Combining neutrophil and macrophage biomarkers to detect active disease in ANCA vasculitis: a combinatory model of calprotectin and urine CD163.

Background: CD163 and calprotectin have been proposed as biomarkers of active renal vasculitis. This study aimed to determine whether the combination of serum/urine calprotectin (s/uCalprotectin) and urinary soluble CD163 (suCD163) increases their individual performance as activity biomarkers. Methods: We included 138 patients diagnosed with ANCA vasculitis (n = 52 diagnostic phase, n = 86 remission). The study population was divided into the inception (n = 101) and the validation cohorts (n = 37). We determined the s/uCalprotectin and suCD163 concentration using enzyme-linked immunoassay at the diagnostic or at the remission phase. Receiver operating characteristic (ROC) curves were conducted to assess the biomarkers' classificatory values. We elaborated a combinatorial biomarker model in the inception cohort. The ideal cutoffs were used in the validation cohort to confirm the model's accuracy in the distinction between active disease and remission. We added the classical ANCA vasculitis activity biomarkers to the model to increase the classificatory performance. Results: The concentrations of sCalprotectin and suCD163 were higher in the diagnostic compared with the remission phase (P = .013 and P < .0001). According to the ROC curves, sCalprotectin and suCD163 were accurate biomarkers to discern activity [area under the curve 0.73 (0.59-0.86), P = .015 and 0.88 (0.79-0.97), P < .0001]. The combinatory model with the best performance in terms of sensitivity, specificity and likelihood ratio included sCalprotectin, suCD163 and haematuria. Regarding the inception and the validation cohort, we obtained a sensitivity, specificity and likelihood ratio of 97%, 90% and 9.7, and 78%, 94% and 13, respectively. Conclusions: In patients with ANCA vasculitis, a predictive model combining sCalprotectin, suCD163 and haematuria could be useful in detecting active kidney disease.

Impact of dialysate sodium concentration on vascular refilling.

BACKGROUND: Although relationship between dialysate sodium concentration and hemodynamic stability has been well studied over the years, outcomes of absolute blood volume (ABV) maintenance and vascular refilling volume (Vref ) modifications were not included, as its analysis has not been easily accessible to direct investigation. However, recent studies report a simple and feasible methodology to assess ABV and Vref during hemodialysis (HD) treatments. It is the aim of this study to analyze whether sodium concentration in dialysate modifies ABV drop and Vref . METHODS: The study was performed in 19 patients under HD. During three different sessions, sodium concentration in dialysate was randomized to three different profiles: low sodium concentration (LNa, 138 mEq/L), neutral sodium concentration (NNa, 140 mEq/L), and high sodium concentration (HNa, 143 mEq/L). ABV and Vref were calculated using Kron et al methodology. RESULTS: Predialysis values of the measured parameters showed similar results for the three profiles. Sodium concentration showed an effect on ABV drop, Vref, and vascular refilling fraction (Fref ). Pair-wise comparison revealed mean ABV decreased 0.21 L less when using HNa profile versus LNa profile (p = 0.027), a mean Vref increase of 0.39 L (p = 0.038), and a mean Fref increase of 9.94% (p = 0.048). CONCLUSIONS: This study shows that the use of HNa profiles increases Vref and Fref and reduces ABV drop during dialysis treatments when compared to LNa profiles.

Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: Toward an Individualized Approach.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens, proteinase 3 (PR3), and myeloperoxidase (MPO), typically involves small blood vessels of the respiratory tract and kidneys. It includes distinct clinical syndromes: microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), and eosinophilic GPA. GPA is commonly associated with PR3-ANCA, while MPA is associated with MPO-ANCA. AAVs have a complex pathogenesis, influenced by genetics and environmental factors. There is evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation and injury, with effector T cells and activation of the alternative pathway of the complement also involved. Advances in immunosuppressive treatment have drastically reduced mortality of AAV in the past decades, opting for a more individualized approach. Careful assessment of ANCA specificity, disease activity, organ damage, and quality of life allows for a tailored immunosuppressive therapy. Contemporary AAV treatment is characterized by regimens that minimize the cumulative exposure to glucocorticoids and cyclophosphamide, and novel approaches including complement blockage and immunosuppressant combinations might be the standard of care in the future. In this review, we examine the pathogenesis, clinical approach, and evidence-based treatment options for the management of AAV patients.

