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Background: Patient-reported outcome measures are increasingly used by clinicians to support communication in telephone- or face-to-face consultations with patients. A renal disease questionnaire has been developed, but not sufficiently evaluated through clinimetrics in clinical setting. Hence, we aimed to evaluate the content validity, construct validity and the test–retest reliability of a renal disease questionnaire to be used for clinical decision-making. Methods: A content, construct validity and test–retest reliability study was conducted in 3 nephrology outpatient clinics in Central Denmark Region, Denmark. Content validity (face validity, comprehensibility and relevance) was assessed among 8 patients and 6 clinicians. Reliability was assessed by asking outpatients with chronic kidney disease to complete the questionnaire twice. Reliability was assessed by kappa statistics and agreement by percentage. Construct validity was determined using 4 a priori defined hypotheses and comparing 2 known groups. Results: Five new domains emerged, 6 items were rephrased and 3 items were removed following the content validity test. A total of 160 patients completed the questionnaire with median 8 days (IQR 2 days) between assessments. The test–retest reliability parameters of the single items in the questionnaire were substantial to almost perfect as all the observed weighted kappa values ranged from 0.61 to 0.91, 95% CI (0.34 to 0.95). In total, 61% of the single items showed almost perfect agreement. In total, 3 of the 4 hypotheses were accepted and 44% of the items showed satisfying known-group discriminative validity. Conclusion: A renal disease questionnaire used for clinical decision-making in outpatient follow-up showed acceptable content validity and substantial to almost perfect reliability. Sufficient construct validity was not established. Incorporating the questionnaire into routine clinical practice may improve the evaluation of disease burden in patients with chronic kidney disease. Plain English summary: We ask patients with chronic kidney disease (CKD) in Central Region Denmark to complete a questionnaire before each outpatient visit. The answers they provide are used to support communication with their health care provider. A questionnaire requires testing to ensure it can accurately capture important information about patient's symptoms and quality of life. When questionnaires are used to support communication between patients and health care professionals, they need to have good measurement properties. This means they need to be: (1) trustworthy, (2) relevant to a patient's health condition, (3) consistent and produce stable results every time. We explored the measurement properties of a questionnaire designed to be used in the face-to face outpatient visits for patients with CKD. We found that the questionnaire captured consistent and stable results. Using this questionnaire may help health care professionals to assess the patients´ burden of symptoms with a more patient-centered approach. Potentially, the use of the questionnaire will increase the patients´ ability to cope with their symptoms and strengthen patients´ involvement in the clinical decisions concerning their treatment. [ABSTRACT FROM AUTHOR]

Background: Minimal change nephropathy (MCN) is a common cause of nephrotic syndrome in both adults and children. International guidelines recommend treatment with prednisolone 1 mg/kg/day to adults. This dose is derived from an empirically established dose in children, although children generally attain remission faster and relapse more rapidly than adults. Prednisolone is associated with multiple and serious adverse events. Activated vitamin D has been shown to reduce albuminuria in other glomerular renal diseases with a minimum of adverse events. This study tests the hypothesis that a new treatment regimen in MCN combining reduced dose prednisolone and active vitamin D is as efficient in inducing remission and has fewer and less severe adverse events than standard prednisolone. Furthermore, we aim to establish models allowing for more personalized medicine based on assessment of the individual's prednisolone metabolism.Methods: A randomised controlled multicentre non-inferior unblinded trial including 96 adult, incident patients with biopsy-proven MCN, albuminuria > 3 g/day, and an estimated glomerular filtration rate (eGFR) > 30 ml/min from renal departments in Denmark. Patients are randomised to standard prednisolone (1 mg/kg/day) or reduced prednisolone (0.5 mg/kg/day) and alfacalcidol (0.5 μg/day). The primary outcome is the rate of remissions after 16 weeks and the time from diagnosis to remission. The study will include a saliva test to characterise prednisolone pharmacokinetics and compare them to genetic variations in specific liver enzymes responsible for prednisolone metabolism.Discussion: Reducing the prednisolone dose is expected to reduce the number of severe adverse events. This study will examine if reduced prednisolone dose with active vitamin D but without additional immunosuppression is feasible in the treatment of MCN and will reduce the number of adverse events. The findings can potentially change current guidelines for treatment of MCN in adults. Additional outcomes on inter-individual pharmacokinetic and metabolic variations may allow for a more personalised treatment strategy.Trial Registration: EudraCT 2017-001206-16, ClinicalTrials.gov NCT03210688 . Registered on June 3, 2017. [ABSTRACT FROM AUTHOR]

