Desensitization and crossmatch conversion in deceased donor kidney transplantation.

Recipient allosensitization represents a major barrier to transplantation. Sensitized patients awaiting a deceased donor kidney transplant often face unacceptably long waiting times and are more prone to rejection, even in the absence of a positive crossmatch (XM). Two major strategies have been shown to facilitate the access to transplantation: specific allocation programs designed to enhance the availability of a well-matched allograft; and recipient desensitization to decrease levels of humoral alloreactivity. Over the last two to three decades, a variety of desensitization strategies have been published. Such protocols are based on the use of apheresis for direct alloantibody removal from the circulation, or high dose intravenous immunoglobulin and/or CD20 antibody rituximab for modulation of B cell immunity. An attractive approach may be the application of apheresis for rapid desensitization, with or without XM conversion, immediately before transplantation, a particular challenge because of the short interval between the transplant offer and surgery. It was shown that with currently available treatment strategies many high risk patients can be successfully transplanted within an acceptable time period. However, there is still a need for further improvement, as rejection and graft loss rates may be considerably higher than those documented for non-sensitized patients. Future studies will have to establish more precise diagnostic criteria to optimize treatment allocation and monitoring. Moreover, systematic trials are needed to assess the efficiency of innovative treatment concepts, such as the use of agents that directly affect alloantibody-producing plasma cells.

Peritransplant immunoadsorption for positive crossmatch deceased donor kidney transplantation.

Various desensitization protocols were shown to enable successful living donor kidney transplantation across a positive complement-dependent cytotoxicity crossmatch (CDCXM). Positive crossmatch transplantation, however, is less well established for deceased donor transplantation. We report a cohort of 68 deceased donor renal allograft recipients who, on the basis of broad sensitization (lymphocytotoxic panel reactivity ≥40%), were subjected to a protocol of peritransplant immunoadsorption (IA). Treatment consisted of a single session of immediate pretransplant IA (protein A) followed by posttransplant IA and antilymphocyte antibody therapy. Twenty-one patients had a positive CDCXM, which could be rendered negative by pretransplant apheresis. Solid phase HLA antibody detection revealed preformed donor-specific antibodies (DSA) in all 21 CDCXM-positive and in 30 CDCXM-negative recipients. At 5 years, overall graft survival, death-censored graft survival and patient survival were 63%, 76% and 87%, respectively, without any differences between CDCXM-positive, CDCXM-negative/DSA-positive and CDCXM-negative/DSA-negative recipients. Furthermore, groups did not differ regarding rates of antibody-mediated rejection (24% vs. 30% vs. 24%, p = 0.84), cellular rejection (14% vs. 23% vs. 18%, p = 0.7) or allograft function (median 5-year serum creatinine: 1.3 vs. 1.8 vs. 1.7 mg/dL, p = 0.62). Our results suggest that peritransplant IA is an effective strategy for rapid desensitization in deceased donor transplantation.

Posttransplant HLA alloreactivity in stable kidney transplant recipients-incidences and impact on long-term allograft outcomes.

Humoral alloreactivity is well established to predict adverse allograft outcomes. However, in some recipients, alloantibodies may also occur in the absence of graft dysfunction. We evaluated if and how often complement- and noncomplement-fixing alloantibodies are detectable in stable recipients and whether, in this context, they affect long-term outcomes. Sera obtained from 164 kidney transplant recipients at 2, 6 and 12 months were evaluated by FlowPRA screening and single-antigen testing for detection of IgG- or C4d-fixing HLA panel reactivity and donor-specific antibodies (DSA). Applying stringent criteria, we selected 34 patients with an uneventful 1-year course (no graft dysfunction or rejection) and excellent graft function at 12 months [estimated glomerular filtration rate (eGFR) >or=60 mL/min and proteinuria

In vitro detection of C4d-fixing HLA alloantibodies: associations with capillary C4d deposition in kidney allografts.

Capillary C4d deposition is a valuable marker of antibody-mediated rejection (AMR). In this analysis, flow cytometric detection of alloantibody-triggered C4d deposition to HLA antigen-coated microparticles ([C4d]FlowPRA) was evaluated for its value as a marker for C4d deposition in renal allografts. For comparative analysis, 105 first renal biopsies performed for graft dysfunction and an equal number of concurrent sera were subjected to immunohistochemistry and [C4d] plus standard [IgG]FlowPRA, respectively. C4d deposition/fixation was detected in 17 biopsies and, applying [C4d]FlowPRA HLA class I and II screening, also in a small number of corresponding sera (N = 20). IgG reactivity detected by standard [IgG]FlowPRA was more frequent (49% of sera). Comparing [C4d]FlowPRA screening with capillary C4d staining, we found a high level of specificity (0.92 [95% confidence interval: 0.86-0.98]), which far exceeded that calculated for [IgG]FlowPRA (0.60 [0.50-0.70]). [IgG]FlowPRA screening, however, turned out to be superior in terms of sensitivity (0.94 [0.83-1.05] vs. 0.76 [0.56-0.97] calculated for C4d-fixing panel reactivity). Remarkably, posttransplant single antigen testing for identification of complement-fixing donor-specific alloreactivities failed to improve the predictive value of FlowPRA-based serology. In conclusion, our results suggest that detection of complement-fixing HLA panel reactivity could provide a specific tool for monitoring of C4d-positive AMR.

