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Background: Adjunctive catheter-directed thrombolysis shows variable efficacy in preventing postthrombotic syndrome (PTS), despite restored patency., Objectives: This Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome (CAVA) trial subanalysis investigated the effect of ultrasound-accelerated catheter-directed thrombolysis (UACDT) on patency, reflux, and their relevance in PTS development., Methods: This multicenter, randomized, single-blind trial enrolled patients (aged 18-85 years) with a first iliofemoral deep vein thrombosis and symptom duration ≤14 days. Patency and reflux were assessed by duplex ultrasound at 12 months (T12) and long-term (LT) follow-up (median, 39.5 months; IQR, 24.0-63.0 months). PTS was diagnosed using the Villalta score., Results: UACDT significantly improved patency in all vein segments at T12 (60.3% UACDT vs 25.9% standard treatment [ST]; P = .002) and LT (45.2% UACDT vs 11.9% ST; P < .001). Popliteal patency, however, was similar between groups (87.9% UACDT vs 83.3% ST; P = .487). Reflux was similar between groups at T12 and LT; only popliteal reflux was significantly reduced in the UACDT group at LT (22.6% UACDT vs 44.8% ST; P = .010). Absent iliac patency at T12 was associated with increased PTS risk in the ST group only (odds ratio [OR], 10.84; 95% CI, 1.93-60.78; P = .007). In the UACDT group, popliteal reflux at T12 was associated with moderate-to-severe PTS at T12 (OR, 4.88; 95% CI, 1.10-21.57; P = .041) and LT (OR, 5.83; 95% CI, 1.44-23.63; P = .009). Combined popliteal reflux and absent iliac patency significantly amplified PTS risk (OR, 10.79; 95% CI, 2.41-48.42; P < .001)., Conclusion: UACDT improved patency and reduced popliteal reflux. Iliac patency and popliteal reflux are independently associated with moderate-to-severe PTS and contribute synergistically to its development. However, a proportion of moderate-to-severe PTS cases lacks an evident underlying cause., Competing Interests: Declaration of competing interests H.t.C. reports personal fees from Alveron, Galapagos, AstraZeneca, and Novostia, and he is shareholder with Coagulation Profile; all revenues are deposited at the Cardiovascular Research Institute Maastricht for research. The remaining authors have no disclosures to report., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Ultrafiltration to target weight during haemodialysis is complicated by intradialytic hypotension-associated adverse events (IHAAEs) in 10-30% of dialysis treatments. IHAAEs are caused by critical reductions in absolute blood volume (ABV), due to the interaction of ultrafiltration, refill and compensatory mechanisms. Non-randomised studies have suggested that ABV-guided treatment, using an indicator dilution technique employing the blood volume monitor on the dialysis machine, could reduce the incidence of IHAAEs., Methods: We performed an open-label randomised controlled trial. Patients were randomly assigned to adjustment of target weight guided by ABV measurements or standard care. The primary outcome was the change in the incidence of IHAAEs from baseline, defined as the percentage of treatment episodes in a 4-week period where the patient had a systolic blood pressure <90 mmHg or symptoms of impending hypotension. ABV measurements were compared with anthropomorphometric estimation and the gold standard using isotope dilution., Results: A total of 56 patients were randomised, of whom 29 were allocated to ABV-guided treatment and 27 to standard care. Overall baseline incidence of IHAAEs was 26.0%. ABV-guided treatment significantly reduced the incidence of IHAAEs compared with standard care, with a mean change from baseline of -9.6% [95% confidence interval (CI) -17.3 to -1.8) versus 2.4% (95% CI -2.3-7.2). The adjusted difference between the groups was 10.5% (95% CI 1.3-19.8; P  = .026). ABV measurement had moderate agreement with other methods to estimate blood volume. The sensitivity for the previously suggested threshold of a post-dialysis normalised blood volume of 65 ml/kg was observed to be 74% in this study., Conclusions: ABV-guided volume management significantly reduced IHAAEs compared with standard care. The clinical relevance of the previously suggested threshold of 65 ml/kg cannot be firmly concluded on the basis of our results. If confirmed in a larger trial, this intervention could potentially change dialysis practice and impact patient care in a clinically meaningful way., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Background: An important aspect of end-of-life decisions in dialysis patients is elective withdrawal from dialysis therapy. Several studies have shown that clinical factors, such as comorbidity, play a role in dialysis withdrawal. The role of symptoms of anxiety and depression is largely unknown. The., Methods: A prospective multi-center study has been set up to investigate anxiety and depressive symptoms longitudinally in dialysis patients. Anxiety and depressive symptoms were investigated using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) as baseline. Adverse events, including dialysis withdrawal and mortality were registered during follow-up. Multivariable cox proportional hazard models were used with anxiety and depression as the independent variable and dialysis withdrawal as the outcome variable. Models included age, sex, ethnicity and a set of clinical comorbidities., Results: A total of 687 patients were included between 2012 and 2017, with a median follow-up of 3.2 years. A total of 48 patients (7%) withdrew from dialysis therapy, and subsequently deceased. Anxiety and depressive symptoms at baseline showed an association with dialysis withdrawal with hazard ratios of 2.31 (1.09-4.88) for anxiety and 2.56 (1.27-5.15) for depressive symptoms, independent of somatic comorbidities., Discussion: Withdrawal from dialysis therapy is associated with anxiety and depressive symptoms. Dialysis patients with more severe depressive and anxiety symptoms were more vulnerable for dialysis withdrawal. Insight in factors that play a role in dialysis withdrawal could aid patients and clinicians making an informed decision and develop clinical guidelines., (© 2023. The Author(s).)

