Low immunoglobulin G concentrations are not associated with an increased risk of peritoneal dialysis-related peritonitis.

BACKGROUND: Peritonitis is a common and severe complication of peritoneal dialysis (PD) and is associated with high morbidity and sometimes also with mortality. Identification of risk factors, as well as protective mechanisms for peritonitis, is important to reduce peritonitis-induced morbidity. According to the current literature, IgG concentrations might be associated with peritonitis in PD-treated patients. In this study, we aimed to investigate possible associations between dialysate or serum IgG concentration and peritonitis risk in a longitudinal cohort of PD-treated patients. MATERIALS AND METHODS: We analyzed prospectively collected data obtained during the first standard peritoneal permeability analysis (SPA), performed in incident PD patients, aged > 18 years who started PD treatment in our tertiary-care university hospital from January 1, 1994 until December 31, 2008. Patients were divided in groups according to dialysate or serum IgG concentrations and according to peritonitis incidence. A possible association between low dialysate or serum IgG concentrations and time to the first peritonitis episode was investigated using cox proportional hazard models. RESULTS: 120 patients were included in our analyses with a median follow-up time of 36 (16 - 92) months. No significant association between dialysate, nor serum IgG and time to peritonitis was found (HR 0.27 (95% CI 0.65 - 1.62), p = 0.911 and HR 0.87 (95% CI 0.70 - 1.68), p = 0.708, respectively). Moreover, IgG concentrations were not associated with peritonitis incidence, nor with the recurrence of peritonitis. Finally, we found no significant difference in dialysate or serum IgG concentrations between patients who remained peritonitis-free (58.0 ± 35.6 mg/L in dialysate, 11.1 ± 4.4 g/L in serum), and those who experienced a peritonitis episode during follow-up (59.5 ± 41.9 mg/L in dialysate, 10.3 ± 4.3 g/L in serum), respectively. CONCLUSION: Dialysate or serum IgG are not major determinants of local peritoneal defense against peritonitis.

Combining phosphate binder therapy with vitamin K2 inhibits vascular calcification in an experimental animal model of kidney failure.

BACKGROUND: Hyperphosphataemia is strongly associated with cardiovascular disease and mortality. Recently, phosphate binders (PBs), which are used to bind intestinal phosphate, have been shown to bind vitamin K, thereby potentially aggravating vitamin K deficiency. This vitamin K binding by PBs may offset the beneficial effects of phosphate reduction in reducing vascular calcification (VC). Here we assessed whether combining PBs with vitamin K2 supplementation inhibits VC. METHODS: We performed 3/4 nephrectomy in rats, after which warfarin was given for 3 weeks to induce vitamin K deficiency. Next, animals were fed a high phosphate diet in the presence of low or high vitamin K2 and were randomized to either control or one of four different PBs for 8 weeks. The primary outcome was the amount of thoracic and abdominal aorta VC measured by high-resolution micro-computed tomography (µCT). Vitamin K status was measured by plasma MK7 levels and immunohistochemically analysed in vasculature using uncarboxylated matrix Gla protein (ucMGP) specific antibodies. RESULTS: The combination of a high vitamin K2 diet and PB treatment significantly reduced VC as measured by µCT for both the thoracic (P = 0.026) and abdominal aorta (P = 0.023), compared with MK7 or PB treatment alone. UcMGP stain was significantly more present in the low vitamin K2-treated groups in both the thoracic (P < 0.01) and abdominal aorta (P < 0.01) as compared with high vitamin K2-treated groups. Moreover, a high vitamin K diet and PBs led to reduced vascular oxidative stress. CONCLUSION: In an animal model of kidney failure with vitamin K deficiency, neither PB therapy nor vitamin K2 supplementation alone prevented VC. However, the combination of high vitamin K2 with PB treatment significantly attenuated VC.

Impact of telehealth interventions added to peritoneal dialysis-care: a systematic review.

