Benefit finding in renal transplantation and its association with psychological and clinical correlates: A prospective study.

OBJECTIVES: The identification of positive psychological changes, including benefit finding (BF), in chronic illness has gained substantial interest. However, less is known about BF in the context of a positive medical intervention. End-stage renal disease (ESRD) can be regarded as a burdensome condition, but transplantation is expected to restore physical and psychological functioning to a large extent after a period of illness. The aim of this study was to examine (1) changes in BF from pre- to 12 months post-transplantation, (2) the concurrent association of disease-related characteristics and optimism to BF, and (3) the potential causal relations between BF and distress. METHODS: In this longitudinal study, 319 patients completed questionnaires before, 3 months, 6 months, and/or 12 months post-transplantation. Multilevel models were used for the analyses. Measures included the Illness Cognitions Questionnaire to measure BF, the Life Orientation Test to measure optimism, and the General Health Questionnaire to measure distress. RESULTS: Benefit finding increased from pre- to post-transplantation. Fewer symptoms and comorbidities, and more optimism, were related to more BF over all time-points. The direction of the relation between BF and distress changed over time. Before transplantation, distress predicted an increase in BF, whereas post-transplantation, distress predicted a decrease in BF. The causal relation between BF and distress post-transplantation appeared to be reciprocal. CONCLUSIONS: A positive medical intervention such as renal transplantation might facilitate the development of BF. This study indicates the need for longitudinal research on the relation between BF and psychological health in the face of positive events. Statement of contribution What is already known on this subject? Benefit finding refers to the identification of positive psychological changes following a negative life event. Individuals can experience benefit finding following chronic illness. The positive event of kidney transplantation is associated with improvements in patients' physical and psychological functioning. What does this study add? Benefit finding increases from pre- to post-kidney transplantation. Fewer symptoms and comorbidities, and higher optimism are related to more benefit finding. Before transplantation, distress predicts an increase in benefit finding. After transplantation, there appears to be a reciprocal relation between distress and benefit finding such that distress predicts a decrease in benefit finding and benefit finding predicts a decrease in distress.

Goal disturbance changes pre/post-renal transplantation are related to changes in distress.

OBJECTIVE: Renal transplantation (RTx) is considered the treatment of choice for end-stage renal disease (ESRD) given its association with lower mortality, and improved overall quality of life and psychological functioning compared to dialysis. However, much less is known about which factors underlie these psychological improvements across RTx. Goal theory suggests that experienced disturbances in important goals are related to lower psychological functioning. This study aimed to (1) identify the most disturbed and most important goals for patients before RTx, (2) to examine changes in goal disturbance and goal importance pre/post-RTx, and (3) to examine whether changes in goal disturbance are associated with changes in psychological distress over time, and whether this relationship is mediated by changes in perceived control. METHODS: In this longitudinal study, 220 patients completed questionnaires before and after RTx, including questionnaires to assess goals (GOALS questionnaire), psychological distress (GHQ-12), and perceived control (Mastery scale). RESULTS: End-stage renal disease affected both general and disease-specific goals. Approximately 30% of the patients indicated to experience high or very high disturbance before transplantation. Goal disturbance generally decreased significantly pre- to post-RTx, whereas goal importance did not change significantly pre- to post-RTx. No mediation effect of perceived control was found. Instead, both changes in goal disturbance and perceived control showed independent effects on changes in distress. CONCLUSIONS: Intervention strategies targeting attainable and realistic goal setting, and perceived control in RTx recipients who do not benefit optimally from RTx, might enhance psychological functioning in this population. Statement of contribution What is already known on this subject? Kidney transplantation improves patients' psychological functioning. Experienced disturbances in important life goals are related to lower psychological functioning in chronic illness. What does this study add? Goal disturbance decreases after renal transplantation, and this is related to a decrease in distress over time. Perceived control does not mediate the relationship between goal disturbance and distress pre/post-transplantation. Changes in perceived control have an additional main effect on changes in distress.

Changes of perceived control after kidney transplantation: a prospective study.

