Immunological risk stratification and tailored minimisation of immunosuppression in renal transplant recipients.

BACKGROUND: The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear. METHODS: This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010-June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression. RESULTS: Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk). CONCLUSIONS: Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Outcomes following kidney transplantation in patients with sickle cell disease: The impact of automated exchange blood transfusion.

There are over 12,000 people with sickle cell disease (SCD) in the UK, and 4-12% of patients who develop Sickle Cell Nephropathy (SCN) progress to End Stage Renal Disease (ESRD). Renal transplantation offers the best outcomes for these patients with but their access to transplantation is often limited. Regular automated exchange blood transfusions (EBT) reduce the complications of SCD and may improve outcomes. However, concerns over alloimmunisation limit its widespread implementation. In this retrospective multicenter study, data were collected on 34 SCD patients who received a kidney transplant across 6 London Hospitals between 1997 and 2017. 20/34 patients were on an EBT program, pre or post renal transplantation. Overall patient and graft survival were inferior to contemporaneous UK data in the ESRD population as a whole, a finding which is well-recognised. However, patient survival (CI 95%, p = 0.0032), graft survival and graft function were superior at all time-points in those who received EBT versus those who did not. 4/20 patients (20%) on EBT developed de novo donor specific antibodies (DSAs). 3/14 patients (21%) not on EBT developed de novo DSAs. The incidence of rejection in those on EBT was 5/18 (28%), as compared with 7/13 (54%) not on EBT. In conclusion, our data, while limited by an inevitably small sample size and differences in the date of transplantation, do suggest that long-term automated EBT post renal transplant is effective and safe, with improvement in graft and patient outcomes and no increase in antibody formation or graft rejection.

Summary of the British Transplantation Society UK Guidelines for Hepatitis E and Solid Organ Transplantation.

The incidence and prevalence of hepatitis E virus (HEV) infection has increased in many developed countries over the last decade, predominantly due to infection with genotype 3 (G3) HEV. Infection with HEV G3 is important in transplant recipients because it can persist in immunosuppressed individuals, leading, if untreated, to the development of chronic hepatitis and significant liver fibrosis. The British Transplantation Society (BTS) has developed Guidelines for "Hepatitis E and Solid Organ Transplantation" to inform clinical teams and patients about hepatitis E, to help increase the recognition of persistent hepatitis E infection, and to provide clear guidance on its management. This guideline was published on the BTS website in June 2017 and aims to review the evidence relating to the diagnosis and management of persistent hepatitis E in solid organ transplant recipients and the methods of prevention of HEV infection. In line with previous guidelines published by the BTS, the guideline has used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to rate the strength of evidence and recommendations. This article includes a summary overview of hepatitis E and transplantation with key references, and the statements of recommendation contained within the guideline. It is recommended that the full guideline document is consulted for complete details of the relevant references and evidence base. This may be accessed at https://bts.org.uk/guidelines-standards/.

Summary of the British Transplantation Society Guidelines for Management of the Failing Kidney Transplant.

The British Transplantation Society "Guideline for Transplantation Management of the Failing Kidney Transplant" was published in May 2014. This is the first national guideline in this field. In line with previous guidelines published by the British Transplantation Society, the guideline has used the GRADE system to rate the strength of evidence and recommendations.This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for the management of the failing kidney graft in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at: http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Guidelines.aspx.

Summary of the British Transplantation Society guidelines for transplantation from donors after deceased circulatory death.

The second edition of the British Transplantation Society Guidelines for Transplantation from Donors after Deceased Circulatory Death was published in June 2013. The guideline has been extensively revised since the previous edition in 2004 and has used the GRADE system to rate the strength of evidence and recommendations. This article summarizes the Statements of Recommendation contained in the guideline, which provide a framework for transplantation after deceased circulatory death in the U.K. and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at: http://www.bts.org.uk/MBR/Clinical/Guidelines/Current/Member/Clinical/Current_Guidelines.aspx.

Summary of the British Transplantation Society/Renal Association U.K. guidelines for living donor kidney transplantation.

The third edition of the joint British Transplantation Society/Renal Association guidelines for living donor kidney transplantation was published in May 2011. The guideline has been extensively revised since the previous edition in 2005 and has used the GRADE system to rate the strength of evidence and recommendations. This article summarizes the statements of recommendation contained in the guideline, which provide a framework for the delivery of living kidney donation in the United Kingdom and may be of wide international interest. It is recommended that the full guideline document is consulted for details of the relevant references and evidence base. This may be accessed at http://www.bts.org.uk/transplantation/standards-and-guidelines/ and http://www.renal.org/clinical/OtherGuidelines.aspx (transplantation is welcome to add a web link in this article to/through its own Web site to increase traffic).

Summary of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease After Solid Organ Transplantation.

The third edition of the British Transplantation Society Guidelines for the Prevention and Management of CMV Disease after Solid Organ Transplantation was published in March 2011. This article summarizes the important changes and advances in management in this rapidly evolving field. The pros and cons of universal, or targeted anti-cytomegalovirus (CMV) prophylaxis, and pre-emptive anti-CMV therapy are discussed, especially with respect to advances in CMV polymerase chain reaction monitoring. The evidence for oral anti-CMV prophylaxis using valganciclovir is presented, together with a summary of the treatment of CMV disease and emerging fields such as CMV vaccination, CMV genotyping, and drug resistance.

Testis morphology in patients with idiopathic hypogonadotropic hypogonadism.

BACKGROUND: Adult patients with idiopathic hypogonadotropic hypogonadism (IHH) typically present with absent puberty and therefore have prepubertal testes. IHH is recognized as one of the few curable causes of male infertility and is often effectively treated with either gonadotropins or pulsatile GnRH therapy. The objective of this study was to determine the structure of the testis prior to initiation of treatment. METHODS AND RESULTS: Eight adult IHH patients with prepubertal testes (<4 ml), with no previous gonadotropin therapy and with no history of cryptorchidism underwent open bilateral testicular biopsy prior to the initiation of hormonal treatment. The testes of all patients showed seminiferous cords separated by interstitium composed of blood vessels, connective tissue cells and collagen fibres but typical adult Leydig cells were absent. The cords contained only Sertoli cells and early type A spermatogonia. The spermatogonia mostly resided in the centre of the cords and were often large, typical of gonocytes. Sertoli cells appeared immature with ovoid nuclei devoid of infoldings and cytoplasm that lacked polarity. Tight junctional complexes commonly found connecting adult Sertoli cells were lacking. CONCLUSIONS: These results demonstrate that the immature testes from patients with the severe form of IHH possess early spermatogonia that could possibly reinitiate spermatogenesis with appropriate hormone stimulation. Therefore, the immature testis of this IHH subset resembles those of prepubertal boys and may provide important biologic and genetic insights into testicular development.

AA amyloidosis complicating hyperimmunoglobulinemia D with periodic fever syndrome: a report of two cases.

AA amyloidosis is the most serious potential complication of the inherited autoinflammatory syndromes and frequently results in end-stage renal failure. Although this complication is well recognized in familial Mediterranean fever, tumor necrosis factor receptor-associated periodic syndrome, and Muckle-Wells syndrome, there is only 1 previous published report of its occurrence in hyperimmunoglobulinemia D with periodic fever syndrome (HIDS). We report 2 further cases of patients with AA amyloidosis in HIDS, both of whom developed dialysis-dependent renal failure, and we describe the outcome of the first renal transplant in this setting.