Improving home haemodialysis: Stability evaluation of routine clinical chemistry analytes in blood samples of haemodialysis patients

Introduction: A growing number of dialysis patients is treated with home haemodialysis. Our current pre-analytical protocols require patients to centrifuge the blood sample and transfer the plasma into a new tube at home. This procedure is prone to errors and precludes accurate bicarbonate measurement, required for determining dialysate bicarbonate concentration and maintaining acid-base status. We therefore evaluated whether cooled overnight storage of gel separated plasma is an acceptable alternative. Materials and methods: Venous blood of 34 haemodialysis patients was collected in 2 lithium heparin blood collection tubes with gel separator (LH PSTTM II, REF 367374; Becton Dickinson, New Jersey, USA). One tube was analysed directly for measurement of bicarbonate, potassium, calcium, phosphate, glucose, urea, lactate, aspartate aminotransferase (AST), and lactate dehydrogenase (LD); whereas the other was centrifuged and stored unopened at 4 °C and analysed 24 h later. To measure analyte stability after 24 h of storage, the mean difference was calculated and compared to the total allowable error (TEa) which was used as acceptance limit. Results: Potassium (Z = - 4.28, P < 0.001), phosphate (Z = - 3.26, P = 0.001), lactate (Z = - 5.11, P < 0.001) and AST (Z = - 2.71, P = 0.007) concentrations were higher, whereas glucose (Z = 4.00, P < 0.001) and LD (Z = 3.13, P = 0.002) showed a reduction. All mean differences were smaller than the TEa and thus not clinically relevant. Bicarbonate (Z = 0.69, P = 0.491), calcium (Z = - 0.23, P = 0.815) and urea (Z = 0.81, P =0.415) concentrations were stable. Conclusions: Our less complex, user-friendly pre-analytical procedure resulted in at least 24 h stability of analytes relevant for monitoring haemodialysis, including bicarbonate. This allows shipment and analysis the next day

Impact of Polypharmacy on Health-Related Quality of Life in Dialysis Patients

INTRODUCTION: Dialysis patients are often prescribed a large number of medications to improve metabolic control and manage coexisting comorbidities. However, some studies suggest that a large number of medications could also detrimentally affect patients' health-related quality of life (HRQoL). Therefore, this study aims to provide insight in the association between the number of types of medications and HRQoL in dialysis patients. METHODS: A multicentre cohort study was conducted among dialysis patients from Dutch dialysis centres 3 months after initiation of dialysis as part of the ongoing prospective DOMESTICO study. The number of types of medications, defined as the number of concomitantly prescribed types of drugs, was obtained from electronic patient records. Primary outcome was HRQoL measured with the Physical Component Summary (PCS) score and Mental Component Summary (MCS) score (range 0–100) of the Short Form 12. Secondary outcomes were number of symptoms (range 0–30) measured with the Dialysis Symptoms Index and self-rated health (range 0–100) measured with the EuroQol-5D-5L. Data were analysed using linear regression and adjusted for possible confounders, including comorbidity. Analyses for MCS and number of symptoms were performed after categorizing patients in tertiles according to their number of medications because assumptions of linearity were violated for these outcomes. RESULTS: A total of 162 patients were included. Mean age of patients was 58 ± 17 years, 35% were female, and 80% underwent haemodialysis. The mean number of medications was 12.2 ± 4.5. Mean PCS and MCS were 36.6 ± 10.2 and 46.8 ± 10.0, respectively. The mean number of symptoms was 12.3 ± 6.9 and the mean self-rated health 60.1 ± 20.6. In adjusted analyses, PCS was 0.6 point lower for each additional medication (95% confidence interval [95% CI]: −0.9 to −0.2; p = 0.002). MCS was 4.9 point lower (95% CI: −8.8 to −1.0; p = 0.01) and 1.0 point lower (95% CI: −5.1–3.1; p = 0.63) for the highest and middle tertiles of medications, respectively, than for the lowest tertile. Patients in the highest tertile of medications reported 4.1 more symptoms than in the lowest tertile (95% CI: 1.5–6.6; p = 0.002), but no significant difference in the number of symptoms was observed between the middle and lowest tertiles. Self-rated health was 1.5 point lower for each medication (95% CI: −2.2 to −0.7; p < 0.001). DISCUSSION/CONCLUSION: After adjustment for comorbidity and other confounders, a higher number of medications were associated with a lower PCS, MCS, and self-rated health in dialysis patients and with more symptoms