AIMS: The aim of this study was to determine if kidney transplantation is associated with increases of perceived control and how changes of perceived control affect the course of psychological distress until 1 year after transplantation. BACKGROUND: Low levels of perceived control are associated with reduced well-being among dialysis patients. DESIGN: Prospective longitudinal cohort study. METHODS: Perceived control (Mastery Scale) and psychological distress (GHQ-12) were prospectively assessed before (T0; n = 470) and three (T1; n = 197), six (T2; n = 210) and twelve (T3; n = 183) months after transplantation. Differences between T1 and T0 perceived control were used to stratify the sample into three groups (control gain, stable control and control loss). Socio-demographic and clinical variables, including complications, were examined as potential correlates and the course of psychological was distress compared across groups. Data were collected between July 2008 - July 2013. RESULTS: Perceived control showed a small increase overall, with 35·1%, 50·0% and 14·9% reporting gain, stable level and loss respectively. Patients with secondary schooling were overrepresented in the control loss group. The course of psychological distress varied across perceived control change groups, with patients in the control gain group experiencing a significant reduction in psychological distress. CONCLUSION: A considerable number of patients report increased levels of perceived control after transplantation that are associated with a subsequent decrease in psychological distress. Results emphasize the importance of perceived control and could inform interventions to facilitate well-being after kidney transplantation.

Are patient and relationship variables associated with participation of intimate partners in couples research?

BACKGROUND: Recruitment of participants for studies focusing on couples facing illness is a challenging task and participation decline may be associated with nonrandom factors creating bias. This study examines whether patient and relationship characteristics are associated with partner participation in research. METHOD: Patients invited to participate in a cross-sectional study on adaptation and quality of life after renal transplantation were asked to forward information about an add-on study to their partners. RESULTS: A total of 456 participating patients had a partner; 293 of the partners showed interest in the study and 206 actually completed the questionnaire. Backward logistic regression analyses revealed that demographic, illness, and personal characteristics of the patient were not associated with partner interest in the study nor actual partner participation. However, partners who indicated interest in the study showed more active engagement toward the patients (as reported by the patients). Furthermore, patients of partners who actually completed the questionnaire reported less negative affect and higher relationship satisfaction than patients whose partner did not participate in the study. DISCUSSION: It is encouraging that of the large number of variables tested, only 2 were associated with the participation of partners. Nevertheless, well-functioning couples appear to be overrepresented in our study, calling for specific effort to include marital distressed couples in research focusing on dyadic adaptation to illness.

Great expectations? Pre-transplant quality of life expectations and distress after kidney transplantation: a prospective study.

OBJECTIVES: Previous research suggests that prior to kidney transplantation, patients overestimate their post-transplant quality of life (QoL). The current study aimed to corroborate these findings, identify determinants of QoL overestimation, examine its association with subsequent distress, and clarify the role of optimism. DESIGN: Prospective observational study. METHODS: Physical, psychological, and social QoL expectations, actual QoL, and distress (GHQ-12) of participants (56% male) were prospectively assessed before (T0; n = 228) and 3 (T1; n = 149), 6 (T2; n = 146), and 12 (T3; n = 114) months after successful transplantation. RESULTS: Patients who were treated with haemodialysis before transplantation reported greater physical QoL overestimation than those who received treatment with peritoneal dialysis. Neither physical nor social QoL overestimation at T1 was prospectively associated with increased distress at T2 or T3. The interaction between optimism and social QoL overestimation at T1 (ß = -.56, p < .001) for distress at T2 was significant, with patients low in optimism experiencing more distress after QoL overestimation. CONCLUSIONS: QoL overestimation is not associated with subsequent distress. Findings suggest that patients low in optimism are more vulnerable to distress following QoL overestimation. STATEMENT OF CONTRIBUTION: What is already known on this subject? Kidney transplantation improves patients' quality of life. Prior to kidney transplantation, patients overestimate the scale of this improvement. What does this study add? Quality of life overestimation is not associated with subsequent distress. When optimism is low, kidney transplant recipients experience higher distress following quality of life overestimation.

SLC22A2 is associated with tubular creatinine secretion and bias of estimated GFR in renal transplantation.