Introduction: The optimal nadroparin dose in patients undergoing hemodialysis is difficult to determine in clinical practice. Anti-Xa levels ≥ 0.4 IU/mL and < 2.0 IU/mL are suggested to prevent thrombus formation within the extracorporeal circuit whilst minimizing bleeding risk. We aimed to characterize the variability in the association between dose and anti-Xa levels, identify patient and dialysis characteristics that explained this variability, and optimize nadroparin dosing based on the identified characteristics., Methods: Anti-Xa samples were collected in patients who received intravenous nadroparin as thromboprophylaxis during routine dialysis sessions. A population pharmacodynamic model was developed using non-linear mixed-effects modelling. The percentage of patients ≥ 0.4 IU/mL (efficacy) and < 2.0 IU/mL (safety) was simulated for different doses, patient and dialysis characteristics., Results: Patients (n = 137) were predominantly receiving standard hemodialysis (84.7% vs. hemodiafiltration 15.3%) and had a mean bodyweight of 76.3 kg (± 16.9). Lean body mass (LBM), mode of dialysis, and dialyzer partially explained between-subject variability in anti-Xa levels. Patients on hemodiafiltration and those receiving hemodialysis with a high LBM (≥ 80 kg) had a low probability (< 29%) of anti-Xa levels ≥ 0.4 IU/mL during the entire dialysis session. All patients, except hemodialysis patients with a low LBM (< 50 kg), had a high probability (> 70%) of peak anti-Xa levels < 2.0 IU/mL., Conclusion: Mainly patients receiving hemodiafiltration and those receiving hemodialysis with a high LBM can benefit from a higher nadroparin dose than currently used in clinical practice, while having anti-Xa levels < 2.0 IU/mL., (© 2022. The Author(s).)

Objectives: Magnetic resonance venography (MRV) is underutilized in the evaluation of thrombus properties prior to endovascular treatment but may improve procedural outcomes. We therefore investigated the clinical impact of using a dedicated MRV scoring system to assess thrombus characteristics prior to endovascular intervention for iliofemoral deep vein thrombosis (DVT)., Methods: This is a post hoc analysis of data from the CAVA trial ( Clinicaltrials.gov :NCT00970619). MRV studies of patients receiving ultrasound-accelerated catheter-directed thrombolysis (CDT) for iliofemoral DVT were reviewed. Thrombus age-related imaging characteristics were scored and translated into an overall score (acute, subacute, or old). MRV scores were compared to patient-reported complaints. MRV-scored groups were compared for CDT duration and success rate., Results: Fifty-six patients (29 men; age 50.8 ± 16.4 years) were included. Using MRV, 27 thrombi were classified acute, 17 subacute, and 12 old. Based on patient-reported complaints, 11 (91.7%) of these old thrombi would have been categorized acute or subacute, and one (3.7%) of the acute thrombi as old. Average duration of CDT to > 90% restored patency differed significantly between groups (p < 0.0001): average duration was 23 h for acute thromboses (range: 19-25), 43 h for subacute (range: 41-62), and 85 h for old thromboses (range: 74-96). CDT was almost eleven times more successful in thromboses characterized as acute and subacute compared to old thromboses (OR: 10.7; 95% CI 2.1-55.5)., Conclusion: A dedicated MRV scoring system can safely discriminate between acute, subacute, and old thromboses. MRV-based selection is predictive of procedural duration and success rate and can help avoid unnecessary complications., Key Points: • Thrombus age, characterized by MRV as acute, subacute, and old, can predict CDT duration and probability of success. • Accurate pre-interventional MRV-based thrombus aging has the potential to facilitate identification of eligible patients and may thus prevent CDT-related complications., (© 2022. The Author(s).)

Objective: To investigate the impact of the coronavirus pandemic on mental health in hemodialysis patients, we assessed depression, anxiety and quality of life with valid mental health measures before and after the start of the pandemic., Methods: Data were used from 121 hemodialysis patients from the ongoing prospective multicenter DIVERS-II study. COVID-19 related stress was measured with the Perceived Stress Scale - 10, depression with the Beck Depression Inventory - second edition (BDI-II)), anxiety with the Beck Anxiety Inventory (BAI) and quality of life with the Short Form - 12 (SF-12). Scores during the first and second COVID-19 wave in the Netherlands were compared to data prior to the pandemic with linear mixed models., Results: No significant differences were found in BDI-II, BAI and SF-12 scores between before and during the pandemic. During the first wave, 33% of participants reported COVID-19 related stress and in the second wave 37%. These patients had higher stress levels (mean difference (MD) 4.7 (95%CI 1.5; 8.0), p = 0.005) and BDI-II scores (MD 4.9 (95%CI 0.7; 9.0), p = 0.021) and lower SF-12 mental component summary scores (MD -5.3 (95%CI -9.0, -1.6), p = 0.006) than patients who did not experienced COVID-19 stress. These differences were already present before the pandemic., Conclusion: The COVID-19 pandemic does not seem to influence mental health in hemodialysis patients. However, a substantial subgroup of patients with pre-existent mental health problems may be more susceptible to experience COVID-19 related stress., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Symptoms of anxiety are often unrecognized and untreated in dialysis patients. We investigated the diagnostic accuracy of two widely used screening tools for anxiety in hemodialysis patients., Methods: For this cross-sectional validation study, chronic hemodialysis patients from eight dialysis centers in the Netherlands were included. The Beck Anxiety Inventory (BAI) and Hospital Anxiety and Depression Scale-Anxiety subscale (HADS-A) were validated by the Mini International Neuropsychiatric Inventory (MINI) diagnostic interview. Receiver operating characteristic curves were used to determine the optimal cut-off values., Results: Of 65 participants, 13 (20%) were diagnosed with one or more anxiety disorders on the MINI, of which 5 were included in the analysis. ROC curves showed a good diagnostic accuracy of the BAI and HADS-A. The optimal cut-off value for the BAI was ≥13 (sensitivity 100%, specificity 85%) and for the HADS-A was ≥10 (sensitivity 80%, specificity 100%)., Conclusions: Based on our limited data, both the BAI and the HADS-A seem to be valid screening instruments for anxiety in hemodialysis patients that can be used in routine dialysis care. The HADS-A consists of fewer items and showed fewer false-positive results than the BAI, which might make it more useful in clinical practice.

