell infiltrates. We treated the refractory rejection with B‐cell infiltrates with a single 200 mg/body dose of rituximab and obtained an improvement. The pathological findings after administering rituximab consisted of mild tubulitis classified as Banff borderline, and elimination of the nodular B‐cell infiltrates. At present, 20 months after renal transplantation, the patient continues to maintain stable renal function, with a good serum creatinine concentration (0.87 mg/dL).
Effects of anti‐hypertensive treatment on graft function and proteinuria in a kidney transplant from an elderly hypertensive donor
Authors: Kobayashi Akimitsu , Yamamoto Hiroyasu , Matsuoka Kentaro , Ito Hideyuki , Yamamoto Izumi , Kawamura Yoshimi , Tanno Yudo , Yaginuma Tatsuhiro , Mitome Jun , Hayakawa Hiroshi , Miyazaki Yoichi , Utsunomiya Yasunori , Yamaguchi Yutaka , Hosoya Tatsuo
Published: August 2010

Abstract:  Hypertension is a common complication after kidney transplantation and adversely affects graft and patient survival. Strategies for anti‐hypertensive therapy in an allograft from a hypertensive donor with arteriolosclerosis and the target blood pressure have not been clearly defined. Here, we report the case of deteriorating transplanted kidney function after anti‐hypertensive treatment. A 40‐yr‐old man had received a kidney transplant from a living relative donor (his 69‐yr‐old father), who was hypertensive and had severe arteriolosclerosis. The recipient showed good allograft function immediately (s‐Cr 1.8 mg/dL); however, blood pressure and proteinuria increased markedly two wk after transplantation (blood pressure 180/90, urinary protein 3.4 g/d). We then started anti‐hypertensive agents (a calcium channel blocker and an angiotensin II receptor blocker). Blood pressure and proteinuria were corrected to the normal range within two wk of starting the treatment (blood pressure 130/80, urinary protein 0.3 g/d). However, his kidney function continued to deteriorate (s‐Cr 2.7 mg/dL). A biopsy, performed at that time, revealed glomerular collapse, advanced interstitial fibrosis and severe arteriolosclerosis, with no evidence of rejection. These findings could have been the result of renal allograft hypoperfusion. We then reduced the anti‐hypertensive agents on day 45 after transplantation and observed improved allograft function within a week (s‐Cr 1.6 mg/dL). This case suggests that renal hemodynamic responses may be impaired and renal perfusion may not be appropriately maintained in an allograft with severe arteriolosclerosis at a blood pressure level suitable for the recipient. Anti‐hypertensive treatment should be performed carefully when the allograft is from an elderly hypertensive donor.