Validity and reliability of the Patient-Reported Outcomes Measurement Information System (PROMIS®) using computerized adaptive testing in patients with advanced chronic kidney disease.

BACKGROUND: The Patient-Reported Outcomes Measurement Information System (PROMIS®) has been recommended for computerized adaptive testing (CAT) of health-related quality of life. This study compared the content, validity, and reliability of seven PROMIS CATs to the 12-item Short-Form Health Survey (SF-12) in patients with advanced chronic kidney disease. METHODS: Adult patients with chronic kidney disease and an estimated glomerular filtration rate under 30 mL/min/1.73 m2 who were not receiving dialysis treatment completed seven PROMIS CATs (assessing physical function, pain interference, fatigue, sleep disturbance, anxiety, depression, and the ability to participate in social roles and activities), the SF-12, and the PROMIS Pain Intensity single item and Dialysis Symptom Index at inclusion and 2 weeks. A content comparison was performed between PROMIS CATs and the SF-12. Construct validity of PROMIS CATs was assessed using Pearson's correlations. We assessed the test-retest reliability of all patient-reported outcome measures by calculating the intraclass correlation coefficient and minimal detectable change. RESULTS: In total, 207 patients participated in the study. A median of 45 items (10 minutes) were completed for PROMIS CATs. All PROMIS CATs showed evidence of sufficient construct validity. PROMIS CATs, most SF-12 domains and summary scores, and Dialysis Symptom Index showed sufficient test-retest reliability (intraclass correlation coefficient ≥ 0.70). PROMIS CATs had a lower minimal detectable change compared with the SF-12 (range, 5.7-7.4 compared with 11.3-21.7 across domains, respectively). CONCLUSION: PROMIS CATs showed sufficient construct validity and test-retest reliability in patients with advanced chronic kidney disease. PROMIS CATs required more items but showed better reliability than the SF-12. Future research is needed to investigate the feasibility of PROMIS CATs for routine nephrology care.

Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

Trends in home dialysis use differ among age categories in past two decades: A Dutch registry study.

BACKGROUND: Although the number of patients with end-stage kidney disease is growing, the number of patients who perform dialysis at home has decreased during the past two decades. The aim of this study was to explore time trends in the use of home dialysis in the Netherlands. METHODS: Dialysis episodes of patients who started dialysis treatment were studied using Dutch registry data (RENINE). The uptake of home dialysis between 1997 through 2016 was evaluated in time periods of 5 years. Home dialysis was defined as start with peritoneal dialysis or home haemodialysis, or transfer to either within 2 years of dialysis initiation. All analyses were stratified for age categories. Mixed model logistic regression analysis was used to adjust for clustering at patient level. RESULTS: A total of 33 340 dialysis episodes in 31 569 patients were evaluated. Mean age at dialysis initiation increased from 62.5 ± 14.0 to 65.5 ± 14.5 years in in-centre haemodialysis patients, whereas it increased from 51.9 ± 15.1 to 62.5 ± 14.6 years in home dialysis patients. In patients <65 years, the uptake of home dialysis was significantly lower during each 5-year period compared with the previous period, whereas kidney transplantation occurred more often. In patients ≥65 years, the incidence of home dialysis remained constant, whereas mortality decreased. CONCLUSIONS: In patients <65 years, the overall use of home dialysis declined consistently over the past 20 years. The age of home dialysis patients increased more rapidly than that of in-centre dialysis patients. These developments have a significant impact on the organization of home dialysis.

Differences in hospitalisation between peritoneal dialysis and haemodialysis patients.