Supine/left decubitus scanning: a valuable alternative to supine/prone scanning in CT colonography.

The purpose was to evaluate supine/left decubitus as an alternative to supine/prone scanning in computed tomographic colonography (CT colonography). Fifty patients were randomised to supine/prone, another 50 to supine/left decubitus scanning. Patients were scanned using a single-slice CT scanner. The colon was divided into eight segments. Comparisons of distension, breathing artefacts, residus and polyp detection were made between the two groups as well as between the different positions. Adequate distension was found in approximately 85, 97 and 95% of segments in the supine, prone and left decubitus positions, respectively. Combined scanning increased the percentage of adequate distension to 98.5% for prone-supine and 97.7% for left decubitus-supine scanning ( P<0.0005 compared to supine, P=0.001 compared to left decubitus and P=0.046 compared to prone scanning). Absence of residual material was found in approximately 62.7, 69.7 and 64% of segments in the supine, prone and left decubitus positions, respectively. Combined scanning increased this percentage to approximately 99% for both groups. No significant differences towards distension or residual material were found between combined supine-prone or supine-left decubitus scanning. In the supine-prone group, combined scanning additionally revealed four lesions and improved conspicuity in two cases of stalked polyps. In the supine-left decubitus group, combined scanning additionally revealed two lesions and improved conspicuity in one stalked polyp. There were significantly fewer breathing artefacts with left decubitus scanning than prone scanning ( P=0.005). A strong positive correlation was found between breathing artefacts and the age of patients in both patient groups. Colonic distension and preparation is improved by using supine and prone or supine and left decubitus scanning in combination, with a subsequent improved polyp detection. There were no significant differences between the two scanning protocols. Prone scanning, however, is hampered by breathing artefacts, especially in the elderly. Therefore, supine-left decubitus scanning is considered a valuable alternative to supine-prone scanning for the elderly.

Dietary fecal tagging as a cleansing method before CT colonography: initial results polyp detection and patient acceptance.

PURPOSE: To compare reduced colonic cleansing based on dietary fecal tagging (FT) with standard (non-FT) colonic cleansing with regard to patient acceptance, sensitivity, and specificity. MATERIALS AND METHODS: In 50 patients (FT group), FT was performed by means of diet, magnesium citrate, and a barium suspension. In another 50 patients (non-FT group), preparation was based on polyethylene glycol administration. All patients underwent conventional colonoscopy after computed tomographic (CT) colonography. Sensitivity and specificity for polyp detection were calculated by using conventional colonography as the reference standard. At CT colonography, fecal residue was evaluated. Patients were interviewed to determine discomfort, side effects, sleep quality, final opinion on examination comfort, and whether they would be reluctant to undergo the same examination again. RESULTS: FT left more fecal residue but improved differentiation from polyps (FT specificity, 88% [30 of 34 patients]; non-FT, 77% [23 of 30 patients]). Sensitivities were comparable: FT, 88% (14 of 16 patients); non-FT, 85% (17 of 20 patients). FT significantly reduced discomfort, side effects, and sleep disturbance, and resulted in an improved final opinion of how comfortable the examination was (P <.05). Although FT improved patient willingness to repeat the examination, this improvement was not statistically significant (P >.05). CONCLUSION: FT offers the patient a well-tolerated preparation and improves specificity, with improved differentiation of polyps from residual stool.

Thyropathic endemic dystrophy in an area of the Arges Valley.

The authors carried out a clinical, chemical and medico-social study of an endemic focus in the Arges Valley. Iodine deficiency and partially water hardness constitute the main goitrogenic factors. Owing to the curative-prophylactic means, the goitre frequency substantially decreased in school children (from 98.5% in 1949 to 18.3% in 1969) and serious forms of the third degree did not occur in the last 14 years. A certain percentage of diffuse goitre still remains in school children besides the residual pathology before the iodized prophylaxis. In the period when the prophylaxis with KI (potassium iodine) troches was neglected, a slight increase of goitre frequency was found in the investigated groups.