Background: Differences in symptom burden, treatment satisfaction and autonomy between patients receiving peritoneal dialysis and haemodialysis could be reflected by a difference in symptom dimensions of anxiety and depression. The aim of this study is to assess differences in prevalence and symptom dimensions of anxiety and depression between patients receiving peritoneal dialysis and haemodialysis., Methods: Baseline data from the Depression Related Factors and Outcomes in Dialysis Patients With Various Ethnicities and Races Study were used. Symptoms of anxiety and depression were measured with the Beck Anxiety Inventory and Beck Depression Inventory- second edition. Linear and logistic regression models were used to compare anxiety and depression total scores and somatic and subjective/cognitive symptom dimension scores between patients receiving peritoneal dialysis and haemodialysis, adjusted for potential confounders., Results: In total, 84 patients receiving peritoneal dialysis and 601 patients receiving haemodialysis were included. Clinically significant symptoms of anxiety and depression were present in respectively 22% and 43% of the patients, with no differences between dialysis modality. Both modalities scored high on the somatic symptom dimensions and on individual somatic items. Almost all patients reported symptoms related to loss of energy and sleep., Conclusion: No differences in symptom dimensions of anxiety and depression were found between patients receiving peritoneal dialysis and haemodialysis. The high prevalence of somatic symptom dimensions in both groups underscores the possible interaction between somatic and psychiatric symptoms in dialysis patients and the need for early recognition and treatment of symptoms of anxiety and depression regardless of treatment modalities.

Objective: To investigate the effectiveness of a guided internet-based self-help intervention for hemodialysis patients with depressive symptoms., Method: Chronic hemodialysis patients from nine Dutch hospitals with a depression score on the Beck Depression Inventory - second edition (BDI-II) of ≥10, were cluster-randomized into a five modules guided internet-based self-help problem solving therapy intervention or a parallel care-as-usual control group. Clusters were based on hemodialysis shift. The primary outcome depression was measured with the BDI-II. Analysis was performed with linear mixed models., Results: A total of 190 hemodialysis patients were cluster-randomized to the intervention (n = 89) or control group (n = 101). Post-intervention measurement was completed by 127 patients (67%) and more than half of the patients (54%) completed the intervention. No significant differences were found on the BDI-II score between the groups (mean difference - 0.1, 95%CI -3.0; 2.7, p = 0.94). Per protocol sensitivity analysis showed comparable results. No significant differences in secondary outcomes were observed between groups., Conclusions: Guided internet-based self-help problem solving therapy for hemodialysis patients with depressive symptoms does not seem to be effective in reducing these symptoms as compared to usual care. Future research should examine how to best design content and accessibility of an intervention for depressive symptoms in hemodialysis patients., Trial Registration: Dutch Trial Register: Trial NL6648 (NTR6834) (prospectively registered 13th November 2017)., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background The CAVA (Ultrasound-Accelerated Catheter-Directed Thrombolysis Versus Anticoagulation for the Prevention of Post-Thrombotic Syndrome) trial did not show a reduction of post-thrombotic syndrome (PTS) after additional ultrasound-accelerated catheter-directed thrombolysis in patients with acute iliofemoral deep vein thrombosis at 1-year follow-up. This prespecified analysis of the CAVA trial aimed to determine the impact of additional thrombolysis on outcomes of PTS at long-term follow-up. Methods and Results Patients aged 18 to 85 years with a first-time acute iliofemoral deep vein thrombosis were included and randomly assigned (1:1) to either standard treatment plus ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. The primary outcome was the proportion of PTS (Villalta score ≥5 on 2 occasions ≥3 months apart or venous ulceration) at the final follow-up visit. Additionally, PTS according to the International Society on Thrombosis and Haemostasis (ISTH) consensus definition was assessed to allow external comparability. Major bleedings were the main safety outcome. At a median follow-up of 39.0 months (interquartile range, 23.3-63.8), 120 patients (79.8%) participated in the final follow-up visit: 62 from the intervention group and 58 from the standard treatment group. PTS developed in 19 (30.6%) versus 26 (44.8%) patients, respectively (odds ratio [OR], 0.54; 95% CI, 0.26 to 1.15 [ P =0.11]), with an absolute difference between groups of -14.2% (95% CI, -32.0% to 4.8%). Using the ISTH consensus definition, a significant reduction in PTS was observed (29 [46.8%] versus 40 [69.0%]) (OR, 0.40; 95% CI, 0.19-0.84 [ P =0.01]) with an absolute difference between groups of -22.2% (95% CI, -39.8% to -2.8%). No new major bleedings occurred following the 12-month follow-up. Conclusions The impact of additional ultrasound-accelerated catheter-directed thrombolysis on the prevention of PTS was found to increase with time. Although this study was limited by its sample size, the overall findings indicate a reduction of mild PTS without impact on quality of life. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00970619.