CD4-positive T cells and M2 macrophages dominate the peritoneal infiltrate of patients with encapsulating peritoneal sclerosis

Background Encapsulating peritoneal sclerosis (EPS) is a severe complication of peritoneal dialysis (PD). Previously, it has been shown that infiltrating CD4-positive T cells and M2 macrophages are associated with several fibrotic conditions. Therefore, the characteristics of the peritoneal cell infiltrate in EPS may be of interest to understand EPS pathogenesis. In this study, we aim to elucidate the composition of the peritoneal cell infiltrate in EPS patients and relate the findings to clinical outcome. Study Design, Setting, and Participants We studied peritoneal membrane biopsies of 23 EPS patients and compared them to biopsies of 15 PD patients without EPS. The cellular infiltrate was characterized by immunohistochemistry to detect T cells(CD3-positive), CD4-positive (CD4+) and CD8-positive T cell subsets, B cells(CD20-positive), granulocytes(CD15-positive), macrophages(CD68-positive), M1(CD80-positive), and M2(CD163-positive) macrophages. Tissues were analysed using digital image analysis. Kaplan-Meier survival analysis was performed to investigate the survival in the different staining groups. Results The cellular infiltrate in EPS biopsies was dominated by mononuclear cells. For both CD3 and CD68, the median percentage of area stained was higher in biopsies of EPS as opposed to non-EPS patients (p<0.001). EPS biopsies showed a higher percentage of area stained for CD4 (1.29%(0.61-3.20)) compared to CD8 (0.71%(0.46-1.01), p = 0.04), while in the non-EPS group these cells were almost equally represented (respectively 0.28% (0.05-0.83) versus 0.22%(0.17-0.43), p = 0.97). The percentage of area stained for both CD80 and CD163 was higher in EPS than in non-EPS biopsies (p<0.001), with CD163+ cells being the most abundant phenotype. Virtually no CD20-positive and CD15-positive cells were present in biopsies of a subgroup of EPS patients. No relation was found between the composition of the mononuclear cell infiltrate and clinical outcome. Conclusions A characteristic mononuclear cell infiltrate consisting of CD4+ and CD163+ cells dominates the peritoneum of EPS patients. These findings suggest a role for both CD4+ T cells and M2 macrophages in the pathogenesis of EPS

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-beta 1, and vascular endothelial growth factor

Introduction: Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFb1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods: Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results: Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGF beta 1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGF beta 1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 +/- 4.5 vs. 0.91 +/- 0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions: Peritoneal expression of CCN2, TGF beta 1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study

Health-related quality of life and symptom burden in patients on haemodialysis

BACKGROUND: Patients on haemodialysis generally experience poor health-related quality of life (HRQoL) and a broad range of physical and mental symptoms, but it is unknown whether this differs between younger and older patients. We aimed to describe the trajectories of HRQoL and symptom burden of patients &lt; 70 and ≥ 70 years old, and to assess the impact of symptom burden on HRQoL.METHODS: In incident Dutch haemodialysis patients, HRQoL and symptoms were measured with the 12-item Short Form Health Survey and Dialysis Symptom Index. We used linear mixed models for examining the trajectories of HRQoL and symptom burden during the first year of dialysis, and linear regression for the impact of symptom burden on HRQoL.RESULTS: In 774 patients, the trajectories of physical HRQoL, mental HRQoL, and symptom burden were stable during the first year of dialysis. Compared with patients aged &lt; 70 years, patients ≥ 70 years reported similar physical HRQoL (mean difference -0.61, 95% CI -1.86; 0.63), better mental HRQoL (1.77, 95% CI 0.54; 3.01), and lower symptom burden (-2.38, 95% CI -5.08; 0.32). With increasing symptom burden, physical HRQoL declined more in older than in younger patients (β -0.287 versus -0.189, respectively, p-value for interaction = 0.007). For mental HRQoL, this decrease was similar in both age groups (β -0.295 versus -0.288, P = 0.847).CONCLUSIONS: Older haemodialysis patients generally experience a better mental HRQoL and a (non-statistically significant) lower symptom burden, compared to younger patients. Their physical HRQoL declines more rapidly with increasing symptom burden.</p