Objectives This study aimed to characterize the association between HLA alleles and ANCA-associated vasculitis (AAV) in a genetically homogeneous population, and to analyse the contribution of specific HLA molecule amino acid sequences to the risk of AAV. Methods We included 187 Danish patients with AAV and 1070 healthy controls. All were HLA typed at two-field resolution. The association of HLA alleles to PR3- or MPO-AAV was analysed. The contribution of the dominant molecular motifs of the HLA-DPB1 molecule to the risk of AAV was investigated by association studies that included specific amino acid sequences of the hypervariable regions in exon 2. Results Ninety-four percent of patients with PR3-AAV were carriers of HLA-DPB1*04:01 while all patients with PR3-AAV were carriers of an HLA-DPB1*04 allele, and 85% were homozygous. This was significantly more than in the control group (P < 0.0001). The association was even stronger when HLA-DPB1*04:02 and -DPB1*23:01 were included. HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01 share amino acids in positions 8–9, 69, 76 and 84–87 within the hypervariable regions, but only positions 69 and 84–87 contributed significantly to the disease risk. HLA-DRB1*15 was associated with an increased risk of developing PR3-AAV, while HLA-DRB1*04, -DRB1*07 and -DQB1*03 were associated with a reduced risk of kidney involvement in PR3-AAV. MPO-AAV was only weakly associated with HLA class I alleles. Conclusion PR3-AAV is strongly associated with the HLA-DPB1 alleles HLA-DPB1*04:01, -DPB1*04:02 and -DPB1*23:01, which share amino acid sequences crucial for the peptide-binding groove. [ABSTRACT FROM AUTHOR]

• A large patient cohort was tested with qPCR for EBV-DNA in plasma and whole blood. • Primary infection, T-cell and Hodgkin lymphomas were predominant EBV diseases. • WHO qPCR for EBV-DNA had a low positive predictive value for proven EBV disease. • The analysis had an excellent negative predictive value for proven EBV disease. • The risk of diagnostic latency was high for patients with EBV-positive lymphoma. Quantitative polymerase chain reaction (qPCR) for Epstein–Barr virus (EBV)-DNA is an important diagnostic tool for EBV-associated disease, but interpretation of its clinical significance is challenging. We assessed the diagnostic and clinical performance of WHO-standardised qPCR for EBV-DNA (WHO EBV-qPCR) in plasma and whole blood (WB) for proven EBV disease in a prospectively accrued patient cohort. Central Denmark Region patients, tested with WHO EBV-qPCR from November 2017 to March 2019, were screened for EBV disease. Incidence (IR) was estimated by Poisson regression. Sensitivity, specificity, positive and negative predictive values (PPV, NPV) were calculated for EBV-qPCR in plasma and WB. Risk of diagnostic latency was compared between patients with EBV-positive and EBV-negative lymphomas. EBV disease was diagnosed in 95 of 1484 participants (IR: 16.3 per 1000 patientyears 95%CI; 13.3–19.9). Sensitivity and specificity of WHO EBV-qPCR in plasma was 82.4% (95% CI; 74.2–90.7%) and 87.8% (95% CI; 85.6–90%), yielding a PPV of 32.2% (95% CI; 24.9–39.5%) and NPV of 98.6% (95% CI; 97.7–99.5%) for proven EBV disease. Sensitivity and NPV were comparable in WB, while specificity and PPV decreased to 66.9% (95% CI; 60.6–73.1%) and 18.1% (95% CI; 7.5–28.7%). Risk of diagnostic latency was 2.3-fold (95% CI 1.4–4.1) higher for patients with EBV-positive compared with EBV-negative lymphomas. WHO EBV-qPCR in plasma and WB have a low PPV but a high NPV for proven EBV disease. Implementation of WHO EBV-qPCR could improve interpretation and facilitate EBV-positive lymphoma diagnosis. [ABSTRACT FROM AUTHOR]