Genome-wide association studies reported SLC22A2 variants to be associated with serum creatinine. As SLC22A2 encodes the organic cation transporter 2 (OCT2), the association might be due to an effect on tubular creatinine handling. To test this hypothesis we studied the association of SLC22A2 polymorphisms with phenotypes of net tubular creatinine secretion: fractional creatinine excretion (FEcreat) and bias of estimated glomerular filtration rate (eGFR). We also studied the association with end-stage renal disease (ESRD) and graft failure (GF) in renal transplant recipients. SLC22A2 single nucleotide polymorphisms (SNPs), rs3127573 and rs316009, were genotyped in 1,142 ESRD patients receiving renal transplantation and 1,186 kidney donors as controls. GFR was measured with (125)I-iothalamate clearance. Creatinine clearance was also assessed. FEcreat was calculated from the simultaneous clearances of creatinine and (125)I-iothalamate. Donor rs316009 was associated with FEcreat (beta -0.053, P = 0.024) and with estimated [modification of diet in renal disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)] but not measured GFR. In line with this, donor rs316009 was associated with bias of the MDRD and CKD-EPI but not the Cockroft-Gault equation. Both SNPs were associated with ESRD: odds ratios [95% CI] 1.39 [1.16-1.67], P = 0.00065, and 1.23 [1.02-1.48], P = 0.042, for rs3127573 and rs316009, respectively. Neither SNP was associated with GF. Thus, SLC22A2 is associated with phenotypes of net tubular creatinine secretion and ESRD.

The making of a pan-European organ transplant registry.

A European patient registry to track the outcomes of organ transplant recipients does not exist. As knowledge gleaned from large registries has already led to the creation of standards of care that gained widespread support from patients and healthcare providers, the European Union initiated a project that would enable the creation of a European Registry linking currently existing national databases. This report contains a description of all functional, technical, and legal prerequisites, which upon fulfillment should allow for the seamless sharing of national longitudinal data across temporal, geographical, and subspecialty boundaries. To create a platform that can effortlessly link multiple databases and maintain the integrity of the existing national databases crucial elements were described during the project. These elements are: (i) use of a common dictionary, (ii) use of a common database and refined data uploading technology, (iii) use of standard methodology to allow uniform protocol driven and meaningful long-term follow-up analyses, (iv) use of a quality assurance mechanism to guarantee completeness and accuracy of the data collected, and (v) establishment of a solid legal framework that allows for safe data exchange.

UMOD as a susceptibility gene for end-stage renal disease.

BACKGROUND: In recent genetic association studies, common variants including rs12917707 in the UMOD locus have shown strong evidence of association with eGFR, prevalent and incident chronic kidney disease and uromodulin urinary concentration in general population cohorts. The association of rs12917707 with end-stage renal disease (ESRD) in a recent case-control study was only nominally significant. METHODS: To investigate whether rs12917707 associates with ESRD, graft failure (GF) and urinary uromodulin levels in an independent cohort, we genotyped 1142 ESRD patients receiving a renal transplantation and 1184 kidney donors as controls. After transplantation, 1066 renal transplant recipients were followed up for GF. Urinary uromodulin concentration was measured at median [IQR] 4.2 [2.2-6.1] yrs after kidney transplantation. RESULTS: The rs12917707 minor allele showed association with lower risk of ESRD (OR 0.89 [0.76-1.03], p = 0.04) consistent in effect size and direction with the previous report (Böger et al, PLoS Genet 2011). Meta-analysis of these findings showed significant association of rs12917707 with ESRD (OR 0.91 [0.85-98], p = 0.008). In contrast, rs12917707 was not associated with incidence of GF. Urinary uromodulin concentration was lower in recipients-carriers of the donor rs12917707 minor allele as compared to non-carriers, again consistent with previous observations in general population cohorts. CONCLUSIONS: Our study thus corroborates earlier evidence and independently confirms the association between UMOD and ESRD.

A randomized clinical trial of living donor nephrectomy: a plea for a differentiated appraisal of mini-open muscle splitting incision and hand-assisted laparoscopic donor nephrectomy.

