Anaclitic and Introjective psychopathology and the interpersonal function of perfectionsiam/self-criticism.

Blatt (1974, 2004) put forward that the phenomenological field of psychopathology could be subdivied into an anaclitic and an introjective cluster. Each of these clusters is underlain by a specific predisposing personality style that entails vulnerability for specific ‘triggering’ stressors. The theory of Blatt refers strongly to the classical psychoanalytic theory on the hysterical and obsessional dimensions in psychopathology, and also converges with contemporary theories, like cognitive-behavioural formulations on sociotropic and autonomous depression (Beck, 1983). Robins, Ladd, Welkowitz, Blaney, Diaz, and Kutcher (1994) reviewed theoretical writings on anaclitic and introjective psychopathology and concluded that the personality trait hypothesized to predispose for anaclitic psychopathology, namely interpersonal dependency, can be subdivided into three core characteristics: Concern about what others think, Pleasing Others, and Dependency; and that the personality trait hypothesized to predispose for introjective psychopathology, namely self-criticism/autonomy, can be subdivided into three clusters as well: Perfectionism/Self-criticism, Need for Control, and Defensive Separation. Robins et al. (1994) constructed the Personal Style Inventory-II to measure these theoretical constructs. However, inquiry into the factor structure of this questionnaire suggested that the perfectionism/self-criticism subscale was associated equally strong with both types of psychopathology (e.g. Bagby, Parker, Joffe, Shuller, & Gilchrist, 1998). These findings seem to be in conflict with the results obtained with the Depressive Experiences Questionnaire (DEQ; Blatt, D’Aflitti, & Quinlan, 1976) that suggest that self-criticism is specifically associated with introjective psychopathology. However, the self-criticism scale of the DEQ comprises a mixture of items that measure self-criticism and items that measure an excessively autonomous and aloof interpersonal stance. Thus, the observed specific associations might be due to the interpersonal content of the scale, and not to its self-critical content. In the present paper, the authors studied interviews with 31 outpatients in a mixed qualitative/quantitative way to obtain a more clinical picture of the prevalence of the different PSI-II characteristics in anaclitic and introjective psychopathology. In line with the results of the studies into the factor structure of the PSI-II, our results suggest that Concern about what Others Think, Dependency, and Pleasing Others are characteristics that underlie anaclitic psychopathology; that Defensive Separation and Need for Control underlie introjective psychopathology; and that Perfectionism/Self-criticism is associated with both types of psychopathology. Closer consideration of the perfectionistic/self-critical interview fragments revealed that perfectionism/self-criticism has a different interpersonal motivation in anaclitic than in introjective subjects. Anaclitic subjects tend to be perfectionistic/self-critical to attract other people; introjective subjects tend to be perfectionistic/self-critical to keep the other at a distance and/or to keep control over the other. Thus, we conclude that perfectionism/self-criticism was not specifically associated with introjective nor with anaclitic psychopathology, unless we took into account its interpersonal function. In the context of clinical practice, these results prompt for careful exploration of the interpersonal aspect of perfectionism/self-criticism, in order to obtain a clear view on the connection between this characteristic and the manifest psychopathology of a patient. Future research should consider the hypothesis that the self-criticism scale of the DEQ is associated with introjective psychopathology because it does not merely measure self-criticism, but also an aloof and controlling interpersonal stance

Histological picture of antibody-mediated rejection without donor-specific anti-HLA antibodies: Clinical presentation and implications for outcome

In this cohort study (n = 935 transplantations), we investigated the phenotype and risk of graft failure in patients with histological criteria for antibody-mediated rejection (ABMR) in the absence of circulating donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA), and compared this to patients with definite ABMR and HLA-DSA-positivity. The histological picture did not differ between HLA-DSA-positive (n = 85) and HLA-DSA-negative (n = 123) cases of ABMR histology, apart from increased complement split product 4d (C4d) deposition in the peritubular capillaries in HLA-DSA-positive cases. Histology of ABMR without HLA-DSA was more transient than DSA-positive ABMR, and patients with ABMR histology without HLA-DSA had graft survival superior to that of HLA-DSA-positive patients, independent of concomitant T cell-mediated rejection (38.2%) or borderline changes (17.9%). Multivariate analysis showed that the risk of graft failure was not higher in patients with histological picture of ABMR (ABMRh ) in the absence of HLA-DSA, compared to patients without ABMRh . Despite an association between C4d deposition and HLA-DSA-positivity, using C4d deposition as alternative for the DSA criterion in the diagnosis of ABMR, as proposed in Banff 2017, did not contribute to the prognosis of graft function and graft failure. We concluded that biopsies with ABMRh but without detectable HLA-DSA represent a distinct, often transient phenotype with superior allograft survival.status: publishe