BACKGROUND: Dialysis is associated with frequent hospitalisations. Studies comparing hospitalisations between peritoneal dialysis (PD) and haemodialysis (HD) report conflicting results and mostly analyse data of patients that remain on their initial dialysis modality. This cohort study compares hospitalisations between PD and HD patients taking into account transitions between modalities. METHODS: The Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes collected hospitalisation data of patients who started dialysis between 2012 and 2017. Primary outcome was hospitalisation rate, analysed with a multi-state model that attributed each hospitalisation to the current dialysis modality. RESULTS: In total, 695 patients (252 PD, 443 HD) treated in 31 Dutch hospitals were included. The crude hospitalisation rate for PD was 2.3 ( ± 5.0) and for HD 1.4 ( ± 3.2) hospitalisations per patient-year. The adjusted hazard ratio for hospitalisation rate was 1.1 (95%CI 1.02-1.3) for PD compared with HD. The risk for first hospitalisation was 1.3 times (95%CI 1.1-1.6) higher for PD compared with HD during the first year after dialysis initiation. The number of hospitalisations and number of hospital days per patient-year were significantly higher for PD. The most common causes of PD and HD hospitalisations were peritonitis (23%) and vascular access-related problems (33%). CONCLUSION: PD was associated with higher hospitalisation rate, higher risk for first hospitalisation and higher number of hospitalisations compared with HD. Since the PD hospitalisations were mainly caused by peritonitis, more attention to infection prevention is necessary for reducing the number of hospitalisations in the future.

Itching in dialysis patients: impact on health-related quality of life and interactions with sleep problems and psychological symptoms-results from the RENINE/PROMs registry.

BACKGROUND: Itching (pruritus) is common in dialysis patients, but little is known about its impact on health-related quality of life (HRQOL), sleep problems and psychological symptoms. This study investigates the impact of itching in dialysis patients by looking into the persistence of itching, the effect of itching on the course of HRQOL and the combined effect of itching with sleep problems and with psychological symptoms on HRQOL. METHODS: Data were obtained from the RENINE/PROMs registry and included 2978 dialysis patients who completed patient-reported outcome measures between 2018 and 2020. Itching, sleep problems and psychological symptoms were assessed with the Dialysis Symptom Index (DSI) and HRQOL with the 12-item Short Form Health Survey. Effects of itching on HRQOL and interactions with sleep problems and psychological symptoms were investigated cross-sectionally and longitudinally using linear regression and linear mixed models. RESULTS: Half of the patients experienced itching and in 70% of them, itching was persistent. Itching was associated with a lower physical and mental HRQOL {-3.35 [95% confidence interval (CI) -4.12 to -2.59) and -3.79 [95% CI -4.56 to -3.03]}. HRQOL remained stable during 2 years and trajectories did not differ between patients with or without itching. Sleep problems (70% versus 52%) and psychological symptoms (36% versus 19%) were more common in patients with itching. These symptoms had an additional negative effect on HRQOL but did not interact with itching. CONCLUSIONS: The persistence of itching, its impact on HRQOL over time and the additional effect on HRQOL of sleep problems and psychological symptoms emphasize the need for recognition and effective treatment of itching to reduce symptom burden and improve HRQOL.

Comorbidity is not associated with dialysis modality choice in patients with end-stage kidney disease.

AIM: Over the past years the proportion of home dialysis patients has decreased in the Netherlands. In addition, the home dialysis use varies significantly among centres. It is unclear whether this is the result of differences in comorbidity, or other factors. Our aim was to investigate the association between comorbidity and dialysis modality choice. METHODS: The multi-centre DOMESTICO cohort study collected comorbidity data of patients who started dialysis in 35 Dutch centres from 2012 to 2016. Comorbidity was assessed by the Charlson comorbidity index. Home dialysis was defined as any peritoneal dialysis or home haemodialysis treatment during follow-up. Multivariable logistic regression analysis was used to assess the association between comorbidity and dialysis modality, with a mixed model approach to adjust for clustering of patients within dialysis centres. RESULTS: A total of 1358 patients were included, of whom 628 were treated with home dialysis. In crude mixed model analyses, the probability of receiving home dialysis was lower when comorbidity score was higher: having a high comorbidity score resulted in an odds ratio of 0.74 (95% CI 0.54-1.00) when compared with patients without comorbidities. After adjustments for age, sex, ethnic background, body mass index and dialysis vintage, there was no association between comorbidity and home dialysis. CONCLUSION: Comorbidity was not significantly associated with home dialysis choice, after adjustment for several confounding factors including age and body mass index. Future studies should aim at unravelling the centre-specific characteristics that probably play a role in dialysis modality choice.

Clinical presentation and long-term follow-up of dopamine beta hydroxylase deficiency.