Background:  The CAVA trial did not show the anticipated risk reduction for postthrombotic syndrome (PTS) after thrombus removal via additional ultrasound-accelerated catheter-directed thrombolysis (UACDT) in patients with acute iliofemoral deep vein thrombosis (IFDVT). Difficulties in achieving an effective degree of recanalization through thrombolysis may have influenced outcomes. We therefore assessed whether successful UACDT (restored patency ≥ 90%) did reduce the development of PTS., Methods:  This CAVA trial post hoc analysis compared the proportion of PTS at 1-year follow-up between patients with successful UACDT and patients that received standard treatment only. In addition, clinical impact as well as determinants of successful thrombolysis were explored., Results:  UACDT was initiated in 77 (50.7%) patients and considered successful in 41 (53.2%, interrater agreement κ  = 0.7, 95% confidence interval 0.47-0.83). PTS developed in 15/41 (36.6%) patients in the successful UACDT group versus 33/75 (44.0%) controls ( p  = 0.44). In this comparison, successful UACDT was associated with lower Venous Clinical Severity Score (3.50 ± 2.57 vs. 4.82 ± 2.74, p  = 0.02) and higher EuroQOL-5D (EQ-5D) scores (40.2 ± 36.4 vs. 23.4 ± 34.4, p  = 0.01). Compared with unsuccessful UACDT, successful UACDT was associated with a shorter symptom duration at inclusion ( p  = 0.05), and higher rates of performed adjunctive procedures ( p  < 0.001) and stent placement ( p  < 0.001)., Conclusion:  Successful UACDT was not associated with a reduced proportion of PTS 1 year after acute IFDVT compared with patients receiving standard treatment alone. There was, however, a significant reduction in symptom severity and improvement of generic quality of life according to the EQ-5D. Better patient selection and optimization of treatment protocols are needed to assess the full potential of UACDT for the prevention of PTS., Trial Registration Number:  ClinicalTrials.gov number, NCT00970619., Competing Interests: C.H.A.W. reports grants from ZonMw, grants from Maastricht University Medical Center, and grants from BTG International Group, during the conduct of the study., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Early thrombus removal might prevent post-thrombotic syndrome by preserving venous function and restoring flow. Previous trials comparing additional catheter-directed thrombolysis to standard treatment showed conflicting outcomes. We aimed to assess the benefit of additional ultrasound-accelerated catheter-directed thrombolysis for the prevention of post-thrombotic syndrome compared with standard therapy in patients with iliofemoral deep-vein thrombosis., Methods: We did a multicentre, randomised, single-blind, allocation-concealed, parallel group, superiority trial in 15 hospitals in the Netherlands. Patients aged 18-85 years with a first-time acute iliofemoral deep-vein thrombosis and symptoms for no more than 14 days were randomly assigned (1:1) to either standard treatment with additional ultrasound-accelerated catheter-directed thrombolysis or standard treatment alone. Randomisation was done with a web-based automatic programme and a random varying block size (2-12), stratified by age and centre. Standard treatment included anticoagulant therapy, compression therapy (knee-high elastic compression stockings; 30-40 mmHg), and early ambulation. Additional ultrasound-accelerated catheter-directed thrombolysis was done with urokinase with a starting bolus of 250 000 international units (IU) in 10 mL NaCl followed by a continuous dose of 100 000 IU/h for a maximum of 96 h through the Ekos Endowave-system. Adjunctive percutaneous transluminal angioplasty, thrombosuction, or stenting was performed at the discretion of the physician who performed the intervention. The primary outcome was the proportion of patients with post-thrombotic syndrome at 12 months diagnosed according to the original Villalta criteria-a Villalta-score of at least 5 on two consecutive occasions at least 3 months apart or the occurrence of venous ulceration-and was assessed in a modified intention-to-treat population of all randomly assigned patients who passed screening and started treatment. The safety analysis was assessed in the same modified intention-to-treat population. This study is complete and is registered at ClinicalTrials.gov, NCT00970619., Findings: Between May 28, 2010, and Sept 18, 2017, 184 patients were randomly assigned to either additional ultrasound-accelerated catheter-directed thrombolysis (n=91) or standard treatment alone (n=93). Exclusion because of screening failure or early withdrawal of informed consent resulted in 77 patients in the intervention group and 75 in the standard treatment group starting allocated treatment. Median follow-up was 12·0 months (IQR 6·0-12·0). 12-month post-thrombotic syndrome occurred in 22 (29%) patients allocated to additional treatment versus 26 (35%) patients receiving standard treatment alone (odds ratio 0·75 [95% CI 0·38 to 1·50]; p=0·42). Major bleeding occurred in four (5%) patients in the intervention group, with associated neuropraxia or the peroneal nerve in one patient, and no events in the standard treatment group. No serious adverse events occurred. None of the four deaths (one [1%] in the intervention group vs three [4%] in the standard treatment group) were treatment related., Interpretation: This study showed that additional ultrasound-accelerated catheter-directed thrombolysis does not change the risk of post-thrombotic syndrome 1 year after acute iliofemoral deep-vein thrombosis compared with standard therapy alone. Although this trial is inconclusive, the outcome suggests the possibility of a moderate beneficial effect with additional ultrasound-accelerated catheter-directed thrombolysis. Further research is therefore warranted to better understand this outcome in the context of previous trials, preferably by combining the available evidence in an individual patient data meta-analysis., Funding: The Netherlands Organisation for Health Research and Development (ZonMw), Maastricht University Medical Centre, BTG-Interventional Medicine., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Studies show mixed results on the association between depressive symptoms and adverse clinical outcomes in patients on dialysis therapy. Ethnicity may play a role in these heterogeneous results. No studies have investigated the interplay between ethnicity and depressive symptoms on clinical outcome in this patient population. This study aims to examine interaction between ethnicity and depressive symptoms on hospitalization and mortality in dialysis patients., Methods: A multi-ethnic cohort in 10 dialysis centers included 687 dialysis patients between 2012 and 2017, with an average follow-up of 3.2 years. Depressive symptoms were measured using the Beck Depression Inventory. Interaction was assessed by investigating excess risk on an additive scale using both absolute rates and relative risks. Multivariable regression models included demographic, social, and clinical variables., Results: Adverse outcomes are more pronounced in native patients, compared to immigrant patients. The risk for mortality and hospitalization is considerably higher in native patients compared to immigrants. An excess risk on an additive scale indicates the presence of possible causal interaction., Conclusions: Depressive symptoms are a risk factor for hospitalization and mortality, especially in native dialysis patients. Adverse clinical events associated with depressive symptoms differ among ethnic groups. This differential association could play a role in the conflicting findings in literature. Ethnicity is an important factor when investigating depressive symptoms and clinical outcome in dialysis patients. Future research should focus on the possible mechanisms and pathways involved in these differential associations.

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., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Patients undergoing chronic dialysis often display sustained elevations of inflammation markers and also have a high prevalence of depressive symptoms. Although multiple studies demonstrated cross-sectional associations between inflammation markers and depressive symptoms in this patient group, longitudinal associations have not been examined. We therefore investigated whether longitudinal associations exist between inflammation markers and depressive symptoms in chronic dialysis patients., Methods: Data of three consecutive measurements of an observational, prospective cohort study among chronic dialysis patients were used. At baseline, 6-month, and 12-month follow-up, patients completed the Beck Depression Inventory, and inflammation markers (high-sensitivity C-reactive protein [HsCRP], interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor α) were measured. We examined cross-sectional associations between inflammation markers and depressive symptoms using linear regression models. The longitudinal association between inflammation and depressive symptoms was assessed using a linear mixed model analyses., Results: A total of 513 patients were included. Cross-sectional associations were found between HsCRP and depressive symptoms at baseline (β = 0.9, confidence interval [CI] = 0.4-1.4) and 6-month follow-up (β = 1.1, CI = 0.3-2.0), and between IL-1β and depressive symptoms at 6-month follow-up (β = 1.3, CI = 0.8-1.8) and 12-month follow-up (β = 1.2, CI = 0.4-1.9). Inflammation makers (HsCRP, IL-6, IL-1β, IL-10, and tumor necrosis factor α) at baseline were not associated with depressive symptoms at follow-up and vice versa., Conclusions: We confirmed the presence of cross-sectional associations between inflammation markers and depressive symptoms in chronic dialysis patients, but with our longitudinal data, we found no longitudinal associations. This supports an associative instead of a causal relationship between inflammation and depressive symptoms.

