Renal transplantation in pre-school children

This short report describes the outcome of 13 renal transplants in 11 children under 5 years of age. Nine (82%) of the 11 recipients are alive; 2 children died with functioning grafts. Approximately 50% of grafts are functioning at 5 years post transplantation. Children with congenital kidney malformations can be successfully managed to transplantation.     

BK Polyomavirus Subtype III in a Pediatric Renal Transplant Patient with Nephropathy

BK polyomavirus (BKV) is an emerging pathogen in immunocompromised individuals. BKV subtype III is rarely identified and has not previously been associated with disease. Here we provide the whole-genome sequence of a subtype III BKV from a pediatric kidney transplant patient with polyomavirus-associated nephropathy.     

Venous Thromboembolism in Pediatric Hematopoietic Cell Transplant: A Multicenter Cohort Study

Hematopoietic cell transplant (HCT) is associated with a proinflammatory, procoagulant environment that places recipients at increased risk of venous thromboembolism (VTE). Although the incidence of VTE in adult HCT recipients has been extensively studied, similar data for children are lacking. We conducted a multicenter retrospective study to analyze the prevalence of VTE and associated risk factors in a large cohort of patients who underwent HCT at tertiary care US children's hospitals. The Pediatric Health Information System database, a large administrative database that contains clinical and resource utilization data from 49 freestanding children's hospitals in the United States, was used to extract data. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify HCT recipients, VTE events, post-HCT complications, and associated risk factors up to 1 year post-transplant. Data on patients who received HCT from January 2010 through September 2014 were collected. A total of 4158 unique patients mean ± standard deviation age at transplant admit, 8.8 ± 6.5 years; range, birth to 33.4 years) were identified. After HCT 290 subjects (6.9%) developed VTE. VTE prevalence was greater in patients aged ≥ 13 versus <13 years (8.54% versus 6.33%; P = .01) and in recipients of allogeneic versus autologous grafts (7.7% versus 5%; P ≤ .01). VTE was associated with prolonged median duration of hospitalization (81 versus 54 days; P ≤.01) and increased 1-year mortality (13.9% versus 5.9%; P ≤ .01). Infections and presence of any graft-versus-host disease (GVHD) were significantly associated with VTE occurrence in recipients of allogenic grafts. Prevalence of VTE in patients who underwent HCT at pediatric tertiary care hospitals is about 7%. Age ≥ 13 years and allogeneic grafts were significant pre-HCT VTE risk factors, with GVHD and infections seen more frequently in patients with VTE.     

肾移植患者环孢素A血药浓度监测的临床分析

目的：研究肾移植术后患者环孢素A（CsA）浓度与临床疗效之间的关系。方法：采用荧光偏振免疫法。结果：正常组分别与中毒组、排异组之间血药浓度有显著性差异。结论：环孢素A血药浓度监测必须结合临床，综合考虑各方面的因素，实现个体化给药。     

Induction Therapy in Renal Transplant Recipients: A Review

Transplant science has improved significantly over the last decade. Influenced by novel advancements, rejection rates and short-term graft losses diminished substantially. Induction therapy was shown to reduce rejection rates and improve short-term graft survival. In this article, we discuss the most commonly used induction agents and the choice of induction therapy in different renal transplant recipient subgroups. The medical literature as well as our own experience was used to prepare this review. At this time, induction therapy is commonly used in upwards of 80%, of renal transplant recipients. Depleting agents are the most frequently used agents and they account for more than 75% of all induction therapies in the United States. Currently, there is no consensus regarding the choice of induction therapy. The type of induction therapy is generally selected based on a comprehensive evaluation of the recipient and the donor’s immunological risks, the risk of developing opportunistic infection and malignancy, recipient comorbidities, financial burden and the choice of maintenance immunosuppressive regimen.     

Rejection of an HL—A Identical Renal Transplant

A 38-year-old man suffering from chronic glomerulonephritis received a kidney from his HL—A identical sister. The HL—A identity was fully established by tissue typing with well-specified antisera and by mixed lymphocyte culture tests. One year after transplantation kidney function deteriorated, and repeated biopsies of the transplant, I¹³¹-Hippuran renography, and arteriography showed that the kidney was undergoing a chronic rejection. It is suggested that incompatibilities with regard to weak histocompatibility systems might have been responsible for the rejection of a human kidney.     

Renal tumours in children.