Dopamine beta hydroxylase (DBH) deficiency is an extremely rare autosomal recessive disorder with severe orthostatic hypotension, that can be treated with L-threo-3,4-dihydroxyphenylserine (L-DOPS). We aimed to summarize clinical, biochemical, and genetic data of all world-wide reported patients with DBH-deficiency, and to present detailed new data on long-term follow-up of a relatively large Dutch cohort. We retrospectively describe 10 patients from a Dutch cohort and 15 additional patients from the literature. We identified 25 patients (15 females) from 20 families. Ten patients were diagnosed in the Netherlands. Duration of follow-up of Dutch patients ranged from 1 to 21 years (median 13 years). All patients had severe orthostatic hypotension. Severely decreased or absent (nor)epinephrine, and increased dopamine plasma concentrations were found in 24/25 patients. Impaired kidney function and anemia were present in all Dutch patients, hypomagnesaemia in 5 out of 10. Clinically, all patients responded very well to L-DOPS, with marked reduction of orthostatic complaints. However, orthostatic hypotension remained present, and kidney function, anemia, and hypomagnesaemia only partially improved. Plasma norepinephrine increased and became detectable, while epinephrine remained undetectable in most patients. We confirm the core clinical characteristics of DBH-deficiency and the pathognomonic profile of catecholamines in body fluids. Impaired renal function, anemia, and hypomagnesaemia can be part of the clinical presentation. The subjective response to L-DOPS treatment is excellent and sustained, although the neurotransmitter profile in plasma does not normalize completely. Furthermore, orthostatic hypotension as well as renal function, anemia, and hypomagnesaemia improve only partially.

Funnel plots of patient-reported outcomes to evaluate health-care quality: Basic principles, pitfalls and considerations.

A funnel plot is a graphical method to evaluate health-care quality by comparing hospital performances on certain outcomes. So far, in nephrology, this method has been applied to clinical outcomes like mortality and complications. However, patient-reported outcomes (PROs; eg, health-related quality of life [HRQOL]) are becoming increasingly important and should be incorporated into this quality assessment. Using funnel plots has several advantages, including clearly visualized precision, detection of volume-effects, discouragement of ranking hospitals and easy interpretation of results. However, without sufficient knowledge of underlying methods, it is easy to stumble into pitfalls, such as overinterpretation of standardized scores, incorrect direct comparisons of hospitals and assuming a hospital to be in-control (ie, to perform as expected) based on underpowered comparisons. Furthermore, application of funnel plots to PROs is accompanied by additional challenges related to the multidimensional nature of PROs and difficulties with measuring PROs. Before using funnel plots for PROs, high and consistent response rates, adequate case mix correction and high-quality PRO measures are required. In this article, we aim to provide insight into the use and interpretation of funnel plots by presenting an overview of the basic principles, pitfalls and considerations when applied to PROs, using examples from Dutch routine dialysis care.

Allocation to highly sensitized patients based on acceptable mismatches results in low rejection rates comparable to nonsensitized patients.

Whereas regular allocation avoids unacceptable mismatches on the donor organ, allocation to highly sensitized patients within the Eurotransplant Acceptable Mismatch (AM) program is based on the patient's HLA phenotype plus acceptable antigens. These are HLA antigens to which the patient never made antibodies, as determined by extensive laboratory testing. AM patients have superior long-term graft survival compared with highly sensitized patients in regular allocation. Here, we questioned whether the AM program also results in lower rejection rates. From the PROCARE cohort, consisting of all Dutch kidney transplants in 1995-2005, we selected deceased donor single transplants with a minimum of 1 HLA mismatch and determined the cumulative 6-month rejection incidence for patients in AM or regular allocation. Additionally, we determined the effect of minimal matching criteria of 1 HLA-B plus 1 HLA-DR, or 2 HLA-DR antigens on rejection incidence. AM patients showed significantly lower rejection rates than highly immunized patients in regular allocation, comparable to nonsensitized patients, independent of other risk factors for rejection. In contrast to highly sensitized patients in regular allocation, minimal matching criteria did not affect rejection rates in AM patients. Allocation based on acceptable antigens leads to relatively low-risk transplants for highly sensitized patients with rejection rates similar to those of nonimmunized individuals.