BACKGROUND: Telehealth could potentially increase independency and autonomy of patients treated with peritoneal dialysis (PD). Moreover, it might improve clinical and economic outcomes. The demand for telehealth modalities accelerated significantly in the recent COVID-19 pandemic. We evaluated current literature on the impact of telehealth interventions added to PD-care on quality of life (QoL), clinical outcomes and cost-effectiveness. METHODS: An electronic search was performed in Embase, PubMed and the Cochrane Library in order to find studies investigating associations between telehealth interventions and: i. QoL, including patient satisfaction; ii. Standardized Outcomes in Nephrology (SONG)-PD clinical outcomes: PD-related infections, mortality, cardiovascular disease and transfer to hemodialysis (HD); iii. Cost-effectiveness. Studies investigating hospitalizations and healthcare resource utilization were also included as secondary outcomes. Due to the heterogeneity of studies, a meta-analysis could not be performed. RESULTS: Sixteen reports (N = 10,373) were included. Studies varied in terms of: sample size; design; risk of bias, telehealth-intervention and duration; follow-up time; outcomes and assessment tools. Remote patient monitoring (RPM) was the most frequently studied intervention (11 reports; N = 4982). Telehealth interventions added to PD-care, and RPM in particular, might reduce transfer to HD, hospitalization rate and length, as well as the number of in-person visits. It may also improve patient satisfaction. CONCLUSION: There is a need for adequately powered prospective studies to determine which telehealth-modalities might confer clinical and economic benefit to the PD-community.

Influence of pH and phosphate concentration on the phosphate binding capacity of five contemporary binders. An in vitro study.

AIM: Hyperphosphataemia is associated with increased mortality and morbidity in end stage renal disease. Despite phosphate binder therapy, a large proportion of patients do not reach the treatment target. In five contemporary binders we explored the influence of pH and phosphate concentration on phosphate binding. This interaction could be of relevance in clinical practice. METHODS: Phosphate binding was quantified in vitro in 25 mL of purified water containing phosphate concentrations of 10, 15 and 20 mM and baseline pH values of 3.0 or 6.0, with a binder over 6 h. Lanthanum carbonate, calcium acetate/magnesium carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide, 67 mg of each, were used. The experiments were performed in duplicate. The primary outcome was the difference in the amount of bound phosphate for each binder after 6 h in solutions at two different pH values. Secondary outcomes were the influence of phosphate concentration on phosphate binding, next to binding patterns and phosphate binder saturation. RESULTS AND CONCLUSION: In this specific in vitro setting, lanthanum carbonate, sevelamer carbonate, calcium carbonate and sucroferric oxyhydroxide bound more phosphate in the solution with baseline pH of 3.0. Differences however were small except for lanthanum carbonate. Calcium acetate/magnesium carbonate was most effective in a solution with baseline pH of 6.0. All phosphate binders bound more phosphate in solutions with higher concentrations of phosphate. Sevelamer carbonate, calcium acetate/magnesium carbonate and sucroferric oxyhydroxide bound most phosphate in the first hour and reached maximum binding capacity in less than 6 h.

Oral health in patients with end-stage renal disease: A scoping review.

OBJECTIVES: In patients with end stage, renal disease a high rate of morbidity and mortality is present. Studies suggest that end stage renal disease may affect oral health. Therefore, the aim of this study was to perform a scoping review on periodontal disease, dental caries, xerostomia, and hyposalivation in end stage renal disease patients. MATERIALS AND METHODS: A literature search (in PubMed and Embase.com) was performed up to September 29, 2020, in collaboration with a medical information specialist. Included outcome variables were the community periodontal index, probing pocket depth, gingival index, bleeding on probing, decayed-missing-filled-teeth, carious-absent-obturated index, Xerostomia Inventory and the (un)stimulated whole salivary flow rate. RESULTS: Forty three out of 1293 studies were included in the final review comprising 7757 end stage renal disease patients. The average age was 58.3 ± 29.4 years. 28.2%-78.8% of patients reported xerostomia and the (un)stimulated salivary flow rates were significantly lower. Higher community periodontal index scores were measured in end stage renal disease patients. More decayed-missing-filled-teeth were recorded, but no differences were found between groups. CONCLUSIONS: Xerostomia and hyposalivation were highly prevalent in end stage renal disease patients. Patients have more deepened pockets, but an equal number of carious teeth compared to healthy controls.

Identifying prognostic risk factors for poor outcome following COVID-19 disease among in-centre haemodialysis patients: role of inflammation and frailty.