Due to continuing migration there is more interest in the mental health status of immigrants. The aim of this study is to determine the prevalence of depressive/anxiety symptoms in immigrant and native dialysis patients, and to explore if patient characteristics can explain differences. The Beck depression inventory and the beck anxiety inventory were used. Differences between native and immigrant patients were explored using logistic regression models adjusted for patient characteristics. The prevalence of depressive symptoms was 35% for 245 native patients and 50% for 249 immigrant patients. The prevalence of anxiety symptoms was 35% for native patients and 50% for immigrant patients. In addition, the prevalence for co-morbid depressive and anxiety symptoms was 20% for native patients and 32% for immigrant patients. Crude ORs for depressive/anxiety symptoms for immigrant patients versus native patients were 1.8 (1.2-2.5) and 1.7 (1.2-2.5), respectively. After adjustment for patient characteristics ORs remained the same. Clinicians should be aware that immigrant dialysis patients are more prone to develop depressive and anxiety symptoms. Cultural factors might play a role and should therefore be assessed in future research.

Objective: Among immigrant chronic dialysis patients, depressive and anxiety symptoms are common. We aimed to examine the association of acculturation, i.e. the adaptation of immigrants to a new cultural context, and depressive and anxiety symptoms in immigrant chronic dialysis patients., Methods: The DIVERS study is a prospective cohort study in five urban dialysis centers in the Netherlands. The association of five aspects of acculturation ("Skills", "Social integration", "Traditions", "Values and norms" and "Loss") and the presence of depressive and anxiety symptoms was determined using linear regression analyses, both univariate and multivariate., Results: A total of 249 immigrant chronic dialysis patients were included in the study. The overall prevalence of depressive and anxiety symptoms was 51% and 47%, respectively. "Skills" and "Loss" were significantly associated with the presence of depressive and anxiety symptoms, respectively ("Skills" β=0.34, CI: 0.11-0.58, and "Loss" β=0.19, CI: 0.01-0.37; "Skills" β=0.49, CI: 0.25-0.73, and "Loss" β=0.33, CI: 0.13-0.53). The associations were comparable after adjustment. No significant associations were found between the other subscales and depressive and anxiety symptoms., Conclusion: This study demonstrates that less skills for living in the Dutch society and more feelings of loss are associated with the presence of both depressive and anxiety symptoms in immigrant chronic dialysis patients., (Copyright © 2016. Published by Elsevier Inc.)

Treatment goals for patients with CKD are often unrealized for many reasons, but support by nurse practitioners may improve risk factor levels in these patients. Here, we analyzed renal endpoints of the Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse Practitioners (MASTERPLAN) study after extended follow-up to determine whether strict implementation of current CKD guidelines through the aid of nurse practitioners improves renal outcome. In total, 788 patients with moderate to severe CKD were randomized to receive nurse practitioner support added to physician care (intervention group) or physician care alone (control group). Median follow-up was 5.7 years. Renal outcome was a secondary endpoint of the MASTERPLAN study. We used a composite renal endpoint of death, ESRD, and 50% increase in serum creatinine. Event rates were compared with adjustment for baseline serum creatinine concentration and changes in estimated GFR were determined. During the randomized phase, there were small but significant differences between the groups in BP, proteinuria, LDL cholesterol, and use of aspirin, statins, active vitamin D, and antihypertensive medications, in favor of the intervention group. The intervention reduced the incidence of the composite renal endpoint by 20% (hazard ratio, 0.80; 95% confidence interval, 0.66 to 0.98; P=0.03). In the intervention group, the decrease in estimated GFR was 0.45 ml/min per 1.73 m(2) per year less than in the control group (P=0.01). In conclusion, additional support by nurse practitioners attenuated the decline of kidney function and improved renal outcome in patients with CKD.

Objective: To map the relation between metformin prescription and renal function in an outpatient setting. To investigate whether there is an association between renal function, metformin concentration and lactate concentration., Design: Pilot for a prospective observational cohort study., Method: We included outpatients with diabetes mellitus type 2 who were treated with metformin. At inclusion, we determined the HbA1c, lactate, metformin and creatinine concentrations and the estimated glomerular filtration rate (eGFR). Information on the prescribed dosage of metformin was acquired from patient files. Our primary outcome measure was the number of patients in whom the dose was not adjusted to the renal function. Our secondary outcome measure was the difference in median lactate concentration between patients with a normal (≤ 2.5 mg/l) and an increased (> 2.5 mg/l) metformin concentration., Results: Eighty-eight patients were included, 12 (14%) of whom had an eGFR ≤ 30, 31 (36%) an eGFR of 30-50 and 44 (50%) an eGFR > 51 ml/min/1.73 m2. In 27 (31%) of all patients, the daily dose of metformin exceeded the dose recommended in the practice guidelines. The 28 patients with an increased metformin concentration had a significantly higher median lactate concentration: 2.3 mmol/l compared to 1.5 mmol/l for the 60 patients with a normal metformin concentration (p < 0.0001)., Conclusion: Our study shows that in outpatient practice, the metformin dose is not sufficiently adjusted to a reduced renal function in 31% of the patients. The accumulation of metformin appears to be associated with an increased lactate concentration and a reduced renal function. Extra attention to the dose of metformin in reduced renal clearance is therefore recommended.

Strict implementation of guidelines directed at multiple targets reduces vascular risk in diabetic patients. Whether this also applies to patients with chronic kidney disease (CKD) is uncertain. To evaluate this, the MASTERPLAN Study randomized 788 patients with CKD (estimated GFR 20-70 ml/min) to receive additional intensive nurse practitioner support (the intervention group) or nephrologist care (the control group). The primary end point was a composite of myocardial infarction, stroke, or cardiovascular death. During a mean follow-up of 4.62 years, modest but significant decreases were found for blood pressure, LDL cholesterol, anemia, proteinuria along with the increased use of active vitamin D or analogs, aspirin and statins in the intervention group compared to the controls. No differences were found in the rate of smoking cessation, weight reduction, sodium excretion, physical activity, or glycemic control. Intensive control did not reduce the rate of the composite end point (21.3/1000 person-years in the intervention group compared to 23.8/1000 person-years in the controls (hazard ratio 0.90)). No differences were found in the secondary outcomes of vascular interventions, all-cause mortality or end-stage renal disease. Thus, the addition of intensive support by nurse practitioner care in patients with CKD improved some risk factor levels, but did not significantly reduce the rate of the primary or secondary end points.