Antibodies against ARHGDIB are associated with long-term kidney graft loss.

The clinical significance of non-HLA antibodies on renal allograft survival is a matter of debate, due to differences in reported results and lack of large-scale studies incorporating analysis of multiple non-HLA antibodies simultaneously. We developed a multiplex non-HLA antibody assay against 14 proteins highly expressed in the kidney. In this study, the presence of pretransplant non-HLA antibodies was correlated to renal allograft survival in a nationwide cohort of 4770 recipients transplanted between 1995 and 2006. Autoantibodies against Rho GDP-dissociation inhibitor 2 (ARHGDIB) were significantly associated with graft loss in recipients transplanted with a deceased-donor kidney (N = 3276) but not in recipients of a living-donor kidney (N = 1496). At 10 years after deceased-donor transplantation, recipients with anti-ARHGDIB antibodies (94/3276 = 2.9%) had a 13% lower death-censored covariate-adjusted graft survival compared to the anti-ARHGDIB-negative (3182/3276 = 97.1%) population (hazard ratio 1.82; 95% confidence interval, 1.32-2.53; P = .0003). These antibodies occur independently from donor-specific anti-HLA antibodies (DSA) or other non-HLA antibodies investigated. No significant relations with graft loss were found for the other 13 non-HLA antibodies. We suggest that pretransplant risk assessment can be improved by measuring anti-ARHGDIB antibodies in all patients awaiting deceased-donor transplantation.

Anxiety Symptoms, Mortality, and Hospitalization in Patients Receiving Maintenance Dialysis: A Cohort Study.

RATIONALE & OBJECTIVE: Anxiety symptoms are common in dialysis patients and have a large impact on quality of life. The association of anxiety symptoms with adverse clinical outcomes in dialysis patients is largely unknown. This study examined the association of anxiety symptoms with hospitalization and mortality in patients receiving maintenance dialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Maintenance dialysis patients treated at 10 dialysis centers in the Netherlands between 2012 and 2016. EXPOSURES: Time-varying symptoms of anxiety and depression using the Beck Anxiety Inventory and Beck Depression Inventory. OUTCOMES: All-cause mortality, 1-year hospitalization rate, and hospital length of stay. ANALYTICAL APPROACH: Cox proportional hazards and Poisson regression models adjusted for sociodemographic and clinical variables. Sensitivity analyses included multiple imputation of missing data and restriction to incident patients only. RESULTS: 687 patients were included, composed of 433 prevalent and 242 incident dialysis patients. Median follow-up time was 3.1 (IQR, 3.0-3.5) years, during which 172 deaths occurred. 22% of patients had anxiety symptoms and 42% had depressive symptoms. Anxiety symptoms were associated with all-cause mortality and 1-year hospitalization rate and length of stay in all multivariable models. Anxiety symptoms showed a clear dose-response relationship with mortality. LIMITATIONS: Depression and anxiety often coexist and share symptoms. The observational design of this study limits inferences about causal mechanisms between anxiety and clinical outcomes. CONCLUSIONS: Anxiety symptoms are independently associated with increased risk for mortality and 1-year hospitalization. Anxiety symptoms are a clinically relevant risk factor for morbidity and mortality in dialysis patients and warrant further research on effective treatment.

A paired kidney analysis on the impact of pre-transplant anti-HLA antibodies on graft survival.

