Our functional evaluation of AIP mutations is consistent with a tumor-suppressor role for AIP and its involvement in familial acromegaly. The abnormal expression and subcellular localization of AIP in sporadic pituitary adenomas indicate deranged regulation of this protein during tumorigenesis.

SummaryThrombotic microangiopathies (TMAs) are frequently difficult to differentiate clinically, and measurement of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) remains vital in thrombotic thrombocytopenic purpura (TTP) diagnosis. We retrospectively reviewed cases referred for ADAMTS13 testing, using UK TTP Registry screening data. Of a total 810 cases, 350 were confirmed as TTP. The 460 non-TTP cases comprised secondary TMAs (24Á57%) and haemolytic uraemic syndrome (HUS) (27Á17% aHUS, 2Á83% Shiga-like toxin-producing E. coli [STEC]-HUS); the remainder were TMAs with no clear association, not TMAs, or had no confirmed diagnosis. ADAMTS13 levels were significantly lower in TTP than STEC-HUS, aHUS and other TMAs. TTP patients had significantly lower platelet count (15 9 10 9 /l; range 0-96) than aHUS (57 9 10 9 /l; range 13-145, P < 0Á0001) or STEC-HUS (35 9 10 9 /l; range 14-106, P < 0Á0001); they also had lower creatinine levels (92 lmol/l; range 43-374) than aHUS (255 lmol/l; range 23-941, P < 0Á0001) and STEC-HUS (324 lmol/l; range 117-639, P < 0Á0001). However, 12/34 (35Á3%) aHUS patients had a platelet count <30 9 10 9 /l and 26/150 (17Á3%) of TTP patients had a platelet count >30 9 10 9 /l; 23/ 150 (15Á3%) of TTP patients had a creatinine level >150 lmol/l. This study highlights the wide variety of TMA presentations, and confirms the utility of ADAMTS13 testing in TTP diagnosis.

De novo HLA donor specific antibodies (DSA) following transplantation are associated with alloimmune injury and allograft failure. Blood transfusions are allogeneic, and when given posttransplant (PTBT) they may independently increase the risk of HLA antibody development. This study aims to analyse the development of HLA transfusion specific antibodies (TSA) to blood donors of transfusions given post-transplant and examine the impact on clinical outcomes. 244 blood donors of transfusions received by 86 transplant patients (46 who developed a DSA post transfusion and 40 who remained DSA negative) were HLA typed. De novo TSA developed against 150/244(61.5%) blood donors. In 70/150(46.7%) cases the TSA was of shared HLA antibody specificity with a DSA response in the recipient (DSA+=TSA+). This occurred when there was a greater overall HLA match between the blood and transplant donor. DSA+=TSA+ patients had increased risk of allograft failure [p=0•0025] and AMR [p=0•02] compared with the DSA+≠TSA+ patients. To conclude, PTBT may elicit de novo HLA antibodies. Enhanced HLA matching between the blood and transplant donor is more likely to result in a DSA and TSA of shared antibody specificities. Transfusion avoidance or the use of HLA matched or selected blood may reduce this risk and improve outcomes.

Preoperative DM and RI were important predictors of 5-year mortality after CABG. Patients with RI alone had a higher mortality rate than patients with DM alone, but this difference was largely accounted for by age and other comorbidities. The combination of DM and RI doubled the 5-year mortality rate after CABG independently of potential confounding factors.

There are conflicting data about the role of transplant nephrectomy and immunosuppression withdrawal on the development of allosensitization and the impact on re-transplantation. We divided 109 first graft recipients into two groups according to whether they underwent nephrectomy (NX+, n = 61) or their graft was left in situ (NXÀ, n = 48). Sera were assessed for HLA-A/B/Cw/DR/DQ antibodies at the time of NX/transplant failure and after 3, 6, 12, 24 months. The NX+ group showed a higher rate of donor specific antibody (DSA) and non-DSA human leukocyte antigen (HLA) antibody production at all the time points. Multivariable analysis showed that nephrectomy was a strong, independent risk factor for the development of DSAs after 12 and 24 months (P = 0.005 and 0.008). In the NXÀ group, low tacrolimus levels correlated with DSA formation (AUC 0.817, P = 0.002; best cut-off level 2.9 ng/ml). Analysis with a standardized pool of UK donors showed a more difficult grade of HLA matchability following nephrectomy compared with the NXÀ group. Nephrectomy is followed by the long-term production of DSA and non-DSA HLA antibodies and negatively impacts on the chances of finding a HLA-compatible kidney. Tacrolimus levels ≥3 ng/ml are protective against the development of allosensitization and could facilitate re-transplantation in the NXÀ group. Transplant International 2019; 32: 949-959

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The development of AKI after CABG is a serious event associated with worse midterm survival. This excess mortality cannot be explained simply by coexisting comorbidity and surgical complexity.

BackgroundClinical practice guidelines (CPGs) are widely used to inform the development of protocols for clinical management. Previous work has demonstrated that the quality of CPGs varies widely. This systematic review aimed to determine the quality of CPGs in kidney transplantation in the UK.MethodsCPGs in kidney transplantation published between 2010 and 2017 were identified through searches of MEDLINE, NHS NICE Evidence, and websites of relevant UK societies. Using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool, three appraisers rated the quality of CPGs across six domains, the overall quality of each CPG, and whether it should be recommended for future use. Domain scores were calculated, and inter‐rater reliability using the intraclass correlation coefficient (ICC) was reported.ResultsThirteen CPGs met the inclusion criteria. The domain ‘clarity of presentation’ scored highest, followed closely by ‘scope and purpose’. The poorest scoring domains were ‘applicability’ and ‘editorial independence’. Editorial independence also had the widest range of scores. Of the 13 CPGs, one was not recommended for future use, seven were recommended for use with modifications, and five for future use with no need for modification. Mean overall CPG quality was 5 (range 3–6) of a maximum score of 7, and mean inter‐rater reliability was substantial with an ICC of 0·71.ConclusionUK CPGs scored satisfactorily, although with wide variation in how well each domain scored both within and across CPGs. The quality of UK CPGs can still be improved.