Monocyte Apoptosis in Uremia Is Normalized with Continuous Blood Purification Modalities

D’Intini, Vincenzo; Bordoni, Valeria; Bolgan, Irene; Bonello, Monica; Brendolan, Alessandra; Crepaldi, Carlo; Gastaldon, Fiorella; Levin, Nathan W.; Bellomo, Rinaldo; Ronco, Claudio

doi:10.1159/000074918

Cited by 22 publications

(16 citation statements)

References 16 publications

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“…This may be due to a greater accumulation of toxic factors during the acute event, as compared to patients who had a better baseline renal function. Abnormal apoptosis rates in chronic uremic patients have been previously reported by our group [18,19]. Interestingly, the plasma of CRS type 1 subjects demonstrated a stronger apoptogenic effect compared with that reported in CKD patients from our prior studies (a more than 3-fold increase).…”

Section: Discussionsupporting

confidence: 64%

“…The impaired cellular host defense is associated with an elevated degree of monocyte apoptosis in end-stage renal disease patients on long-term hemodialysis, CAPD, as well as those in predialytic uremia [17]. We have previously shown that uremic plasma could increase in vitro apoptosis rates in U937, a human monocytic cell line [18,19]. Recent studies have investigated the immune-modulation in the failing human heart and have shown activation of inflammatory cytokines in the myocardium and peripheral monocytes leading to monocyte phenotype transition, myocyte apoptosis, and activation of matrix metalloproteinase [20,21].…”

Section: Introductionmentioning

confidence: 99%

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Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis

Virzì¹,

Torregrossa²,

Cruz³

et al. 2012

Cardiorenal Med

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Background: Cardiorenal syndrome (CRS) type 1 is characterized by a rapid worsening of cardiac function leading to acute kidney injury (AKI). An immune-mediated damage and alteration of immune response have been postulated as potential mechanisms involved in CRS type 1. In this pilot study, we examined the possible role of the immune-mediated mechanisms in the pathogenesis of this syndrome. The main objective was to analyze in vitro that plasma of CRS type 1 patients was able to trigger a response in monocytes resulting in apoptosis. The secondary aim was to evaluate TNF-α and IL-6 plasma levels of CRS type 1 patients. Methods: Fifteen patients with acute heart failure (AHF) and CRS type 1 were enrolled and 20 healthy volunteers without AHF or AKI were recruited as control group. Plasma from these two groups was incubated with monocytes and, subsequently, cell apoptosis was evaluated. In addition, the activity of caspase-8 was assessed after 24 h incubation. Quantitative determination of TNF-α and IL-6 levels was performed. Results: Plasma-induced apoptosis was significantly higher in CRS type 1 patients compared with healthy controls at 72 h (78 vs. 11%) and 96 h (81 vs. 11%). At 24 h, the activity of caspase-8 was significantly higher in monocytes incubated with plasma from the CRS type 1 group. TNF-α (2.39 vs. 28.49 pg/ml) and IL-6 (4.8 vs. 16.5 pg/ml) levels were significantly elevated in the CRS type 1 group (p < 0.01). Conclusions: In conclusion, there is a defective regulation of monocyte apoptosis in CRS type 1 patients, and inflammatory pathways may have a central role in the pathogenesis of CRS type 1 and may be fundamental in damage to distant organs.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis

Virzì¹,

Torregrossa²,

Cruz³

et al. 2012

Cardiorenal Med

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“…This may indicate a higher degree of microinflammation among HD patients. These findings are in agreement with previous studies in HD and in PD patients [20][21][22] .…”

Section: Discussionsupporting

confidence: 94%

HLA-DR Expression and Apoptosis: A Cross-Sectional Controlled Study in Hemodialysis and Peritoneal Dialysis Patients