Background: Guidelines have set goals for risk factor management in chronic kidney disease (CKD) patients. These goals are often not met. In this analysis, we set out to assess the quality of risk factor management in CKD and to identify factors that determine the quality of care (QoC). For that purpose, baseline data of the MASTERPLAN (Multifactorial Approach and Superior Treatment Efficacy in Renal Patients with the Aid of Nurse practitioners) study have been used. MASTERPLAN is a multicentre study which evaluates the effect of a multifactorial intervention in prevalent CKD patients on cardiovascular (CV) events and progression of kidney failure., Methods: QoC was quantified using a score based on the number of 11 defined treatment goals on target. The maximum score per patient was 11., Results: The average (±SD) QoC score was 6.7 (±1.5). The average score per centre ranged from 5.9 to 6.9. In a multivariable analysis, centre proved to be a significant, independent determinant of QoC with a difference up to 0.7 between centres. This difference remained when adjustments were made for those risk factors primarily treated by pharmacotherapy. Other factors that were significantly related to the QoC were estimated glomerular filtration rate, Caucasian race, diabetes mellitus, diabetic nephropathy as cause of kidney disease and previous kidney transplantation., Conclusions: In CKD patients, risk factors for progression of kidney failure and CV events were inadequately controlled. Treatment centre proved to be an important determinant of QoC. This data may point towards the physician's interest and preference as important determinants of QoC. This is a potentially modifiable determinant of the quality of patient care [Trial registration ISRCTN registry: 73187232 (http://isrctn.org)].

We present a patient with a rare cause of ectopic ACTH-dependent Cushing's syndrome, caused by a pheochromocytoma. The case provides clues for a detailed discussion on the pitfalls and diagnostic difficulties in establishing the correct underlying cause of ACTH-dependent Cushing's syndrome. It clearly demonstrates that the relative contributions of clinical, biochemical, and radiological clues in establishing the correct underlying cause of Cushing's syndrome may differ considerably between Cushing's disease and Cushing's syndrome due to ectopic overproduction of ACTH. In addition, the literature concerning ACTH-producing pheochromocytomas is reviewed.

Case report of a 62-year-old woman who developed acute renal failure due to nephrocalcinosis, also called acute phosphate nephropathy, after large bowel cleansing in preparation for colonoscopy using oral sodium phosphate solution (Phosphoral, de Witt, Cheshire, UK). Subsequently her renal insufficiency resolved only partially resulting in stage 4 chronic kidney disease. In retrospect multiple risk factors for this condition (hypertension, diuretics, AT-II receptor blocker, female gender, advanced age and volume depleting due to vomiting and nausea) were identified. If these factors had been taken into consideration prior to prescribing this drug, acute and chronic renal failure would have been prevented. Future investigation of potential risk factors and the exact mechanism of this complication is necessary to identify those patients prone to develop this complication. In the meantime prescribing physicians should be made aware of this complication. On the basis of the current state of knowledge the evidence seems to be quite compelling not to prescribe these drugs in patients with one or more associated risk factors. It could even be argued that these drugs should not be prescribed at all.

Treatment of patients with IgA nephropathy (IgAN) depends on a reliable assessment of disease progression based on measurements of glomerular filtration rate (GFR), proteinuria, hypertension, and tubulointerstitial changes. We sought to determine whether progression could be predicted from analysis of glomerular and tubulointerstitial inflammation in biopsies taken at an early stage of IgAN. We retrospectively analyzed biopsies from 50 patients, relating the subsequent clinical course to infiltration with B- and T-lymphocytes, granule membrane protein of 17 kDa (GMP-17) positive cytotoxic T cells, macrophages, fibroblasts, and tubulointerstitial expression of human leukocyte antigen-D related (HLA-DR). At biopsy, 19 patients had decreased GFR while 13 of 31 patients with normal GFR and progressive IgAN differed significantly from 18 non-progressors in the level of proteinuria and in the severity of scores for mesangial proliferation, tubular atrophy, interstitial fibrosis, and interstitial infiltrates. On multivariate regression analysis these differences disappeared; however, associations with GMP-17-positive cytotoxic T-lymphocytes in intact renal tubules and of B-lymphocytes in the interstitium remained significant. Our study may have identified a marker of disease progression in early stages of IgAN.

The plastic hardener methyl ethyl ketone peroxide (MEKP) is an unstable peroxide that releases free oxygen radicals. Ingestion of this compound induces widespread liver necrosis that is often fatal, extensive ulceration with subsequent scarring, and stenosis of the proximal digestive tract in survivors. Severe metabolic acidosis occurs due to the accumulation of formic acid and other organic acids inducing neurologic damage, such as optic nerve lesions. A 53-year-old man unintentionally ingested approximately 120 ml of a 33% solution of this compound in dimethylphtalate. The patient was treated with the free radical scavenger N-acetylcysteine to counteract free radical-mediated damage and with hemodialysis to remove accumulated organic acids. Although our patient demonstrated considerable edema and ulceration of the distal esophagus, stomach and duodenum in the acute phase, there was never any sign of liver damage or neurological damage, nor were there any demonstrable lesions in the proximal digestive tract three weeks after the event. Treatment with a combination of N-acetylcysteine and haemodialysis may be a promising therapy for this severe and potentially life-threatening intoxication.