Adherence to preventive measures after SARS-CoV-2 vaccination and after awareness of antibody response in kidney transplant recipients in the Netherlands:a nationwide questionnaire study

BACKGROUND: Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyse the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate its effectiveness.METHODS: In this large-scale, national questionnaire study, questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorised as non-responder (≤50 BAU/mL), low-responder (&gt;50 ≤ 300 BAU/mL) or high-responder (&gt;300 BAU/mL), and shared with participants as a correlate of protection. Participants of whom demographics on sex and age, blood samples and completed questionnaires were available, were included. Our study took place between February 2021 and January 2022. The primary outcome of adherence before and after vaccination was assessed between August and October 2021 and compared via the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and non-adherence, and adherence on acquiring SARS-CoV-2 infection. This study is registered at ClinicalTrials.gov (NCT04841785).FINDINGS: In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after vaccination (4.56, IQR 4.11-4.78 and 4.22, IQR 3.67-4.67, p &lt; 0.001). Adherence after awareness of antibody response was analysed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to non-responders, low- and high-responders reported higher non-adherence. Higher adherence was associated with lower infection rates before and after vaccination (OR 0.67 [0.51-0.91], p = 0.008 and OR 0.48 [0.28-0.86], p = 0.010).INTERPRETATION: Adherence decreased after SARS-CoV-2 vaccination and in KTRs who were aware of a subsequent antibody response compared with those without. Preventive measures in this vulnerable group seem to be effective, regardless of vaccination status. This study starts a debate on sharing antibody results with the patient and future studies should elucidate whether decreased adherence in antibody responders is justified, also in view of future pandemics.FUNDING: The Netherlands Organization for Health Research and Development and the Dutch Kidney Foundation.</p

Onverwachte gevolgen van monoklonale gammopathie

Monoclonal gammopathy of undetermined significance (MGUS) is a common haematological disorder characterized by the presence of a monoclonal protein (M-protein). MGUS is considered an asymptomatic 'innocent' pre-malignant precursor condition of - mostly - multiple myeloma, without indication for treatment. We present three cases illustrating that MGUS can lead to serious problems. The first patient, a 51-year-old female, presented with polyneuropathy due to anti-MAG antibodies related to IgM MGUS. The second patient, a 37-year-old female, presented with proteinuria due to immunotactoid glomerulopathy caused by renal monoclonal IgG deposition associated with MGUS. The third patient, a 55-year-old female, presented with severe bleeding caused by an aspecific inhibitor of the coagulation cascade as part of IgG MGUS. In conclusion, in addition to the risk of progression to an overt haematological malignancy, MGUS can lead to severe symptoms and significant organ damage by auto-antibody activity or pathological accumulation in tissues of its toxic M-protein

Systemic vasculitis in myelodysplastic syndromes

The development of immunological abnormalities in various neoplasms is a rather common phenomenon. The prevalence of life-threatening systemic vasculitis in malignancy, however, is much lower. Nonetheless we found an unexpected frequency of several autoimmune manifestations, including systemic vasculitis, in certain myelodysplastic syndromes.We illustrate this finding with the case of a 43-year-old man with signs of polyarteritis nodosa-like systemic vasculitis during progression of chronic myelomonocytic leukaemia. Subsequently, we review the literature on the combination of myelodysplastic syndromes and systemic vasculitis and discuss the prognostic consequences, considerations for treatment and possible pathophysiological mechanisms.Univ Med Ctr Utrecht, Dept Haematol, Utrecht, NetherlandsUniv Fed Sao Paulo, Dept Haematol, Sao Paulo, BrazilUniv Med Ctr Utrecht, Dept Hypertens & Nephrol, Utrecht, NetherlandsUniv Fed Sao Paulo, Dept Haematol, Sao Paulo, BrazilWeb of Scienc