BACKGROUND: Pre-transplant donor-specific anti-human leucocyte antigen (HLA) antibodies (DSAs) are associated with impaired kidney graft survival while the clinical relevance of non-donor-specific anti-HLA antibodies (nDSAs) is more controversial. The aim of the present paired kidney graft study was to compare the clinical relevance of DSAs and nDSAs. METHODS: To eliminate donor and era-dependent factors, a post hoc paired kidney graft analysis was performed as part of a Dutch multicentre study evaluating all transplantations between 1995 and 2005 with available pre-transplant serum samples. Anti-HLA antibodies were detected with a Luminex single-antigen bead assay. RESULTS: Among 3237 deceased donor transplantations, we identified 115 recipient pairs receiving a kidney from the same donor with one recipient being DSA positive and the other without anti-HLA antibodies. Patients with pre-transplant DSAs had a significantly lower 10-year death-censored graft survival (55% versus 82%, P=0.0001). We identified 192 pairs with one recipient as nDSA positive (against Class I and/or II) and the other without anti-HLA antibodies. For the patients with nDSAs against either Class I or II, graft survival did not significantly differ compared with patients without anti-HLA antibodies (74% versus 77%, P = 0.79). Only in patients with both nDSAs Class I and II was there a trend towards a lower graft survival (58%, P = 0.06). Lastly, in a small group of 42 recipient pairs, 10-year graft survival in recipients with DSAs was 49% compared with 68% in recipients with nDSAs (P=0.11). CONCLUSION: This paired kidney analysis confirms that the presence of pre-transplant DSAs in deceased donor transplantations is a risk marker for graft loss, whereas nDSAs in general are not associated with a lower graft survival. Subgroup analysis indicated that only in broadly sensitized patients with nDSAs against Class I and II, nDSAs may be a risk marker for graft loss in the long term.

Effect of initial immunosuppression on long-term kidney transplant outcome in immunological low-risk patients.

BACKGROUND: Few studies have evaluated the effect of different immunosuppressive strategies on long-term kidney transplant outcomes. Moreover, as they were usually based on historical data, it was not possible to account for the presence of pretransplant donor-specific human-leukocyte antigen antibodies (DSA), a currently recognized risk marker for impaired graft survival. The aim of this study was to evaluate to what extent frequently used initial immunosuppressive therapies increase graft survival in immunological low-risk patients. METHODS: We performed an analysis on the PROCARE cohort, a Dutch multicentre study including all transplantations performed in the Netherlands between 1995 and 2005 with available pretransplant serum (n = 4724). All sera were assessed for the presence of DSA by a luminex single-antigen bead assay. Patients with a previous kidney transplantation, pretransplant DSA or receiving induction therapy were excluded from the analysis. RESULTS: Three regimes were used in over 200 patients: cyclosporine (CsA)/prednisolone (Pred) (n = 542), CsA/mycophenolate mofetil (MMF)/Pred (n = 857) and tacrolimus (TAC)/MMF/Pred (n = 811). Covariate-adjusted analysis revealed no significant differences in 10-year death-censored graft survival between patients on TAC/MMF/Pred therapy (79%) compared with patients on CsA/MMF/Pred (82%, P = 0.88) or CsA/Pred (79%, P = 0.21). However, 1-year rejection-free survival censored for death and failure unrelated to rejection was significantly higher for TAC/MMF/Pred (81%) when compared with CsA/MMF/Pred (67%, P < 0.0001) and CsA/Pred (64%, P < 0.0001). CONCLUSION: These results suggest that in immunological low-risk patients excellent long-term kidney graft survival can be achieved irrespective of the type of initial immunosuppressive therapy (CsA or TAC; with or without MMF), despite differences in 1-year rejection-free survival.

Physical performance in patients treated with nocturnal hemodialysis - a systematic review of the evidence.

BACKGROUND: Patients treated with conventional hemodialysis have poor physical performance, explained by insufficient metabolic clearance and shortage of time by time-consuming dialysis. Nocturnal hemodialysis improves metabolic control and results in increased spare time. Our aim is to investigate whether physical performance in nocturnal hemodialysis is superior to conventional hemodialysis. METHODS: A systematic search was conducted in MEDLINE, Embase, CINAHL, PhycInfo and Web of Science until January 2018. Primary outcomes were physical performance, activity, strength and muscle mass in home or in-center nocturnal hemodialysis. Methodological quality was assessed with the Newcastle-Ottawa scale. RESULTS: Ten studies met the inclusion criteria, including 2 RCTs, evaluating 526 nocturnal hemodialysis patients with a mean follow-up of 15, 3 months. The methodological quality of 4 studies was limited. Physical capacity tests were done in 3 studies with different methodology: short-physical performance battery, exercise spirometry and 6-min walk test. The latter 2 showed significant improvements in physical performance. Four studies assessed lean mass using dual-energy X-ray absorptiometry (2×) and bioelectrical impedance analysis (2×), of which 1 demonstrated increased lean body and skeletal muscle mass. In 5 studies a Quality of Life questionnaire was used, of which 2 showed improved physical component score. CONCLUSIONS: The evidence on the effect of nocturnal hemodialysis on physical performance is either of insufficient methodological quality or only measures isolated aspects of physical performance. As literature emphasizes the importance of physical activity on clinical outcomes, it is necessary to conduct larger studies of high methodological quality using capacity tests for answering the question whether nocturnal hemodialysis can improve physical performance of patients with end-stage renal disease. TRIAL REGISTRATION: NTR4715, Netherlands Trial Register. Registered 30 July 2014.

