CD4+CD25+ T regulatory cells in renal transplantation.

The immune response to an allograft activates lymphocytes with the capacity to cause rejection. Activation of CD4+CD25+Foxp3+T regulatory cells (Treg) can down-regulate allograft rejection and can induce immune tolerance to the allograft. Treg represent <10% of peripheral CD4+T cells and do not markedly increase in tolerant hosts. CD4+CD25+Foxp3+T cells include both resting and activated Treg that can be distinguished by several markers, many of which are also expressed by effector T cells. More detailed characterization of Treg to identify increased activated antigen-specific Treg may allow reduction of non-specific immunosuppression. Natural thymus derived resting Treg (tTreg) are CD4+CD25+Foxp3+T cells and only partially inhibit alloantigen presenting cell activation of effector cells. Cytokines produced by activated effector cells activate these tTreg to more potent alloantigen-activated Treg that may promote a state of operational tolerance. Activated Treg can be distinguished by several molecules they are induced to express, or whose expression they have suppressed. These include CD45RA/RO, cytokine receptors, chemokine receptors that alter pathways of migration and transcription factors, cytokines and suppression mediating molecules. As the total Treg population does not increase in operational tolerance, it is the activated Treg which may be the most informative to monitor. Here we review the methods used to monitor peripheral Treg, the effect of immunosuppressive regimens on Treg, and correlations with clinical outcomes such as graft survival and rejection. Experimental therapies involving ex vivo Treg expansion and administration in renal transplantation are not reviewed.

The incidence of IgG4-positive plasma cells staining TIN in patients with biopsy-proven tubulointerstitial nephritis.

AIM: IgG4 disease is rare. However, IgG4 tubulointerstitial nephritis (TIN) is the most common renal manifestation. IgG4 disease is usually associated with elevated serum IgG4 levels and other organ involvement, low-density renal lesions on enhanced CT imaging and immune activation. The incidence of IgG4-TIN may be underestimated, as staining for IgG4 is not routine. This study sought to describe the prevalence of previously undiagnosed IgG4-TIN. Due to the complexity of the diagnosis, we only attempt to look at IgG4-positive plasma cell TIN as a potential indication for IgG4 renal disease. METHODS: A retrospective review of native renal biopsies performed between 2002 and 2012 with a primary diagnosis of TIN was selected. Samples for which interstitial nephritis was secondary to a glomerular disease were excluded. The tissues were stained for IgG4 and scored by two blinded observers. Demographic and follow-up details were collected. This study was approved by the local ethics committee. RESULTS: 82 cases of interstitial nephritis from a total of 1238 renal biopsies (2002-2012) were available after staining for further assessment. 12 samples demonstrated staining consistent with the criteria for IgG4-positive plasma cell TIN, of which 3 had mildly positive staining, 7 moderately positive staining and 2 had markedly positive staining. There were no statistically significant differences in the baseline characteristics between the positive and negative staining groups. CONCLUSIONS: A number of cases of IgG4-positive plasma cell TIN were observed histologically that had been previously diagnosed as non-specific chronic TIN. IgG4-positive plasma cell TIN made up 1% of all renal biopsies performed over 10 years and 13% of all biopsies demonstrating TIN not related to glomerular disease. IgG4 staining should be considered routinely in biopsies demonstrating primary TIN.

RENEW-a renal redesign project in predialysis patient care.