Assessing the Complex Causes of Kidney Allograft Loss

BACKGROUND: Although graft loss is a primary endpoint in many studies in kidney transplantation and a broad spectrum of risk factors has been identified, the eventual causes of graft failure in individual cases remain ill studied. METHODS: We performed a single-center cohort study in 1000 renal allograft recipients, transplanted between March 2004 and February 2013. RESULTS: In total, 365 graft losses (36.5%) were identified, of which 211 (57.8%) were due to recipient death with a functioning graft and 154 (42.2%) to graft failure defined as return to dialysis or retransplantation. The main causes of recipient death were malignancy, infections, and cardiovascular disease. The main causes of graft failure were distinct for early failures, where structural issues and primary nonfunction prevailed, compared to later failures with a shift towards chronic injury. In contrast to the main focus of current research efforts, pure alloimmune causes accounted for only 17.5% of graft failures and only 7.4% of overall graft losses, although 72.7% of cases with chronic injury as presumed reason for graft failure had prior rejection episodes, potentially suggesting that alloimmune phenomena contributed to the chronic injury. CONCLUSIONS: In conclusion, this study provides better insight in the eventual causes of graft failure, and their relative contribution, highlighting the weight of nonimmune causes. Future efforts aimed to improve outcome after kidney transplantation should align with the relative weight and expected impact of targeting these causes.status: publishe

Occurrence of Diabetic Nephropathy After Renal Transplantation Despite Intensive Glycemic Control: An Observational Cohort Study

OBJECTIVE: The kinetics and risk factors of diabetic nephropathy after kidney transplantation remain unclear. This study investigated the posttransplant occurrence of diabetic nephropathy and the contribution of posttransplant glycemic control. RESEARCH DESIGN AND METHODS: We performed a single-center prospective cohort study of 953 renal allograft recipients and 3,458 protocol-specified renal allograft biopsy specimens up to 5 years after transplantation. The effects of pretransplant diabetes and glycemic control (glycated hemoglobin levels) on the posttransplant histology were studied. RESULTS: Before transplantation, diabetes was present in 164 (17.2%) renal allograft recipients, primarily type 2 (n = 146 [89.0%]). Despite intensive glycemic control (glycated hemoglobin 7.00 ± 1.34% [53 ± 14.6 mmol/mol], 6.90 ± 1.22% [52 ± 13.3 mmol/mol], and 7.10 ± 1.13% [54 ± 12.4 mmol/mol], at 1, 2, and 5 years after transplantation), mesangial matrix expansion reached a cumulative incidence of 47.7% by 5 years in the pretransplant diabetes group versus 27.1% in patients without diabetes, corresponding to a hazard ratio of 1.55 (95% CI 1.07-2.26; P = 0.005). Mesangial matrix expansion was not specific for diabetic nephropathy and associated independently with increasing age. Pretransplant diabetes was associated with posttransplant proteinuria but not with estimated glomerular filtration rate, graft failure, or any other structural changes of the glomerular, vascular, or tubulointerstitial renal compartments. The occurrence of diabetic nephropathy was independent of posttransplant glycated hemoglobin levels. CONCLUSIONS: Mesangial matrix expansion, an early indicator of diabetic nephropathy, can occur rapidly in patients with diabetes before transplantation, despite intensive glycemic control. Prevention of diabetic nephropathy requires more than pursuing low levels of glycated hemoglobin.status: publishe

Eplet Mismatch Load and De Novo

BACKGROUND: In kidney transplantation, evaluating mismatches of HLA eplets—small patches of surface-exposed amino acids of the HLA molecule—instead of antigen mismatches might offer a better approach to assessing donor-recipient HLA incompatibility and improve risk assessment and prediction of transplant outcomes. METHODS: To evaluate the effect of number of eplet mismatches (mismatch load) on de novo formation of donor-specific HLA antibodies (DSAs) and transplant outcomes, we conducted a cohort study that included consecutive adult kidney recipients transplanted at a single center from March 2004 to February 2013. We performed retrospective high-resolution genotyping of HLA loci of 926 transplant pairs and used the HLAMatchmaker computer algorithm to count HLA eplet mismatches. RESULTS: De novo DSAs occurred in 43 (4.6%) patients. Multivariable analysis showed a significant independent association between antibody-verified eplet mismatch load and de novo DSA occurrence and graft failure, mainly explained by DQ antibody-verified eplet effects. The association with DQ antibody-verified eplet mismatches was linear, without a safe threshold at which de novo DSA did not occur. Odds for T cell– or antibody-mediated rejection increased by 5% and 12%, respectively, per antibody-verified DQ eplet mismatch. CONCLUSIONS: Eplet mismatches in HLA-DQ confer substantial risk for de novo DSA formation, graft rejection, and graft failure after kidney transplantation. Mismatches in other loci seem to have less effect. The results suggest that antibody-verified HLA-DQ eplet mismatch load could be used to guide personalized post-transplant immunosuppression. Adoption of molecular matching for DQA(1) and DQB(1) alleles could also help to minimize de novo DSA formation and potentially improve transplant outcomes