INTRODUCTION: The pandemic of coronavirus disease (COVID-19) has highly affected patients with comorbidities and frailty who cannot self-isolate, such as individuals undergoing haemodialysis. The aim of the study was to identify risk factors for mortality and hospitalisation, which may be useful in future disease spikes. METHODS: We collected data retrospectively from the electronic medical records of all patients receiving a diagnosis of COVID-19 between 11th March and 10th May 2020 undergoing maintenance haemodialysis at four satellite dialysis units from the Royal Free London NHS Foundation Trust, London, UK. Mortality was the primary outcome, and the need for hospitalization was the secondary one. RESULTS: Out of 746 patients undergoing regular haemodialysis, 148 symptomatic patients tested positive for SARS-CoV-2 by RT-PCR and were included in the analysis. The overall mortality rate was 24.3%. By univariate analysis, older age, ischaemic heart disease, lower systolic blood pressure, lower body mass index (BMI) and higher frailty scores were associated with higher rates of mortality (all p value < 0.05). The laboratory factors associated with mortality were higher values of WBC, neutrophil counts, neutrophil to lymphocyte ratios (NLR), C-reactive protein (CRP), bilirubin, ferritin, troponin, and lower serum albumin level (all p value < 0.05). In the logistic regression, mortality was associated with older age and higher CRP, while high levels of NLR and CRP were associated with the need for hospitalization. DISCUSSION: Haemodialysis patients are susceptible to COVID-19 and have a high mortality rate. Our study identifies prognostic risk factors associated with poor outcome including age, frailty and markers of inflammation, which may support more informed clinical decision-making.

Frailty score before admission as risk factor for mortality of renal patients during the first wave of the COVID pandemic in London.

Background: Frailty is a known predictor of mortality and poor outcomes during hospital admission. In this large renal retrospective cohort study, we investigated whether frailer COVID-19 positive renal patients had worse outcomes. Design: All SARS-Cov-2 positive renal patients aged ≥18 years who presented to the emergency department at the Royal Free Hospital or at the satellite dialysis centres from 10th of March until the 10th of May 2020, with recent data on frailty, were included. The follow up was until 26th of May 2020. Age, gender, ethnicity, body mass index, chronic kidney disease stage, modality of renal replacement therapy, co-morbidities, Rockwood clinical frailty score (CFS), C reactive protein and the neutrophil-to-lymphocyte count were collected at presentation. The primary outcome was the overall mortality rate following COVID-19 diagnosis. Secondary outcomes included the need for hospital admission. Results: A total of 200 renal patients were SARS-Cov-2 positive. In the 174 patients who had a CFS recorded, the age was 65.4 years ± 15.8 (mean ± SD) and 57,5% were male. At the end of follow up, 26% had died. Frail patients (CFS 5-7) were more than three times more likely to die compared to less frail patients (CFS of 1-4) (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.0-10.6). 118 patients (68%) required admission, but there was no difference in hospital admission rates for frail vs non-frail patients (OR 0.6, CI 0.3-1.7). Conclusions: Frailty is a better predictor of mortality than age and co-morbidities in COVID-19 positive renal patients.

The role of kidney transplantation and phosphate binder use in vitamin K status.

BACKGROUND: Cardiovascular disease is the leading cause of death in end-stage renal disease and is strongly associated with vascular calcification. Both kidney transplantation and phosphate binders may lower the risk of vascular calcification. Vascular calcification is actively inhibited by vitamin-K-dependent matrix γ-carboxyglutamic acid protein (MGP). Whether kidney transplantation or phosphate binders affect vitamin K status is unknown. Therefore, we studied the influence of kidney transplantation and phosphate binder use on vitamin K status. METHODS: We measured plasma desphospho-uncarboxylated MGP (dp-ucMGP), a marker reflecting low vitamin K status, in a cross-sectional study of patients on hemodialysis (n = 82), peritoneal dialysis (n = 31) or who recently received a kidney transplantation (n = 36). By medication inventory, we assessed phosphate binder use. With linear regression, we assessed the influence of kidney transplantation and phosphate binder use on natural-log-transformed dp-ucMGP, adjusting for potential confounders. RESULTS: Mean age of patients was 52±13 years; 102 (68%) were male. Dp-ucMGP levels were significantly lower in kidney transplant recipients (median 689 pmol/L) compared to patients on dialysis (median 1537 pmol/L, p<0.001). Eighty-nine patients on dialysis used phosphate binders. Using any phosphate binder was not associated with dp-ucMGP levels (median 1637 pmol/L, p = 0.09) compared to no phosphate binders (median 1142 pmol/L). Twenty-six patients used sevelamer monotherapy, which was associated with higher dp-ucMGP levels (median 1740 pmol/L, p = 0.04) after adjusting for age, sex and vitamin K antagonist use. CONCLUSIONS: Recent kidney transplantation is associated with lower dp-ucMGP levels suggesting improved vitamin K status after transplantation. Sevelamer monotherapy is associated with higher dp-ucMGP levels suggesting worsening of vitamin K status. Both findings warrant more attention to vitamin K status in patients on dialysis, as vitamin K is necessary for protection against vascular calcification.