BACKGROUND: An ageing population and geographical growth, along with an increase in the number of people that reside in specific location, are increasing the demand for renal replacement therapies. Hospital-based haemodialysis units are struggling to cope with the associated physical, staffing and cost demands. Home-based dialysis therapies are known to be more cost effective with superior social, physical health and survival outcomes. METHODS: 'RENEW, a renal redesign project, examined the pre-dialysis health care experience of renal patients to find opportunities to improve patient care outcomes and increase the uptake of home-based dialysis therapies. This article details two crucial parts of the approach to change management: (i) diagnostics-an inclusive, client focused, multidisciplinary approach to identify issues relating to the pre-dialysis journey-and (ii) solution design-an inclusive problem-solving approach to identify and marry solutions to the issues identified during diagnostics. RESULTS: Based on feedback from patients/caregivers and staff interviews, utilizing a clinical redesign methodology, a new model of care was developed, implemented and subsequently embedded into clinical practice. The results have been evident via improved care coordination, enhanced patient preparation for dialysis, improved patient psychosocial welfare and, importantly, an increased number of patients planned for and commencing home dialysis. This has empowered patients by giving them the confidence, knowledge and skills to be actively engaged in their own care. The project resulted in significant expenditure avoidance. CONCLUSION: Change management strategies with successful implementation are vital components of evolving clinical practice to achieve both clinical and organizational goals.

Examining internet-delivered cognitive behaviour therapy for patients with chronic kidney disease on haemodialysis: A feasibility open trial.

OBJECTIVE: Treating depression among patients with chronic kidney disease (CKD) is imperative because of its high prevalence and health-related costs. However, many patients with CKD experience significant barriers to effective face-to-face psychological treatments. Internet-delivered cognitive behaviour therapy (iCBT) may help overcome the treatment barriers. The aim of the present study was to explore the acceptability and preliminary efficacy of iCBT for depression and anxiety among patients with CKD on haemodialysis. METHODS: A single-group open trial design involving 22 patients on dialysis and an established iCBT treatment for anxiety and depression was employed. The primary outcomes were symptoms of depression, anxiety and general psychological distress. The secondary and tertiary outcomes were disability, quality of life, kidney disease-related loss and kidney disease burden. A generalised estimation equation modelling technique was employed. RESULTS: Clinically significant improvements (avg. % of improvement) were observed in the primary outcomes of depression (34%), anxiety (31%) and general distress (26%), which were maintained or further improved to 3-month follow-up. Improvements were also observed for quality of life (12%) and kidney disease-related loss (30%). However, no improvements in disability and kidney disease burden were found. High levels of acceptability were reported and relatively little clinician time (99.45min; SD=14.61) was needed to provide the treatment. CONCLUSION: The present results provide encouraging support for the potential of iCBT as an innovative way of increasing access to effective psychological treatment for CKD patients. These results provide much needed support for further research in this area. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry: ACTRN12613000103763.

Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study.

BACKGROUND: Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA. METHODS: Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012. Outcomes included haemoglobin (Hb) concentration, ESA dosing, mortality rates and receipt of dialysis and renal transplantation. Subgroup analyses were conducted for selected outcomes. RESULTS: Of 6035 enrolled subjects, 5723 (94.8%) met analysis criteria; 1795 (29.7%) received dialysis and 238 (3.9%) underwent renal transplantation. Mean (standard deviation) Hb concentration at commencement of extended dosing was 11.0 (1.5) g/dL. Mean [95% confidence interval (CI)] Hb 12 months after commencement of extended dosing (primary outcome) was 11.6 g/dL (11.5, 11.6) overall and was similar across countries, with no differences between subjects previously treated with an ESA versus ESA-naïve subjects, subjects with versus without prior renal transplant or diabetics versus non-diabetics. Weekly ESA dose gradually decreased following commencement of extended DA dosing and was similar across subgroups. The decrease in weekly DA dose was accompanied by an increase in the proportion of patients receiving iron therapy. Hb concentrations declined following changes in ESA labels and treatment guidelines. The mortality rate (95% CI) was 7.06 (6.68, 7.46) deaths per 100 years of follow-up. Subjects alive at study end had stable Hb concentrations in the preceding year, while those who died had lower and declining Hb concentrations in their last year. CONCLUSIONS: Long-term, extended dosing of DA maintained Hb concentrations in patients already treated with an ESA and corrected and maintained Hb in ESA-naïve patients.

The impact of tunnelled vascular catheters on time to arteriovenous fistula creation.

