Clinical outcomes after ABO-incompatible renal transplantation: a systematic review and meta-analysis.

BACKGROUND: ABO-incompatible renal transplantation (ABOi-rTx) is increasingly used to overcome organ shortage. Evidence about its non-inferiority in comparison with ABO-compatible renal transplantation (ABOc-rTx) needs to be analysed at early and late timepoints. We aimed to investigate differences in outcome after ABOi-rTX and ABOc-rTX. METHODS: We did a systematic review and meta-analysis of observational studies published up until Dec 31, 2017, that reported outcome data (≥1 year of follow-up) after ABOi-rTx and included an ABO-compatible control group, by searching the Cochrane Central Register of Controlled Trials (CENTRAL), Embase Ovid, MEDLINE Ovid, and PubMed. Trials on recipients of ABOi-rTx were assessed, if an ABO-compatible control group was included and if outcome data on at least graft or recipient survival with 1 year or more of follow-up were available. Exclusion criteria included case reports, editorials, reviews and letters, animal studies, meeting papers, studies unable to extract data, non-renal solid organ and bone-marrow transplant studies, and deceased donor ABOc-rTx. Data were extracted from published reports. Primary endpoints were all-cause mortality and graft survival at 1, 3, 5, and more than 8 years after transplantation. In the meta-analysis, we used a fixed-effects model if the I2 value was 0, and both a fixed-effects and random-effects model if I2 was more than 0. This study is registered with PROSPERO, number CRD42018094550. FINDINGS: 1264 studies were screened and 40 studies including 49 patient groups were identified. 65 063 patients were eligible for analysis, 7098 of whom had undergone ABOi-rTx. Compared with ABOc-rTx, ABOi-rTx was associated with significantly higher 1-year mortality (odds ratio [OR] 2·17 [95% CI 1·63-2·90], p<0·0001; I2=37%), 3 years (OR 1·89 [1·46-2·45], p<0·0001; I2=29%), and 5 years (OR 1·47 [1·08-2·00], p=0·010; I2=68%) following transplantation. Death-censored graft survival was lower with ABOi-rTx than with ABOc-rTx at 1 year (OR 2·52 [1·80-3·54], p<0·0001; I2=61%) and 3 years (OR 1·59 [1·15-2·18], p=0·0040; I2=58%) only. Graft losses were equivalent to that of ABOc-rTx after 5 years and patient survival after 8 years. No publication bias was detected and the results were robust to trial sequential analysis until 5 years after transplantation; thereafter, data became futile or inconclusive. INTERPRETATION: Despite progress in desensitisation protocols and optimisation of ABOi-rTx procedures, excess mortality and loss of kidney grafts was found compared with ABOc-rTx within the first 3 years after transplantation. Only long-term outcomes after 5 years yielded equivalent survival rates and organ function. Awareness of the increased risks of infection, organ rejection, and bleeding could improve care of patients and promote efforts towards paired kidney exchange programmes. FUNDING: None.

Clinical and radiological findings in long-term intracranial pressure monitoring.

BACKGROUND: Advantages of telemetric devices for long-term intracranial pressure (ICP) measurement have been mentioned several times in the literature. However, descriptions of associated complications are lacking. Therefore, the presented observational study focused on clinical and radiological findings after insertion of an intraparenchymal telemetric ICP monitor. METHODS: Between April 2010 and February 2013, 185 telemetric ICP catheters were implanted for diagnostic purposes. All patients were clinically followed. Radiological, microbiological and clinical data were analysed. RESULTS: One brain abscess (0.5 %) and two cutaneous infections (1.1 %) occurred in 185 patients. Staphylococcus spp. could be detected in all cases. Six patients (3.2 %) suffered from single new-onset seizures and one patient (0.5 %) from a temporary hemiparesis. Intracerebral haemorrhages occurred in 15.6 %, most of the time as small punctate bleedings. Perifocal oedematous reactions surrounding inserted telemetric catheters could be observed in 46.9 %. Multiple imaging studies revealed a tendency of complete oedema resolution over time. CONCLUSIONS: Infectious as well as haemorrhagic complication rates are well comparable with the common literature. The long-term implantation of an ICP probe does not seem to increase the risk of wound infections or brain abscess formation. Surprisingly, very high numbers of oedematous reactions after insertion of the intraparenchymal ICP monitor were seen. Reasons therefore could only be speculated upon.

Altered monocytic phenotypes are linked with systemic inflammation and may be linked to mortality in dialysis patients.

The major causes for increased morbidity and mortality among chronic kidney disease patients are cardiovascular diseases and infection. A causal link between an activated immune system and aggravated atherosclerosis has been postulated that skews the system towards inflammatory responses. Previously, we demonstrated a positive association of pro-inflammatory cytokines with monocytic Y-box binding protein-1 (YB-1) expression and vessel wall infiltration in hemodialysis patients. Here, we question whether the responsiveness and cytokine repertoire of monocytes is altered by pre-activation and how this correlates with survival. EDTA whole blood from hemodialysis patients (n = 45) and healthy controls (n = 34) was collected and leukocytes challenged with LPS. The distribution of monocyte subsets, YB-1acetyl content, and serum cytokine levels were determined. Compared to controls, dialysis patients have fewer classical (Mo1) and more intermediate (Mo2) and non-classical (Mo3) monocytes. In response to LPS, the Mo2 subset significantly increases (p < 0.001) in control subjects, but not in hemodialysis patients; increased CD86 expression indicates a positive response to LPS. Based on the changes within Mo2, subjects could be classified as responders or non-responders: 60% non-responders were seen in the dialysis cohort versus only 35% among healthy controls. YB-1 acetylation is higher in dialysis patients, independent of LPS stimulation. In this small cohort with 72 months follow-up period intracellular YB-1acetyl levels, IL-6, uPAR, and IP10 correlated with excess mortality in the dialysis cohort. Changes in YB-1 acetylation and serum cytokines may, at a given time point, possibly predict the long-term outcome and thus provide a legacy effect in hemodialysis patients.

Cold shock Y-box binding protein-1 acetylation status in monocytes is associated with systemic inflammation and vascular damage.

BACKGROUND AND AIMS: In dialysis patients, vascular morbidities are highly prevalent and linked to leukocyte extravasation, especially of polarized monocytes. Experimental data demonstrate that phenotypic changes in monocytes require Y-box binding protein-1 (YB-1) upregulation. METHODS: We determined YB-1 expression in circulating and vessel-invading monocytes from healthy controls and dialysis patients to correlate results with intima plaque formation and systemic inflammation. RESULTS: Compared to healthy subjects, dialysis patients have fewer classical and more intermediate and non-classical monocytes. Post-translationally modified YB-1 (lysine 301/304 acetylation) is detected at high levels in the nucleus of adherent and invading CD14+CD68+ monocytes from umbilical cord and atherosclerosis-prone vessels. The content of non-acetylated YB-1 is significantly decreased (p < 0.001), whereas acetylated YB-1 is correspondingly increased (p < 0.001) throughout all monocyte subpopulations, such that the overall content remains unchanged. CONCLUSIONS: In dialysis patients the YB-1 acetylation status is higher with prevailing diabetes and intima plaque formation. Pro-inflammatory mediators TNFα, IL-6, uPAR, CCL2, M-CSF, progranulin, ANP, and midkine, as well as anti-inflammatory IL-10 are significantly increased in dialysis patients, emphasizing a systemic inflammatory milieu. Strong positive correlations of monocytic YB-1 content are seen with ANP, IP-10, IL-6, and IL-10 serum levels. This is the first study demonstrating an association of cold shock protein YB-1 expression with inflammation in hemodialysis patients.