Patient-reported outcome measures: selection of a valid questionnaire for routine symptom assessment in patients with advanced chronic kidney disease - a four-phase mixed methods study.

BACKGROUND: Patient-reported outcome measures (PROMs) are becoming increasingly important in healthcare. In nephrology, there is no agreement on which chronic kidney disease (CKD) symptom questionnaire to use. Therefore, the aim of this study is to select a valid symptom questionnaire for routine assessment in patients with advanced CKD. METHODS: A four-phase mixed methods approach, using qualitative and quantitative research methods, was applied. First, a systematic literature search was conducted to retrieve existing symptom questionnaires. Second, a symptom list was created including all symptoms in existing questionnaires and symptoms mentioned in interviews with patients with CKD, from which symptom clusters were identified. Next, questionnaires were selected based on predefined criteria regarding content validity. Last, two online feedback panels of patients with CKD (n = 151) and experts (n = 6) reviewed the most promising questionnaires. RESULTS: The literature search identified 121 questionnaires, of which 28 were potentially suitable for symptom assessment in patients with advanced CKD. 101 unique symptoms and 10 symptom clusters were distinguished. Based on predefined criteria, the Dialysis Symptom Index (DSI) and Palliative Care Outcome Scale-Renal Version (IPOS-Renal) were selected and reviewed by feedback panels. Patients needed 5.4 and 7.5 min to complete the DSI and IPOS-Renal, respectively (p < 0.001). Patients experienced the DSI as more specific, complete and straightforward compared to the IPOS-Renal. CONCLUSIONS: The DSI was found to be valid and reliable, the most relevant, complete, and comprehensible symptom questionnaire available for routine assessment in patients with advanced CKD. Routine PROMs collection could be of great value to healthcare, both at individual patient and national level. Feedback on scores and involvement of healthcare providers may promote adaptation and implementation in healthcare.

Pretransplant C3d-Fixing Donor-Specific Anti-HLA Antibodies Are Not Associated with Increased Risk for Kidney Graft Failure.

Background Complement-fixing antibodies against donor HLA are considered a contraindication for kidney transplant. A modification of the IgG single-antigen bead (SAB) assay allows detection of anti-HLA antibodies that bind C3d. Because early humoral graft rejection is considered to be complement mediated, this SAB-based technique may provide a valuable tool in the pretransplant risk stratification of kidney transplant recipients.Methods Previously, we established that pretransplant donor-specific anti-HLA antibodies (DSAs) are associated with increased risk for long-term graft failure in complement-dependent cytotoxicity crossmatch-negative transplants. In this study, we further characterized the DSA-positive serum samples using the C3d SAB assay.Results Among 567 pretransplant DSA-positive serum samples, 97 (17%) contained at least one C3d-fixing DSA, whereas 470 (83%) had non-C3d-fixing DSA. At 10 years after transplant, patients with C3d-fixing antibodies had a death-censored, covariate-adjusted graft survival of 60%, whereas patients with non-C3d-fixing DSA had a graft survival of 64% (hazard ratio, 1.02; 95% confidence interval, 0.70 to 1.48 for C3d-fixing DSA compared with non-C3d-fixing DSA; P=0.93). Patients without DSA had a 10-year graft survival of 78%.Conclusions The C3d-fixing ability of pretransplant DSA is not associated with increased risk for graft failure.