PURPOSE: The purpose of this study is to examine the effect of the presence of tunnelled vascular catheter (TVC) on physician referral and surgeon review and operating patterns and ultimately time of creation of permanent haemodialysis (HD) access. METHODS: A retrospective analysis of TVC and arteriovenous fistulae (AVF) databases in 2010. Physician referral time and surgical time to operation were compared between patients commencing HD with TVC and a control group who commenced HD with AVF. RESULTS: The AVF group (n = 27) commenced HD with an AVF and TVC group (n = 49) commenced HD via a TVC. Time from physician referral to surgeon review in the AVF vs. TVC group was 29 vs. 35 days (p = 0.6). Time from surgeon review to access creation was 43 vs. 50 days (p = 0.4). However, in the TVC group, the time from TVC insertion to physician referral to a surgeon was an additional 109 ± 20 days. Subgroup analysis of 11 TVC patients (23%) presenting at end stage without AVF (crash starters) had a TVC to physician referral time of 103 ± 75 days, physician referral to surgeon review of 14.4 ± 4 days and surgeon review to AVF of 67 ± 23 days. CONCLUSIONS: The presence of a TVC is associated with a significant delay (>3 months) before physicians make a referral for surgeon review. There was no surgeon-related delay to access creation related to the presence of a TVC.

High-sensitivity troponin as a predictor of cardiac events and mortality in the stable dialysis population.

BACKGROUND: High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker used in diagnosing myocardial injury. The clinical utility and the variation of this biomarker over time remain unclear in hemodialysis (HD) and peritoneal dialysis (PD) patients. We sought to determine whether hs-cTnT concentrations were predictive of myocardial infarction (MI) and death and to examine hs-cTnT variability over a 1-year period. METHODS: A total of 393 nonacute HD and PD patients (70% HD and 30% PD) were followed in a prospective observational study for new MI and death. RESULTS: Median hs-cTnT was 57 ng/L (interquartile range, 36-101 ng/L) with no observed difference between HD and PD patients (P = 0.11). Incremental increases in mortality (P = 0.024) and MI (P = 0.001) were observed with increasing hs-cTnT quartiles. MI incidence increased significantly across quartiles in both HD and PD patients (P = 0.012 and P = 0.025, respectively), whereas mortality increased only in HD patients (P = 0.015). For every increase of 25 ng/L in hs-cTnT, the unadjusted hazard ratio (HR) was 1.10 for mortality in the whole group (95% CI, 1.04-1.16, P = 0.001) and 1.16 for MI (95% CI, 1.08-1.23, P < 0.001). Adjusted HR for mortality was 1.07 (95% CI, 1.01-1.15, P = 0.04) and 1.14 for MI (95% CI, 1.06-1.22, P < 0.001). Changes in hs-cTnT from baseline concentrations after 1 year were minimal (55 ng/L vs 53 ng/L, P = 0.22) even in patients who had an MI (P = 0.53). CONCLUSIONS: hs-cTnT appears to have a useful role in predicting MI and death in the dialysis population. Over a 1-year period concentrations remained stable even in patients who sustained a new cardiac event.

How do clinical and psychological variables relate to quality of life in end-stage renal disease? Validating a proximal-distal model.

PURPOSE: The aims of this study were to: (1) validate the proximal-distal (PD) model in predialysis and early dialysis and (2) examine the role of hemoglobin on quality of life (QoL) in these patient groups. METHODS: Cross-sectional observational studies of 475 participants recruited from four major university teaching hospitals were conducted. The multi-sample structural equation modeling with latent composite techniques was employed to test the PD model. Seven factors were measured, including QoL, positive affect, depression, physical functioning, kidney disease symptoms, comorbidity and hemoglobin. RESULTS: The results showed that both the equality-constrained and equality-unconstrained PD models were supported by fit statistics. The chi square difference test of the two models was non-significant, indicating that the PD model was consistent across groups. The alternative models were rejected by fit statistics, suggesting that hemoglobin does not impact on psychological states but QoL. CONCLUSIONS: This study validates the PD model across the end-stage renal disease (ESRD) patient groups and shows a hierarchical causal relationship between clinical factors, physical functioning, psychological states and QoL, with hemoglobin as an exception. This model provides an empirical framework for integrating and studying a range of clinical factors and health outcomes in ESRD.