A randomized controlled trial was designed to compare various outcome variables of the retroperitoneal mini-open muscle splitting incision (MSI) technique and the transperitoneal hand-assisted laparoscopic technique (HAL) in performing living donor nephrectomies. Fifty living kidney donors were randomized to MSI or HAL. Primary endpoint was pain experience scored on a visual analogue scale (VAS). After MSI living donors indicated lower median (range) VAS scores at rest than HAL living donors on postoperative day 2.5 [10 (0-44) vs. 15 (0-70), P = 0.043] and day 3 [7 (0-28) vs. 10 (0-91), P = 0.023] and lower VAS scores while coughing on postoperative day 3 [20 (0-73) vs. 42 (6-86), P = 0.001], day 7 [8 (0-66) vs. 33 (3-76), P < 0.001] and day 14 [2 (0-17) vs. 12 (0-51), P = 0.009]. The MSI technique also resulted in reduced morphine requirement, better scores on three domains of the RAND-36, reduced costs and reduced CRP and IL-6 levels. The HAL technique was superior in operating time and postoperative decrease of hemoglobin level. The MSI technique is superior to the HAL technique in performing living donor nephrectomies with regard to postoperative pain experience. This study reopens the discussion of the way to go in performing the living donor nephrectomy.

The role of personal characteristics in the relationship between health and psychological distress among kidney transplant recipients.

Although kidney transplantation improves overall quality of life and physical functioning, improvements of psychological distress are often modest. However, apparent stressors such as comorbidity are only weakly associated with psychological distress and their impact differs considerably between patients. Wilson and Cleary proposed a theoretical model to explain these relationships. This model has been supported by research, but has never been applied in a population of kidney transplant recipients. Findings of the current study are based on a cross-sectional study carried out in 2008 in the northern Netherlands. An elaborated version of Wilson and Cleary's model specifying hypothesized relationships of objective health, functional status, subjective health, personal characteristics and psychological distress was evaluated with structural equation modelling. After elimination of non-significant paths the final model provided a good fit for the data, X(2) (2)=4.23, p=0.12; RMSEA=0.047, CI(RMSEA) (0; 0.11); ECVI=0.060, ECVI(sat)=0.059. Results suggest that objective health has an indirect effect on psychological distress, in size comparable to the effects exerted by functional status and subjective health. Personal characteristics are the strongest determinant of psychological distress, but are directly and indirectly affected by objective health. Results indicate that poor health might cause psychological distress by increasing coping demands while simultaneously decreasing coping resources.

CUBN as a novel locus for end-stage renal disease: insights from renal transplantation.

Chronic kidney disease (CKD) is a complex disorder. As genome-wide association studies identified cubilin gene CUBN as a locus for albuminuria, and urinary protein loss is a risk factor for progressive CKD, we tested the hypothesis that common genetic variants in CUBN are associated with end-stage renal disease (ESRD) and proteinuria. First, a total of 1142 patients with ESRD, admitted for renal transplantation, and 1186 donors were genotyped for SNPs rs7918972 and rs1801239 (case-control study). The rs7918972 minor allele frequency (MAF) was higher in ESRD patients comparing to kidney donors, implicating an increased risk for ESRD (OR 1.39, p = 0.0004) in native kidneys. Second, after transplantation recipients were followed for 5.8 [3.8-9.2] years (longitudinal study) documenting ESRD in transplanted kidneys--graft failure (GF). During post-transplant follow-up 92 (9.6%) cases of death-censored GF occurred. Donor rs7918972 MAF, representing genotype of the transplanted kidney, was 16.3% in GF vs 10.7% in cases with functioning graft. Consistently, a multivariate Cox regression analysis showed that donor rs7918972 is a predictor of GF, although statistical significance was not reached (HR 1.53, p = 0.055). There was no association of recipient rs7918972 with GF. Rs1801239 was not associated with ESRD or GF. In line with an association with the outcome, donor rs7918972 was associated with elevated proteinuria levels cross-sectionally at 1 year after transplantation. Thus, we identified CUBN rs7918972 as a novel risk variant for renal function loss in two independent settings: ESRD in native kidneys and GF in transplanted kidneys.

Gastrointestinal symptoms in kidney transplant recipients: what about silent sufferers?