Background: Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) carries a high risk of morbidity and mortality, with outcomes modified by treatment and an incidence that may be increasing. We examined temporal changes in incidence and mortality during 2000-15 using nationwide healthcare registries., Methods: Patients with incident AAV were identified using International Classification of Diseases Version 10 (ICD10) codes and grouped according to inclusion year (Period 1: 2000-04, Period 2: 2005-09, Period 3: 2010-15). Log link cumulative incidence regression adjusted for age, sex, renal function, cardiovascular disease, diabetes, hypertension and advanced disease severity were used to model survival., Results: We identified 1631 patients (52% male), corresponding to an incidence of 18.5 persons/million/year (Period 1: 15.1, Period 2: 18.5, Period 3: 21.4). The slope of incident serologic ANCA testing was steeper than that of AAV (P = 0.002). Mean [standard deviation (SD)] age was 60.2 (16.7) years and mean (SD) follow-up was 6.8 (4.7) years. A total of 571 (35%) patients died (5-year mortality of 22.1%), with an absolute risk ratio (ARR) for Periods 2 and 3 compared with Period 1 of 0.80 [confidence interval (CI) 0.65-0.98, P = 0.031] and 0.39 (CI 0.31-0.50, P < 0.001). About 274 patients developed end-stage renal disease (ESRD) [16.8% (Period 1: 23.3%, Period 2: 17.6%, Period 3: 12.5%)], with ARR decreasing over time: Period 2 0.61 (CI 0.42-0.87, P = 0.007) and Period 3 0.57 (CI 0.39-0.83, P = 0.003). The overall risk of death associated with ESRD or chronic kidney disease was 1.74 (CI 1.29-2.37, P < 0.001) and 1.58 (CI 1.21-2.07, P < 0.001)., Conclusions: Incidence of ANCA testing and AAV diagnosis increased over the test period. Falls over time in mortality and ESRD risk may relate to earlier diagnosis and changes in treatment practice., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Older people are the largest and fastest growing group of patients with end-stage renal disease (ESRD), and, due to advanced age and a heavy burden of comorbidities, they are usually not candidates for renal transplantation or home-based dialysis treatment. Some of the barriers for home treatment are non-modifiable, but the majority of physical disabilities and psychosocial problems can be overcome provided that assistance is offered to the patients at home.In the present review, we describe the programs for assisted peritoneal dialysis (PD) in France and Denmark, respectively. In both nations, assisted PD is totally publicly funded, and the cost of assisted PD is comparable to the cost of in-center HD. Assisted continuous ambulatory PD (aCAPD) is the preferred modality in France whereas assisted automated PD (aAPD) is the preferred modality in Denmark. Assistants are professional nurses or healthcare technicians briefly educated by expert PD nurses from the dialysis unit.The establishment of a program for assisted PD may increase the number of patients actually treated with PD and may reduce the risk of PD technique failure and prolong PD duration. Compared with autonomous PD patients, patients on assisted PD may have shorter patient survival and peritonitis-free survival indicating that, besides advanced age and the burden of comorbidities, dependency on help may be an independent risk factor for poorer outcome.Assisted PD is an evolving dialysis modality, and may in the future prove to be a feasible complementary alternative to in-center hemodialysis (HD) for the growing group of dependent older patients with ESRD., (Copyright © 2015 International Society for Peritoneal Dialysis.)

Background: The vitamin D receptor activator paricalcitol has been shown to reduce albuminuria. Whether this is a unique property of paricalcitol, or common to all vitamin D analogues, is unknown. The primary aim of this study was to evaluate the effect of alfacalcidol on proteinuria, measured as 24 hour (24 h) albuminuria, in patients with chronic kidney disease (CKD) stage 4-5 being treated for secondary hyperparathyroidism (sHPT)., Methods: A retrospective single-center study including adult patients with CKD 4-5, undergoing treatment for sHPT with alfacalcidol, with macroalbuminuria in minimum one 24 h urine collection. Patients were identified in a prospectively collected database of all patients with S-creatinine > 300 μM or creatinine clearance < 30 ml/min. The observation period was from 1st of January 2005 to 31st of December 2009. Phosphate binders and alfacalcidol were provided to patients free of charge., Results: A total of 146 macroalbuminuric patients were identified, and of these, 59 started alfacalcidol treatment during the observation period. A 12% reduction in 24 h albuminuria was seen after starting treatment. In 19 patients with no change in renin-angiotensin-aldosteron-system (RAAS) inhibition, the reduction in albuminuria was 16%. The reduction remained stable over time (9%) in a subgroup of patients (n = 20) with several urine collections before and after the start of alfacalcidol-treatment., Conclusion: The present study supports experimental and clinical data on antiproteinuric actions of activated vitamin D analogues, and suggests that this may be a class-effect.

Objectives: Plasma exchange (PE) has been shown to improve renal outcome in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and severe renal failure; however the effect of PE in AAV with moderate renal impairment is controversial., Methods: A single-centre, retrospective one-year follow-up study, including patients with renal AAV and eGFR <60 ml/min/1.73 m2. Since 2007, all patients with renal AAV and eGFR <60 ml/min/1.73 m2 had PE in addition to induction therapy with cyclophosphamide and prednisolone. Patients admitted from 1999 to 2007 that did not receive PE served as controls. The primary outcome was the combination of death, end-stage renal disease, and relapses after one year., Results: A significant reduction in the primary endpoint was observed following the addition of PE (25% vs. 43%, p=0.04). Furthermore, a greater improvement in renal function after one year was observed among surviving PE treated patients not on dialysis (ΔeGFR 36.1 vs. 19.7 ml/min, p=0.03). There was a significant reduction in serious adverse events in the PE treated group (4% vs. 30%, p=0.02) despite no differences in types and doses of induction immunosuppressive therapy. The advantageous effect of PE was related to the presence of anti-proteinase3 (PR3)-antibodies and also evident among patients with plasma creatinine less than 500 μM., Conclusions: This study suggests the use of PE in addition to standard induction treatment with cyclophosphamide and glucocorticoids to patients with renal PR3-AAV and an estimated-GFR <60 ml/min/1.73m2.