ACEIs for cardiovascular risk reduction--have we taken our eye off the ball?

BACKGROUND: Hypertensive patients have an increased risk of cardiovascular (CV) events. There is debate whether angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) offer similar reductions in CV risk. OBJECTIVE: This article discusses some of the recent evidence for the prevention of CV events and mortality with ACEIs and ARBs, and the rationale for using an ACEI as the preferred agent for comprehensive CV risk reduction in specific patient populations. DISCUSSION: ACEIs and ARBs are structurally and functionally very different agents; they are not interchangeable. Prescriptions for ARBs are increasing in Australia. However, clinical trial evidence suggests possible advantages of ACEIs over ARBs, particularly in terms of survival benefit. Many patients with hypertension have other CV risk factors that may affect medication choice. The aim of treatment should not be just to lower blood pressure, but to reduce absolute CV risk.

Is bigger better? A retrospective analysis of native renal biopsies with 16 Gauge versus 18 Gauge automatic needles.

AIM: Percutaneous renal biopsy (PRB) remains the gold standard for the diagnosis of renal disease; however, the tissue yield which relates to the optimal needle size used for native-kidney biopsies has not been clearly established. Our study compares the sample adequacy and complication rates using 16 gauge (G) and 18 gauge (G) automatic needles on native kidney PRB. METHODS: A retrospective analysis was performed of native-kidney biopsies at two centres, one exclusively using 16G and the other exclusively using 18G needles. All samples were assessed by a single centralized pathology service. We compared patient characteristics, indications, diagnoses, adequacy of tissue samples, and complications. RESULTS: A total of 934 native-kidney biopsies were performed with real time ultrasound guidance: 753 with Bard Max Core 16G × 16 cm needles, and 181 with Bard Magnum 18G × 20 cm needles. The median (range) of total glomeruli count per biopsy was higher in the 16G group compared with the 18G group (19 (0-66) vs. 12 (0-35), P < 0.001), despite having fewer cores per biopsy (2 (0-4) vs. 3 (1-4), P < 0.001). The 16G group provided a greater proportion of adequate biopsy samples (94.7% vs. 89.4%, P = 0.001). There was no significant difference in the frequency of total complications between the 16G and 18G groups (3.7% vs. 2.2%, P = 0.49). CONCLUSION: This retrospective study demonstrates 16G needles provide more glomeruli, more diagnostically adequate renal tissue, with fewer cores without a significant increase in complications compared with 18G needles. Based on these observations, 16G needles should be considered as the first line option in native-kidney PRB.

The effects of biocompatible compared with standard peritoneal dialysis solutions on peritonitis microbiology, treatment, and outcomes: the balANZ trial.

BACKGROUND: A multicenter, multi-country randomized controlled trial (the balANZ study) recently reported that peritonitis rates significantly improved with the use of neutral-pH peritoneal dialysis (PD) solutions low in glucose degradation products ("biocompatible") compared with standard solutions. The present paper reports a secondary outcome analysis of the balANZ trial with respect to peritonitis microbiology, treatment, and outcomes. METHODS: Adult incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. RESULTS: The safety population analysis for peritonitis included 91 patients in each group. The unadjusted geometric mean peritonitis rates in those groups were 0.30 [95% confidence interval (CI): 0.22 to 0.41] episodes per patient-year for the biocompatible group and 0.49 (95% CI: 0.39 to 0.62) episodes per patient-year for the control group [incidence rate ratio (IRR): 0.61; 95% CI: 0.41 to 0.90; p = 0.01]. When specific causative organisms were examined, the rates of culture-negative, gram-positive, gram-negative, and polymicrobial peritonitis episodes were not significantly different between the biocompatible and control groups, although the biocompatible group did experience a significantly lower rate of non-pseudomonal gram-negative peritonitis (IRR: 0.41; 95% CI: 0.18 to 0.92; p = 0.03). Initial empiric antibiotic regimens were comparable between the groups. Biocompatible fluid use did not significantly reduce the risk of peritonitis-associated hospitalization (adjusted odds ratio: 0.80; 95% CI: 0.48 to 1.34), but did result in a shorter median duration of peritonitis-associated hospitalization (6 days vs 11 days, p = 0.05). Peritonitis severity was more likely to be rated as mild in the biocompatible group (37% vs 10%, p = 0.001). Overall peritonitis-associated technique failures and peritonitis-related deaths were comparable in the two groups. CONCLUSIONS: Biocompatible PD fluid use was associated with a broad reduction in gram-positive, gram-negative, and culture-negative peritonitis that reached statistical significance for non-pseudomonal gram-negative organisms. Peritonitis hospitalization duration was shorter, and peritonitis severity was more commonly rated as mild in patients receiving biocompatible PD fluids, although other peritonitis outcomes were comparable between the groups.