A ten-year series of renal tumours in children up to 14 years of age was collected from the files of the Finnish Cancer Register. After histological evaluation of the material, 74 cases were accepted as primary renal tumours. Fifty-eight of these were typical Wilms' tumours, three rhabdomyosarcomas, six foetal hamartomas and seven unclassified malignant tumours. Wilms' tumours were classified into three types on the basis of the histological differentiation. The total five year survival in the Wilms group was 50 per cent with no difference between patients over and under the age of one year. Of the subtypes of Wilms' tumours the sarcomatous type showed worse prognosis than average; only three out of 16 patients were alive after a five-year follow-up time. None of the patients with foetal hamartoma died of tumour, although two fatalities, connected with the surgery, were recorded. The value of histological classification of Wilms' tumours and the importance of the recognition of the foetal hamartoma is emphasized.     

A Case of Enterocytozoon bieneusi Infection in an HIV-Negative Renal Transplant Recipient

 Reported here is a case of microsporidiosis that occurred in an HIV-negative renal transplant recipient. The patient developed protracted diarrhea 18 months following transplant surgery. Many spores of Enterocytozoon bieneusi were detected in stool smears using a modified trichrome staining method. Identification was confirmed using the polymerase chain reaction. Histological examination of duodenal biopsies revealed numerous spores in the cytoplasm of enterocytes. Tacrolimus and steroid regimens were decreased, treatment with mycophenolate mofetil was discontinued, and the patient was given albendazole and metronidazole for 2 weeks. The diarrhea resolved after 15 days of treatment; 2 months later the patient had recovered completely. A more systematic search for microsporidia using specific staining procedures should be performed in transplant recipients who develop severe diarrhea.     

Role of Electron Microscopy in Transplant Renal Pathology

The crucial role that electron microscopy plays in diagnostic renal pathology is undisputed. By allowing recognition of findings not identifiable by light microscopic evaluation, electron microscopy has contributed significantly to the understanding of renal diseases and has proven to be of unquestionable value in many diagnostic situations. However, the percentage of cases in which electron microscopic examination adds important information that is either key for establishing or confirming a diagnosis or provides valuable data that influence patient's management remains controversial. This figure depends on the renal biopsy service that is surveyed, but it is reported that on the average ultrastructural evaluation is of value in approximately 30 to 45% of the cases. Correct interpretation of a renal biopsy depends on the ability to correlate light, immunofluorescence, and ultrastructural findings. In contrast, the role of electron microscopy in the examination of renal transplant specimens remains controversial. Many centers do not use routine electron microscopy to examine these specimens and insist that there are only a few specific indications that require ultrastructural evaluation. There is general agreement among renal pathologists that electron microscopy is of importance in the evaluation of renal specimens from patients with proteinuria to distinguish between transplant glomerulopathy, recurrent or de novo glomerulonephritis in order to correctly manage these patients and predict survival of the graft. The other possible indications are much more controversial. This paper summarizes and critically reviews the literature available on this subject and defines recommendations based on the information available at the current time.     

Renal pathology in hematopoietic cell transplantation recipients.

Hematopoietic cell transplantation-associated renal injury may be related to a combination of factors including chemotherapy, radiation, infection, immunosuppressive agents, ischemia, and graft-versus-host disease. Renal biopsy specimens from hematopoietic cell transplant recipients at two institutions (Stanford University Medical Center and Oregon Health & Science University) were reviewed in correlation with clinical data. Fifteen cases were identified (post hematopoietic cell transplant time 0.7-14.5 years), including six with autologous hematopoietic cell transplant. Indications for renal biopsy included proteinuria (n=13; nephrotic range in 8), increased serum creatinine (n=10), or both (n=6). Many patients had multiple pathologic findings on renal biopsy. Membranous glomerulonephritis was the most common diagnosis (n=7), including two patients with autologous hematopoietic cell transplant and five with evidence of chronic graft-versus-host disease elsewhere. Four membranous glomerulonephritis patients achieved sustained remission with rituximab therapy. Other glomerular pathology included focal segmental glomerulosclerosis (n=1) and minimal change disease (n=1). Evidence of thrombotic microangiopathy was common (in isolation or combined with other pathology), as was acute tubular necrosis and tubulointerstitial nephritis. Of 14 patients with follow-up (2-64 months, mean 19 months), 6 had chronic renal insufficiency (serum creatinine >1.5 mg/dl), 2 had end stage renal disease, and 6 had essentially normal renal function. Our retrospective study shows that renal dysfunction in hematopoietic cell transplant recipients is often multifactorial, and biopsy may reveal treatable causes. Membranous glomerulonephritis is seen in autologous and allogeneic hematopoietic cell transplant recipients, and may respond to anti-B-cell therapy, which has implications regarding pathogenesis and relationship to graft-versus-host disease.     