Effect of Beta-Blocker Cardioselectivity on Vascular Refilling in Hemodialysis Patients.

BACKGROUND: ß-Blockers are the most frequently prescribed cardioprotective drugs in hemodialysis (HD) patients, despite their weak evidence. We sought to evaluate the effects of ß-blockers on vascular refilling during HD treatments and examine whether carvedilol, for being noncardioselective and poorly dialyzable, associates more impact than others. METHODS: The study was performed in a cohort of maintenance HD patients from a tertiary center. All patients had previous ß-blocker prescription. We conducted a prospective crossover study and measured vascular refilling volume (Vref) and vascular refilling fraction (Fref) in 2 circumstances: under ß-blocker treatment (ßb profile) and without ß-blocker effect (non-ßb profile). RESULTS: Twenty patients were included, 10 of whom were treated with carvedilol. Predialysis values were comparable between the 2 profiles. Although the ßb profile showed lower Vref and higher ABV drop, these differences did not reach statistical significance. Data showed an increase in Fref in the non-ßb profile (70.01 ± 6.80% vs. 63.14 ± 11.65%; p = 0.015). The ßb profile associated a significantly higher risk of intradialytic hypotension (IDH) (risk ratio 2.40; 95% CI: 1.04-5.55). When analyzing separately the carvedilol group, patients dialyzed under drug effect experienced a significant impairment in Vref, Fref, and refilling rate. CONCLUSIONS: Administering ß-blockers before HD associated a higher risk of IDH and a decrease in Fref. Patients dialyzed under carvedilol effect showed an impaired refilling, probably related to its noncardioselectivity and lower dializability.

Absolute blood volume variations and vascular refilling in hemodialysis patients.

The imbalance between ultrafiltration volume (UF) and vascular refilling is considered a major cause for intradialytic hypotension. Recent studies report a noninvasive method to estimate vascular refilling (VREF ) by determining absolute blood volume (ABV). It was the aim of the study to analyze variations in ABV in a group of hemodialysis (HD) patients and examine VREF . Thirty one stable chronic HD patients were studied, aged 71.07 ± 13.31 years. Dialysis duration and UF requirements were based on physician prescription. VREF was calculated as: VREF  = VUF  - ΔV where ΔV is ABV variation during dialysis treatment. ABV at the beginning of the dialysis was 6.00 ± 2.39 L (92.82 ± 33.17 ml/kg) and at the end 5.38 ± 2.32 L (82.07 ± 31.41 ml/kg). Prescribed UF was 2.64 ± 0.83 L. Mean VREF was 2.05 ± 0.80 L, with a refilling fraction of 75.75 ± 12.79%. VREF was strongly correlated with UF volume (r2 0.877), and with pre-dialysis volume overload (r2 0.617). Patients under beta-blocker treatment showed significantly lower FREF . ABV measurement is an easy and noninvasive method that allows us to study VREF during HD. We found a strong correlation between VREF and UF.

Absolute blood volume variations during hemodialysis: Does dialysate temperature play a role?

BACKGROUND: Vascular refilling occurs to preserve hemodynamic stability during hemodialysis (HD). Recent studies report a feasible and noninvasive method to determine absolute blood volume (ABV), and estimate vascular refilling during HD. The objective of this study is to analyze if lowering dialysate temperature modifies variations in ABV during HD. METHODS: The study was performed in 50 patients under HD. During two different sessions, relative blood volume was assessed using dialysate temperatures of 35.5°C (cool dialysate) and 36.5°C (neutral dialysate). ABV and vascular refilling were calculated using Kron et al methodology. RESULTS: Thirty-nine intradialytic morbid events (IMEs) were observed in 30 patients, 14 under cool dialysate and 25 during neutral dialysate. We did not found statistically differences in ABV or in refilling volume between cool and neutral temperature. When analyzing apart only those patients who presented IME, we observed lower drop in ABV in the 35.5°C dialysate treatments (0.57 L) versus 36.5°C dialysate treatments (0.71 L). When cool dialysate was used, the vascular refilling fraction tended to be higher, but data did not turn statistically significant. CONCLUSIONS: In selected groups of patients the use of cool dialysate induces lower ABV variations that could improve hemodynamic stability during HD treatments.