The effect of low glucose degradation product, neutral pH versus standard peritoneal dialysis solutions on peritoneal membrane function: the balANZ trial.

BACKGROUND: The balANZ trial recently reported that neutral pH, low glucose degradation product (biocompatible) peritoneal dialysis (PD) solutions significantly delayed anuria and reduced peritonitis rates compared with conventional solutions. This article reports a secondary outcome analysis of the balANZ trial with respect to peritoneal membrane function. METHODS: Adult, incident PD patients with residual renal function were randomized to receive either biocompatible or conventional (control) PD solutions for 2 years. Peritoneal equilibration tests were performed at 1, 6, 12, 18 and 24 months. Peritoneal small solute clearances and ultra-filtration (UF) were measured at 3, 6, 9, 12, 18 and 24 months. RESULTS: Of the 185 patients recruited into the trial, 85 patients in the Balance group and 82 patients in the control group had peritoneal membrane function evaluated. Mean 4-h dialysate:plasma creatinine ratios (D:P Cr 4h) at 1 month were significantly higher in the Balance group compared with controls (0.67 ± 0.10 versus 0.62 ± 0.10, P = 0.002). Over the 2-year study period, mean D:P Cr 4 h measurements remained stable in the Balance group but increased significantly in controls [difference -0.004 per month, 95% confidence interval (95% CI) -0.005 to -0.002, P < 0.001]. Similar results were obtained for dialysate glucose ratios (D/D0 glucose). Peritoneal UF was significantly lower in the Balance group than in controls at 3 and 6 months. Over the 2-year study period, peritoneal UF increased significantly in the Balance group but remained stable in controls (difference 24 mL/day/month, 95% CI 9-39, P = 0.002). No differences in peritoneal small solute clearances, prescribed dialysate fill volumes or peritoneal glucose exposure were observed between the two groups. CONCLUSIONS: Biocompatible and conventional PD solutions exert differential effects on peritoneal small solute transport rate and UF over time. Adequately powered trials assessing the impact of these differential membrane effects on PD technique and patient survival rates are warranted.

Change process during synchronised conversion to a once-monthly erythropoiesis-stimulating agent (ESA) administration at a single satellite haemodialysis unit.

BACKGROUND: There are currently no published data on the impact of changes to practice caused by introducing coordinated once-monthly erythropoiesis-stimulating agent (ESA) administration. OBJECTIVE: This study aimed to measure staff satisfaction during and after ESA synchronisation within a single satellite haemodialysis unit. DESIGN: A quantitative survey using a Likert scale was distributed to dialysis nurses pre-synchronisation and during follow-up at three and nine months post-synchronisation. Secondary outcomes included monitoring of haemoglobin (Hb) levels. RESULTS: A total of 19 respondents completed the surveys. By nine months post-synchronisation, most nurses responded that ESA synchronisation was not a time-consuming task, did not increase their workload, had saved them time and was simpler for the unit. Additionally, most nurses reported that they had coped well with the change and that they wanted ESA synchronisation to be permanently introduced. At 8 months post-synchronisation, 53.3% of patients had an Hb level > 11 g/dl and < 12 g/dl. CONCLUSION: Changes to practice resulting from ESA synchronisation did not appear to negatively impact nurse workplace satisfaction.

