Systemic and local complement activation in peritoneal dialysis patients via conceivably distinct pathways.

BACKGROUND: Despite several advantages compared to haemodialysis (HD), peritoneal dialysis (PD) remains an underused dialysis technique due to its high technique failure rate related to membrane fibrosis and peritonitis events. Previous work has suggested a harmful role for the complement system in these processes, highlighting the need for a more comprehensive examination in PD. METHODS: Plasma levels of C1q, mannose-binding lectin (MBL), Properdin, Factor D, C3d/C3-ratio and soluble membrane attack complex (sC5b-9) were determined in PD patients (n = 55), HD patients (n = 41), non-dialysis chronic kidney disease (CKD) patients (n = 15) and healthy controls (n = 14). Additionally, C1q, MBL, Properdin, Factor D and sC5b-9 levels were assessed in the peritoneal dialysis fluid (PDF). In a subgroup, interleukin-6, matrix metalloproteinase-2 (MMP-2), myeloperoxidase (MPO) and elastase were measured in the PDF. RESULTS: PD patients had significantly higher systemic levels of sC5b-9 compared to healthy controls, CKD and HD patients (p < 0.001). Plasma levels of C1q and C3d/C3-ratios were significantly associated with systemic sC5b-9 levels (p < 0.001). Locally, sC5b-9 was detected in the PDF of all PD patients, and levels were approximately 33% of those in matched plasma, but they did not correlate. In the PDF, only Properdin levels remained significantly associated with PDF sC5b-9 levels in multivariate analysis (p < 0.001). Additionally, PDF levels of sC5b-9 positively correlated with elastase, MPO and MMP-2 levels in the PDF (p < 0.01). CONCLUSIONS: Our data reveal both systemic and local complement activation in PD patients. Furthermore, these two processes seem independent considering the involvement of different pathways and the lack of correlation.

Outcomes of COVID-19 in peritoneal dialysis patients: A report by the European Renal Association COVID-19 Database.

BACKGROUND: The clinical course of COVID-19 in peritoneal dialysis (PD) patients has so far only been analysed in relatively small, often single-centre case series. Therefore, we studied patient- and disease-related characteristics and outcomes of COVID-19 in a larger European cohort of PD patients. METHODS: We used data from the European Renal Association COVID-19 Database (ERACODA) on PD and haemodialysis (HD) patients with COVID-19 (presentation between February 2020 and April 2021). Hazard ratios (HR) for mortality at 3 months were calculated using Cox proportional-hazards regression. In addition, we examined functional and mental health status among survivors at this time point as determined by their treating physician. RESULTS: Of 216 PD patients with COVID-19, 80 (37%) were not hospitalised and 136 (63%) were hospitalised, of whom 19 (8.8%) were admitted to an intensive care unit. Mortality at 3 months for these subgroups was 18%, 40%, and 37%, respectively (p = 0.0031). Compared with HD patients, PD patients had higher mortality (crude HR: 1.49; 95% CI: 1.33-1.66), even when adjusted for patient characteristics and disease severity (adjusted HR: 1.56; 95% CI: 1.39-1.75). Follow-up data on 67 of 146 patients who survived COVID-19 showed functional recovery to pre-COVID-19 levels in 52 (78%) and mental recovery in 58 patients (87%) at 3 months after the COVID-19 diagnosis. CONCLUSION: The mortality rate in the first 3 months after presentation with COVID-19 is high, especially among PD patients who were hospitalised. PD patients with COVID-19 had a higher mortality risk than HD patients. The majority of surviving patients recovered both functionally and mentally from COVID-19 within 3 months.

Differences in shuntflow (Qa), cardiac function and mortality between hemodialysis patients with a lower-arm fistula, an upper-arm fistula, and an arteriovenous graft.

BACKGROUND: High-flow vascular accesses may contribute to cardiovascular morbidity and mortality in hemodialysis patients. Since shuntflow (Qa) varies between vascular access types, the current study aims to investigate differences in left ventricular hypertrophy (LVH), systolic and diastolic function parameters, and all-cause mortality between patients with a lower-arm arteriovenous fistula (AVF), an upper-arm AVF, and an arteriovenous graft (AVG). METHODS: A post hoc analysis of 100 patients was performed in a single-center, prospective observational study. Echocardiography examinations were performed prior to the dialysis session. Qa measurements were performed using ultrasound dilution. Patient groups were categorized by vascular access type. Cox proportional hazards models were used to investigate the association of shunt type with all-cause mortality with adjustment for potential confounders including, amongst others, age, sex, diabetes, the duration of hemodialysis treatment, shunt vintage, and Qa. RESULTS: Patients with an upper-arm AVF had significantly (p < 0.001) higher Qa (median 1902, IQR 1223-2508 ml/min) compared to patients with a lower-arm AVF (median 891, IQR 696-1414 ml/min) and patients with an AVG (median 881, IQR 580-1157 ml/min). The proportion of patients with LVH and systolic and diastolic echocardiographic parameters did not differ significantly between groups. Survival analysis showed that an upper-arm AVF was associated with a significantly lower all-cause mortality (p = 0.04) compared to a lower-arm AVF. CONCLUSIONS: Patients with an upper-arm fistula had a higher Qa but similar systolic and diastolic cardiac function. Patients with an upper-arm fistula had a significantly lower risk of all-cause mortality compared with patients with a lower-arm fistula.

Changes in cerebral oxygenation and cerebral blood flow during hemodialysis - A simultaneous near-infrared spectroscopy and positron emission tomography study.

Near-infrared spectroscopy (NIRS) is used to monitor cerebral tissue oxygenation (rSO2) depending on cerebral blood flow (CBF), cerebral blood volume and blood oxygen content. We explored whether NIRS might be a more easy applicable proxy to [15O]H2O positron emission tomography (PET) for detecting CBF changes during hemodialysis. Furthermore, we compared potential determinants of rSO2 and CBF. In 12 patients aged ≥ 65 years, NIRS and PET were performed simultaneously: before (T1), early after start (T2), and at the end of hemodialysis (T3). Between T1 and T3, the relative change in frontal rSO2 (ΔrSO2) was -8 ± 9% (P = 0.001) and -5 ± 11% (P = 0.08), whereas the relative change in frontal gray matter CBF (ΔCBF) was -11 ± 18% (P = 0.009) and -12 ± 16% (P = 0.007) for the left and right hemisphere, respectively. ΔrSO2 and ΔCBF were weakly correlated for the left (ρ 0.31, P = 0.4), and moderately correlated for the right (ρ 0.69, P = 0.03) hemisphere. The Bland-Altman plot suggested underestimation of ΔCBF by NIRS. Divergent associations of pH, pCO2 and arterial oxygen content with rSO2 were found compared to corresponding associations with CBF. In conclusion, NIRS could be a proxy to PET to detect intradialytic CBF changes, although NIRS and PET capture different physiological parameters of the brain.