The 'Stichting Werkgroep Antibioticabeleid' (SWAB; Dutch Working Party on Antibiotic Policy) has developed an evidence-based guideline for the empirical antimicrobial treatment of complicated urinary tract infections (UTIs) in hospitalised adult patients. The choice of treatment is based on recent Dutch data on the resistance ofuropathogens to the most frequently used antibiotics. The first choice for empirical antibiotic treatment in a patient with a complicated UTI is a 2nd or 3rd generation cephalosporin or the combination of amoxicillin and gentamicin. Amoxicillin-clavulanic-acid intravenously is the second empirical choice. The treatment duration must be at least 10 days. The treatment must be adjusted after the results of the urine culture become known and made more specific if possible. Oral treatment can be given if the patient's clinical situation allows it. There are separate recommendations for the treatment ofUTIs in the following patient categories: men, pregnant women, patients with a urinary catheter, patients with diabetes mellitus and patients with renal diseases, congenital polycystic kidney disease or pyocystis.

Background: Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets.A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population., Design: MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study.

Background: Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease (CVD). In addition, patients with renal disease are exposed to a myriad of risk factors that increase their risk even further. The treatment of risk factors in these patients is paramount to reducing cardiovascular risk and for attenuating renal failure progression. It is well known that lifestyle interventions are difficult, and that medical treatment targets are seldom met. A multifactorial approach with the aid of nurse practitioners has shown to be beneficial for achieving treatment goals and reducing events in patients with diabetes mellitus and with heart failure. We propose that this will also hold for the CKD population., Trial Design: A multicenter randomized clinical trial will be performed to study whether intensive medical care delivered by a nurse practitioner and a nephrologist will reduce cardiovascular risk compared to care provided by the nephrologist alone. The acronym MASTERPLAN describes the study: Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Eight hundred patients will be randomized to physician care or nurse practitioner support. For all patients the same set of guidelines and treatment goals will apply. Both groups will receive treatment according to current guidelines and have access to specific cardioprotective medication. Nurse practitioners will intensify therapy by promoting lifestyle intervention, and meticulous implementation of relevant guidelines. Patients will be followed-up for 5 yrs after baseline. Primary endpoints are all-cause mortality, cardiovascular morbidity and cardiovascular mortality.

Fibronectin (FN) is an extracellular matrix component which appears in different isoforms, due to alternative mRNA splicing of the ED-A, ED-B, and IIICS regions, and subsequent post-translational modifications. The FN isoforms, some of which occur specifically during fetal development and in fibrogenic diseases, have been reported to play a role in various biological functions, such as regulation of the matrix assembly, adhesion, and proliferation. The contribution of these FN isoforms to the pathogenesis of chronic renal diseases, which are also fibrogenic disorders, is not well known. This study therefore examined the distribution of FN isoforms in renal diseases by immunohistochemistry, with a panel of isoform-specific monoclonal antibodies (MAbs), applied to 63 abnormal renal biopsies and ten normal controls. Normal kidneys contained total FN (MAb IST4) both in the mesangial and in the interstitial extracellular matrix (ECM), but only traces of ED-A-positive FN (MAb IST9), and no ED-B-positive FN (MAb BC1) or oncofetal FN (MAb FDC6) was found in normal renal tissue. All patients with renal disease demonstrated increased total FN staining of the interstitium and the mesangium. Periglomerular fibrotic lesions and fibrous crescents showed massive accumulation of total FN, whereas the amount of total FN in the ECM of obsolescent glomeruli was decreased, compared with that in normal mesangial ECM. Oncofetal (FDC6), EDB-negative (MAb IST6), ED-A-positive, and ED-B-positive FN isoforms were found in glomerular ECM accumulations and in fibrous crescents. Tubulointerstitial fibrotic lesions predominantly contained the ED-A-positive FN isoform, whereas in globally sclerotic glomeruli, predominantly ED-B-positive FN was observed. The expression of FN isoforms was similar in all renal diseases studied. These results show that in various renal diseases, oncofetal (FDC6) FN and ED-A- and ED-B-positive isoforms of FN accumulate at locations of chronic lesions, independently of the aetiology of the disease. The deposition of these isoforms in human renal tissue may play a role in the modulation of the immune response by attracting monocytes and lymphocytes to the injured kidney. Furthermore, because the ED-B-positive FN isoform is highly susceptible to proteolytic degradation, its accumulation may play a role in scar formation and tissue repair. ED-B-positive FN forms a temporary scaffold supporting the cells, which can easily be cleared by proteolytic degradation once new tissue has been produced at the site of injury.

All glomerular kidney disorders with the exception of minimal change disease are characterized by a progressive decline of renal function in association with progressive glomerulosclerosis and tubulointerstitial fibrosis of the kidneys involved. This almost universal association seems to suggest that the progressive loss of kidney function results from a fibrogenic pathogenetic mechanism that serves as a final common pathway with the initial insult to the glomerulus initiating a cascade of events including an early inflammatory phase followed by a fibrogenic response in the glomerular and the tubulointerstitial compartments of the kidneys. The present review will address the pathogenesis of this fibrogenic process covering the interplay between glomerular and tubulointerstitial events, the roles of recruited and resistant cells, cytokines, growth factors and the extracellular matrix.

Background: The insertion-deletion (I/D) polymorphism of the angiotensin converting enzyme gene is a diallelic polymorphism that constitutes a genetic influence on the progression of renal diseases such as IgA nephropathy. Patients with the DD genotype have an accelerated progression towards end stage renal failure in these diseases. The role of the I/D polymorphism in the pathogenesis of diabetic nephropathy in IDDM is unresolved., Patients and Methods: We therefore set out to study the contribution of the I/D polymorphism in 79 patients (age 39.5 +/- 7.6 years (mean +/- SD) with end stage renal failure due to diabetic nephropathy, who were recipients of a combined kidney-pancreas transplantation (n = 60), or who were on the waiting list for such a procedure (n = 19). The control series consisted of 82 patients (age 39.5 +/- 9.6 years) without microalbuminuria after fifteen years of IDDM., Results: The ACE genotype distribution in patients was not in accordance with the Hardy-Weinberg equilibrium due to a significant overrepresentation of the DD genotype (X2 = 8.9, p = 0.01). This resulted in a significant increase of the D-allele frequency in the cases compared to controls (X2 = 4.9, p = 0.03). The presence of one D-allele did not increase the risk of end stage renal failure (odds ratio ID/II = 1.0, 95% CI 0.4-2.2). The presence of the DD genotype increased the risk of end stage renal failure twofold compared to the other genotypes (odds ratio 2.1, 95% CI 1.1-4.0). The risk estimate seemed slightly higher in patients with good metabolic control (odds ratio 2.6, 95% CI 1.0-7.1), than in patients with poor control (odds ratio 1.6, 95% CI 0.59-4.3)., Conclusion: It is concluded that the risk of end-stage renal failure in patients with IDDM is twofold increased in patients with the DD genotype as compared to patients with other genotypes.