Effects of biocompatible versus standard fluid on peritoneal dialysis outcomes.

The clinical benefits of using "biocompatible" neutral pH solutions containing low levels of glucose degradation products for peritoneal dialysis compared with standard solutions are uncertain. In this multicenter, open-label, parallel-group, randomized controlled trial, we randomly assigned 185 incident adult peritoneal dialysis patients with residual renal function to use either biocompatible or conventional solution for 2 years. The primary outcome measure was slope of renal function decline. Secondary outcome measures comprised time to anuria, fluid volume status, peritonitis-free survival, technique survival, patient survival, and adverse events. We did not detect a statistically significant difference in the rate of decline of renal function between the two groups as measured by the slopes of GFR: -0.22 and -0.28 ml/min per 1.73 m(2) per month (P=0.17) in the first year in the biocompatible and conventional groups, respectively, and, -0.09 and -0.10 ml/min per 1.73 m(2) per month (P=0.9) in the second year. The biocompatible group exhibited significantly longer times to anuria (P=0.009) and to the first peritonitis episode (P=0.01). This group also had fewer patients develop peritonitis (30% versus 49%) and had lower rates of peritonitis (0.30 versus 0.49 episodes per year, P=0.01). In conclusion, this trial does not support a role for biocompatible fluid in slowing the rate of GFR decline, but it does suggest that biocompatible fluid may delay the onset of anuria and reduce the incidence of peritonitis compared with conventional fluid in peritoneal dialysis.

An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study.

BACKGROUND: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population. METHODS: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible. Retrospective and/or prospective data including haemoglobin levels and erythropoiesis-stimulating agent (ESA) dosing were collected for 6 months before and 12 months after DA initiation. Mean Hb levels were calculated every 3 months, and ESA dose was converted to a geometric mean weekly DA equivalent dose and summarized monthly. RESULTS: Data from 4278 patients showed that patients receiving ESA treatment before DA Q2W/QM initiation had a mean (95% confidence interval) Hb level of 11.9 g/dL (11.8-12.0 g/dL) at initiation and 11.6 g/dL (11.6-11.7 g/dL) at Months 10-12, with mean ESA dose of 22 µg/week (21-23 µg/week) prior to initiation, 16 µg/week (15-16 µg/week) at initiation and 16 µg/week (15-16 µg/week) at Month 12. In ESA-naive patients, Hb levels increased from 10.3 g/dL (10.2-10.3 g/dL) at initiation to 11.7 g/dL at Months 4-6 and were maintained at a mean level of 11.7 g/dL (11.7-11.8 g/dL) at Months 10-12, with mean ESA dose of 16 µg/week (16-17 µg/week) at initiation and 16 µg/week (16-17 µg/week) at Month 12. In the 85% of patients receiving DA at extended intervals (Q2W or less frequently) at Month 12, 12 patients (0.3%) experienced DA-related adverse reactions. CONCLUSION: DA Q2W/QM was an effective treatment of anaemia in the general CKD-NoD patient population and a dose increase was not required in patients switching from a previous ESA regimen.

The psychosocial correlates of quality of life in the dialysis population: a systematic review and meta-regression analysis.

PURPOSE: The psychosocial correlates of quality-of-life (QoL) research in end-stage renal disease (ESRD) are important in identifying risk and protective factors that may account for the QoL variability. Thus, the present study provides a meta-analysis of these research results. METHODS: Published studies reporting associations between any psychosocial factors and QoL were retrieved from Medline, Embase, and PsycINFO. Mean effect sizes were calculated for the associations across psychosocial constructs (affect, stress, cognitive appraisal, social support, personality attributes, and coping process). Multiple hierarchical meta-regressions were applied to moderator analyses. RESULTS: Eighty-one studies covering a combined sample of 13,240 participants were identified resulting in 377 effect sizes of the association between psychosocial factors and QoL. The overall effect size of the association was medium (0.38). Stress, affect, and cognitive appraisal had the largest effect sizes. Location of study, dialysis type, gender, age and QoL domains measured (general well-being, subjective QoL, and health-related QoL) were significant substantive moderators for the associations. CONCLUSIONS: The present study shows that there is a moderate association between psychosocial variables and QoL in patients with ESRD, consistent across different QoL domains. The psychosocial constructs that have the strongest association with QoL are stress, affect, and cognitive appraisal.