A Comparison of HLA Data of the North American Black with African Black and North American Caucasoid Populations

For purposes of genetic comparison, the available HLA data on United States and African Black, together with United States Caucasoid populations, are summarized. Antigen frequencies and pairwise linkage disequilibria are presented for the HLA-A, -B and -C loci in Black populations typed for the 1975 Histocompatibility Testing Workshop. The Black population samples comprise 356 North American Blacks and 411 African Blacks of whom 222 were Bantu. These are compared with a sample of 503 American Caucasoids. All significant linkage disequilibria between the A and B loci found in North American Blacks were also present in the North American Caucasoids. Between the B and C loci, Bw35 and Cw4 were in strong linkage disequilibrium in all groups. Significantly stron association between the A and C loci (Aw28 with Cw3) were observed only in the African Blacks. There were unique disequilibria both in the American Caucasoids and African Blacks. Although the frequencies of many antigens in U.S. Blacks lie between those in Africans and U.S. Caucasoids, there are exceptions such as Aw33, Bw35, Cw4.     

Withdrawal of Immunosuppression in Pediatric Liver Transplant Recipients in Korea

Purpose

We identified pediatric liver transplant recipients with successful withdrawal of immunosuppression who developed tolerance in Korea.

Materials and Methods

Among 105 pediatric patients who received liver transplantation and were treated with tacrolimus-based immunosuppressive regimens, we selected five (4.8%) patients who had very low tacrolimus trough levels. Four of them were noncompliant with their medication and one was weaned off of immunosuppression due to life threatening posttransplant lymphoproliferative disorder. We reviewed the medical records with regard to the relationship of the donor-recipients, patient characteristics and prognosis, including liver histology, and compared our data with previous reports.

Results

Four patients received the liver transplantation from a parent donor and one patient from a cadaver donor. A trial of withdrawal of the immunosuppressant was started a median of 45 months after transplantation (range, 14 months to 60 months), and the period of follow up after weaning from the immunosuppressant was a median of 32 months (range, 14 months to 82 months). None of the five patients had rejection episodes after withdrawal of the immunosuppression; they maintained normal graft function for longer than 3 years (median, 38 months; range, 4 to 53 months). The histological findings of two grafts 64 and 32 months after weaning-off of the medication showed no evidence of chronic rejection.

Conclusion

The favorable markers for successful withdrawal of immunosuppression were 1) long-term (> 3 years) stable graft function, 2) no rejection for longer than 1 year after withdrawal of immunosuppression, 3) non-immune mediated liver diseases, and 4) pediatric patients.     

Histopathological evidence of North American blastomycosis in Italy: report of two cases

No clinical reports of blastomycosis in Italy have been published until now. We here report two cases of histologically diagnosed, unexpected cutaneous involvement in patients, aged 78 and 52 years, living in North Italy and never having been abroad. The histological differential diagnosis between blastomycosis and other fungal pathogens is discussed. Even in the absence of culture the present cases can confidently be considered as genuine examples of Blastomyces dermatitidis infection in Italy.     

A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators

BACKGROUND: Patients with Crohn's disease often have relapses. Better treatments are needed for the maintenance of remission. Although methotrexate is an effective short-term treatment for Crohn's disease, its role in maintaining remissions is not known. METHODS: We conducted a double-blind, placebo-controlled, multicenter study of patients with chronically active Crohn's disease who had entered remission after 16 to 24 weeks of treatment with 25 mg of methotrexate given intramuscularly once weekly. Patients were randomly assigned to receive either methotrexate at a dose of 15 mg intramuscularly once weekly or placebo for 40 weeks. No other treatments for Crohn's disease were permitted. We compared the efficacy of treatment by analyzing the proportion of patients who remained in remission at week 40. Remission was defined as a score of 150 or less on the Crohn's Disease Activity Index. RESULTS: Forty patients received methotrexate, and 36 received placebo. At week 40, 26 patients (65 percent) were in remission in the methotrexate group, as compared with 14 (39 percent) in the placebo group (P=0.04; absolute reduction in the risk of relapse, 26.1 percent; 95 percent confidence interval, 4.4 percent to 47.8 percent). Fewer patients in the methotrexate group than in the placebo group required prednisone for relapse (11 of 40 [28 percent] vs. 21 of 36 [58 percent], P=0.01). None of the patients who received methotrexate had a severe adverse event; one patient in this group withdrew because of nausea. CONCLUSIONS: In patients with Crohn's disease who enter remission after treatment with methotrexate, a low dose of methotrexate maintains remission.