Initiation of peritoneal dialysis in the first weeks after catheter insertion: A comparison of a neutral-pH, low-GDP PD fluid and a conventional PD fluid
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BACKGROUND: Chronic exposure to peritoneal dialysis (PD) fluid is associated with development of functional and structural alterations of the peritoneal membrane. The exact time point at which these changes actually occur is not known. Whether changes to the peritoneum occur immediately after installation of PD fluids and whether there is a difference between neutral-pH, low glucose degradation product (low-GDP) PD fluids and conventional PD fluids is not known either. MATERIALS AND METHODS: We performed an observational study. Markers related to inflammation, fibrosis, mesothelial activation, and cytokines/growth factors were measured in effluents immediately after PD-catheter insertion and during the first days and weeks of PD treatment in patients using either dianeal® or physioneal®. RESULTS: Peritoneal response was observed instantly upon insertion of the PD catheter and instillation of PD fluids and persisted during daily PD therapy. Particularly during the first contacts of the peritoneum with PD fluids, high levels of cytokines and biomarkers were observed. In general, CA125 is slightly higher with dianeal. There is no difference between the fluids in hyaluronic acid (HA), IL-6, IL-8, MCP-1, VEGF, and TGFß-1 levels. CONCLUSION: Implantation of the Tenckhoff catheter and installation of PD fluids induce inflammation, which in the first days resembles an acute inflammatory response. More continuous infusion of PD fluids further enhances peritoneal inflammation. The use of the bicarbonate/lactate-buffered, neutral-pH, low-GDP PD fluid physioneal exerts lower CA125 levels, lower D/P4 creatinine, but similar inflammatory response compared to conventional dianeal PD fluids in this early stage of PD therapy.
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Increased risk of graft failure and mortality in Dutch recipients receiving an expanded criteria donor kidney transplant.

Survival of expanded criteria donor (ECD) kidneys and their recipients has not been thoroughly evaluated in Europe. Therefore, we compared the outcome of ECD and non-ECD kidney transplantations in a Dutch cohort, stratifying by age and diabetes. In all first Dutch kidney transplants in recipients ≥18 years between 1995 and 2005, both relative risks (hazard ratios, HR) and adjusted absolute risk differences (RD) for ECD kidney transplantation were analysed. In 3062 transplantations [recipient age 49.0 (12.8) years; 20% ECD], ECD kidney transplantation was associated with graft failure including death [HR 1.62 (1.44-1.82)]. The adjusted HR was lower in recipients ≥60 years of age [1.32 (1.07-1.63)] than in recipients 40-59 years [1.71 (1.44-2.02) P = 0.12 for comparison with ≥60 years] and recipients 18-39 years [1.92 (1.42-2.62) P = 0.03 for comparison with ≥60 years]. RDs showed a similar pattern. In diabetics, the risks for graft failure and death were higher than in the nondiabetics. ECD kidney grafts have a poorer prognosis than non-ECD grafts, especially in younger recipients (<60 years), and diabetic recipients. Further studies and ethical discussions should reveal whether ECD kidneys should preferentially be allocated to specific subgroups, such as elderly and nondiabetic individuals.

Development and initial validation of prescribing quality indicators for patients with chronic kidney disease.

BACKGROUND: Quality assessment is a key element for improving the quality of care. Currently, a comprehensive indicator set for measuring the quality of medication treatment in patients with chronic kidney disease (CKD) is lacking. Our aim was to develop and validate a set of prescribing quality indicators (PQIs) for CKD care, and to test the feasibility of applying this set in practice. METHODS: Potential indicators were based on clinical practice guidelines and evaluated using the RAND/UCLA Appropriateness Method. This is a structured process in which an expert panel assesses the validity of the indicators. Feasibility was tested in a Dutch primary care database including >4500 diabetes patients with CKD. RESULTS: An initial list of 22 PQIs was assessed by 12 experts. After changing 10 PQIs, adding 2 and rejecting 8, a final list of 16 indicators was accepted by the expert panel as valid. These PQIs focused on the treatment of hypertension, albuminuria, mineral and bone disorder, statin prescribing and possible unsafe medication. The indicators were successfully applied to measure treatment quality in the primary care database, but for some indicators the number of eligible patients was too small for reliable calculation. Results showed that there was room for improvement in the treatment quality of this population. CONCLUSIONS: We developed a set of 16 PQIs for measuring the quality of treatment in CKD patients, which had sufficient content and face validity as well as operational feasibility. These PQIs can be used to point out priority areas for improvement.