It is generally accepted that the severity of renal insufficiency in patients correlates with the severity of tubulointerstitial abnormalities, but not with the severity of glomerular abnormalities in kidney biopsies. We recently challenged this view by demonstrating significant correlations of glomerular structural abnormalities with renal function in a histomorphometric study of biopsies from patients with various kidney diseases. We set out to confirm these findings in biopsies from patients with a single disease entity. IgA nephropathy was selected. An additional objective of the study was to determine the prognostic value of our histological predictors of renal function. Histomorphometric measurements were done in silver- and PAS-stained paraffin sections of biopsies from 83 patients with primary IgA nephropathy. The results were correlated with creatinine clearance at the time of biopsy. The prognostic value of the histomorphometric parameters and of several clinical characteristics were determined in a Cox proportional hazard model. All glomerular histomorphometric indices correlated with the severity of renal insufficiency, but quantitative estimates of the glomerular deposition of periodic acid-Schiff positive extracellular matrix (PAS-index) seemed to be the most important glomerular structural-functional correlate (r = 0.53, p<0.001). However, the correlation of quantitative estimates of the severity of interstitial extracellular matrix accumulation with renal function (quantitative interstitial index) was superior (r = 0.76, p<0.001). Creatinine clearance at biopsy and initial proteinuria were the strongest clinical predictors of renal survival. The severity of tubulointerstitial extracellular matrix accumulation was the strongest histological predictor of an adverse outcome. In conclusion, quantitative estimates of the severity of glomerular and tubulointerstitial extracellular matrix accumulation both correlate well with the severity of renal failure in biopsies from patients with IgA nephropathy. Creatinine clearance at biopsy, initial proteinuria and the severity of tubulointerstitial extracellular matrix accumulation are the best predictors of renal survival. On a more general note, the paradigm of the absence of correlation of glomerular pathology with renal function should be abandoned.

General agreement exists on the correlation of renal insufficiency with the severity of tubulointerstitial abnormalities in the biopsy. This could not be shown for the severity of glomerular pathology by semiquantitative methods. The relation between renal function and glomerular pathology was therefore evaluated in patients with various kidney diseases using quantitative measurements. Fifty-five patients and ten controls were studied. Histomorphometric measurements of renal biopsies were obtained for both frozen and paraffin sections and were correlated with serum creatinine values. The frozen sections were stained with an indirect immunoperoxidase technique using antibodies against collagen types I, IV, V, VI, laminin, fibronectin, decorin and heparansulphate proteoglycan core protein. The contribution of each component to the composition of the mesangial extracellular matrix was scored with a semiquantitative technique. All glomerular histomorphometric indices correlated with the severity of renal insufficiency expressed as serum creatinine at the time of biopsy. However, quantitative estimates of the glomerular deposition of periodic acid-Schiff positive extracellular matrix seemed to be the most important structural correlate of renal function (r = 0.524, p = 0.0001). Semiquantitative estimates of interstitial extracellular matrix accumulation were less correlated with renal function (r = 0.370, p = 0.01). The composition of the mesangial extracellular matrix did not differ in patients and controls, with the exception of the extent of laminin staining, which was significantly higher in patients. The extent of fibronectin staining in patients correlated with the severity of glomerular structural abnormalities. This study demonstrates that the severity of renal insufficiency in a variety of renal diseases correlates with the severity of glomerular pathology, when quantitative scoring is applied.

The degree of impairment of renal function in patients with chronic renal failure correlates closely with the extent of fibrosis in the tubulointerstitium, i.e. of interstitial extracellular matrix (ECM) accumulation. The composition of this pathological extracellular matrix and the relation between the ECM composition on the one hand and the severity of histological changes and renal function on the other has not been investigated. This prompted us to perform the present study. The severity of histological abnormalities and the composition of the interstitial ECM were assessed using a semiquantitative scoring technique in 57 biopsies from patients with kidney disease of diverse etiology and variable degrees of renal failure and were contrasted with the results of 9 control biopsies. Tissue sections were stained with an indirect immunoperoxidase technique using antibodies against collagen I, III, IV, V, VI, laminin, fibronectin, decorin and heparansulphate proteoglycan core protein (HSPG). Collagen IV, laminin and HSPG were virtually absent from the interstitium in controls. These components were more widely distributed in patients and the extent of their deposition correlated with the severity of interstitial histological abnormalities. In patients with severe interstitial damage the deposition became diffuse. Collagen type I and III were already diffusely distributed in the interstitium of controls and did not increase significantly as interstitial damage became more severe. However, the extent of collagen III staining in patients was significantly higher than in controls. Decorin staining showed a patchy distribution both in patients and controls. The overall distribution was significantly increased in patients. The extent of the deposition of both collagen V and VI was significantly increased in patients when compared with controls. Only the distribution of collagen V correlated with the severity of histological abnormalities. Our findings suggest that an increased interstitial deposition of extracellular matrix substances which are generally regarded as basement membrane components contributes more to the development of interstitial fibrosis and renal failure than the deposition of the fiber forming interstitial collagens type I and III, which are prominent in controls and in patients irrespective of the severity of histological abnormalities. Decorin staining was significantly enhanced in patients and was found to be the best predictor both of the severity of interstitial fibrosis and of renal failure. This could mean that decorin is important in human renal pathology. Collagen V and VI staining was significantly increased in patients when compared with controls. To our knowledge this is the first study in which this is demonstrated.

A self-administered health-assessment questionnaire (HAQ) was completed by 38 Dutch rheumatoid arthritis (RA) patients and the results compared to those obtained objectively when the same subjects were interviewed and asked to perform standardised tasks included in the HAQ. The results of the interview and the questionnaire showed a high degree of overall correlation and inter-component correlation. The correlation was comparable in outpatients with milder disease and in patients with more severe disease and was not influenced by age. The questionnaire offers a valid approach to the assessment of the functional disability of RA patients.