Cal¹,

Cruz²,

Corradi³

et al. 2008

Blood Purif

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Background: Altered HLA-DR expression and apoptosis have been described to reflect a state of immunological dysfunction in uremia. Here, we performed a cross-sectional, controlled study to evaluate monocyte HLA-DR expression and apoptosis in dialyzed chronic kidney disease patients. Methods: Monocyte HLA-DR expression was determined in 81 hemodialysis (HD) and 51 peritoneal dialysis (PD) patients and 40 healthy controls. By triple-color flow cytometry, we analyzed the percentage of monocytes in whole blood, the percentage of HLA-DR+ monocytes and the mean fluorescence intensity. Using U937 cell line incubated with the patients’ plasma, we analyzed the percentage of apoptosis induced after 96 h. Results: Both HD and PD patients had lower, but statistically not significant, monocyte HLA-DR expression compared to controls (96.47 ± 3.83% and 96.64 ± 3.29% respectively, versus 98.42 ± 1.05%). However, mean fluorescence intensity of HLA-DR was significantly higher in PD (149.35 ± 80.96) than in HD (99.20 ± 40.46), and controls (73.25 ± 27.78, p < 0.001). Apoptosis was higher in both HD and PD (35.14 ± 6.77 and 14.37 ± 5.03%) compared to controls (11.30 ± 2.03%, p < 0.001), and significantly higher in HD compared to PD. Conclusion: A reduced inflammatory state and the continuous solute removal in PD may attenuate immune dysfunction in uremia. In HD but not in PD patients, there was a significant correlation between the percentage of HLA-DR+ monocytes with apoptosis (R = 0.230, p = 0.04).

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“…We have previously reported that independent of hemodialysis (HD) treatment, uremia is a state that induces apoptosis, but we have also observed that patients on peritoneal dialysis (PD) have a markedly lower rate of monocyte apoptosis -essentially similar to that in healthy volunteers [11] . The occurrence of lower apoptosis rates in PD patients leads one to postulate that the continuous purifi cation of blood and uremic apoptotic mediators with continuous PD may have a benefi cial effect compared to the intermittent accumulation in HD patients.…”

Section: Introductionmentioning

confidence: 81%

Effect of Daily Hemodialysis on Monocytes Apoptosis

et al. 2005

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Uremia is associated with a state of immune dysfunction with increased susceptibility to infection and malignancy possibly related to dysregulation of immune system cell apoptosis. Peritoneal dialysis can restore plasma apoptosis activity on monocytes compared to intermittent hemodialysis. Whether the continuous modality or diverse clearance mechanisms involved are responsible is unknown. Apoptosis rates correlate with phagocytic function highlighting the benefit of efficient toxin clearance. The plasma of 16 patients on daily hemodialysis (D-HD) was incubated with U937 monocytes and compared to 18 hemodialysis (HD) patients, 5 chronic renal failure (CRF) subjects and 5 healthy volunteers (controls). Apoptosis was evaluated by immunofluorescence microscopy dyes (Hoechst 33342, propidium iodide) and annexin V cytoflowmetry at 96 h. Plasma-induced U937 apoptosis (mean values) was significantly enhanced in D-HD (18.8 ± 4.1), HD (19.67 ± 5.5) and CRF patients (20.8 ± 4.7) compared to controls (9.6 ± 3.6; p < 0.05 for CRF vs. controls, HD vs. controls and D-HD vs. controls). No significant differences were observed between D-HD, HD and CRF sera on apoptosis rate, caspase-3 activity and phagocytic capacity of U937 monocytes. This study demonstrates that the plasma of various HD schedules was unable to reduce monocyte apoptosis induced by uremia.

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Monocyte Apoptosis in Uremia Is Normalized with Continuous Blood Purification Modalities

Cited by 22 publications

References 16 publications

Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis

Cardiorenal Syndrome Type 1 May Be Immunologically Mediated: A Pilot Evaluation of Monocyte Apoptosis

HLA-DR Expression and Apoptosis: A Cross-Sectional Controlled Study in Hemodialysis and Peritoneal Dialysis Patients

Effect of Daily Hemodialysis on Monocytes Apoptosis

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