CONTEXT: Transplantation improves health-related quality of life in patients with end-stage renal disease. However, primarily because of adverse effects of medication, among other gastrointestinal symptoms, health-related quality of life is not completely restored to normal. Although many patients have various gastrointestinal symptoms only a small proportion may be reported spontaneously. OBJECTIVE: To evaluate the prevalence of gastrointestinal symptoms in kidney transplant recipients, also the difference between spontaneously reported symptoms and symptoms elicited by specific questioning was assessed. The burden of these symptoms in daily life also was analyzed. DESIGN: A single-center, sequential, mixed method study to assess the difference between spontaneous patient reports of gastrointestinal symptoms and active screening by a questionnaire in kidney transplant patients. PATIENTS: In February 2008, patients received a questionnaire on gastrointestinal symptoms; notes in medical records were consulted for patients scoring less than 100. In June 2008, those patients received a second, extended questionnaire aimed to assess the burden of gastrointestinal symptoms in daily life. RESULTS: Ninety-two of 513 patients eventually proved to have gastrointestinal symptoms. Completed questionnaires were compared with notes in the patients' files of the past year. A total of 51 of these 92 patients appeared to have not mentioned their gastrointestinal symptoms during the outpatient clinic visits. Of these 51 patients, 37 reported a significant impact of gastrointestinal symptoms on daily life. CONCLUSIONS: The silent sufferer exists. Specific questioning helps to improve communication concerning bothersome gastrointestinal symptoms. To assess the burden of these symptoms, a validated questionnaire should be developed.

Matrix metalloproteinases as profibrotic factors in terminal ileum in Crohn's disease.

BACKGROUND: Returning stenosis in Crohn's disease (CD) patients is poorly understood. After resection, newly developed strictures are seen within 10 years in 50% to 70%. Matrix metalloproteinases (MMPs) are involved in matrix-turnover processes. This study analyzes spatial expression of MMP-1, MMP-3, MMP-9, tissue inhibitor of MMP-1, and collagen III to get better insight in tissue remodeling of terminal ileum of CD patients. METHODS: Expressions were analyzed on mRNA and the protein level (MMP-1, MMP-3) in segments from resected terminal ileum from CD and control patients. In CD, macroscopic distinction was made between proximal resection margin, prestenotic, and stenotic tissue. Immunohistochemistry allowed for expression analyses transmurally. RESULTS: MMP-1 and MMP-3 gene expression was up-regulated (P < 0.05) in both prestenotic and stenotic tissue. MMP-1 protein was significantly up-regulated in submucosal and muscular tissue of prestenotic parts and in muscular tissue of stenotic Crohn samples. MMP-3 protein was significantly up-regulated in all layers of prestenotic and stenotic Crohn samples. Even in submucosa of proximal resection margin tissue, MMP-3 expression was significantly higher than in controls. CONCLUSION: Surprisingly, in proximal resection margin tissue up-regulated MMP-3 was seen. This suggests that in nonresected terminal ileum, in which anastomosis is made, tissue turnover is present, which may account for the high recurrence of intestinal strictures.

Shortage of donation despite an adequate number of donors: a professional attitude?

BACKGROUND: A major problem in the field of transplantation is the persistent shortage of donor organs and tissues for transplantation. This study was initiated to (1) chart the donor potential for organs and tissue in The Netherlands and (2) to identify factors influencing whether donation is discussed with next of kin. METHODS: A registration form was constructed to obtain information at time of death of patients about the demographic characteristics, diagnosis, and medical suitability for donation. A prospective study was conducted among 11 hospitals in The Netherlands that gathered 4,877 filled-in forms equaling 8% to 10% of the people dying in a hospital in The Netherlands per year. RESULTS: In the year of the study, organs were retrieved from 22 donors and tissues from 264 donors in the 11 hospitals. The organ potential is estimated at a maximum of 38.7 per million population per year. A mere 5% of the physicians got a 100% score on criteria and contraindications for donation. Factors of influence on receiving consent for donation were the will of the donor, using a protocol, giving verbal information to the relatives, and presence of the partner of the deceased patient. For 26% of the potential tissue donors and 69% of the potential organ donors, donation was discussed with the relatives. Consent for tissue donation was obtained in 27%, and consent for organ donation was obtained in 60%. CONCLUSIONS: In The Netherlands, when taking into account current refusal percentages, 320 to 360 organ donations and 5,800 tissue donations could be effectuated if organ donation is posed to all possible donors. For this, knowledge of medical criteria and contraindications for donation by the physicians and their willingness to discuss donation with next of kin must be improved.