Psychosocial risk and protective factors for depression in the dialysis population: a systematic review and meta-regression analysis.

OBJECTIVE: Research into the association between psychosocial factors and depression in End-Stage Renal Disease (ESRD) has expanded considerably in recent years identifying a range of factors that may act as important risk and protective factors of depression for this population. The present study provides the first systematic review and meta-analysis of this body of research. METHODS: Published studies reporting associations between any psychosocial factor and depression were identified and retrieved from Medline, Embase, and PsycINFO, by applying optimised search strategies. Mean effect sizes were calculated for the associations across five psychosocial constructs (social support, personality attributes, cognitive appraisal, coping process, stress/stressor). Multiple hierarchical meta-regression analysis was applied to examine the moderating effects of methodological and substantive factors on the strength of the observed associations. RESULTS: 57 studies covering 58 independent samples with 5956 participants were identified, resulting in 246 effect sizes of the association between a range of psychosocial factors and depression. The overall mean effect size (Pearsons correlation coefficient) of the association between psychosocial factor and depression was 0.36. The effect sizes between the five psychosocial constructs and depression ranged from medium (0.27) to large levels (0.46) with personality attributes (0.46) and cognitive appraisal (0.46) having the largest effect sizes. In the meta-regression analyses, identified demographic (gender, age, location of study) and treatment (type of dialysis) characteristics moderated the strength of the associations with depression. CONCLUSION: The current analysis documents a moderate to large association between the presence of psychosocial risk factors and depression in ESRD.

Studying psychosocial adaptation to end-stage renal disease: the proximal-distal model of health-related outcomes as a base model.

OBJECTIVE: Studying psychosocial adaptation in end-stage renal disease (ESRD) is increasingly important, as it may explain the variability in health outcomes unaccounted for by clinical factors. The Brenner et al. proximal-distal model of health-related outcomes provides a theoretical foundation for understanding psychosocial adaptation and integrating health outcomes, clinical, and psychosocial factors (Brenner MH, Curbow B, Legro MW. The proximal-distal continuum of multiple health outcome measures: the case of cataract surgery. Med Care. 1995;33(4 Suppl):AS236-44). This study aims to empirically validate the proximal-distal model in the dialysis population and examine the impact of psychosocial factors on the model. METHODS: A cross-sectional observational study was conducted with a sample of long-term dialysis patients (n=201). Eleven factors: quality of life (QoL), depression, positive affect, comorbidity, symptoms, physical functioning, disease accommodation, loss, self-efficacy, illness acceptance, and social support were measured by standardized psychometric scales. A three-month average of hemoglobin was used. Latent composite structural equation modeling was used to examine the models. RESULTS: The proximal-distal model with slight modification was supported by fit statistics [χ(2)=16.04, df=13, P=.25, root mean square error of approximation (RMSEA)=0.024], indicating that the impact of clinical factors on QoL is mediated through a range of functional and psychological factors, except for hemoglobin which impacts directly on QoL. The model with additional psychosocial factors was also supported by fit statistics (χ(2)=43.59, df=41, P=.36, RMSEA=0.018). These additional factors mainly impact on symptom status, psychological states, and QoL components of the model. CONCLUSION: The present study supported the proximal-distal model in the dialysis population and demonstrated the considerable impact of psychosocial factors on the model. The proximal-distal model plus psychosocial factors as a biopsychosocial model can be applied to studying psychosocial adaptation in ESRD.